Self-awareness, self-regulation, and self- transcendence (S-ART): a framework for understanding the neurobiological mechanisms of mindfulness

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Citation Vago, David R., and David A. Silbersweig. 2012. Self-Awareness, Self-Regulation, and Self-Transcendence (S-ART): a Framework for Understanding the Neurobiological Mechanisms of Mindfulness. Front. Hum. Neurosci. 6. doi:10.3389/fnhum.2012.00296.

Published Version doi:10.3389/fnhum.2012.00296

Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:32689444

Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA REVIEW ARTICLE published: 25 October 2012 HUMAN NEUROSCIENCE doi: 10.3389/fnhum.2012.00296 Self-awareness, self-regulation, and self-transcendence (S-ART): a framework for understanding the neurobiological mechanisms of mindfulness

David R. Vago*andDavid A. Silbersweig

Functional Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Boston, MA, USA

Edited by: Mindfulness—as a state, trait, process, type of meditation, and intervention has proven Amishi P. Jha, University of Miami, to be beneficial across a diverse group of psychological disorders as well as for general USA stress reduction. Yet, there remains a lack of clarity in the operationalization of this Reviewed by: construct, and underlying mechanisms. Here, we provide an integrative theoretical Jeremy R. Gray, Michigan State University, USA framework and systems-based neurobiological model that explains the mechanisms by Judson Brewer, Yale University which mindfulness reduces biases related to self-processing and creates a sustainable School of Medicine, USA healthy mind. Mindfulness is described through systematic mental training that develops *Correspondence: meta-awareness (self-awareness), an ability to effectively modulate one’s behavior David R. Vago, Functional (self-regulation), and a positive relationship between self and other that transcends Neuroimaging Laboratory, Department of Psychiatry, Brigham self-focused needs and increases prosocial characteristics (self-transcendence). This and Women’s Hospital, Harvard framework of self-awareness, -regulation, and -transcendence (S-ART) illustrates a Medical School, 75 Francis Street, method for becoming aware of the conditions that cause (and remove) distortions Boston, MA 02115, USA. or biases. The development of S-ART through meditation is proposed to modulate e-mail: [email protected] self-specifying and narrative self-networks through an integrative fronto-parietal control network. Relevant perceptual, cognitive, emotional, and behavioral neuropsychological processes are highlighted as supporting mechanisms for S-ART, including intention and motivation, attention regulation, emotion regulation, extinction and reconsolidation, prosociality, non-attachment, and decentering. The S-ART framework and neurobiological model is based on our growing understanding of the mechanisms for neurocognition, empirical literature, and through dismantling the specific meditation practices thought to cultivate mindfulness. The proposed framework will inform future research in the contemplative sciences and target specific areas for development in the treatment of psychological disorders.

Keywords: mindfulness, meditation, contemplative, self-regulation, self-awareness, self, brain networks

“To study the Way is to study the self. To study the self is to forget old contemporary model that is heavily influenced by Jon Kabat- the self. To forget the self is to be enlightened by all things. To be Zinn’s Mindfulness-Based Stress Reduction (MBSR) course, an enlightened by all things is to remove the barriers between one’s self adaptation of specific Buddhist techniques intended for general and others.” (Dogen, 2002) stress reduction (Kabat-Zinn, 1990). The historical model for training the mind has similar goals to the contemporary west- ern medical model: both are interested in reducing suffering, INTRODUCTION enhancing positive emotions, and improving quality of life. In the last two decades, the concept of mindfulness as a state, Although the contemporary view of the concept, “mindful- trait, process, and intervention has been successfully adapted ness” is increasingly becoming part of popular culture, there in contexts of clinical health and psychology, especially with remains no single “correct” or “authoritative version” of mindful- relation to treating stress and targeting emotion dysregulation. ness and the concept is often trivialized and conflated with many Operationalizing mindfulness has been somewhat challenging common interpretations. Mindfulness is described as (1) A tem- given the plurality of cultural traditions from which the con- porary state of non-judgmental, non-reactive, present-centered cept originates, the difficulty with which it is measured, and its attention and awareness that is cultivated during meditation distinction from its common usage [see Baer (2003); Dimidjian practice; (2) An enduring trait that can be described as a dispo- and Linehan (2003);BrownandRyan(2004); Grossman (2008); sitional pattern of cognition, emotion, or behavioral tendency; Gethin (2011)]. (3) A meditation practice; (4) An intervention. Dispositional Generally speaking, there are two models for cultivating mind- mindfulness is now measured by at least eight self-report scales fulness in the context of meditation practice—a 2500-year old that are often uncorrelated with each other (Grossman and Van historical model that is rooted in Buddhist science and a 25-year Dam, 2011). These semantic differences are problematic in the

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laboratory setting. Here we attempt to address this conceptual remember.” Most conceptualizations of mindfulness from the problem by synthesizing a comprehensive conceptual framework Buddhist perspective emphasize a close and constant connection of self-processing in the context of neurobiological mechanisms between the functions of memory and attention (Thera, 1962). In by which mindfulness functions and that focuses on the goals of fact, on closer examination, mindfulness can be described as the mindfulness-based meditation practice: to reduce suffering and continuous discriminative attentional capacity for encoding and create a sustainable healthy mind. recollecting experiences efficiently—without forgetfulness or dis- The proposed framework for understanding mindfulness traction, and in the appropriate context (Thera, 1962; Analayo, focuses on self-processing and the underlying neural sys- 2003; Wallace, 2006); however, from the classical Buddhist con- tems involved in self-awareness, -regulation, and -transcendence text, views on the concept of mindfulness vary considerably (S-ART). Different approaches to understanding mindfulness (Dreyfus, 2011; Dunne, 2011). The Satipatthana¯ Sutta, one of the may focus on one aspect more than another—S-ART attempts most influential Buddhist texts, describes the practice of mind- to synthesize a unified framework that integrates the traditional fulness as a direct path to the “cessation of suffering,” and as a Buddhist and contemporary models. The S-ART framework fundamental quality or skill amongst a set of mental qualities operates using the underlying premise that our perception, cog- developed through specific meditation practices (Analayo, 2003). nitions, and emotions related to our ordinary experiences can be So as to avoid confusion, we refer to the attentional skill here as, distorted or biased to varying degrees. Depending on certain dis- “mindful awareness.” positional factors, these biases are sometimes pathological, but In the Buddhist context, suffering (Pali: dukkha) is related exist on a spectrum and may therefore be present without any to a lack of awareness for the following fundamental char- clear psychopathology. Within this framework, mindfulness is acteristics of experience: (1) Habitual craving or attachment described to reduce such biases through specific forms of mental (to sensory/mental objects we like) and/or aversion (to sen- training that develop meta-awareness of self (self-awareness), an sory/mental objects we don’t like); (2) All phenomena (includ- ability to effectively manage or alter one’s responses and impulses ing the concept of self) are impermanent (they arise and pass (self-regulation), and the development of a positive relationship away). The characteristics are thought to be based on an inflated between self and other that transcends self-focused needs and sense of self-importance or self-loathing (Thera, 1962). These increases prosocial characteristics (self-transcendence). In sup- characteristics of suffering are incorporated into the more con- port of S-ART, six neurocognitive component mechanisms that temporary model of suffering illustrated in Figure 1,inwhich are highly integrated and strengthened together through inten- habitual information processing biases reify a dysfunctional self- tional mental strategies underlying the practice and cultivation schema. In order to reduce suffering, the path of mindful- of mindfulness are proposed to modulate networks of self- ness is described to specifically place great emphasis on four processing and reduce bias. These mechanisms include intention particular tightly coupled qualities or skills which are devel- and motivation, attention and emotion regulation, extinction and oped through the prescribed meditative techniques, including reconsolidation, prosociality, non-attachment, and de-centering. (1) A balanced intensity of effort and diligence (Pali: at¯ api¯ ), Thus, rather than reducing mindfulness down to a unitary (2) Wisdom of clear discernment or phenomenal clarity (Pali: dimension, the S-ART describes mindfulness in a broader frame- sampajaˇna), (3) Mindful awareness, and (4) Freedom from desire work of perceptual, physiological, cognitive, emotional, and and discontent (Pali: vineyya loke abhijjha-domanassa¯ . m), a form behavioral component processes. of equanimity. Equanimity (Pali, upekkha¯)istranslatedas“on- looking” or “watching things as they arise” and is described to OPERATIONALIZING MINDFULNESS—INTEGRATING THE involve a balance of arousal without hyperexcitability or fatigue HISTORICAL AND CONTEMPORARY PERSPECTIVES (Buddhaghosa, 1991). The application of equanimity involves DEFINING MEDITATION AND MINDFULNESS FROM THE HISTORICAL impartiality without bias or discrimination arising from a sense of PERSPECTIVE detachment from the attraction or aversion to ongoing experience In the historical Buddhist context, the term meditation is used to (Gunaratana, 2002; Wallace, 2006; Bodhi, 1999). Phenomenal translate the Sanskrit term bhävana and its Tibetan equivalent clarity refers to the intensity (or perceptual acuity) in which sgoms. Etymologically, the Sanskrit term connotes the notion of each moment is experienced. Qualities like equanimity and clar- “cultivation,” or “causing to become” and the Tibetan equivalent, ity develop over time along with mindful awareness, while one refers to “development of familiarity” (Thera, 1962; Rahula, 1974; learns to neither suppress nor fixate on what is arising in sen- Bodhi, 1999; Jinpa, 2009). In light of these definitions, it should sory experience moment to moment. In concert with the other be clear that a traditional emphasis of most meditation practice three qualities, mindful awareness is thought to be critical for is that of mental development, in which the practitioner is culti- improving access and insight toward subject-object relations, vating a general sense of well-being and virtue along with a level such that the most fundamental nature of objects (including of deep familiarity with one’s inner mental landscape, and one’s the self) is perceived “as they truly are,” without distortions or patterns of behavior (i.e., nature of mind) (Rahula, 1974; Bodhi, biases inherent in cognition (Thera, 1962; Brown and Ryan, 2004; 1999; Wallace, 2011). Wallace, 2006). This undistorted form of insight or experienc- One of the original translations of sati into the English word, ing is also referred to as “bare attention,” perception without mindfulness, was by Davids (1882). It was translated from the interpretation (Thera, 1962; Analayo, 2003). The four qualities, Pali root, sati (Sanskrit: smr.ti), literally meaning “memory,” and including mindful awareness, critically facilitate the develop- closely related to the verb, sarati, referring to the process, “to ment of an advanced self-monitoring system that is the first

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FIGURE 1 | Reification of the dysfunctional narrative self based on causal influences for integrating self-identity (“ME”) over time Beck’s cognitive triad—a model for psychopathology (Beck, 1976). and negative feedback in a dysfunctional narrative that leads Dysfunctional attitudes, rumination, and negative self-focus reify the to affect-biased attention at both sensory-perceptual and cognitive self-narrative for the past, present, and future. The arrows depict levels. essential step to S-ART—gaining awareness of suffering as it is flip side of mindlessness as described in other contexts of contem- described herein. Mindful awareness is also described to be specif- porary usage. For example, The Oxford English Dictionary (3rd ically applied in a comprehensive way across four domains of edition) defines the common usage of mindful (mindfulness) as, experience: toward the body, toward feelings/sensations or affec- “full of care”; heedful, thoughtful, and references the opposite of tive tone, one’s current mental state, and toward the matrix of “extreme carelessness” (Dictionary, 2002). Langer (1989)defines interrelationships amongst all phenomena arising in one’s con- mindfulness as “sense of situational awareness,” and emphasizes sciousness (Buddhaghosa, 1991; Analayo, 2003; Wallace, 2011). that mindfulness refers to the active construction of new cate- It is important for the reader to be clear that this histori- gories and meanings when one pays attention to the stimulus cal description of mindful awareness be seen as a critical skill, properties of primarily external situations. She also emphasizes amongst others, developed in the meditation practices outlined that mindfulness can be attributed to cognitive flexibility, an exec- in Buddhist teachings. It is this combination of four qualities utive function allowing for ease in switching set. While such def- along with the four applications of mindfulness that provide initions are distinctly different from the concept of mindfulness the historical framework for mindfulness, as the path toward as we have described it above, there is likely overlapping psycho- reduced suffering and realization. Thus, our current framework logical processes between them. There is also a common practice on S-ART reflects the qualities that are emphasized here in the of “cherry picking” aspects of the meditation practices described historical perspective and outline a skill set of processes that and adding it to a clinical intervention or an education curricu- co-arise with mindful awareness and help create a sustainable lum and calling it, “mindfulness.” Although there may be benefits healthy mind. to doing such modifications, there are conceptual dangers for sci- Emphasis from most traditional texts has also been on ethical entific investigation of such modifications without qualifying the conduct (Pali: Sila) and ethical dimensions of mindfulness so that use of the term in the particular context which it is used. actions along the path of reduced suffering continually remain “wholesome” (Thera, 1962; Buddhaghosa, 1991; Bodhi, 1999). MEDITATION PRACTICES THAT CULTIVATE MINDFULNESS Ethical conduct is based on the conception of universal love and Although there is a heterogeneity amongst styles of meditation compassion for all living beings. This quality is reflected in self- practice, the S-ART framework focuses on the two core practices transcendence and the quality with which one brings awareness typically described as focused attention (FA), a type of concen- to oneself and those around us. Furthermore, the ethical empha- trative practice and insight or open monitoring (OM), a type of sis suggests the practitioner call to mind the various beneficial and receptive practice (Buddhaghosa, 1991) (for detailed description detrimental mental states in existence so that one does not forget of the practices, see (Lutz et al., 2007, 2008b). The two practices how particular patterns of behavior make one feel. Thus, one has are outlined such that once the practitioner is able to stabilize further motivation to show sympathy and compassion for those the mind, decrease mental proliferation (i.e., rumination), and around us who are experiencing negative mental states (Gethin, develop a fully absorbed state of concentration on an object like 2011). The ethical dimension is part of a constellation of positive the breath using FA, he/she can move on to OM and other more qualities that is evidently also necessary for the advancement of advanced receptive practices that have no object of focus, but the practitioner (Thera, 1962; Buddhaghosa, 1991). rather are receptive to all other physical and mental phenom- The multi-dimensional skill set underlying the construct of ena that arise (Thera, 1962; Wallace, 2006). The cultivation of mindfulness we are attempting to operationalize can be also be ethical qualities (e.g., loving-kindness, compassion, forgiveness) conceptually distinguished from the more familiar notion for the through specific forms of meditation practices are also described

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to supplement these two core practices (Goldstein, 1976; Wallace, mainstream clinical literature, mindfulness has been described 2006; Lutz et al., 2007; Salzberg, 2011), support explicit ethi- as a form of attention that is purposeful, non-reactive, non- cal development, and has accompanied most mindfulness-based judgmental, and in the present moment (Kabat-Zinn, 1990; interventions (MBIs). In combination, these meditation prac- Baer, 2003; Bishop et al., 2004; Carmody, 2009). This concep- tices are thought to facilitate the development of S-ART. Each tualization for mindfulness originally proposed by Kabat-Zinn process model illustrated in section “Mindfulness-Based Mental has been successfully incorporated into a number of evidenced- Training: Methods for Adaptive Self-Functioning and Integrating based clinical interventions, namely MBSR (Kabat-Zinn, 1990), Self-Specific Networks Supporting S-ART” describes the over- Mindfulness-based Cognitive Therapy (MBCT) for prevention of lapping component processes that are mapped onto self-specific depression relapse (Segal et al., 2002), Mindfulness-based Relapse brain networks outlined for the S-ART framework. Prevention (MBRP) for prevention of substance use relapse in It should be noted that some traditions have equated both addiction (Bowen et al., 2010), Relaxation Response for cardio- insight and FA practice with mindfulness and have referred to vascular health and wellness (Benson, 2000), Acceptance and these individual types of meditation styles as “mindfulness med- Commitment Therapy (ACT) for a wide range of psycholog- itation” (Kabat-Zinn, 1990; Brown and Ryan, 2004; Cahn and ical problems (Hayes et al., 2006), and Dialectical Behavior Polich, 2006).Thereisnoruleconcerningtheabilitytoachieve Therapy (DBT) for the treatment of borderline personality disor- the desired resultant states through any particular order of learn- der (Linehan, 1993). The successes of MBIs have been measured ing these practices, or whether they are practiced simultaneously, intermsofdecreasingclinicalsymptomsandimprovingoverall or through the practice of one method alone. Wallace (2006) mental health and well-being. The changes are based on the gen- emphasizes that mindfulness is cultivated in Samatha practice, eral framework of a manualized 8-week program of meditation and applied in the practice of Vipassana (insight), although oth- and gentle Hatha yoga training, including 26 h of formal instruc- ers (Lutz et al., 2007) would argue that mindfulness can be tion (8 classes/2.5-h/ea.), variable amount of meditation time cultivated in both FA and OM practice, a position we take at home (45 min/day; averages reported of 246 min/week), plus here. Samatha practice has 10 sequential stages of development an all-day 6-h class during the 6 week (in some cases half-day) (directed attention, continuous attention, resurgent attention, (Carmody and Baer, 2009). This contemporary form of mind- close attention, tamed attention, pacified attention, fully paci- fulness training is also encouraged to be used during ordinary fied attention, single-pointed attention, attentional balance, and activities like walking, standing, and eating (Kabat-Zinn, 1982; finally samatha) that could foreseeably be examined indepen- Baer, 2003). Although there has yet to be a systematic study of dently as one progresses in the practice longitudinally. The stages the relationship between the magnitude of measured outcomes are described at length by the eighth-century Indian Buddhist and class time, a recent review of class contact hours and effect contemplative Kamalashila (Lama Xiv et al., 2001)andalsoby sizes found that reductions in number of in-class hours does not the Buddhist scholar Alan Wallace (Wallace, 2006). Only the necessarily lead to compromised outcomes (Carmody and Baer, first four stages would be considered a concentration practice, 2008). In fact, there have been reported improvements in clinical the later stages of practice correspond to deeper, more subtle symptoms and executive function in short-term training of spe- states of profound stillness and absorption (Pali: jhanas). Such cific mindfulness-based practices as short as three 20 min sessions absorptive states cultivate an experience of non-duality between (Zeidan et al., 2010) and changes in white matter connectivity subject-object relations, is thought to be experienced with joy after 11 h of training (Tang et al., 2010). and elation, and is associated with strong decreases in craving In attempts to measure the psychotherapeutic outcomes of (aversion) for positive (negative) states. Jhanas also have states MBIs, metrics for quantifying states and traits related to the of absorption that are progressive and potentially measurable construct of mindfulness have been created. Dispositional mind- through phenomenological changes in experience of the medi- fulness is currently measured by at least eight scales, items tator. To achieve the 10th stage of samatha apparently requires of which were originally generated by psychology faculty and an exceptionally high level of mastery, which could take years graduate students reportedly familiar with the construct of of training and upwards of 10,000 h of formal practice (Wallace, mindfulness and mindfulness-based psychotherapies (Feldman 2006). Other meditative practices can also be considered a con- et al., 2007; Cardaciotto et al., 2008). The scales include the centrative practice. For example, transcendental meditation (TM) Mindful Attention Awareness Scale Brown (MAAS) (Brown centers attention on the repetition of a mantra; however, the and Ryan, 2003), Southampton Mindfulness Questionnaire method places primary emphasis on the resultant states of con- (SMQ) (Chadwick et al., 2008), Philadelphia Mindfulness Scale tinued practice related to an absence of concentrative effort and (PHLMS) (Cardaciotto et al., 2008), Toronto Mindfulness Scale the development of a witnessing, thought-free “transcendental (TMS) (Lau et al., 2006), Freiburg Mindfulness Inventory awareness” (Mahesh Yogi, 1995). (FMI) (Walach et al., 2006), Revised Cognitive and Affective Mindfulness Scale (CAMS-R) (Feldman et al., 2007), Kentucky CONTEMPORARY DEFINITIONS OF MINDFULNESS Inventory of Mindfulness Skills (KIMS) (Baer et al., 2004), and Contemporary psychology and psychiatry have adopted secular- Five Facet Mindfulness Questionnaire (FFMQ) (Baer et al., 2006). ized forms of mindfulness practice as an approach for increas- The FFMQ has the advantage over other measures given that it ing awareness and responding skillfully to mental processes was developed based on the items of five existing self-report mea- that contribute to emotional distress and maladaptive behav- sures. Factor analyses of these measures resulted in five facets ior (Kabat-Zinn, 1990; Bishop et al., 2004; Carmody, 2009). In of mindfulness including (1) An enhanced capacity for noticing

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or attending to internal and external experiences (OBSERVING); Herein, we expand upon these component processes by focusing (2) An enhanced capacity for noting and labeling internal on neural systems of self-processing and mapping neurocognitive experiences (feelings, images, and thoughts; DESCRIBING); (3) processes that support mindfulness-based meditation practices An enhanced capacity for acting with present-centered aware- onto such systems. ness rather than on “automatic pilot”—lost in the past or the future (acting with AWARENESS); (4) An enhanced ability BIASED SELF-PROCESSING: A CONTEMPORARY MODEL FOR to take a non-evaluative, non-judgmental stance toward inner SUFFERING thoughts, images, and feelings and outer experiences (NON- The common thread that ties the historical and contemporary JUDGEMENT); and (5) An enhanced ability to allow thoughts, models of mindfulness together in the S-ART framework is an images, and feelings to come and go without reacting to them element of suffering and a distorted or biased sense of self, one’s or getting carried away by them (NON-REACTIVITY). These relation to others, events, and the external world. In studies of five facets have shown very consistent changes with meditation attention to emotion in the general population or in a clini- training and symptom improvement (Baer, 2011). Each of the cal population, bias has referred to the tendency or extent to measures has their respective internal validity; however serious which emotional stimuli with either a negative or positive valence methodological and conceptual issues remain in the interpreta- may be processed differently in comparison to neutral material. tion of changes on the FFMQ and amongst all the self-report Interestingly, one of the goals of mindfulness-based practice is measures of mindfulness (see Grossman and Van Dam, 2011). to make no such distinction between positive, negative, or neu- For example, there is a strong possibility for semantic differences tral valence and treat all incoming stimuli with impartiality and in understanding by responders, there is a variability in defini- equipoise. In relation to self-processing, affect-biased attention is tions of mindfulness from the Buddhist traditions and amongst associated with distortions in initial attention allocation toward the measures themselves, features of prosocial behavior or affec- momentary experience and/or subsequent information process- tive style transformation are not accounted for, and there is strong ing that either follows immediately after an emotional stimulus or potential bias in inventory developers and responders (Grossman, is associated with real or imagined stimuli from the past or distant 2008). In addition, many of these measures rely heavily on future. The capture of perceptual resources by a given stimulus reverse-scored items in which an endorsement of the low end of is influenced not only by the characteristics of the stimulus itself, a trait scale does not imply the strong presence of its opposite but also by higher control systems acting upon the representations (Grossman and Van Dam, 2011). Although there is clearly bene- of stimuli. Attentional selection is therefore determined by the fit in using these self-report methods, the aforementioned critical outcome of competition between these multiple and potentially issues should prevent clinical research from confirming the effi- “biased” representations of the world and of one’s perception of cacy of traditional systems based on these self-report measures self in relation to the world. and provide caution in making claims about potential mecha- Through either dispositional or experiential factors, atten- nisms (Carmody, 2009; Grossman and Van Dam, 2011). Lastly, in tional bias can reflect facilitated attentional engagement toward consideration of elucidating contemporary definitions of mind- (or away from) stimuli that are contextually self-relevant (e.g., fulness, one should consider Jon Kabat–Zinn’s original intention threat for fear-related disorders), or a difficulty in disengagement forusingtheterm,“...(weused)thewordmindfulness intention- from such stimuli (Cisler et al., 2009). While engagement refers ally as an umbrella term to describe our work ...By ‘umbrella to an enhanced tendency to orient and select a given stimulus term’ I mean that it is used in certain contexts as a place-holder or location for processing, disengagement refers to the process for the entire dharma, that it is meant to carry multiple meanings by which selection and facilitated processing is withdrawn or and traditions simultaneously” (Kabat-Zinn, 2011). inhibited (Yiend, 2010). Facilitated engagement may translate to To date, there have been relatively few attempts at operational- hypervigilance or enhanced monitoring and artificially increased izing mindfulness into distinct cognitive-neuro-psycho-social perception of threat in everyday experiences, the consequence of processes or proposing a conceptual mechanistic model (see Baer, which is that all threatening stimuli (real or imagined) attract 2003; Brown and Ryan, 2003; Bishop et al., 2004; Shapiro et al., attention, consuming resources and affecting sensory-perceptual 2006; Baer et al., 2009; Carmody, 2009; Fletcher et al., 2010; systems before there is full subjective awareness (Mathews and Williams, 2010). These models have been mostly clinically ori- Mackintosh, 1998). On the other hand, avoidance refers to both ented and all have emphasized four major themes common to automatic and strategic forms of emotion regulation in which many existing psychotherapeutic approaches [see Castonguay and elaborative or evaluative processing is reduced and threat value Beutler (2005)]: (1) a present-centered orientation of awareness; is deflated. Disengagement delays are similar to what meditation (2) An attitude that consists of a constellation of positive state- practitioners refer to as “mental stickiness” and describes our nat- like qualities (open-hearted, non-judgmental; accepting) toward ural tendency to dedicate resources to an object of engagement to thoughts and feelings; (3) a positive intention or motivational the extent that few resources remain to capture any other per- component for clinical change or spiritual incentive; (4) devel- tinent environmental information until one is able to disengage opment of a form of decentering or psychological distancing (“let go”) and re-orient. Over time, hypervigilance, avoidance, from one’s thoughts and emotions. More recently, Holzel et al. and disengagement delays can become habitual, contextually self- (2011a) identified very specific component mechanisms by which relevant, and highly crystalized sensory-affective-motor scripts mindfulness functions, including attention and emotion regula- and schemas that dictate tendencies toward behavior. This form tion, body awareness, and a change in the perspective on the self. of affect-biased attention has shown to play a major role in

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causally influencing and maintaining disordered affective states a vulnerability or risk for triggering psychopathology becomes such as anxiety and depression. For example, in one of the progressively stronger over one’s lifespan (i.e., repeated negative most accepted models of psychopathology, Beck (1964)origi- self-schema), suggesting a “kindling” effect, stoking a fire that nallyproposed,“...theprocessingofexternaleventsorinternal makes the reified self more difficult to change. The reification of stimuli is biased and therefore systematically distorts the indi- the dysfunctional narrative self (NS) illustrates the contemporary vidual’s construction of his or her experiences, leading to a understanding of suffering and the S-ART framework provides variety of errors (e.g., overgeneralization, selective abstraction, mechanisms through which mindfulness practice can unravel the personalization). Underlying these distorted interpretations are cycle of dysfunctional attitudes toward the self and toward one’s dysfunctional beliefs incorporated into relatively enduring cog- relationship with the world. nitive structures or schemas” (Beck, 2008). Studies have demon- strated that individuals with either a diagnosed clinical disorder NETWORKS FOR SELF-PROCESSING THAT SUPPORT S-ART or a known vulnerability demonstrate affect-biased attention The framework for the development of S-ART rests upon exist- that is contextually self-relevant (Yiend, 2010). Individuals with ing brain networks that support systems of self-processing. These such biases may not necessarily have apparent psychopathology, systems are proposed to be subject to modulation through but more likely fall somewhere on a spectrum of function on specific mechanisms cultivated by mindfulness-based medita- which one extreme is pathological. Success of both cognitive and tion practices and which are identified in the following section mindfulness-based therapy relies on the removal of such dys- “Mindfulness-Based Mental Training: Methods for Adaptive Self- functional beliefs and distortions (through different means). The Functioning and Integrating Self-Specific Networks Supporting meditation practitioner, whom may not even be a risk for devel- S-ART.” The networks identified in the S-ART framework elabo- oping psychopathology likely has attentional or emotional biases rates upon past conceptualizations of self (James, 1892; Damasio, that are more subtle to detect. 1999; Gallagher, 2000; Legrand, 2007; Northoff and Panksepp, The model of a psychopathological self-schema is depicted in 2008) and distinguishes between two functional aspects of self- Figure 1 in which habitual negative beliefs about the self (includ- specifying processes, (1) non-conscious sensory-affective-motor ing their personal world and future), become reified through processing, referred to here as the experiential enactive self (EES); the continuous reinforcement of a feedback loop of affect-biased (2) an agentic, self-as-subject acting as awareness in the present attention influencing subjective and behavioral symptoms and moment, referred to as an experiential phenomenological self vice-versa. Formation of dysfunctional attitudes incorporated (EPS). The S-ART also distinguishes between self-specifying pro- within cognitive schemas produce automatized, efficient implicit cesses and self-related processes, which refer to the evaluative self- memories, and motor programs that represent skewed informa- as-object, reflecting the autobiographical narrative reconstructed tion processing from early perceptual stages to the cognitive inter- from the past or projected into the future. This self-reflective pretation (Beck, 1976, 2008). When these maladaptive scripts form of self-processing is referred to here as NS (Christoff et al., and schemas are active repeatedly throughout one’s daily life, 2011). Enaction, refers to the sensorimotor coupling between the itcanleadtoruminationormentalproliferation,inwhicha organism and the environment which guides embodied action stream of mental events feed off each other with no connec- (Varela et al., 1991). The EES is conceptualized similarly to the tion to the original sense impression that initiated the stream of “the physical self” described by James (James, 1890) and the “the thought. Ruminative behavior is often characterized as reducing proto-self” described by Damasio; whereas, the EPS is described information processing capacity, producing general interference similarly as the “core-self” (Damasio, 1999). This framework is by effects with ongoing task demands, and impacting ability to no means an exhaustive account of the nature of self, but is rather deploy top-down control (Yiend, 2010). This impact on informa- a simplified parcellation that is relevant to scaffold our conceptual tion processing capacity also colors the emotional tone of one’s account of self-specific processing and is susceptible to influence ongoing experience, reducing the opportunity for awareness of bythepracticeofmindfulness. one’sthoughtsorpatternsofbehaviorinresponsetoparticular There is now evidence for the existence of large scale neu- contextual triggers. ral networks for which the three mutually dependent systems of The reified representation of self depicted in Figure 1 has self referred to here can be mapped onto both functionally and a distinct pattern of perceptual, physiological, cognitive, emo- with strong anatomical specificity. One caveat to consider in the tional, and somatic activity related to each context and each interpretation of these networks is that many of the identified time in which the self is actively engaging with the external substrates do not have functional roles that are reducible to defini- or internal world. At each repeated exposure to the individ- tive functional categories, but are rather contextually dependent ual contextual features of any biased self-schema, there is a and operate on a dynamic, functional gradient which allows hypothesized non-conscious pattern completion of the entire for some functional overlap. Networks underlying self-specifying dysfunctional system that facilitates habitual forms of processing (EES and EPS) and NS processes have specifically been shown and blocks novel interpretations about oneself (e.g., positively to involve functionally distinct, and potentially competing, brain framed memories and self-schemas) and the external sensory networks that can be broadly distinguished by their contrasting world (e.g., efficient engagement and disengagement). Pattern roles in primary modes of sensation-perception, and attention completion refers to the ability of a network to retrieve an entire to the external world versus internally directed mentation involv- previously stored output pattern from a partially presented ing long-term memory [see Buckner and Carroll (2007);Vincent input pattern, increasing synaptic efficacy (Marr, 1971). Thus, et al. (2008)]. At the core of these two networks are the dorsal

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attention system (DAS) and the hippocampal-cortical memory THE ENACTIVE EXPERIENTIAL SELF (EES) system (HCMS), a component of the brain’s default network The EES network integrates efferent and reafferent processes and (Vincent et al., 2008)(SeeFigure 2). The HCMS is described as a highlights the fact that representational content can be actively task negative network given its anticorrelation with goal-directed mediating behavior while being completely outside the focus of task performance; whereas, the networks identified as the EES awareness (Roeser and Peck, 2009). Current research suggests and EPS have been identified as task-positive networks given its non-conscious processes related to self/identity involve repeated positive correlation with goal-directed activity (Fox et al., 2005; associative conditioning of interactions between the body, the Broyd et al., 2009). Furthermore, several recent studies show that environment, and the processes involving exteroception, proprio- spontaneous activity within the DAS and the HCMS is negatively ception, kinesthesia, and interoception (Damasio, 1999; Legrand, correlated—leading to their being described as anticorrelated 2007; Craig, 2009; Lenggenhager et al., 2009). Exteroception brain systems (Fox et al., 2005; Vincent et al., 2008). The task- includes the processing of information from all the five senses positive network is functionally parcellated here into the EPS and (vision, audition, olfaction, taste, touch), proprioception— EES in order to account for the differences in phenomenological the body in space, kinesthesia—the sense of movement from representation of experience that is primary sensory-perceptual musculoskeletal feedback, and interoception—the sensation and awareness (i.e., EPS), and non-conscious processing (i.e., EES). perception from the internal milieu and visceral organs, including

FIGURE 2 | Self-networks and neurocognitive systems supporting parahippocampal gyrus; HF, hippocampal formation; RSP, S-ART. This working model represents a parcellation of task positive retrosplenial cortex; PCC, posterior cingulate cortex; Dorsal ACC, (self-specifying: EPS and EES), task negative (NS), and integrative dorsal anterior cingulate cortex; DLPFC, dorsolateral prefrontal cortex; fronto-parietal control networks. It also represents the individual VLPFC, ventrolateral prefrontal cortex; TP, temporal pole, LTC, lateral components of the attentional systems and prosociality network purported temporal cortex; TPJ, temporoparietal junction; sPL, superior parietal lobe; to be modulated by mindfulness. The substrates for six component pIPL, posterior inferior parietal lobe; aIPL, anterior inferior parietal lobe; mechanisms of mindfulness within a framework of S-ART are also nAcc, nucleus accumbens; VSP, ventrostriatal pallidum; dstriatum, dorsal represented. EPS, experiential phenomenological self; EES, experiential striatum; S1, primary somatosensory cortex; AIC, anterior insular cortex; enactive self; NS, narrative self; FPCN, fronto-parietal control network; FEF, PIC, posterior insular cortex; sgACC, subgenual anterior cingulate cortex; frontal eye fields; DMPFC, dorsal-medial prefrontal cortex; AMPFC, anterior VMpo, ventromedial posterior nucleus; sc, superior colliculus; medial prefrontal cortex; VMPFC, ventromedial prefrontal cortex; PHG, BLA, basolateral amygdala; CE, central nucleus.

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heart rate, digestion, body temperature, and perspiration, among contrast to non-meditators) were found to have increased BOLD- others. The self-specifying sensory-motor convergence that is related activity in areas related to EES during FA/OM or similar proposed to contribute to the EES network can be localized to meditation practices (Lazar et al., 2000; Ritskes et al., 2003; a distributed set of interconnected spinothalamocortical regions Brefczynski-Lewis et al., 2007). In a similar population of med- [including the periaqueductal gray (PAG) and parabrachial itators, morphological increases in gray matter (GM) volume and nucleus (PBN), midbrain colliculi, thalamus, hypothalamus, concentration were found in areas related to EES, including the and posterior insular cortex (PIC)], all of which are known cerebellum, left SMA, thalamus, caudate, striatum, and parasym- to be closely involved in monitoring (orienting and tracking), pathetic control centers of the medulla (Pagnoni and Cekic, 2007; deciphering, and controlling interoceptive feedback at a non- Luders et al., 2009; Vestergaard-Poulsen et al., 2009). Similar conscious level (Damasio, 1999; Critchley et al., 2004; Corbetta findings have been found in long-term practitioners experienc- et al., 2008; Craig, 2008; Northoff and Panksepp, 2008). Self- ing a peak concentrative state using SPECT to detect cerebral relevant information first attributes some emotional tone in blood flow (CBF) (Newberg et al., 2010). One study found that the ventral posterior nucleus (Vpo) of the thalamus before activation in EES-specific areas (right putamen, PIC) negatively being somatotopically represented in the posterior and ante- correlated with individual depression scores (Beck Depression rior insula (PIC/AIC) (Craig, 2004). The insula somatotopi- inventory), supporting a role for mindfulness in homeostatic and cally and hierarchically integrates salient activity and “feel- motor function-specific regulation of emotion (Farb et al., 2010). ings” progressively in the posterior to anterior direction, where A few other studies have specifically found functional changes in non-conscious homeostatic and motor functions are mapped the striatum during meditation. Studies by Lou et al. (1999, 2005) in the most posterior aspects of the insula and more con- report decreased activity in the caudate during meditation, while textually based relations to one’s conscious experience includ- others report increases in the caudate-putamen (Lazar et al., 2000; ing hedonic, motivational, social, and emotional feelings are Tang et al., 2009; Baerentsen et al., 2010) and the ventral striatum represented more anteriorly (Critchley et al., 2004; Craig, (Kjaer et al., 2002). 2009). The EES also involves neural systems involved in prepara- THE EXPERIENTIAL PHENOMENOLOGICAL SELF (EPS) tory behavior and pre-motor aspects of goal-directed action Distinctions have been made in phenomenology and the study selection, many overlapping with the DAS. These non-conscious of consciousness to portray a form of self-specifying experience enactive systems are represented in association somatosen- in which there exists present-centered awareness, and in which sory cortices, the pulvinar, intraparietal sulcus (IPS), frontal the contents of awareness represented at the level of EES are eye fields (FEF), supplementary motor area (SMA), pre-motor accessible to cognitive systems of modulation, control, and ampli- area (PMA), cerebellum, dorsal basal ganglia, superior pari- fication (Block, 1996; Gallagher, 2000; Crick and Koch, 2003; etal lobe, and ventral lateral prefrontal cortex (VLPFC) (Decety, Raffone and Pantani, 2010). The EPS has been referred to as the 1996; Posner and Rothbart, 2009; Ashby et al., 2010; Gallese “minimal self ”(Gallagher, 2000), “agentic I”(James, 1892), the and Sinigaglia, 2010). These functionally specified areas are “knower” and “core-self” (Damasio, 2010), all implying the sense described to be tightly coupled in discrete networks of inten- of being the immediate subject of experience in the present and tional motor preparation and action (Haggard, 2005; Gallese to taking a first person perspective (FPP) without reflection or and Sinigaglia, 2010), early perceptual processing (Brown et al., evaluation (Tagini and Raffone, 2010). The EPS is proposed to 2011), search and detection (Corbetta and Shulman, 2002). be a form of higher order conscious, volitional awareness related Based on monkey lesion studies and neuroimaging findings, to exteroceptive and interoceptive experience. This includes the the VLPFC is implicated as a crucial part of the circuitry immediate motivational, social, and affective feelings associated in which associations are made between sensory cues and with experience, along with top-down attentional control mech- the actions or choices that they specify (Ridderinkhof et al., anisms found within attentional networks. Top-down processing 2004). Motor learning and procedural aspects of emotional provides support for exogenous or endogenous forms of engage- memory formation and expression are conditioned over time, ment, sustained attention, endogenous disengagement capacity, implying automatization and non-conscious enactive represen- accessibility and storage of information, and executive control tation through repeated forms of stimulus-response behavior. mechanisms to regulate encoding, retrieval, and commands for More conscious forms of specialization have been associated the expression of attention (Dehaene et al., 1994; Block, 1996; with right VLPFC activity (e.g., response inhibition) and it Laberge, 2000; Botvinick, 2007; Legrand, 2007; Craig, 2009). is likely that bilateral VLPFC plays multiple roles in both The right DLPFC and dorsal ACC have been thought to act non-conscious and conscious forms of processing, especially in in an “executive” capacity for this system, such that they may its integrated role with DLPFC, other motor areas, and the be responsible for vigilance and alertness—monitoring perfor- medial temporal lobe (Aron et al., 2004; Dillon and Pizzagalli, mance or arousal levels and regulating them accordingly (Posner 2007). and Rothbart, 1998; Raz and Buhle, 2006). Along with activ- State-dependent, sustained functional activation of the EES ity in the temporo-parietal junction (TPJ), these structures have network is likely to represent embodied enaction to support been often associated with capabilities that involve modulat- the phenomenological awareness of sensory and mental activ- ing and maintaining response readiness in preparation for an ity and regulation of attention so mind wandering is less fre- impending stimulus (Raz and Buhle, 2006; Posner and Rothbart, quent. In a number of studies, experienced meditators (in 2009).

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According to Craig (2008, 2009), the AIC represents an ulti- implicated in present-centered episodic awareness (DMPFC) and mate “global emotional moment” of the sentient self at one sensory areas (SI, SII) (Kilpatrick et al., 2011). Andrews-Hanna moment of time. The AIC in humans is unique in that it is et al. (2010) also demonstrated that a FPP episodic judgment thought to integrate the higher order, social, emotional, moti- task concerning one’s present situation activated a distinct net- vational, and cognitive components of subjective feeling states work referred to as the dorsomedial PFC (DMPFC) subsystem, through its strong functional and anatomical connectivity with including the TPJ, lateral temporal cortex (LTC), and temporal the ACC, ventral medial pre-frontal cortex (VMPFC), and lateral pole (TP). There appears to be a role for this subsystem with EPS prefrontal cortex (PFC). This uniquely human aspect of process- circuitry and prosocial behavior. Another study found that inte- ing high resolution interoceptive information places the AIC in a roceptive awareness (in contrast to exteroceptive awareness) in strong position to handle phenomenological experience related to individuals trained in MBSR recruited decreased DMPFC activ- conscious awareness and likely provides improved self-regulation ity and negative functional connectivity with PIC (Farb et al., and autonomic control (Gilbert et al., 2010). Furthermore, AIC 2012), suggesting a critical role for DMPFC in modulating pri- activation has been repeatedly shown to be inversely corre- mary interoceptive areas. The precuneus is also involved in con- lated with posteromedial cortex (PMC) [including precuneus, texts involving a FPP, as well as visuo-spatial imagery, execution PCC, retrosplenial cortex (RSP)] in functional imaging studies of and preparation of motor behavior, episodic memory retrieval, awareness and task-related attention (Craig, 2009). The PCC and and agency (Cavanna and Trimble, 2006). Furthermore, the pre- RSP have more often been associated with the NS network, sug- cuneus and surrounding PMC are amongst the brain structures gesting a mechanism for contrasting momentary awareness with displaying the highest resting metabolic rates (i.e., 35% more glu- self-reflection. cose consumption than any other brain area), suggesting a tonic A number of recent studies investigating neurobiological sub- role in self-processing. Interestingly, the precuneus is character- strates of mindfulness have indicated very specific changes in the ized by transient decreases in tonic activity during engagement function and structure of the insula and its connectivity with in NS-processing or in default mode forms of rest (Cavanna other structures related to experiential self-processing and body and Trimble, 2006). The precuneus has been found to be acti- awareness. In terms of morphometry, two cross-sectional studies vated during FA > Rest, and in OM > Rest, suggesting it play comparing GM morphometry between experienced meditators a key role in self-induced transitions between meditative and (8 weeks) and naïve controls have shown greater cortical thick- discursive rest states (Manna et al., 2010). These data further sup- ness and GM concentration in the right anterior insula (Lazar port that mindfulness training facilitates volitional flexibility for et al., 2005; Holzel et al., 2008). A more recent study however switching between the self as subject and object. Moreover, future (Holzel et al., 2011b) did not find such a change. Long-term research will have to clarify how EPS networks interact with exec- vipassana meditation practitioners (>6000 h experience) have utive attention and primary interoceptive brain areas through shown increased GM concentration in the AIC (Holzel et al., context-specific modalities of present-centered awareness. 2008), and functional increases in insular cortex have been found In the context of pain, there has been mixed results in terms during mindfulness and compassion meditative states (Farb et al., of insular activity. For example one study of experienced med- 2007; Lutz et al., 2008a; Manna et al., 2010; Ives-Deliperi et al., itators (39–1820 weeks of meditation practice), in comparison 2011). A number of MBI studies have demonstrated the func- to non-meditators, showed decreased left PIC and SII activation tional role of insular cortex in states associated specifically with in the anticipation period that continued through the experi- the EPS. For example, meditators using an experiential FPP (in ence of pain (Brown and Jones, 2010). In contrast, two studies comparison to an evaluative focus) toward a group of valenced showed no difference during anticipation and stronger activation trait descriptive words resulted in a pronounced shift away from in pain-related areas (mid-cingulate, insula, SII, and thalamus) midline cortices toward a right lateralized network comprised of during experience of pain and while maintaining a “mindful the VLPFC and DLPFC. In addition, increases in BOLD activ- state” (Grant et al., 2010a; Gard et al., 2012). Greater bilateral ity were found specifically in right AIC, somatosensory cortex activation in the PIC, along with somatosensory areas corre- (SII) and the IPL (in comparison to control subjects) (Farb et al., sponding to the nose and throat, was found in meditators given 2007). Strong functional coupling was found between the right brief training experience (4 × 20 min sessions) while practicing PIC and mPFC in novices that was not present in the medi- FA meditation (Zeidan et al., 2011). Zeidan et al. (2011)also tators, who showed more significant connectivity between right showed decreased activity in the PIC and somatosensory areas PIC and DLPFC. This suggests a fundamental neural dissociation corresponding to the site of pain stimulus while meditating in between critical structures related to interoception and evaluation the context of noxious stimuli. Interestingly, right AIC and dACC that are habitually integrated, but dissociated through medita- negatively correlated with pain intensity, while OFC activity neg- tion training. Manna et al. (2010)foundtheleftAICclusterin atively correlated with pain unpleasantness (Zeidan et al., 2011). OM practice to be positively correlated with areas related to exec- These studies of acute pain suggest meditators modulate primary utive monitoring and attention in the left hemisphere (anterior interoceptive pain processing (in comparison to controls) during PFC and sPL, STG). Further studies of meditation have found pain experience and affective dimensions of pain processing are similar increases in right AIC activity coupled with decreases in diminished. posterior parietal cortex and cortical midline structures (Creswell While most meditation practitioners often report having et al., 2007; Holzel et al., 2007; Farb et al., 2010), while others enhanced awareness of body sensations, there is a paucity of have found increased functional connectivity between areas also good evidence that they actually do so (Nielsen and Kaszniak,

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2006; Khalsa et al., 2008). For example, one study in particular with the amygdala and ventral striatal pallidal complex (including compared two groups of advanced meditators (Tibetan and nucleus accumbens), supporting the representation of affective Kundalini practitioners; >15 years formal practice) against a and motivational states through a gradient of non-conscious and control group of non-meditators at two different time points conscious forms of affective appraisal. Through an interaction on a common interoceptive heart-beat detection task and pulse with the sgACC, there is evidence suggesting a mechanism for detection task (Khalsa et al., 2008). During pulse detection, par- appraising the value of stimuli with respect to current goals and ticipants took their non-dominant wrist pulse and were required decisions, while some data suggest a role in modulating emo- to judge whether a train of exteroceptive stimuli (800-Hz, 50-ms tion and disengagement through executive control mechanisms tones) were simultaneous or non-simultaneous with pulse sensa- (Drevets et al., 2008; Roy et al., 2012). Increased NS activity tions. On neither task did the meditators perform better in terms during goal-directed tasks is often associated with excessive and of perceptual accuracy. Given the sufficient power and control repetitive elaboration or rumination, decreasing efficiency of the of the study, it is possible that awareness of heartbeat synchrony attentional system and capacity of information processing in gen- may not be a good general index of the type of awareness that eral, further supporting the claim that increased NS processing is cultivated by mindfulness training. Future studies will have can lead to negative health outcomes (Brewer, 1993; Mogg et al., to examine more subtle forms of interoceptive awareness that 1995; Rimes and Watkins, 2005; Grimm et al., 2009). appear to recruit the left AIC, for example. Other sensory modal- A number of studies investigating forms of psychopathology ities that are targets of the contemplative practice will have to be have reported decreased task-induced deactivation of the NS net- explored as well. For example, tai chi practitioners have shown to work, suggesting increased mind-wandering and self-reflection have superior tactile acuity compared to non-practitioners (Kerr during ongoing task demands (see Broyd et al., 2009). A few stud- et al., 2008). ies on states of meditation have reported decreased task-related mind wandering and increased task-related deactivation of NS THE EVALUATIVE NARRATIVE SELF (NS) activity (Farb et al., 2007; Ott et al., 2010b; Brewer et al., 2011). The NS is an evaluative, reflective form of identification that fol- Some studies of meditative states have shown a similar effect lows experience in narrative form, described in some contexts as in the context of distraction, suggesting increased engagement, the “Me-self” or “material me,” the sum total of all a person can and decreased mind-wandering and reactivity to distractions call their own across physical, social, or psychological domains: (Anderson et al., 2007; Brefczynski-Lewis et al., 2007; Pagnoni “That looks like me,” “Am I a nice guy?,” “I feel anxious” (Brewer, et al., 2008; Grant and Rainville, 2009; Farb et al., 2010; Manna 1993; Craig, 2004; Damasio, 2010; Tagini and Raffone, 2010). et al., 2010). Similarly, increased functional connectivity has been The NS is also reflected in metacognitive knowledge, access to found within areas specific to the NS network (e.g., mPFC) knowledge people have about their cognitive abilities (“I have a and regions of primary interoceptive awareness of meditators bad memory”), about cognitive strategies (“to remember a phone (∼1000 h practice) (Jang et al., 2010; Brewer et al., 2011), while number I should rehearse it”), about tasks (“categorized items are studies using the PCC as a seed found increased connectivity with easier to recall”), etc. (Flavell, 1979). There may very well be dis- dorsal ACC and DLPFC at rest and in the dorsal ACC during tinctsubstratesacrosseachdomainasthereislikelydistinctforms meditation (Brewer et al., 2011). These correlations between anti- of “me-self” in as many social relationships as there are individu- correlated networks may be interpreted as evidence for increased als who recognize each one uniquely. The common feature in the integration and volitional control in recruiting networks when NS is an awareness of a specific object, “me” to which identifica- contextually appropriate. For example, Josipovic et al. (2011) tion with, and evaluation of, specific characteristics are made. The demonstrate that such correlations are stronger during FA medi- recurrent feedback of self-identification embedded in cognitive tation, but smaller during OM forms of practice. self-schemas perpetuates a stable sense of self. This is illustrated Across a number of different MBI studies (Lazar et al., 2005; in the dysfunctional representation in Figure 1. Pagnoni and Cekic, 2007; Holzel et al., 2008, 2010, 2011b; The NS is mediated by the HCMS—a network of cortical mid- Luders et al., 2009; Vestergaard-Poulsen et al., 2009; Grant et al., line structures sometimes referred to as the “E-network” due its 2010a), increases in GM volume and density (in comparison evaluative nature (Northoff and Bermpohl, 2004; Legrand, 2007; to non-meditating controls) have been found using voxel-based Schmitz and Johnson, 2007; Legrand and Ruby, 2009). This net- morphometry (VBM) in hippocampus and PCC. Such changes work includes the VMPFC, pre- and subgenual anterior cingulate further suggest meditation training increases efficiency of mem- cortex (pACC; sgACC), medial parietal cortex (MPC), PCC, and ory networks related to the NS, forseeably providing more control RSP (see Figure 3). Because of the dense reciprocal projections over its expression. Increased GM concentration in the right hip- with anterior thalamus and hippocampus, the RSP and MPC pocampus has also been attributed to training in arousal regula- both aid in the repeated construction of identity in time and tion, suggesting another mechanism for regulating the self toward space through moment-to-moment episodic memory formation more adaptive trajectories of self-experience. The S-ART frame- (Peters et al., 2009; Spreng et al., 2009). Through interactions work suggests mindfulness critically involves working memory, between PMC and subcortical limbic structures (e.g., hippocam- efficiency of memory encoding, retrieval, and extinction pro- pus, amygdala), there is a progressive accumulation of an “auto- cesses, all aspects of hippocampal and parahippocampal activity. biographical self,” a set of memories that make up the individual’s These data also suggest an enhanced ability for pattern separa- unique past, current state, and expected future (Zelazo et al., tion (transforming similar representations into highly dissimilar, 2007; Spreng et al., 2009). The VMPFC is heavily interconnected non-overlapping representations), inhibition of mental contents

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FIGURE 3 | Mindfulness process model—concentrative practice. have a positive, negative, or neutral valence and are likely to proliferate FA meditation using the breath as the object of focus is illustrated endlessly unless awareness and de-centering promote response as an example, but the processes are proposed to be the same inhibition and disengagement. Motor learning provides a framework across concentration styles of practice. Intention is formed along with for automatization and mindfulness skill development. Effortful control motivation to practice before an executive “set” is created. is reduced through continued practice. Through practice, awareness Executive set is supported by the working memory system in itself becomes the object of attention in meta-awareness as the order to implement and maintain practice instructions. Focused meta-function is acquired as a skill. Clarity, as a form of attentional networks are recruited and sustained along with support by phenomenal intensity during practice increases as does equanimity, component mechanisms including executive monitoring, emotion which refers to impartiality reducing later attentional and emotional regulation, and response inhibition. Unintended objects of distraction stages of strategic processing that could potentially involve can include any stimulus available to extero- or interoceptive sensory prolonged sympathetic arousal, cognitive elaboration, or ruminative and mental processes. Affective responses to unintended objects can qualities.

or behavioral schemas that are unrelated to the focal goal in work- active during such effortful and controlled processing includ- ing memory, and facilitation of attentional disengagement from ing inhibition of set-switching, and inhibitory control (e.g., as distractor stimuli. in go-nogo tasks) (Posner and Petersen, 1990). The FPC has also been implicated in top-down monitoring and described by AN INTEGRATIVE FRONTO-PARIETAL CONTROL NETWORK FOR S-ART some as the “supervisory attentional gateway” (SAG) controlling Exploration of the current literature suggests that an integra- stimulus-independent and stimulus-oriented cognition (Burgess tive network supported by mindfulness may improve efficiency et al., 2007). Furthermore, FPC has been associated with coor- and guide changes in self-specific, affect-biased attention by inte- dinating information processing between multiple brain regions grating information from the three self-specific networks. The (see Vincent et al., 2008). It is these substrates that support intro- fronto-parietal control system (FPCS) [rostral frontopolar PFC spective meta-monitoring and the relational binding necessary (FPC), right VLPFC, DMPFC, dorsal ACC, DLPFC, AIC, lat- for self-awareness and self-regulation. eral cerebellum, and anterior inferior parietal lobe (aIPL)] is The FPCS has some functional overlap with the EPS network uniquely situated to integrate information coming from the other (including DLPFC, DMPFC, AIC), suggesting present-centered three systems and facilitate global reorganization or plasticity awareness is critical for self-regulation and targeting attentional amongst the networks. The aIPL and DLPFC have been impli- bias. The FPCS has been emphasized by Vincentetal.(2008) cated in working memory, and are thought to contribute to and others (Seeley et al., 2007; Liao et al., 2010; Deshpande regulating attention within this network. As described earlier, et al., 2011) to integrate task positive and task negative net- VLPFC shares conscious and non-conscious roles in recollect- works through executive control and salience processing. There ing mnemonic associations and whether there is conflict in the is now some research to suggest that inadequate integration actions/choices being made in reference to the present context between the self-specifying networks and the NS network may be (Ridderinkhof et al., 2004). The VLPFC has also shown to be a significant contributor to emotion dysregulation (Bressler and

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Menon, 2010),andaffectivebiasedattention(Todd et al., 2012). (>2500 h of practice) found increased cortical thickness in AIC, For example, Bressler and Menon (2010) suggest that salience DLPFC, anterior PFC, and sensory cortices (Lazar et al., 2005). processing by AIC and dorsal ACC play a causal role in switch- Normal age-related decline in GM volume and in attentional ing between task positive and task negative networks (Bressler performance was present in controls but not in meditators, sug- and Menon, 2010). Todd et al. (2012) proposes that affective gesting that meditation slows the natural progression of cortical biased attention operates before conscious cognitive reappraisal thinning over time. or suppression strategies, suggesting poor feedback from the EES network and subsequent prioritization of overlearned habitual MINDFULNESS-BASED MENTAL TRAINING: METHODS FOR responses. It may be the case that the development of meta- ADAPTIVE SELF-FUNCTIONING AND INTEGRATING awareness facilitates the role of FPCS in integration and increased SELF-SPECIFIC NETWORKS SUPPORTING S-ART efficiency of the networks for S-ART. Thus, through mindfulness There is now evidence to suggest that mindfulness practice can training, cognitive and emotional resources are proposed to be modulate and produce enduring neuroplastic changes, including utilized more effectively and in an adaptive fashion. gross morphological changes, across the self-specific networks, The three most widely cited brain areas of activity and gross and an integrative FPCN supporting S-ART. The extant data sup- morphological change during and in response to both FA and port a strong emphasis on activity of the self-specifying networks OM meditation training has been the DLPFC, the ACC, and the and decreased NS activity during baseline and goal-directed insula [see Lutz et al. (2007); Chiesa and Serretti (2010);Rubia activity after mindfulness training. Additionally, increased activ- (2009);Holzeletal.(2011a) for review], suggesting FPCN and ity is commonly found in the EPS network and FPCN during EPS-related processing is heavily influenced through training. meditation practice. Yet, multivariate network types of analyses Across nine different MBI studies (Lazar et al., 2005; Pagnoni have not demonstrated conclusively how all the networks inter- and Cekic, 2007; Holzel et al., 2008, 2010, 2011b; Luders et al., act in the context of meditation training and practice, during 2009; Vestergaard-Poulsen et al., 2009; Grant et al., 2010a; Manna basal states of inactivity, and during goal-directed tasks. Given et al., 2010), differences in GM volume and density (in compar- the role of the FPCN in executive control and in integrating ison to non-meditating controls) have been found using MRI in information between task positive and task negative networks, the dorsal and rostral ACC, suggesting a prominent role for the mindfulness may effectively facilitate context-appropriate switch- FPCN. Tang et al. (2007, 2009, 2010) show that as little as five ing between anticorrelated networks, rather than simply increase days (20 min/day) of Integrated Body Mind Training (IBMT), the functional activity of experiental self-processing or suppres- involving components of FA and OM produces greater activa- sion of NS. The evidence suggests state-dependent activation tion in the rACC during rest. From as little as 11 h (over 1 and integration of task positive and task negative networks sup- month) of IBMT, increases in structural connectivity were found port reduction of self-specific biases and may contribute to a indicated by increased fractional anisotropy, an MRI diffusion sustainable healthy mind; however, such hypotheses need to be tensor imaging index indicating the integrity and efficiency of further tested. Here we explicitly describe how three types of white matter connecting ACC to other cortical and subcorti- mindfulness-based meditation practices function by illustrating cal structures. One study investigating acute pain in experienced the putative neurocognitive mechanisms in conceptual process meditators found that mPFC/rACC activation was negatively cor- models (see Figures 3–5) and how each component mechanism related with pain unpleasantness ratings in a non-meditative state may map onto the self-specific networks identified above to (Brown and Jones, 2010). In the control group, the opposite cor- support S-ART. relation was found with overall lower activity, suggesting less attentional control during experience of acute pain. Two studies FOCUSED ATTENTION (FA) CONCENTRATION PRACTICE of samatha-vipassana practitioners (5000 to >10,000 h practice) FA practice involves sustained attention on a specific mental demonstrated increased BOLD activation (compared with non- or sensory object: a repeated sound or mantra, an imagined meditators and within the meditation group) in rostral ACC or physical image, or specific viscerosomatic sensations. The and DMPFC during FA meditation (Holzel et al., 2007; Manna object of focus can be anything, but the method described by the et al., 2010). Manna et al. (2010) also found meditation-specific Satipatthana¯ Sutta identifies a naturally occurring breath focus. In increases in precuneus, bilateral IFG, and right parahippocam- fact, breath is a particularly apt foundation because it integrates pal gyrus during OM > Rest condition. Interestingly, the same conscious awareness with ongoing, dynamic viscerosomatic study found that during the FA meditation, the right IFG and function. The goal of FA practice is to stabilize the mind from dis- left PIC positively correlated with meditation expertise (num- traction, torpor, and hyperexcitability, all of which are predicted ber of hours of practice) (Manna et al., 2010). Given the overlap to be negatively correlated with practice. Effort is hypothesized to across networks, these data further support a role for the FPCN be inversely correlated with practice duration, providing a neu- in improving network interactions in advanced meditators. Many robiological mechanism for advancement of the practitioner and of these activations show dominance in the left hemisphere (in resulting in decreased allocation of explicit cognitive resources comparison to rest), which may reflect increased positive disposi- over time. A process model for FA is illustrated in Figure 3. tions (Davidson and Irwin, 1999) and increased meta-awareness FA practice is described here to involve an underlying frame- (Tagini and Raffone, 2010). Furthermore, advanced meditators work of motor learning that functions to strengthen non- show resistance to age-related decline in FPCN and self-specifying conscious, associative memory processes underlying the EES brain areas. For example, one study of Vipassana practitioners network (and subcortical analogs), and which support the

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conscious, explicit processes recruited during practice. Intention, in thought or emotion, a number of mechanisms supported by a critical component of mindfulness in previous conceptual mod- mindfulness-based practices may facilitate disengagement. The els (see Shapiro et al., 2006), is described to be critical for moti- practitioner is encouraged to continually rest in awareness of vating the practitioner to begin/sustain practice and activating intero- and exteroceptive stimuli, and any cognitive or emotional EES networks that may be the initial steps for extinguishing mal- states that may arise. Through training, the practitioner can learn adaptive habitual perceptual-motor action tendencies. Intention to note and sustain attention on the arising, passing, or absence of and motivation may also target attentional tuning and affective each modality of experience—naturally reducing the frequency of control settings which contribute to affect-biased attention (Todd cognitive evaluation or rumination. Eventually, through training, et al., 2012). The instructions for practice form an executive “set” the process of mental noting becomes effortless and non-reactive, that is created and sustained by working memory processes, while qualities that describe the development of equanimity. At this attentional processes operate to focus and sustain concentration point, efficiency of the attentional system has improved, resulting on the intended object. Alerting, orienting, engagement, and dis- in decreased allotment of attentional resources toward any par- engagement all involve discrete networks (Posner and Petersen, ticular feeling, image, or thought. Cognitive emotion regulation 1990) which complement one another in their contributions to strategies like reappraisal or suppression may be more preva- the FA practice. An executive monitoring function is proposed lent in novice practitioners dealing with distraction, but less so to provide feedback when the goal state of concentration on the in advanced practitioners as attentional systems are strengthened particular object has shifted and to support the attentional pro- and qualities of equanimity arise. One may hypothesize that the cesses related to the return of focus. Meta-awareness is described changes from novice to advanced practitioner may be due to to arise as a highly developed form of executive monitor that the development of psychological processes like non-attachment, allows the practitioner to have awareness as the object of attention de-centering, or from a non-conscious shift in affect-biased atten- while simultaneously maintaining awareness in its natural state, tion and the development of meta-awareness. Whichever the whichever object of attention it may be resting upon. Sensory mechanism, maladaptive scripts and schemas related to the self clarity is presumed to increase in proportion to the strength- are proposed to be extinguished and reconsolidated through a ening of meta-awareness. Given the perspective shift one must combination of FA and OM practice. learn through development of meta-awareness, decentering is Similar meditation practices instruct the practitioner to main- described as a psychological process that may be a mechanism to tain a diffuse form of attention or ambient attentional focus such support disengagement processes and sensory clarity. as “Shikantaza” or “just sitting” in Japanese Soto Zen (Austin, Equanimity and clarity are both processes that support con- 2006); “choiceless awareness” by Krishnamurti (1969), insight centrative practice and are proposed to increase in terms of meditation from Theravada (Pali: Vipassana)(Lutz et al., 2007), efficiency and phenomenal quality through time and prac- and “absolute rest,” by other western Buddhist teachers (You ng, tice. Similar to the Buddhist description (see Section “Defining 2010). Vipassana, has also been translated as “removing the veil Meditation and Mindfulness from the Historical Perspective”), of ignorance” (Gunaratana, 2002), such that this stage of med- equanimity refers to response inhibition and emotion regulation itation practice explicitly aims at providing insight into one’s processes that reduce later attentional and emotional stages of self-related processes. In advanced practices, the practitioner can strategic processing potentially involving prolonged sympathetic reside in a non-dual level of awareness, referred to by the Buddhist arousal, cognitive elaboration, or ruminative qualities which may Abhidharma scholars as a clear understanding of no distinc- arise in response to an object of distraction. Increased clarity of tion between knowing subject and perceived or known object experience is proposed to operate as one develops an increased (Dunne, 2011). Some Buddhist traditions have referred to this phenomenal awareness of the breath and objects of distraction non-dual practice as “Open Presence” (Thangru and Johnson, arise and disappear, without necessarily affecting the cognitive 2004; Lutz et al., 2007), “open awareness,” “rig.pa” in Tibetan access of the contents of conscious experience. forms of Dzogchen (Rinpoche et al., 2006), or “phyag.chen” in Mahamudra (Thangru and Johnson, 2004). Non-dual prac- OPEN MONITORING (OM) RECEPTIVE PRACTICE tice involves the decreased reliance on engagement and disen- Figure 4 illustrates a process model for the receptive practice, gagement processes, mental noting or labeling techniques. Such OM, which is described in detail elsewhere. Novices begin by changes in the practice are likely to affect the relationship the actively monitoring and labeling external (exteroceptive) or inter- practitioner has with his/her own thoughts, so that cognitive nal (interoceptive) domains of the five senses, including viscero- structures related to ones’ thought and emotion that represent somatic states and inner speech. The specific sensory modal- reality are “de-fused” from what is considered reality itself (Hayes ities provide the scaffolding for meta-awareness to develop in et al., 2003; Dunne, 2011). each domain and in relation to self-related processing. There is an explicit distinction between engagement and disengagement ETHICAL ENHANCEMENT (EE) PRACTICES with an object early on in the practice. Provided the frame- The diminishing of grasping, aversion, and delusion that arises work of motor learning, advancement of the practitioner is likely in insight meditation practice naturally leads the practitioner to automatize aspects of attentional processing and improve to greater loving-kindness toward oneself and others (Salzberg, efficiency of engagement and disengagement processes, thereby 2011). The cultivation of loving-kindness (Pali; metta), or for- reducing bias associated with orienting of attention. For exam- giveness can also have very explicit instructions for visualization ple, when distraction arises, and the practitioner gets “stuck” and is based on the premise that all beings want to be happy.

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FIGURE 4 | Mindfulness process model—open monitoring receptive and absent in phenomenal conscious awareness is a form of emotion practice. OM meditation with no object of focus (ambient attention) is regulation and contributes to extinction and reconsolidation of maladaptive illustrated as an example, but the processes are proposed to be the same procedural and declarative memories that represent sensory-affective-motor across receptive styles of practice. Intention is formed along with motivation scripts and schemas. Affective responses may arise in response to an object of to practice before an executive “set” is created. The working memory system attention with a positive, negative, or neutral valence and are likely to proliferate helps to maintain motivation and practice instructions. Ambient (diffuse) unless awareness and de-centering promote response inhibition and attentional networks are recruited and sustained along with support by disengagement. Over time and continued practice, effortful control is reduced component mechanisms including executive monitoring, emotion regulation, and awareness itself becomes the object of attention as meta-awareness is and response inhibition. Mental noting and labeling of stimuli arising, passing, cultivated as a skill. Clarity and Equanimity increases through practice.

The following excerpt comes from one of the original teachings into contact with every day, but who does not give rise to strong of loving-kindness practice. positive nor strong negative emotions. For a “difficult” person, the practitioner is encouraged to choose an enemy, or someone Even as a mother protects with her life strongly disliked. Furthermore, the practitioner is encouraged Her child, her only child, to break down the barriers between self and other by practic- So with a boundless heart ing loving-kindness repeatedly, achieving impartiality toward the Should one cherish all living beings four persons, including him/herself, the close friend, the neutral (Karaniya metta sutta, 1.8) person, and the hostile person. The EE practice is illustrated in Figure 5. Contemporary instruction for the cultivation of loving- Compassion practice has also been described as an EE style of kindness can be found in the works of Sharon Salzberg (Salzberg practice; however, without the simultaneous cultivation of open and Bush, 1999) and by Matthieu Ricard (Ricard, 2003), but presence along with the generation of compassion, the practice such practices are based on the method found in Buddhaghosa’s has been described to be unsuccessful (see Lutz et al., 2007). 5th century text, the Path to Purification (Buddhaghosa, 1991). Compassion practice is also described as an enactive, emergent This traditional approach is characterized by progressive cultiva- process of factors in the attentional and affective domains, the tion of loving-kindness toward oneself, a good friend, a neutral intentional and insight domains, and the embodied and engaged person, a difficult person, all four of the above equally, and domainsofsubjectiveexperience(Halifax, 2012). Similar to the then gradually the entire universe. The loving-kindness is culti- metta practice described above is Tonglen, a Tibetan Buddhist vated in reference to a specific declarative (episodic) memory of term for the meditation technique translated as “giving and each particular individual or event. The practitioner is encour- taking” or “sending and receiving” in which the practitioner visu- aged to avoid choosing someone to whom they are sexually alizes taking onto oneself the suffering of others on the in-breath, attracted or who is dead (Ricard, 2003). For a “neutral” person, and on the out-breath giving happiness, joy, and kindness (Lama the practitioner is encouraged to choose someone they may come Xiv et al., 2001; Lutz et al., 2007).

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FIGURE 5 | Mindfulness process model. Ethical-enhancement (EE) others’ suffering continues recurrently as part of sustained episodic practice. Intention is formed along with motivation to practice before an memory recall. With clarity and equanimity for affective reactivity, OM executive “set” is created within the working memory system in order to practice allows the practitioner to remain mindfully aware of difficult implement and maintain practice instructions. Focused attentional networks emotions while the declarative (episodic) memory is positively reappraised. are recruited for orienting toward sustained episodic memory recall Negative associations are extinguished and reconsolidated into more involving mentalizing and shared experience. OM practice is described to adaptive or positive memories using prosocial/empathic concern for the supplement EE practice facilitating awareness of any modality of object of meditation. Continuous reappraisal along with prosocial concern experience that arises. The processes are proposed to be the same across is thought to enhance exposure, extinction, and reconsolidation processes ethical styles of practice that require imagined suffering or a particular such that new episodic memories are laid down and inhibit older declarative memory [of someone or something]. Mentalizing one’s own or maladaptive forms of the memory.

SIX COMPONENT NEUROCOGNITIVE MECHANISMS OF (3) emotion regulation; (4) memory extinction and reconsoli- MINDFULNESS dation; (5) prosociality; (6) non-attachment and de-centering. As illustrated, mindfulness is not a unitary construct and the Here we describe the neurobiological substrates of each mecha- process models are an attempt to illustrate the cognitive and nism and provide support from the extant contemplative science psychological processes that support the meditation practices. literature. These component processes provide the proposed mechanisms by which mindfulness works to increase S-ART—the framework for INTENTION AND MOTIVATION reducing self-specific biases and sustaining a healthy mind. The S- As originally proposed by Shapiro and colleagues (2006), ART framework includes six component supportive mechanisms intention is one of the fundamental building blocks out of which underlying the practice and cultivation of mindfulness as a state an array of neurocognitive mechanisms may emerge to effec- and trait: (1) intention and motivation; (2) attention regulation; tively cultivate mindfulness. Intention and motivation are based

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on inter-related aspects of affective style and biological disposi- tracking internally driven, approach forms of motivation (Heller tion, driving goal-directed behavior (Davidson and Irwin, 1999; et al., 2009) as well as regulating aspects of craving associated Ryan and Deci, 2000). External and internal motivation have with more phasic nAcc activity (Robbins and Everitt, 1996). More been distinguished as two unique classes of motivation. Although recent data suggests that decreased ventrolateral PFC (VLPFC) both classes refer to incentives of reward, external motivation activity may also be evidence for increased approach behavior and arises from the desire to approach (avoid) an externally imposed expression of positive affect (Light et al., 2011). The contribu- reward (punishment); while internal motivation arises from a tions of these substrates to habits and automatization are typically more automatic, internally driven desire to obtain reward, or sat- described to be hard-wired, but through FA/OM and ethical isfy one’s needs (Davidson et al., 2000; Ochsner and Gross, 2005; based practices, it is proposed that extinction and reconsolida- Rothman et al., 2011). People are clearly motivated to practice tion mechanisms (see Section “Extinction and reconsolidation”) by very unique factors with highly varied experiences, incentives, can shift biological set-points and modify pathological scripts and and consequences; however, through advancement of practice, schemas into more adaptive trajectories. motivation is proposed here to become more internally driven There has yet to be extensive investigation of motivation, (i.e., suggesting increased control) and less focused on outcome. intention, and reward in meditation and mindfulness research; Intention refers more specifically to a purposive plan of action however there is some PET data demonstrating increased endoge- that is selected and the timing selected for such action (Krieghoff nous dopamine release in the ventral striatum during Yoga et al., 2011). Nidra meditation (Kjaer et al., 2002), a finding accompanied Motivation and intention are described as a feedback sys- by a reported “decrease desire for action.” Expression of loving- tem for self-schema maintenance. As in any feedback system, kindness, a sense of connectedness, and feelings of trust and coop- sensory input is continually compared to a reference, and dis- eration have all shown to produce increased activity in the ventral crepancy from the reference feeds back into frontal goal-oriented striatum (Cialdini et al., 1997; Bora et al., 2009). Significant networks and eventually to pre-motor-action networks modu- increased activations in rostral ACC and OFC have been found lating functional output. If the reference is some ideal that is in the majority of non-guided meditation studies, suggesting unrealistic or if the interpretation of incoming signals related effects related to attentional focus, but also likely related to tonic to the self are continually negative in valence, then there is an intentional activity. error signal of which the rate of discrepancy reduction may never progress, perpetuating negative affect (Carver and Scheier, 2011). ATTENTION REGULATION Negatively biased cognitions and/or distorted perceptions that Volitional shifting of conscious awareness between objects of involve disinterest, disapproval, or rejection have been shown attention in a serial and/or parallel fashion is suggested to to result in nonsocial, isolating behaviors (including avoidance be a critical process for effectively managing or altering one’s and withdrawal), impaired self-regulation, and psychopathology; responses and impulses. This executive, volitional management of conversely, current data suggest that approach behavior including attention can explicitly control where and when attention shifts more engaging perceptions involving interest, approval, or accep- in top-down fashion. Regulation is also believed to occur from tance typically lead to healthier outcomes (Waikar and Craske, a bottom-up direction, such that cognitive resources are con- 1997; Sin and Lyubomirsky, 2009). Thus, internally driven moti- served and non-conscious afferent-efferent systems interact with vation to engage with experience without craving or aversion (i.e., the environment in an efficient, adaptive feedback loop with top- with equanimity) is suggested to increase self-regulation. down systems. Concentration forms of practice are proposed to Davidson and Irwin (1999) suggest there are two fundamen- increase the efficiency of the attentional system, including the tal resting patterns of neural activity for motivational systems of dissociable, but interrelated sub-components of attentional pro- approach and avoidance. Left anterior PFC activation has been cessing. The subcomponents are identified in the concentrative associated with positive affect and increased right-sided ante- practice process model (Figure 3) and include alerting and ori- rior activation with negative affect, suggesting that individual enting toward an intended object of interest, engaging with the differences in asymmetric activation of these brain regions can object, sustaining attentional focus, executive monitoring and be associated with dispositional differences in a biological set detecting distraction, disengaging from the source of distraction, point for motivation and which may contribute to the overall and re-engaging on the intended object (Posner and Petersen, outcomes of mindfulness training. Davidson and Irwin (1999) 1990; Corbetta and Shulman, 2002; Raz and Buhle, 2006; Posner further delineates functional differences between ventromedial and Rothbart, 2009). and dorsolateral sectors of PFC, suggesting that activation of the Efficiency and stability are also measured by sustained atten- former represent immediate valenced goal states along with acti- tion (i.e., vigilance and alertness), referring to the capacity to vation of the ventral striatopallidum [incl. nucleus accumbens detect unpredictable stimuli over prolonged periods of time (nAcc)], while the latter area DLPFC represent valenced goal (Posner and Rothbart, 1998). Deep engagement, vivid absorp- states in the absence of immediately present incentives. In other tion, or concentration power, is an embodied state of awareness words, DLPFC may contribute to a sustained form of motivation in which no other sensory or internally generated input can arise that remains in working memory during the meditation practice. beyond a perceptual threshold (Rahula, 1974; Bodhi, 1999). Full Furthermore, animal and human research suggest that activity in absorption in an object with focal awareness is critical for stabiliz- the PFC can modulate the ventral striatopallidum and specifically ing the mind during FA meditation; however, it can be maladap- nAcc activity in a top-down manner, postulating a mechanism for tive, such that inhibitory processes can prevent pertinent sensory

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information from arising to conscious awareness, decreasing It is proposed, therefore, that such dispotional factors leads to available cognitive resources for ongoing task demands, and increased diffuse attention to the periphery without improving potentially leading to an overwhelming sensation and mainte- iconic perceptual memory traces to the target focus of an 8-item nance of emotional reactivity related to the object of focus (Mogg array (Fischer et al., 2012). and Bradley, 1998). Regulatory efficiency and stability are also Meta-awareness points to the possibility of taking awareness measured under various conditions of perceptual load or con- itself as an object of attention and can be disambiguated from flicting contexts (e.g., Stroop phenomena), through continued sensory-conceptual domains of self-experience especially evident performance with fewer distractions, through the rapid disen- in the NS (Lutz et al., 2007). Meta-awareness contributes the gagement from an object of focus to another intended object critical mnemonic aspect of mindful awareness responsible for in rapid succession (e.g., attentional blink paradigm, dotprobe monitoring the meditative state so that one may “see and know” task), and through an ability to shift back and forth between when they have lost the focus of attention on the object, or local and global features (e.g., perceptual rivalry task). The neural emotion has become reactive or ruminative. Likewise, the same substrates for these attentional processes are described through meta-awareness serves to determine whether there is dullness S-ART networks. For example, preparatory forms of attention are or too much excitation during the practice and therefore, con- described through EES circuitry, while the substrates for FA and tributes to the phenomenal intensity or clarity in which the executive monitoring are described through EPS and the FPCS. It meditation is experienced (Lutz et al., 2007). Without such a is likely that distinct circuitry may also be identified for arising, highly developed sense of self-awareness, the contents of sub- passing, and restful states of concentration for each modality of jective experience are continually entangled with the patterns focus. of conditioned and consolidated schemas that dictate behavior. Although people generally claim to have full conscious aware- Husserl refers to this abstracting from all objects as “epoche,” or ness of their environment when their focal attention is directed bracketing objects of conscious experience in order to reflect on outward or toward their own internal thoughts, attention research the contents within it (Varela et al., 1991). Meta-awareness may showsthatthisisquitefalse.Infact,itisverylikelythatpar- differ from the EPS only in its relation to the world, from which ticular information from the environment is filtered out unless one is able to study the intentional contents of the mind in a reaching some perceptual or semantically meaningful threshold transcendent, non-conceptual way. before it can gain access to conscious awareness. At a very basic Recent studies have investigated the role of short- and perceptual level, our focal awareness is very small relative to long-term mindfulness-based meditation practice on the sub- therestofthecontextaroundthatfocus,suchthatweexperi- components of the attentional system (alerting, orienting, ence a phenomenon called “change blindness” when cues such engagement, and disengagement), and at the early perceptual and as motion, that normally lead to a shift of attention, are sup- non-conscious stages of processing external stimuli that could pressed and major changes across sensory or semantic modalities reflect changes in attentional bias (Brefczynski-Lewis et al., 2007; in the remainder of the environment are not reported (Simons Chan and Woollacott, 2007; Slagter et al., 2007; Tang et al., 2007; and Levin, 1997; Posner and Rothbart, 2009). There is ample Cahn and Polich, 2009; Hodgins and Adair, 2010; van den Hurk evidence that early stages of attentional processing and fleeting et al., 2010b; Ganaden and Smith, 2011; Vago and Nakamura, perceptual traces of sensory information exist before there is con- 2011). One study that utilized the Attention Network Test (ANT) scious awareness (Pessoa, 2005). Receptive forms of meditation found significantly better executive monitoring at baseline in (i.e., OM) facilitate more diffuse or ambient attentional mech- a group of experienced meditators (4-week intensive retreat) anisms and consequently, phenomenological awareness of the than control subjects (Jha et al., 2007). After MBSR, individu- objects in conscious experience is likely enhanced, without nec- als demonstrated improved endogenous orienting ability, while essarily increasing cognitive access [see (Davis and Thompson, the 4-week retreat group showed improved exogenous alerting- forthcoming)]. Thus, reportability for states of interoception related processes, reflecting the advanced training in receptive and exteroception may not necessarily be improved, while more forms of practice (Jha et al., 2007; Ganaden and Smith, 2011). subtle, non-conscious processes supported through EES may van den Hurk et al. (2010a,b) used the same ANT task with improve in efficiency. These forms of early, non-conscious pro- long-term (∼15 years. practice) meditators and found improved cessing can be measured in pre-categorical, high capacity sensory orienting and executive monitoring ability in comparison to age- memory stores (Sperling, 1960; Chrousos and Gold, 1992), per- matched controls (van den Hurk et al., 2010a). Five days of IBMT, ceptual rivalry, or affect-biased attention (Attar et al., 2010; Todd a receptive practice also demonstrated improvements in executive et al., 2012). Future research in the contemplative sciences will attention using the ANT task (Tang et al., 2007). Several recent likely reveal more subtle changes in non-conscious states of early studies have also reported improvements in sustained attention stages of perceptual and attentional processing. A recent pilot during the performance of other exogenous cueing tasks, or con- study used an iconic memory task, in which an array of eight tinued performance tasks. One longitudinal study (3 months, letters was displayed for 30 ms and a target letter was to be iden- 5 h/day) found that retreatants showed enhanced perceptual dis- tified up to 1000 ms after the trace was removed. The study crimination and vigilance, an observation that remained constant found dispositional mindfulness, non-attachment, and compas- 3 months after the retreat ended (MacLean et al., 2010). These sion in advanced meditators was not associated with accuracy, results suggest a form of plasticity in attention-related networks but positively correlated with the subjects’ ability to identify that can manifest between 5 days and 3 months of intensive a letter adjacent to the correct target and in the larger array. mental training.

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Alerting attention toward a stimulus can operate at very early advanced practitioners, more efficient allocation of resources is levels of perceptual processing (<300 ms) and is sometimes con- observed. sidered an automatic process, taking the form of attentional bias toward, or away from, an object (Mogg et al., 1995). A few hun- EMOTION REGULATION dred milliseconds before an eye movement, visual attention is There is growing evidence that mindfulness training improves directed toward the forthcoming target locations, shifting acti- emotion or self-regulation skills as evident from a variety of self- vations in saccade and attention areas of the brain and enabling report, physiological, and neuroimaging methods (Baer et al., planning of actions toward those locations (Deubel, 2008). In a 2009; Carmody, 2009). One explanatory mechanism underlying sample of female fibromyalgia patients, a preliminary study of alterations in health, brain structure and function may rest on the mindfulness meditation on attentional bias revealed decreased fact that mindfulness-based meditation practices strengthen neu- avoidance at early stages of attention toward pain-related cues in ral systems important for emotion regulation, specifically eval- those patients exposed to 8-weeks of mindfulness training (Vago uative, expressive, and experiential aspects of emotion. Emotion and Nakamura, 2011). Other studies have also showed the influ- regulation is therefore also very similar, if not partially redundant ence of meditation practice on early phases of non-conscious with the concept of self-regulation, referring to the ability to shift attention (Srinivasan and Baijal, 2007; Cahn and Polich, 2009) focus of attention at will, and modulate ongoing emotional activ- and bias (Garland et al., 2010; Paul et al., 2012). For example, ity (e.g., decrease elaborative processing of thoughts/feelings) Srinivasan and Baijal (2007) demonstrated increased mismatch (Gross, 1998; Northoff, 2005; Carver and Scheier, 2011; Koole negativity (MMN) amplitudes in concentrative meditation (Sahaj et al., 2011). In this context, emotion is measured through multi- Samadhi) practitioners immediately before and after practice, ple components including cognitive, viscerosomatic, behavioral, and in contrast to novice practitioners. These studies suggest and physiological responses. enhanced perceptual sensitivity even before conscious forms of In several publications, Davidson (2000, 2004)hasreferredto attention are allocated. emotion regulation in terms of affective style and has described As attentional effort decreases over time and practice (see opportunity for regulation at various dynamics of affective Figures 3 and 4), the efficiency of attentional networks improves chronometry: (1) the threshold to respond; (2) the magni- and more cognitive resources are made available. Increased tude of the response; (3) the rise time to the peak of the efficiency (decreased effort) of attentional networks has been response; (4) the recovery function of the response; and (5) demonstrated elegantly in reduced resource allocation in one the duration of the response. For example, one can consider study of subjects who underwent three months of intensive mind- the recovery function of the response to be rapid (steep) and fulness meditation training and were tested using an attentional- time to the next response as a refractory phase that may be blink paradigm (Slagter et al., 2007). Attentional blink refers reduced in practitioners of mindfulness-based meditative tech- to a deficit in perception of a second target (T2) when pre- niques. Regulation has been described in the literature through sented in rapid succession (<500 ms) following an initial target automatic and controlled strategies (Parkinson and Totterdell, (T1) embedded in a stream of stimuli presented in close tem- 1999; McRae et al., 2011). Automatic regulation refers to the poral proximity (Slagter et al., 2007). This deficit is believed to modulation of affect-related variables at a non-conscious level. result from competition between the two targets for limited atten- For example, homeostatic mediators associated with the stress tional resources. A smaller attentional blink and reduced brain- response and involved in generating affect can be non-consciously resource allocation to T1 was reflected by a smaller T1-elicited regulated through training. Controlled regulation can include P3b, a brain-potential index of resource allocation (Slagter antecedent-focused or response-focused strategies that require et al., 2007). Interestingly, those individuals that showed the some behavioral or cognitive process. Antecedent-focused strate- largest decrease in T1-elicited P3b amplitude generally showed gies focus on controlling the selection or modification of the the greatest reduction in attentional-blink size. Another study context to avoid the emotion altogether or to modify the emo- demonstrated that expert meditators with least hours of expe- tional impact (e.g., by performing a secondary distracting task, rience (10,000–24,000 h) showed increased activity (compared or cognitive reappraisal) (McRae et al., 2011). Response-focused to novices) in the left DLPFC during FA practice (vs. rest), strategies only affect the output of appraisal process and either while expert meditators with the most hours of practice (37,000– augment or suppress behavioral manifestations of one’s emo- 52,000 h) showed decreased activity in left DLPFC than both tional state, such as smiling, frowning, or experiential avoid- groups. Other studies have specifically found improvement in ance (Gross, 1998; Koole et al., 2011). Many of these controlled efficiency, reduced interference and increased control. Manna strategies may be used in novices when emotional reactivity and colleagues (2010) found that right DLPFC deactivation arises as a form of distraction; however, cognitive strategies was positively correlated with expertise, suggesting decreased are less likely in more advanced practitioners. Non-cognitive effort in advanced practitioners during FA meditation. Relative strategies are typically encouraged in dealing with the arising meditation experience (ranging from 82 to 19,200 h) has been and passing of emotions during practice, even when the emo- positively correlated with reduced interference on the Stroop tions are particularly intense or stressful. For example, mental task (Chan and Woollacott, 2007), although Stroop interference noting and labeling the modalities of the emotional experi- was not found in a group of meditators trained in an eight- ence becomes the first line of defense, a technique shown to week MBSR course (Anderson et al., 2007). These data suggest reduce amygdala activity and emotional expression (Lieberman that as meditation practice becomes increasingly effortless in et al., 2007). This is more likely an expression of equanimity

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that naturally arises through continued development of meta- the cognitive-evaluative and sensory-discriminative dimensions awareness. of pain, possibly allowing practitioners to view painful stimuli The S-ART framework supports the notion that mindfulness- more neutrally and with equanimity (Grant et al., 2010b). Grant based practice can strengthen controlled emotion regulation pro- et al. (2010a,b) also demonstrated increased cortical thickness cesses early on in novice practitioners. Most research in the area in dACC that positively correlated with lower pain sensitivity in of emotion regulation includes a focus on various subdivisions the Zen meditators, suggesting an ability to monitor and express of the PFC that have most consistently been implicated in emo- emotions related to pain without a high negative valence (Grant tion and cognitive control processes, including decision-making, et al., 2010a). appraisal, and impulse control. These areas include the OFC, The S-ART framework also supports the idea that DMPFC, ACC, DLPFC, and VLPFC (Davidson and Irwin, 1999; mindfulness-based practice can improve automatic forms Ochsner and Gross, 2005; Phillips et al., 2008). Across a num- of regulation like homeostasis in the face of emotional or physical ber of different MBI studies (Lazar et al., 2005; Holzel et al., stress by protecting the internal milieu from the harmful effects 2008; Luders et al., 2009; Grant et al., 2010a; Holzel et al., 2010), of a stressor, which can be referred to as the “raincoat effect,” and differences in GM volume and density (in comparison to non- by facilitating recovery, which we refer to as the “towel effect.” meditating controls) have been found using MRI in OFC and The raincoat acts as a metaphor for protection, as it protects one lateral PFC. Increased activity in prefrontal areas has also been from getting wet; the towel acts as a metaphor for recovery, as found in experienced meditators (compared to non-meditators) it facilitates drying off when one already has gotten wet. These during meditative states (Jevning et al., 1996; Lazar et al., 2000; metaphors have been used similarly to previous theoretical Holzel et al., 2007, 2011b; Newberg et al., 2010), in some cases models for psychoneuroimmunology (Ader et al., 1987; Feder specifically in lateral PFC (Baron Short et al., 2010; Farb et al., et al., 2009), and are used here to describe the expression of 2007; Raffone and Srinivasan, 2010).Thereissomeevidenceto equanimity that is tightly-coupled with the skills of mindful suggest that abnormal GM concentration and/or functional activ- awareness. Equanimity is supported by psychological processes ity in the left sgACC may be indicative of dysfunctional emotion like decentering and non-attachment, de-coupling the sensory regulation ability and potential for developing depressive sympto- and affective components of the stressor. As a result, sympathetic mology (Drevets et al., 1997). Other areas found to be critical in tone is reduced and hypothalamic-pituitary-adrenal (HPA) their respective interactions with the PFC are the amygdala, hip- axis-mediated mobilization is suppressed. A decreased stress pocampus, striatum (including the nAcc), thalamus, and insula response to innocuous cues and rapid return to physiological (Davidson and Irwin, 1999; Phillips et al., 2008). The uncinate and emotional baseline in response to real threat should be fasciulus (UF) is a tract of fibers connecting limbic structures to apparent across all physiological mediators such as the cate- the PFC which is highly plastic over the course of development cholamines (e.g., epinephrine and norepinephrine) from the and critical for emotion regulation and transformation. There adrenal medulla, glucocorticoids (e.g., cortisol) from the adrenal is growing evidence that dispositional mindfulness may act as a cortex, pituitary hormones (e.g., ACTH, prolactin, and growth marker for improved emotion regulation skills (Creswell et al., hormones) and cytokines (e.g., IL-1, IL-6, and TNF-α)from 2007). For example, increased dispositional mindfulness (mea- cells of the immune system. Mindfulness training is proposed to sured by the MAAS) has been correlated with increased activation reduce the chance for pathophysiological processes or unfavor- of VLPFC and attenuated activation in the amygdala (Lieberman able psychopathological outcomes by preventing perseverative et al., 2007). Garland and colleagues (2009, 2011)proposethat and chronic responses in the presence or imagined presence of positive reappraisal, a cognitive coping strategy, is a mechanism a stress-related physiological challenge and through effective by which mindfulness functions to regulate emotion and stress. habituation to repeated stress-related challenges (McEwen, One study supports these claims by demonstrating dispositional 2008). This form of self-regulation prevents “allostatic load,” mindfulness (assessed by the KIMS) positively correlated with the cumulative wear and tear on the body and brain due to the bilateral activation of DMPFC during reappraisal of negative overactive or inefficiently managed stress response (McEwen, pictures (Modinos et al., 2010). It remains unclear however, to 1998; Sterling and Eyer, 1988). Long-term adverse effects are what extent reappraisal is used in mindfulness practice given avoided, including immunosuppresion, cardiovascular dysfunc- the emphasis on non-cognitive processing. Other studies have tion and disease, accumulation of abdominal fat, loss of bone demonstrated evidence for non-appraisal strategies associated minerals, reproductive impairments, decreased neurogenesis, with mindfulness (Grant et al., 2010b; Gard et al., 2012). In sup- increased neuronal cell death and associated atrophy in the limbic port of more non-cognitive forms of emotion regulation, reduced system (Jameison and Dinan, 2001; Sapolsky, 2003; McEwen, activity in executive, evaluative and emotion areas during acute 2008). pain (PFC, amygdala, hippocampus) have been found in adept The connections of the insular cortex with the thalamus, HPA practitioners of Zen, compared to controls (Grant et al., 2010b). axis and brainstem are thought to provide a mechanism for vis- Meditators with the most experience showed the largest activation cerosomatic and homeostatic feedback to the executive monitor reductions, suggesting a decreased need for effortful control in and regulation of sympathetic tone (Critchley, 2005; Craig, 2009). advanced meditators. Importantly, the lower pain sensitivity and In order to maintain homeostasis, the internal state of the body is higher thresholds for pain in meditators was strongly predicted critical for the parasympathetic division of the autonomic ner- by reductions in functional connectivity between executive and vous system (ANS) to respond effectively to stressors. There are pain-related cortices. Results suggest a functional decoupling of two parasympathetic nerve centers in the brainstem medulla:

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dorsal and ventral. The vagal nuclei promote parasympathetic have found improved function and effective allocation of inflam- tone, increased energy conservation through control of cardiovas- matory responses in novice normal meditators and in subjects cular and visceral function. The ventral vagal nuclei dampen the with major disease diagnoses (e.g., cancer) (Kabat-Zinn et al., sympathetic response specifically by targeting cardiorespiratory 1998; Davidson et al., 2003b; Smith, 2004; Carlson et al., 2007; organs; whereas, the dorsal nuclei target the gut and associated Pace et al., 2010). For example, Davidson and colleagues (2003b) viscera (Porges, 1995). The S-ART framework predicts mindful- found that MBSR produced significant increases in antibody titers ness can facilitate both dorsal and ventral vagal tone through FA to influenza vaccine compared with those subjects in a wait-list on the body in the context of stressors. control group. Interestingly, the magnitude of increase in left- There have been a number of studies reporting on the phys- sided anterior PFC activation in EEG predicted the magnitude iological profile of meditators, which appears to be significantly of antibody titer rise to the vaccine (Davidson et al., 2003b). influenced by meditation practice, and may strongly contribute Pace and colleagues (2010) reported that after 6-weeks of com- to the neuroimmunological profile as well. For example, stud- passion meditation practice, there were reduced innate cytokine ies comparing experienced meditators to controls or short-term (IL-6) and subjective distress responses to a standardized lab- meditators have demonstrated a particular physiological profile oratory psychosocial stressor [Trier Social Stress Test (TSST)]. across styles of practice suggestive of an alert, but hypometabolic Moreover, individuals with meditation practice times above the state in which there is decreased sympathetic nervous sys- median exhibited lower TSST-induced IL-6 and POMS distress tem activity, and increased parasympathetic activity (You ng a nd scores. Taylor, 1998; Benson, 2000; Cahn and Polich, 2006). Across med- itation styles, electromyography has revealed muscle relaxation in EXTINCTION AND RECONSOLIDATION spite of the upright, unsupported posture (Austin, 2006). Skin The elimination of suffering, the end state of mindfulness prac- conductivity, along with oxygen consumption, heart rate, blood tice is described often as “stillness of the mind” (Sanksrit: nir- pressure, cortisol, muscle tone, urinary vanillyl mandelic acid vana)(Buddhaghosa, 1991). The word “Nirvana” has literally (VMA) (a catecholamine metabolite), and rate of breathing all been translated as “blowing out” or “extinction.” In this con- decrease during meditation (Jevning et al., 1992; Benson, 2000; text, it refers to the extinction of the afflictions (Sanskrit: klesha), Lazar et al., 2005; Austin, 2006). Critically, this hypometabolic which prevent happiness and flourishing. (Buddhaghosa, 1991; state has been shown to be qualitatively and quantitatively dif- Analayo, 2003; Bodhi, 1999). Maladaptive habits, distorted per- ferent from simple rest or sleep and more suggestive of a role in ceptions, and biases accumulate through the conditioning or prevention of stress-related hypertension or cardiovascular dis- reification of the NS, most of which are not accessible to con- ease (Young and Taylor, 1998; Cahn and Polich, 2006). Other scious awareness. The narrative one creates about oneself in terms more advanced meditation techniques focus specifically on alter- of self-reflection or future projection becomes increasingly more ing control of breath (e.g., pranayama), and body-temperature rigid as it is conditioned over time through a causal chain of (e.g., Tummo), techniques which may be more highly speci- repetition (see Figure 1). Each trajectory of self-development rep- fied toward impacting automatic regulatory processes. During resents a repeatedly reconstructed, reinforced, and reified NS with seated meditation, at a middle level of samatha, the breathing reliable patterns of subject-object relations that are relative stable rate may drop to only two or three breaths a minute (Lazar and accessed during self-specifying processes. et al., 2000; Austin, 2006), while normal adults at sea level breathe The S-ART framework suggests mindfulness acts as the mas- about fifteen times per minute. The specific and non-specific ter self-regulatory mechanism for de-coupling and efficiently effects of mindfulness-based meditationonhomeostaticregula- integrating experiential and NS modes of processing with the tion are clearly an aspect of self-regulation that needs further potential to transform the reified self from maladaptive trajec- investigation. tories into more positive, adaptive trajectories. This form of Physiological studies have also supported the effects of medi- transformation is hypothesized to use circuitry associated with tation on non-reactivity related to a rapid change back to baseline extinction and reconsolidation. Biases of attention and memory after an emotional response. This rapid regulatory mechanism is related to habitual distortions are proposed to be extinguished proposed to be an objective measure of equanimity. For exam- and reconsolidated; however, the dosage and quality of medita- ple, experienced transcendental meditators (>2 years experience) tion time required for such change remains unclear. Although showed more rapid decreases in skin conductance following aver- change in constitutionally-based temperament or biological dis- sive stimuli (Goleman and Schwartz, 1976), while other studies position is thought to be less likely than those aspects of self have shown decreased startle amplitude (Delgado et al., 2010; that can be modulated by experience and training (Rothbart and Levenson et al., 2012), and other low-level bottom-up forms of Ahadi, 1994; Kagan, 2003), there is evidence that conditioned fear emotion regulation (van den Hurk et al., 2010b). Goldin and can be extinguished (Phelps et al., 2004). Exposure, extinction, Gross (2010) found that social anxiety patients show a more rapid and reconsolidation are critical mechanisms for reducing habit- decrease in activation of the amygdala in response to negative ual anxiety and fear, and in facilitating therapeutic change in past self-beliefs after a MBI (Goldin and Gross, 2010). Additionally, clinical models (Wells and Matthews, 1996; Bishop, 2007; Beck, Britton et al. (2012) demonstrated more rapid decreases in 2008). Extinction does not erase the original association, but is a self-reported state anxiety following a psychosocial stressor (in process of novel learning that occurs when a memory (explicit or comparison to pre-MBCT) (Britton et al., 2012). Other studies implicit) is retrieved and the constellation of conditioned stimuli investigating the effects of meditation on homeostatic regulation that were previously conditioned to elicit a particular behavior

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or set of behavioral responses is temporarily labile and the asso- fact, cortical thickness of the VMPFC has been shown to posi- ciations with each other are weakened through active or passive tively correlate with extinction recall, and functional connectivity means. Changing the association contingency of contextual cues with the hippocampus appears to be related with learned safety and what they mean results in a new memory trace. The new (Milad et al., 2007). The DMPFC and dorsal ACC have been memory trace involves re-consolidated associations of particular shown to be modulatory over the physiological and behavioral contextual stimuli and its previous associations with new stim- expression of fear and thus, may be critical in extinction and uli and behavior (Nader et al., 2000; Quirk and Mueller, 2008). reconsolidation as well (Quirk et al., 2010). Dorsal ACC has The behavioral expression of the new memory is then thought to been shown to be positively correlated with sympathetic activ- be in competition with the previously conditioned memory, with ity related to fear expression; whereas, ventral ACC (including particular pathological-oriented biological dispositions proving pACC and VMPFC) has been more associated with inhibition to increase the time or number of trials necessary for extinc- of expression during extinction, and recall of extinction of fear tion and sensitivity to old fear-based associations (Milad et al., after extinguishing prior conditioned associations (Etkin et al., 2007). Extinction and reconsolidation can depend on numer- 2011). ous factors, such as level-of-processing (Craik, 2002), emotional On a more cellular level, extinction and reconsolidation salience (Kensinger and Schacter, 2005), the amount of attention research has focused on the molecular cascade of events that paid to a stimulus (Loftus, 1979), the expectations at encod- follows experience and results in reorganization of long-term ing regarding how memory will be assessed later (Frost, 1972), memory storage. Some lines of investigation have demonstrated or the reconsolidation-mediated strengthening of memory trace that the presence of kinase activity, which persists in order to (McGaugh, 2000). The closer in time the retrieval occurs to the maintain synaptic potentiation, may be indicative of new memory experience, the more likely weaker components of a memory traces (Wallenstein et al., 2002). Similarly, labeling of epigenetic trace can be reconsolidated given the tendency for weak traces or transcription factors related to expression of various genes to decay over time (i.e., forgetting). It has been reported that the necessary for synaptic plasticity has also been shown to be indica- hypometabolic state of the practitioner may act to facilitate the tive of extinction and reconsolidation processes (Sweatt, 2009). extinction process by creating novel parasympathetic associations Several recent studies have shown that extinction learning in rats with previously anxiety-provoking stimuli (Cahn and Polich, can be accelerated and strengthened through modulation of these 2006). The noting and labeling of sensory, cognitive, and emotive molecular systems as well as through pharmacological noradren- states while in a hypometabolic system, such as during OM prac- ergic and dopamine systems [e.g., D-cycloserine (DCS)] in the tice, is also likely to influence the nature of conditioned response mPFC (Quirk et al., 2010). toward reconsolidation of more positive trajectories. Awareness Although relatively few studies have explored this possibility, alone is proposed to change the conditioned response contin- there is some evidence that mindfulness-based practices involve gency toward one’s patterns of behavior and feelings toward exposure, extinction, and reconsolidation processes [see (Holzel oneself and others, although intentional cognitive processes may et al., 2011a; Treanor, 2011) for review]. Multiple morphomet- also contribute. In association with positive reappraisal strate- ric studies have demonstrated structural changes in the circuitry gies, the practitioner may reflect on a particular emotion and related to extinction following mindfulness training of as lit- decide if it is desirable or undesirable, warranted or unwarranted. tle as 8-weeks (Lazar et al., 2000; Holzel et al., 2008, 2011b; If one finds that one would like to change something about the Luders et al., 2009). Cross sectional studies comparing medi- emotional state one is affected by, one can intentionally act to tators and non-meditators found greater GM concentration in transform the emotions. If, indeed, extinction proves to be a com- the hippocampus of meditators, suggesting enhanced circuitry mon mechanism for many types of habitual sensory, affective, for extinction learning and retention (Holzel et al., 2008; Luders and motor processing in mindfulness training, one can begin to et al., 2009). Aside from the changes noted above in memory- redefine the solid boundaries and limited interactions between related structures, thickness of the mPFC has been found to automatic and controlled processing. be directly correlated with extinction retention after fear con- In both rodents and humans, the brain areas involved in ditioning, suggesting that its increase in size following training conditioning and extinguishing fear include the hippocampus, might explain ability in meditators to modulate fear, a mecha- amygdala, rhinal cortices, and VMPFC. Right DLPFC has also nism that has yet to be fully explored (Milad et al., 2005; Ott been implicated in the extinction of aversive associations, while et al., 2010a; Holzel et al., 2011b). Moreover, GM concentration right VLPFC has been implicated in non-aversive extinction in this region has been correlated with the amount of medita- recall (Morgan and Ledoux, 1999). The cerebellum contributes tion practice. Holzel and colleagues also recently demonstrated to simple associative learning, while the inferior temporal cor- that decreased perceived stress over the 8-weeks of MBSR pos- tices and dorsal striatum are responsible for conditioning and itively correlated with decreased GM concentration in the right habitualizing more complex sensory-affective-motor scripts and amygdala (Holzel et al., 2011b). Previous research has shown that schemas in visuo-spatial contexts (Buckner and Wheeler, 2001). such morphometric changes are associated with improved emo- Structural connectivity between DLPFC and amygdala has also tion regulation and extinction of fear (Milad et al., 2005; Etkin been implicated in learned safety, suggesting effortful control et al., 2011). Functional increases in these regions have also been over expression of fear-related behavior (Pollak et al., 2010). found during meditation or in the context of emotional probes, The VMPFC appears to modulate the amygdala response and suggest a strengthening of the circuitry involved in extinction extinguish the expression of fear in this functional circuitry. In and a critical role for PFC-hippocampal dynamics in mediating

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changes in advanced practitioners. We further propose that the relative to imagined experimenter action strongly activates IPL posited reductions of negative ruminations about the self report- (including TPJ), somatosensory cortex, and precuneus (Ruby and edly due to mindfulness training (Ramel et al., 2004)mayalsobe Decety, 2001; Farrer et al., 2003), while Trancranial Magnetic mediated by the same functional extinction circuitry. Stimulation (TMS) or lesions of the right TPJ has shown to dis- rupt the sense of ownership or agency (Tsakiris et al., 2010)and PROSOCIALITY: IMPROVING SOCIAL COGNITION produce dissociative, out-of-body experiences (Blanke and Arzy, Humans are inherently social beings with a gifted ability for 2005). The OMPFC, has been shown to be specifically involved social cognition—to understand others’ emotions, intentions, in social modulation of reward value, while the mPFC and TPJ and beliefs. Empathic forms of behavior, including empathy, sym- have been shown to be more involved in mentalizing and ToM pathy, and altruism, have been implicated in conceptual models (Frith and Frith, 2012). The right IPL is more often associated and theories about social cognition and associated experience with ToM, whereas the left IPL is more often involved in repre- sharing and prosocial behavior (Hein and Singer, 2008; Eisenberg senting one’s own mental states (Decety and Chaminade, 2003). et al., 2010; Zaki and Ochsner, 2012). Prosocial behavior is typ- The pSTS (including the TPJ) has been shown to be involved ically defined as voluntary behavior intended to benefit another in perceiving biological motion and orienting toward eye gaze (Eisenberg et al., 2010). Major facets of prosociality and inter- (Frith and Frith, 2012).TheACChasbeenshowntobemore relationships include forms of mentalizing and perspective taking. involved in a supervisory role and deciphering conflicting infor- For example, imagining the intentions of others has been called mation. Posterior IFG has been shown to be involved in emotional “theory of mind” (ToM).Empathy is distinct from ToMand refers judgment and has been suggested to play a role in emotion recog- to our ability to share the experiences (emotions and sensations) nition, predicting emotion, and mirroring action (Frith and Frith, of others. It is believed that mindfulness practice can cultivate a 2012). Fan and colleagues (2011) found that the dorsal ACC and framework for interdependence of self in a social network and anterior mid-cingulate cortex (aMCC) were recruited more fre- include a cognitive framework supporting empathy and mental- quently in the cognitive-evaluative form of empathy, while the izing. In such cases, the conceptual form of meta-awareness (i.e., right AIC was found to be involved in the affective-perceptual meta-cognition) allows one to disengage from the contents of form of empathy only, and the left AIC was found to be active in awareness and move toward the experiencing of an other’s sen- both forms of empathy. Singer and others propose the AIC serves sory or affective state (Decety and Chaminade, 2003; Singer and a dual role, a primary mapping of internal states with respect Lamm, 2009). to the self, and the predictive representations or simulation of Although prosociality has a biological basis and dispositional how the same emotional stimuli feel to others (Singer and Lamm, differences in empathic responding and prosocial action exist 2009). from early life onwards (Rothbart and Ahadi, 1994), patterns One suggestion to account for overlap between self-other of empathic responding and related prosocial behavior are rel- neural substrates has been that understanding the intentions atively plastic not only during childhood and adolescence, but of another is also likely to recruit processes underlying insight also during adulthood. Specifically, studies of adults have revealed into oneself. Interestingly when perceivers passively watch tar- enhancements in functional activity of a social-cognitive network gets experiencing pain or reward, their own engagement of brain supporting facets of mentalizing and empathy (Singer and Lamm, areas associated with those states predicts later prosociality (Zaki 2009; de Greck et al., 2012; Fan et al., 2011). This suggests that and Ochsner, 2012). This suggests that increased prosociality some of the neural circuitry underlying empathy can be enhanced may predict decreased differences in the intensity and local- through the practice of forms of mental training designed to izationofneuralactivityinresponsetoone’sownexperience increase positive affect and prosocial behavior across the lifes- in contrast to some target individual’s experience. This would pan. It is now commonly believed that empathic ability affects the support a system of experience sharing or prosocial concern; perception and affective style of others’ behavior toward oneself whereas mentalizing may engage separable neural systems. In (Eisenberg et al., 2010), mutually reinforcing the behavior toward an experiment by Masten et al. (2010), mentalizing is shown each other. Thus, social and moral cognitions and behavior reflect to increase future helping behavior, suggesting a distinct sys- the nature and valence of self and others’ empathic behavior. The tem supporting prosocial behavior through experience sharing S-ART model proposes that plasticity associated with prosocial- and mentalizing. The prosocial system is indicated in Figure 2. ity may be indicative of self-transcendence, dissolving distinctions Research also indicates that positive social behaviors, specifi- between self and other and reflecting loving-kindness to both. A cally maternal nurturing (e.g., licking and grooming), induces greater sense of well-being is likely to depend upon this skill. In positive alterations in the brain and in behavior that promote fact, altruistic behavior has been associated with greater sense of resilience (Champagne and Curley, 2008). Psychosocial factors, well-being and acceptance (Lyubomirsky et al., 2005), suggesting such as decreased levels of denial and avoidant coping behavior, all other stated mechanisms can be modulated by the cultivation increased levels of social engagement, positive emotion, and dis- of prosocial and ethical behavior. positional optimism have all been shown to promote resilience Brain areas that are involved in mentalizing include TPJ, TP, (Feder et al., 2009). Collectively these data establish that our AIC, precuneus, DMPFC, while the ACC, IFG, pSTS, and IPL brains are continuously shaped both functionally and structurally have been implicated more with prosociality and empathic con- by experience on which explicit training can capitalize to pro- cern and experience sharing (Singer and Lamm, 2009; Frith and mote more adaptive brain functioning, especially with relation to Frith, 2012; Fan et al., 2011; Roy et al., 2012). Imagined self-action prosocial behavior.

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In support of the development of prosocial behavior, includ- or non-attachment (Sanskrit: viraga¯ )(Sahdra et al., 2010). In ingmentalizing,empathicconcern,andexperiencesharing, this sense, mindfulness is a relational process. Mindfulness not there have been a number of studies to suggest meditators only helps to support awareness of the self, it transcends the show increased activation of the prosociality circuitry over self-object duality by supporting the realization of the self to be non-meditators. Lutz and colleagues studied novice and expert co-dependent with the relations to objects in experience, result- meditation practitioners that generated a non-referential loving- ing in a characterization of self as empty and groundless. There kindness-compassion meditation state. To probe affective reac- may be clear benefits to developing increased awareness of our tivity, emotional and neutral sounds were presented during the selves and environment, but the platform from which sustained meditation and comparison periods. Concern for others culti- transformation and insight arise is one that includes the rela- vated during this form of meditation enhanced affective pro- tional quality the practitioner brings toward noting and labeling cessing particularly in response to sounds of distress, and this the modalities of experience—one that is free of the choosing, response to emotional sounds was found to be modulated by the evaluating, or projecting that is sometimes described as “grasping, degree of meditation training. The presentation of the emotional aversion, and delusion” (Salzberg, 2011). sounds was associated with increased pupil diameter and dra- Decentering, described as “reperceiving” in past models of matic increased activation of right AIC during meditation (vs. mindfulness (Shapiro et al., 2006), is a therapeutic process that rest) (Lutz et al., 2008a). During meditation, activation in right introduces a “space between one’s perception and response” AIC and mid-insula was greater during presentation of nega- allowing the individual to disengage or “step outside” one’s tive sounds than positive or neutral sounds in expert vs. novice immediate experience in an observer perspective (i.e., fly on the meditators. The strength of activation in insula was also asso- wall) for insight and analysis of one’s habitual patterns of emo- ciated with self-reported intensity of the meditation for both tion and behavior. Decentering may not necessarily be unique to groups. Insula activity was also strongly coupled to heart-rate, mindfulness, as it is described in other therapeutic contexts as suggesting a relationship between generation of compassion and the “observing self” (Deikman, 1982; Fletcher and Hayes, 2005), cardiac function (Lutz et al., 2009). One case study of compassion or “self-as-witness” (Damasio, 2010). Decentering is compared meditation showed similar activity in areas related to empathic to clinical constructs such as defusion or psychological distanc- processing (Engstrom and Soderfeldt, 2010). These results and ing (Fletcher and Hayes, 2005; Ayduk and Kross, 2010). It also other similar studies that demonstrated neural resonances in refers to a process of deautomatization (Ayduk and Kross, 2010), shared experience [see (Zaki and Ochsner, 2012)] support the in which there is an undoing of automatic processes that con- role of limbic circuitry in emotion sharing. The comparison trol perception/interpretation. These processes are described to between meditation vs. rest states between experts and novices enhance a trait-like ability to shift focus of attention at will, and have shown increased activation in amygdala, right TPJ, and right inhibit elaborative processing of thoughts/feelings. For example, pSTS in response to all sounds, suggesting greater detection of, repetitive thinking “I am worthless” vs. recognizing “I am hav- and enhanced mentation in response to emotional human vocal- ing the thought that I am worthless.” The fusion of self and izations for experts in comparison to novices during compassion negative thoughts along with rumination has been shown to meditation. Interestingly, there was a link between expertise in play a critical role in exacerbating negative affect, maintaining compassion and the activation in the right pSTS, a finding that is or heightening anxiety, and increasing cognitive vulnerability to consistent with previous research that indicated pSTS activity pre- psychopathology (Smith and Alloy, 2009). The insight achieved dicted self-reported altruism (Tankersley et al., 2007). Increased through mindfulness-based practices provides awareness that activity in the amygdala may appear to be a counterintuitive find- one’s thoughts are subjective and transient in nature (Safran and ing to traditional models of controlled emotion regulation, but Segal, 1990), thus facilitating non-attachment and subsequently may be more indicative of regulatory states like equanimity. improving satisfaction with life, well-being and interpersonal Together these data indicate that the mental expertise to culti- functioning (Sahdra et al., 2010). vate empathic behavior and positive emotion for others’ suffering Laboratory studies of mindfulness-based meditation practices involves a network of prosociality and social cognition. have yet to identify biological correlates for the psychological constructs of decentering and non-attachment. However, the S- NON-ATTACHMENT AND DE-CENTERING ART framework suggests a significant role for them in relation One of the advanced outcomes or aspects of insight, developed to practice effects and development of meta-awareness. Some of through mindfulness-based meditation practice is the realization the extant data suggest functional dynamics between the self- of “no-self,” which stems from the Buddhist teachings describ- networks may account for the decentering mechanism by which ing the nature impermanence (see Section “Defining meditation mindfulness training promotes flexibility of information pro- and mindfulness from the historical perspective”). This form of cessing between autobiographical and experiential awareness. insight demonstrates that there is no truly existing self (i.e., sub- For example, one study found that the DMPFC is deactivated ject) that continues through life without change and provides the and negatively coupled to PIC during interoceptive awareness practitioner with the critical distinction between the phenomeno- (Farb et al., 2012). Additionally, Farb et al. (2012)foundthat logical experience of oneself and one’s thoughts, emotions, and DMPFC-insula connectivity was absent during exteroceptive feelings that appear “thing-like” (Varela et al., 1991). This real- focus. Another study investigating adept Zen meditators (in com- ization of impermanence of all “thing-like” objects including parison to novices) found stronger connectivity between DMPFC the self is also described as a “release from mental fixations,” and IPL, an area with both narrative and EPS involvement

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(Taylor et al., 2012). These data suggest a mechanism by which first-person self-reports in the neuroimaging acquisition pro- DMPFC may act to integrate narrative and experiential informa- tocols. A neurobiological model (Figure 2) is used to illustrate tion, sustain positive activation in interoceptive areas or decouple functional distinctions between the networks; however, gradients from them without suppression. Other studies have emphasized of non-conscious and conscious processing must be considered, areas from the integrative fronto-parietal network as critical for as functional specification is likely to be graded in nature. The the type of perspective taking required for decentering or non- skillset identified herein is an attempt to dismantle the prac- attachment. For example, one study demonstrated a strong role tices that cultivate mindfulness into component mechanisms so for dACC in mediating the conscious appraisal of emotional expe- that the contemplative sciences can more precisely investigate the rience (Critchley et al., 2004), while another study showed strong dispositional differences amongst practitioners of mindfulness- activity in dACC and DMPFC together (Holzel et al., 2007). based meditation practices and practice-specific changes can be Future studies will have to clarify the neurobiological mechanisms objectively correlated with first-person experience. behind these critical processes. The challenge in this emerging field continues to be dis- ambiguating the concept of mindfulness from more common CONCLUSIONS, CHALLENGES, AND FUTURE DIRECTIONS usage of the term, and eliminating the “black box” or singu- Rather than focusing on reducing mindfulness down to a single lar approach to studying meditation. Amongst all the enthusi- unitary dimension of cognition, we have attempted to illustrate asm for research and clinical application of mindfulness, there the complexity of mechanisms by which mindfulness functions is much foundational basic science and vital clinical trials that to reduce suffering and create a sustainable healthy mind using a remain to be implemented. It is likely that future research in framework of self-processing. Suffering is described using both the contemplative sciences will provide a developmental trajec- a traditional Buddhist perspective and a contemporary model tory of different S-ART-specific subcomponents and individual for psychopathology. Biased self-processing is demonstrated to differences across duration and frequency of practice. Although be a common target for traditional Buddhist and contempo- research is beginning to demonstrate the state effects related rary conceptual models of mindfulness, such that discrepancies to a number of contemplative practices, the continued practice in operationalizing mindfulness can find common mechanisms of FA and OM meditation induces trait changes that have yet by which mindfulness-based mental training functions. In our to be adequately and objectively measured longitudinally across attempts to create a unified framework for understanding the progress as a practitioner. It is assumed that one begins receiv- mechanisms by which mindfulness functions, we operational- ing benefits of the practices immediately upon initial practice; ize the concept in two ways: (1) as a broadly defined method however, explicit durations of practice and dose effects are issues for developing a multidimensional skillset that ultimately leads of concern that should not go unnoticed. As Davidson (2010) to a reduction in self-processing biases and creates a sustainable emphasizes, it remains uncertain whether study participants can healthy mind; (2) A continuous discriminative attentional capac- reliably report on the quality and/or magnitude of their practice. ity that we refer to as “mindful awareness”—a skill amongst a These issues are similar for measurement of intensity or quality set of other skills developed through specific meditation prac- of practice in long-term practitioners as well. It is also critical tices. Our interpretation of mindfulness is thus provided by an that the emerging field examine the adverse effects of long-term empirical framework of S-ART to illustrate a method for becom- practice—effects that typically go unnoticed in clinical trials, but ing aware of [and familiar with] the conditions which cause [and are more prevalent in longer retreats and in practitioners that remove] distortions or biases in the individual’s construction may or may not have a predisposition toward developing psy- of his or her external or internal experience. Through training chopathology. Constructing objective standards for determining in FA, OM, and EE styles of meditation, a sustainable healthy extent of expertise and proficiency in a particular meditation mind is proposed to be supported—reducing maladaptive emo- technique beyond reported hours of formal practice (i.e., time on tions and cognitions common to most ordinary experience, such the cushion) will have to be developed to support self-reported as lustful desire, greed, anger, hatred, worry, etc., increasing facets of mindfulness. pro-social dispositions (e.g., compassion, empathy, and forgive- It is our hope that this framework will help clarify adaptive ness) toward self and other, reducing attachments to thoughts mind-brain-body interactions and their therapeutic relevance in and feelings, and removing biases inherent in habitual forms of the general population and across neuropsychiatric disorders. cognition. Although past reviews have focused on the process of mindful- The S-ART framework outlines specific neural networks of ness from a psychological perspective, we have attempted to focus self-specifying and NS processing along with an integrative on self-processing using a neurocognitive lens, and distinguish fronto-parietal network that is proposed to be supported by between contemporary and historical interpretations of mindful- six neurocognitive processes developed in mindfulness-based ness. The S-ART framework also has attempted to disambiguate meditation practices. These processes are conceptualized as a the term, mindfulness, from other Buddhist concepts (e.g., equa- skillset proposed to facilitate the integration of self-experience nimity, clarity) and integrate them into the multidimensional from both top-down and bottom-up mechanisms. It will be skillset that is strengthened through FA, OM, and EE practices. criticaltoexaminehowthesenetworkschangelongitudinally Future work that builds off of S-ART and the process models through meditation training using advanced multivariate statis- provided will help provide a systematic way to deconstruct the tical network analyses that also consider changes in attentional heterogeneity of meditation practices into component parts and and cognitive bias, reduction of psychological symptoms, and illustrate a representative map for the underlying processes of

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self-transformation. By revealing the neural circuitry and ACKNOWLEDGMENTS further identifying endophenotypes for mindfulness skill devel- The authors wish to thank the reviewers (Jud Brewer and opment, the field of contemplative science may help to bet- Jeremy Gray) along with Evan Thompson, Robert Roeser, Jake ter predict clinical outcomes and potential targets for the Davis, Cliff Saron, Richie Davidson, John Dunne, Sonia Matwin, development of biologically based diagnostic and therapeu- Shinzen Young, and Emily Stern for their helpful comments on tic strategies for those suffering with mental illness and clar- parts of this manuscript. A special acknowledgement to His ify our understanding related to the nature of mind and Holiness the 14th Dalai Lama for his comments on aspects of consciousness. the S-ART framework at Mind & Life XXIV.

REFERENCES (2006). Using self-report assessment Philosophical Psychology of Brown, K. W., and Ryan, R. M. (2003). Ader, R., Cohen, N., and Felten, D. methods to explore facets of mind- Buddhism. Onalaska, WA: Buddhist The benefits of being present: mind- L. (1987). Brain, Behavior, and fulness. Assessment 13, 27–45. Publication Society. fulness and its role in psychological Immunity. Brain Behav. Immun. 1, Baer, R. A., Walsh, E., and Lykins, L. Bora, E., Yucel, M., and Allen, N. B. well-being. J. Pers. Soc. Psychol. 84, 1–6. B. (2009). “Assessment of mind- (2009). Neurobiology of human 822–848. Analayo. (2003). Satipatthana: fulness,” in Clinical Handbook of affiliative behaviour: implications Brown, K. W., and Ryan, R. M. The Direct Path to Awakening. Mindfulness, ed F. Didonna (New for psychiatric disorders. Curr. (2004). Perils and promise in defin- Birmingham, UK: Windhorse York, NY: Springer), 153–171. Opin. Psychiatry 22, 320–325. ing and measuring mindfulness: Publications. Baerentsen, K. B., Stodkilde-Jorgensen, Botvinick, M. M. (2007). Conflict mon- observations from experience. Clin. Anderson, N. D., Lau, M. A., Segal, H.,Sommerlund,B.,Hartmann, itoring and decision making: recon- Psychol. Sci. Pract. 11, 242–248. Z. V., and Bishop, S. R. (2007). T., Damsgaard-Madsen, J., Fosnaes, cilinig two perspectives on anterior Broyd, S. J., Demanuele, C., Debener, Mindfulness-based stress reduc- M., et al. (2010). An investigation cingulate function. J. Cogn. Affect. S.,Helps,S.K.,James,C.J., tion and attentional control. Clin. of brain processes supporting Behav. Neurosci. 7, 356–366. and Sonuga-Barke, E. J. (2009). Psychol. Psychother. 14, 449–463. meditation. Cogn. Process. 11, Bowen, S., Chawla, N., and Marlatt, Default-mode brain dysfunction Andrews-Hanna, J. R., Reidler, J. S., 57–84. G. A. (2010). Mindfulness-Based in mental disorders: a systematic Huang, C., and Buckner, R. L. Baron Short, E., Kose, S., Mu, Q., Relapse Prevention for Addictive review. Neurosci. Biobehav. Rev. 33, (2010). Evidence for the default net- Borckardt, J., Newberg, A., George, Behaviors: A Clinician’s Guide. New 279–296. work’s role in spontaneous cogni- M. S., et al. (2010). Regional York, NY: Guilford Press. Buckner, R. L., and Carroll, D. C. tion. J. Neurophysiol. 104, 322–335. brain activation during meditation Brefczynski-Lewis, J. A., Lutz, A., (2007). Self-projection and the Aron,A.R.,Robbins,T.W.,and shows time and practice effects: Schaefer,H.S.,Levinson,D.B., brain. Trends Cogn. Sci. 11, 49–57. Poldrack, R. A. (2004). Inhibition an exploratory FMRI study. Evid. and Davidson, R. J. (2007). Neural Buckner, R. L., and Wheeler, M. E. and the right inferior frontal cortex. Based. Complement. Alternat. Med. correlates of attentional expertise in (2001). The cognitive neuroscience Trends Cogn. Sci. 8, 170–177. 7, 121–127. long-term meditation practitioners. of remembering. Nat. Rev. Neurosci. Ashby, F. G., Turner, B. O., and Horvitz, Beck, A. T. (1964). Thinking and Proc. Natl. Acad. Sci. U.S.A. 104, 2, 624–634. J. C. (2010). Cortical and basal gan- depression: II. Theory and therapy. 11483–11488. Buddhaghosa, B. (1991). The Path of glia contributions to habit learning Arch. Gen. Psychiatry 10, 561–571. Bressler, S. L., and Menon, V. (2010). Purification (Visuddhimagga). and automaticity. Trends Cogn. Sci. Beck, A. T. (1976). Cognitive Therapy Large-scale brain networks in cogni- Onalaska, WA: Buddhist 14, 208–215. and the Emotional Disorders. tion: emerging methods and princi- Publication Society Pariyatti Attar, C. H., Andersen, S. K., and Madison, CT: International ples. Trends Cogn. Sci. 14, 277–290. Editions. Muller, M. M. (2010). Time course Universities Press. Brewer, B. W. (1993). Self-identity and Burgess, P. W., Dumontheil, I., and of affective bias in visual attention: Beck, A. T. (2008). The evolution of the specific vulnerability to depressed Gilbert, S. J. (2007). The gateway convergent evidence from steady- cognitive model of depression and mood. J. Pers. 61, 343–364. hypothesis of rostral prefrontal cor- state visual evoked potentials and its neurobiological correlates. Am. J. Brewer, J. A., Worhunsky, P. D., Gray, tex (area 10) function. Trends Cogn. behavioral data. Neuroimage 53, Psychiatry 165, 969–977. J. R., Tang, Y. Y., Weber, J., and Sci. 11, 290–298. 1326–1333. Benson, H. (2000). The Relaxation Kober, H. (2011). Meditation expe- Cahn, B. R., and Polich, J. (2006). Austin, J. H. (2006). Zen-Brain Response.NewYork,NY:Harper. rience is associated with differences Meditation states and traits: EEG, Reflections.Cambridge,MA:MIT Bishop, S. J. (2007). Neurocognitive in default mode network activity ERP, and neuroimaging studies. Press. mechanisms of anxiety: an integra- and connectivity. Proc. Natl. Acad. Psychol. Bull. 132, 180–211. Ayduk, O., and Kross, E. (2010). From tive account. Trends Cogn. Sci. 11, Sci. U.S.A. 108, 20254–20259. Cahn, B. R., and Polich, J. (2009). a distance: implications of sponta- 307–316. Britton, W. B., Shahar, B., Szepsenwol, Meditation (Vipassana) and the P3a neous self-distancing for adaptive Bishop, S. R., Lau, M., Shapiro, O., and Jacobs, W. J. (2012). event-related brain potential. Int. J. self-reflection. J.Pers.Soc.Psychol. S., Carlson, L., Anderson, N. Mindfulness-based cognitive ther- Psychophysiol. 72, 51–60. 98, 809–829. D., Carmody, J., et al. (2004). apy improves emotional reactivity Cardaciotto, L., Herbert, J. D., Forman, Baer, R. A. (2003). Mindfulness train- Mindfulness: a proposed opera- to social stress: results from a E. M., Moitra, E., and Farrow, V. ing as a clinical intervention: a con- tional definition. Clin. Psychol. Sci. randomized controlled trial. Behav. (2008). The assessment of present- ceptual and empirical review. Clin. Pract. 11, 230–241. Ther. 43, 365–380. moment awareness and acceptance - Psychol. Sci. Pract. 10, 125–143. Blanke, O., and Arzy, S. (2005). The Brown, C. A., and Jones, A. K. (2010). the Philadelphia Mindfulness Scale. Baer, R. A. (2011). Measuring mind- out-of-body experience: disturbed Meditation experience predicts less Assessment 15, 204–223. fulness. Contemp. Buddhism 12, self-processing at the temporo- negative appraisal of pain: elec- Carlson, L. E., Speca, M., Faris, P., 241–261. parietal junction. Neuroscientist 11, trophysiological evidence for the and Patel, K. D. (2007). One year Baer, R. A., Smith, G. T., and Allen, K. 16–24. involvement of anticipatory neural pre-post intervention follow-up of B. (2004). Assessment of mindful- Block, N. (1996). How can we find responses. Pain 150, 428–438. psychological, immune, endocrine ness by self-report: the Kentucky the neural correlate of con- Brown,H.,Friston,K.,andBestmann, and blood pressure outcomes of inventory of mindfulness skills. sciousness? Trends Neurosci. 19, S. (2011). Active inference, mindfulness-based stress reduction Assessment 11, 191–206. 456–459. attention, and motor prepara- (MBSR) in breast and prostate Baer, R. A., Smith, G. T., Hopkins, Bodhi, B. (1999). A Comprehensive tion. Front. Psychol. 2:218. doi: cancer outpatients. Brain Behav. J., Krietemeyer, J., and Toney, L. Manual of Abhidhamma: The 10.3389/fpsyg.2011.00218 Immun. 21, 1038–1049.

Frontiers in Human Neuroscience www.frontiersin.org October 2012 | Volume 6 | Article 296 | 25 Vago and Silbersweig S-ART: Mechanisms of mindfulness

Carmody, J. (2009). Evolving con- (1997). Reinterpreting the empathy- brain mechanisms and plasticity. Deubel, H. (2008). The time course of ceptions of mindfulness in clini- altruism relationship: when one Am. Psychol. 55, 1196–1214. presaccadic attention shifts. Psychol. cal settings. J. Cogn. Psychother. 23, into one equals oneness. J. Pers. Soc. Davidson, R. J. (2004). Well-being and Res. 72, 630–640. 270–280. Psychol. 73, 481–494. affective style: neural substrates and Dictionary. (2002). Mindful, Adj. Carmody, J., and Baer, R. A. (2008). Cisler, J. M., Bacon, A. K., biobehavioural correlates. Philos. Oxford: Oxford University Press. Relationships between mindfulness and Williams, N. L. (2009). Trans. R. Soc. Lond. B Biol. Sci. 359, Dillon, D. G., and Pizzagalli, D. practice and levels of mindful- Phenomenological characteristics 1395–1411. A. (2007). Inhibition of action, ness, medical and psychological of attentional biases towards threat: Davidson, R. J. (2010). Empirical thought, and emotion: a selective symptoms and well-being in a acriticalreview.Cognit. Ther. Res. explorations of mindfulness: neurobiological review. Appl. Prev. mindfulness-based stress reduction 33, 221–234. conceptual and methodological Psychol. 12, 99–114. program. J. Behav. Med. 31, 23–33. Corbetta, M., Patel, G., and Shulman, conundrums. Emotion 10, 8–11. Dimidjian, S., and Linehan, M. M. Carmody, J., and Baer, R. A. (2009). G. L. (2008). The reorienting system Davidson, R. J., and Irwin, W. (1999). (2003). Defining an agenda for How long does a mindfulness-based of the human brain: from environ- The functional neuroanatomy of future research on the clinical stress reduction program need to ment to theory of mind. Neuron 58, emotion and affective style. Trends application of mindfulness prac- be? A review of class contact hours 306–324. Cogn. Sci. 3, 11–21. tice. Clin.Psychol.Sci.Pract.10, and effect sizes for psychologi- Corbetta, M., and Shulman, G. L. Davidson,R.J.,Irwin,W.,Anderle,M. 166–171. cal distress. J. Clin. Psychol. 65, (2002). Control of goal-directed J., and Kalin, N. H. (2003a). The Dogen (ed.). (2002). The Heart of 627–638. and stimulus-driven attention in neural substrates of affective pro- Dogen’s Shobogenzo. Albany, NY: Carver, C. S., and Scheier, M. F. the brain. Nat. Rev. Neurosci. 3, cessing in depressed patients treated SUNY Press. (2011). “Self-regulation of action 201–215. with venlafaxine. Am. J. Psychiatry Drevets, W. C., Price, J. L., Simpson, and affect,” in Handbook of Self- Craig, A. D. (2004). Human feelings: 160, 64–75. J. R. Jr., Todd, R. D., Reich, Regulation, edsK.D.Vohsand why are some more aware than oth- Davidson, R. J., Kabat-Zinn, J., T., Vannier, M., et al. (1997). R. F. Baumeister (New York, NY: ers? Trends Cogn. Sci. 8, 239–241. Schumacher, J., Rosenkranz, M., Subgenual prefrontal cortex abnor- Guilford Press), 3–21. Craig, A. D. (2008). “Interoception Muller, D., Santorelli, S. F., et al. malities in mood disorders. Nature Castonguay, L. G., and Beutler, L. and emotion,” in Handbook of (2003b). Alterations in brain 386, 824–827. E. (2005). Principles of Therapeutic Emotions, eds J. M. Haviland-Jones, and immune function produced by Drevets, W. C., Savitz, J., and Trimble, Change that Work.NewYork,NY: L. F. Barrett, and M. Lewis (New mindfulness meditation. Psychosom. M. (2008). The subgenual anterior Oxford University Press. York, NY: Guildford Publications), Med. 65, 564–570. cingulate cortex in mood disorders. Cavanna,A.E.,andTrimble,M.R. 272–288. Davidson,R.J.,Jackson,D.C.,and CNS Spectr. 13, 663–681. (2006). The precuneus: a review Craig, A. D. (2009). Emotional Kalin, N. H. (2000). Emotion, Dreyfus, G. (2011). Is mindfulness of its functional anatomy and moments across time: a possible plasticity, context, and regula- present-centred and non- behavioural correlates. Brain 129, neural basis for time perception in tion: perspectives from affective judgmental? A discussion of 564–583. the anterior insula. Philos. Trans. neuroscience. Psychol. Bull. 126, the cognitive dimensions of mind- Chadwick, P., Hember, M., Symes, R.Soc.Lond.BBiol.Sci.364, 890–909. fulness. Contemp. Buddhism 12, J., Peters, E., Kuipers, E., and 1933–1942. Decety, J. (1996). Neural representa- 41–54. Dagnan, D. (2008). Responding Craik, F. I. (2002). Levels of processing: tions for action. Rev. Neurosci. 7, Dunne, J. (2011). Toward an mindfully to unpleasant thoughts past, present and future? Memory 285–297. understanding of non-dual mind- and images: reliability and valid- 10, 305–318. Decety, J., and Chaminade, T. (2003). fulness. Contemp. Buddhism 12, ity of the Southampton mindfulness Creswell,J.D.,Way,B.M.,Eisenberger, When the self represents the other: 71–88. questionnaire (SMQ). Br.J.Clin. N. I., and Lieberman, M. D. (2007). anewcognitiveneuroscienceview Eisenberg, N., Eggum, N. D., and Di Psychol. 47, 451–455. Neural correlates of dispositional on psychological identification. Giunta, L. (2010). Empathy-related Champagne, F. A., and Curley, J. mindfulness during affect labeling. Conscious. Cogn. 12, 577–596. responding: associations with P. (2008). Maternal regulation of Psychosom. Med. 69, 560–565. De Greck, M., Wang, G., Yang, X., prosocial behavior, aggression, and estrogen receptor alpha methyla- Crick, F., and Koch, C. (2003). A Wang, X., Northoff, G., and intergroup relations. Soc. Issues tion. Curr. Opin. Pharmacol. 8, framework for consciousness. Nat. Han, S. (2012). Neural substrates Policy Rev. 4, 143–180. 735–739. Neurosci. 6, 119–126. underlying intentional empathy. Engstrom, M., and Soderfeldt, B. Chan, D., and Woollacott, M. (2007). Critchley, H. D. (2005). Neural mech- Soc. Cogn. Affect. Neurosci. 7, (2010). Brain activation during Effects of level of meditation expe- anisms of autonomic, affective, 135–144. compassion meditation: a case rience on attentional focus: is the and cognitive integration. J. Comp. Dehaene, S., Posner, M. I., and Tucker, study. J. Altern. Complement. Med. efficiency of executive or orienta- Neurol. 493, 154–166. D. M. (1994). Localization of a 16, 597–599. tion networks improved? J. Altern. Critchley, H. D., Wiens, S., Rotshtein, neural system for error-detection Etkin, A., Egner, T., and Kalisch, R. Complement. Med. 13, 651–657. P., Ohman, A., and Dolan, R. J. and compensation. Psychol. Sci. 5, (2011). Emotional processing in Chiesa, A., and Serretti, A. (2010). A (2004). Neural systems support- 303–305. anterior cingulate and medial pre- systematic review of neurobiologi- ing interoceptive awareness. Nat. Deikman, A. J. (1982). The Observing frontal cortex. Trends Cogn. Sci. 15, cal and clinical features of mindful- Neurosci. 7, 189–195. Self: Mysticism and Psychotherapy. 85–93. ness meditations. Psychol. Med. 40, Damasio, A. (1999). The Feeling of Boston, MA: Beacon Press. Fan, Y., Duncan, N. W., De Greck, M., 1239–1252. What Happens: Body and Emotion Delgado, L. C., Guerra, P., Perakakis, and Northoff, G. (2011). Is there Christoff, K., Cosmelli, D., Legrand, in the Making of Consciousness.New P., Vera, M. N., Reyes Del Paso, G., a core neural network in empathy? D., and Thompson, E. (2011). York, NY: Harcourt Brace. and Vila, J. (2010). Treating chronic An fMRI based quantitative meta- Specifying the self for cognitive Damasio, A. (2010). Self Comes to worry: psychological and physiolog- analysis. Neurosci. Biobehav. Rev. 35, neuroscience. Trends Cogn. Sci. 15, Mind: Constructing the Conscious ical effects of a training programme 903–911. 104–112. Brain. New York, NY: Pantheon based on mindfulness. Behav. Res. Farb,N.A.,Anderson,A.K.,Mayberg, Chrousos, G. P., and Gold, P. W. (1992). Books. Ther. 48, 873–882. H., Bean, J., McKeon, D., and Segal, The concepts of stress and stress sys- Davids, R. (1882). Buddhism: Being Deshpande, G., Santhanam, P., and Z. V. (2010). Minding one’s emo- tem disorders. Overview of physical a Sketch of the Life and Teachings Hu, X. (2011). Instantaneous and tions: mindfulness training alters and behavioral homeostasis. JAMA of Gautama, the Buddha.London: causal connectivity in resting state the neural expression of sadness. 267, 1244–1252. SPCK. brain networks derived from func- Emotion 10, 25–33. Cialdini,R.B.,Brown,S.L.,Lewis, Davidson, R. J. (2000). Affective style, tional MRI data. Neuroimage 54, Farb, N. A., Segal, Z. V., and Anderson, B. P., Luce, C., and Neuberg, S. L. psychopathology, and resilience: 1043–1052. A. K. (2012). Mindfulness

Frontiers in Human Neuroscience www.frontiersin.org October 2012 | Volume 6 | Article 296 | 26 Vago and Silbersweig S-ART: Mechanisms of mindfulness

meditation training alters cortical for cognitive science. Trends Cogn. pain-related cortices predicts low does mindfulness meditation work? representations of interocep- Sci. 4, 14–21. pain sensitivity in Zen meditators. Proposing mechanisms of action tive attention. Soc. Cogn. Affect. Gallese, V., and Sinigaglia, C. (2010). Pain 152, 150–156. from a conceptual and neural per- Neurosci. doi: 10.1093/scan/nss066. The bodily self as power for action. Grant, J. A., and Rainville, P. (2009). spective. Perspect. Psychol. Sci. 6, [Epub ahead of print]. Neuropsychologia 48, 746–755. Pain sensitivity and analgesic effects 537–559. Farb, N. A., Segal, Z. V., Mayberg, Ganaden, R., and Smith, S. D. (2011). of mindful states in Zen meditators: Holzel, B. K., Carmody, J., Vangel, M., H., Bean, J., McKeon, D., Fatima, The effects of trait mindfulness on a cross-sectional study. Psychosom. Congleton, C., Yerramsetti, S. M., Z., et al. (2007). Attending to multiple components of attention: Med. 71, 106–114. Gard, T., et al. (2011b). Mindfulness the present: mindfulness medita- evidence from an emotional atten- Grimm, S., Ernst, J., Boesiger, P., practice leads to increases in tion reveals distinct neural modes tion networks test. Can. J. Exp. Schuepbach, D., Hell, D., Boeker, regional brain gray matter density. of self-reference. Soc. Cogn. Affect. Psychol. 64, 328–328. H., et al. (2009). Increased self- Psychiatry Res. 191, 36–43. Neurosci. 2, 313–322. Gard, T., Holzel, B. K., Sack, A. focus in major depressive disor- Holzel,B.K.,Carmody,J.,Evans,K.C., Farrer, C., Franck, N., Georgieff, T., Hempel, H., Lazar, S.W., Vaitl, der is related to neural abnormal- Hoge,E.A.,Dusek,J.A.,Morgan, N., Frith, C. D., Decety, J., and D., et al. (2012). Pain attenua- ities in subcortical-cortical midline L., et al. (2010). Stress reduction Jeannerod, M. (2003). Modulating tion through mindfulness is associ- structures. Hum. Brain Mapp. 30, correlates with structural changes the experience of agency: a positron ated with decreased cognitive con- 2617–2627. in the amygdala. Soc. Cogn. Affect. emission tomography study. trol and increased sensory process- Gross, J. J. (1998). Antecedent- and Neurosci. 5, 11–17. Neuroimage 18, 324–333. ing in the brain. Cereb. Cortex 22, response-focused emotion regula- Holzel,B.K.,Ott,U.,Gard,T.,Hempel, Feder, A., Nestler, E. J., and Charney, 2692–2702. tion: divergent consequences for H.,Weygandt,M.,Morgen,K., D. S. (2009). Psychobiology and Garland, E., Gaylord, S., and Park, J. experience, expression, and phys- et al. (2008). Investigation of mind- molecular genetics of resilience. (2009). The role of mindfulness in iology. J. Pers. Soc. Psychol. 74, fulness meditation practitioners Nat. Rev. Neurosci. 10, 446–457. positive reappraisal. Explore (NY) 5, 224–237. with voxel-based morphometry. Feldman, G., Hayes, A., Kumar, S., 37–44. Grossman, P. (2008). On measuring Soc. Cogn. Affect. Neurosci. 3, Greeson, J., and Laurenceau, J. P. Garland, E., Gaylord, S., Boettige, mindfulness in psychosomatic 55–61. (2007). Mindfulness and emotion R. C., and Howard, M. (2010). and psychological research. J. Holzel, B. K., Ott, U., Hempel, H., regulation: the development and Mindfulness training modifies Psychosom. Res. 64, 405–408. Hackl, A., Wolf, K., Stark, R., et al. initial validation of the Cognitive cognitive, affective, and physio- Grossman, P., and Van Dam, N. T. (2007). Differential engagement and Affective Mindfulness Scale- logical mechanisms implicated (2011). Mindfulness, by any other of anterior cingulate and adjacent Revised (CAMS-R). J. Psychopathol. in alcohol dependence: results name: trials and tribulations of sati medial frontal cortex in adept Behav. Assess. 29, 177–190. of a randomized controlled pilot in western psychology and science. meditators and non-meditators. Fischer, D., Paller, K., and Vago, D. trial. J. Psychoactive Drugs 42, Contemp. Buddhism 12, 219–239. Neurosci. Lett. 421, 16–21. (2012). “The effects of mindfulness 177–192. Gunaratana, B. H. (2002). Mindfulness Ives-Deliperi, V. L., Solms, M., and on iconic memory,” in Mind and Garland, E., Gaylord, S., and in Plain English.Boston,MA: Meintjes, E. M. (2011). The neu- Life Summer Research Institute: Fredrickson, B. (2011). Positive Wisdom Publications. ral substrates of mindfulness: an The Situated and Embodied Mind. reappraisal mediates the stress- Haggard, P. (2005). Conscious inten- fMRI investigation. Soc. Neurosci. 6, (Garrison, NY: Mind and Life reductive effects of mindfulness: an tion and motor cognition. Trends 231–242. Institute). upward spiral process. Mindfulness Cogn. Sci. 9, 290–295. Jameison, K., and Dinan, T. G. (2001). Flavell, J. H. (1979). Metacognition 2, 59–67. Halifax, J. (2012). A heuristic model Glucocorticoids and cognitive func- and cognitive monitoring: a new Gethin, R. (2011). On some definitions of enactive compassion. Curr. Opin. tion: from physiology to pathophys- area of cognitive-developmental of mindfulness. Contemp. Buddhism Support Palliat. Care 6, 228–235. iology. Hum. Psychopharmacol. 16, inquiry. Am. Psychol. 34, 12, 263–279. Hayes, S. C., Luoma, J. B., Bond, 293–302. 906–911. Gilbert, S. J., Gonen-Yaacovi, G., F. W., Masuda, A., and Lillis, J. James, W. (1890). Principles of Fletcher, L. B., and Hayes, S. C. (2005). Benoit,R.G.,Volle,E.,andBurgess, (2006). Acceptance and commit- Psychology. New York, NY: Henry Relational frame theory, acceptance P. W. (2010). Distinct functional ment therapy: model, processes and Holt and Company. and commitment therapy, and a connectivity associated with lateral outcomes. Behav. Res Ther. 44, 1–25. James, W. (1892). Psychology: Briefer functional analytic definition of versus medial rostral prefrontal Hayes, S. C., Strosahl, K. D., and Course. New York, NY: Henry Holt mindfulness. J. Ration. Emot. Cogn. cortex: a meta-analysis. Neuroimage Wilson, K. G. (2003). Acceptance and Company. Behav. Ther. 23, 315–336. 53, 1359–1367. and Commitment Therapy: An Jang,J.H.,Jung,W.H.,Kang,D.H., Fletcher, L. B., Schoendorff, B., and Goldin, P. R., and Gross, J. J. (2010). Experiential Approach to Behavior Byun,M.S.,Kwon,S.J.,Choi,C. Hayes, S. C. (2010). Searching for Effects of mindfulness-based stress Change.NewYork,NY:Guilford H., et al. (2010). Increased default mindfulness in the brain: a process- reduction (MBSR) on emotion reg- Press. mode network connectivity associ- oriented approach to examining the ulation in social anxiety disorder. Hein, G., and Singer, T. (2008). I feel ated with meditation. Neurosci. Lett. neural correlates of mindfulness. Emotion 10, 83–91. how you feel but not always: the 487, 358–362. Mindfulness 2, 41–63. Goldstein, B. J. (1976). The Experience empathic brain and its modulation. Jevning, R., Anand, R., Biedebach, M., Fox, M. D., Snyder, A. Z., Vincent, J. L., of Insight. Boston, MA: Shambhala. Curr. Opin. Neurobiol. 18, 153–158. and Fernando, G. (1996). Effects Corbetta, M., Van Essen, D. C., and Goleman,D.J.,andSchwartz,G.E. Heller, A. S., Johnstone, T., Shackman, on regional cerebral blood flow of Raichle, M. E. (2005). The human (1976). Meditation as an interven- A. J., Light, S. N., Peterson, M. J., transcendental meditation. Physiol. brain is intrinsically organized into tion in stress reactivity. J. Consult. Kolden, G. G., et al. (2009). Reduced Behav. 59, 399–402. dynamic, anticorrelated functional Clin. Psychol. 44, 456–466. capacity to sustain positive emotion Jevning,R.,Wallace,R.K.,and networks. Proc. Natl. Acad. Sci. Grant, J. A., Courtemanche, J., in major depression reflects dimin- Beidebach, M. (1992). The phys- U.S.A. 102, 9673–9678. Duerden, E. G., Duncan, G. H., ished maintenance of fronto-striatal iology of meditation: a review. A Frith, C. D., and Frith, U. (2012). and Rainville, P. (2010a). Cortical brain activation. Proc. Natl. Acad. wakeful hypometabolic integrated Mechanisms of social cognition. thickness and pain sensitivity Sci. U.S.A. 106, 22445–22450. response. Neurosci. Biobehav. Rev. Annu. Rev. Psychol. 63, 287–313. in zen meditators. Emotion 10, Hodgins, H. S., and Adair, K. C. (2010). 16, 415–424. Frost, N. (1972). Encoding and retrieval 43–53. Attentional processes and medita- Jha, A. P., Krompinger, J., and Baime, in visual memory tasks. J. Exp. Grant, J. A., Courtemanche, J., and tion. Conscious. Cogn. 19, 872–878. M. J. (2007). Mindfulness train- Psychol. 95, 317–326. Rainville, P. (2010b). A non- Holzel, B. K., Lazar, S. W., Gard, ing modifies subsystems of atten- Gallagher, I. I. (2000). Philosophical elaborative mental stance and T., Schuman-Olivier, Z., Vago, D. tion. Cogn.Affect.Behav.Neurosci.7, conceptions of the self: implications decoupling of executive and R., and Ott, U. (2011a). How 109–119.

Frontiers in Human Neuroscience www.frontiersin.org October 2012 | Volume 6 | Article 296 | 27 Vago and Silbersweig S-ART: Mechanisms of mindfulness

Jinpa, T. (2009). Is Meditation a C. (2002). Increased dopamine tone conditional Granger causality. Biol. positive affect: does happiness Means of Knowing our Mental during meditation-induced change Cybern. 102, 57–69. lead to success? Psychol. Bull. 131, World? [Online]. Available online of consciousness. Brain Res. Cogn. Lieberman, M. D., Eisenberger, N. I., 803–855. at: http://contemplativemind.word Brain Res. 13, 255–259. Crockett, M. J., Tom, S. M., Pfeifer, MacLean, K. A., Ferrer, E., Aichele, S. press.com/what-is-mindfulness/ Koole, S. L., Van Dillen, L. F., J. H., and Way, B. M. (2007). R.,Bridwell,D.A.,Zanesco,A.P., (Accessed October 15, 2012). and Sheppes, G. (2011). “The Putting feelings into words: affect Jacobs, T. L., et al. (2010). Intensive Josipovic, Z., Dinstein, I., Weber, self-regulation of emotion,” in labeling disrupts amygdala activ- meditation training improves per- J., and Heeger, D. J. (2011). Handbook of Self-regulation,edsK. ityinresponsetoaffectivestimuli. ceptual discrimination and sus- Influence of meditation on anti- Vohs and R. Baumeister (New York, Psychol. Sci. 18, 421–428. tained attention. Psychol. Sci. 21, correlated networks in the brain. NY: Guilford Press), 22–40. Light, S. N., Heller, A. S., Johnstone, T., 829–839. Front. Hum. Neurosci. 5:183. doi: Krieghoff, V., Waszak, F., Prinz, W., Kolden,G.G.,Peterson,M.J.,Kalin, Mahesh Yogi, M. (1995). Science 10.3389/fnhum.2011.00183 and Brass, M. (2011). Neural and N. H., et al. (2011). Reduced right of Being and Art of Living: Kabat-Zinn, J. (1982). An outpatient behavioral correlates of inten- ventrolateral prefrontal cortex activ- Transcendental Meditation.New program in behavioral medicine tional actions. Neuropsychologia 49, ity while inhibiting positive affect York, NY: Penguin Books. for chronic pain patients based on 767–776. is associated with improvement in Manna, A., Raffone, A., Perrucci, M. the practice of mindfulness med- Krishnamurti, J. (1969). Freedom hedonic capacity after 8 weeks of G., Nardo, D., Ferretti, A., Tartaro, itation: theoretical considerations From the Known.NewYork,NY: antidepressant treatment in major A., et al. (2010). Neural correlates and preliminary results. Gen. Hosp. HarperCollins Publishers. depressive disorder. Biol. Psychiatry of focused attention and cognitive Psychiatry 4, 33–47. Laberge, D. (2000). “Networks of 70, 962–968. monitoring in meditation. Brain Kabat-Zinn, J. (1990). Full Catastrophe attention,” in The New Cognitive Linehan, M. M. (1993). Cognitive- Res. Bull. 82, 46–56. Living: Using the Wisdom of Your Neurosciences, ed M. Gazzaniga Behavioral Treatment of Borderline Marr, D. (1971). Simple memory: a the- Body and Mind to Face Stress, (Cambridge: MIT Press), 711–724. Personality Disorder.NewYork,NY: ory for archicortex. Philos. Trans. R. Pain and Illness.NewYork,NY: Lama Xiv, D., Geshe Lobsang, J., Guilford Press. Soc. Lond. B Biol. Sci. 262, 23–81. Delacorte. Lobsang Choephel, G., Russell, Loftus, E. (1979). Eyewitness reliability. Masten, C. L., Eisenberger, N. I., Pfeifer, Kabat-Zinn, J. (2011). Some reflections J., Kamalashila, and Lamrim Science 205, 386–387. J. H., and Dapretto, M. (2010). on the origins of MBSR, skillful Translation Committee. (2001). Lou, H. C., Kjaer, T. W., Friberg, L., Witnessing peer rejection during means, and the trouble with maps. Stages of Meditation: [commentary]. Wildschiodtz, G., Holm, S., and early adolescence: neural correlates Contemp. Buddhism 12, 281–306. Ithaca, NY: Snow Lion Publications. Nowak, M. (1999). A 15O − H2O of empathy for experiences of social Kabat-Zinn, J., Wheeler, E., Light, T., Langer, E. J. (1989). Mindfulness. PET study of meditation and the exclusion. Soc. Neurosci. 5, 496–507. Skillings, A., Scharf, M. J., Cropley, Cambridge, MA: Perseus Books. resting state of normal conscious- Mathews, A., and Mackintosh, B. T. G., et al. (1998). Influence Lau, M. A., Bishop, S. R., Segal, ness. Hum. Brain Mapp. 7, 98–105. (1998). A cognitive model of selec- of a mindfulness meditation-based Z.V.,Buis,T.,Anderson,N.D., Lou, H. C., Nowak, M., and Kjaer, T. W. tive processing in anxiety. Cogn. stress reduction intervention on Carlson, L., et al. (2006). The (2005). The mental self. Prog. Brain Ther. Res. 22, 539–560. rates of skin clearing in patients toronto mindfulness scale: develop- Res. 150, 197–204. McEwen, B. S. (1998). Stress, adap- with moderate to severe psoria- ment and validation. J. Clin. Psychol. Luders, E., Toga, A. W., Lepore, N., and tation, and disease. Allostasis and sis undergoing phototherapy (UVB) 62, 1445–1467. Gaser, C. (2009). The underlying allostatic load. Ann. N.Y. Acad. Sci. and photochemotherapy (PUVA). Lazar, S. W., Bush, G., Gollub, R. L., anatomical correlates of long-term 840, 33–44. Psychosom. Med. 60, 625–632. Fricchione, G. L., Khalsa, G., and meditation: larger hippocampal and McEwen, B. S. (2008). Central effects of Kagan, J. (2003). Biology, context, and Benson, H. (2000). Functional brain frontal volumes of gray matter. stress hormones in health and dis- developmental inquiry. Annu. Rev. mapping of the relaxation response Neuroimage 45, 672–678. ease: understanding the protective Psychol. 54, 1–23. and meditation. Neuroreport 11, Lutz, A., Brefczynski-Lewis, J., and damaging effects of stress and Kensinger, E. A., and Schacter, D. 1581–1585. Johnstone, T., and Davidson, R. J. stress mediators. Eur. J. Pharmacol. L. (2005). Retrieving accurate and Lazar, S. W., Kerr, C. E., Wasserman, (2008a). Regulation of the neural 583, 174–185. distorted memories: neuroimaging R. H., Gray, J. R., Greve, D. N., circuitry of emotion by compassion McGaugh, J. L. (2000). Memory–a cen- evidence for effects of emotion. Treadway, M. T., et al. (2005). meditation: effects of meditative tury of consolidation. Science 287, Neuroimage 27, 167–177. Meditation experience is associated expertise. PLoS ONE 3:e1897. doi: 248–251. Kerr, C. E., Shaw, J. R., Wasserman, with increased cortical thickness. 10.1371/journal.pone.0001897 McRae, K., Ochsner, K. N., and Gross, R.H.,Chen,V.W.,Kanojia,A., Neuroreport 16, 1893–1897. Lutz, A., Slagter, H. A., Dunne, J. J. J. (2011). “The reason in pas- Bayer, T., et al. (2008). Tactile acu- Legrand, D. (2007). Subjectivity and D., and Davidson, R. J. (2008b). sion: a social cognitive neuroscience ity in experienced Tai Chi practi- the body: introducing basic forms of Attention regulation and monitor- approach to emotion regulation,” in tioners: evidence for use dependent self-consciousness. Conscious. Cogn. ing in meditation. Trends Cogn. Sci. Handbook of Self-Regulation,(New plasticity as an effect of sensory- 16, 577–582. 12, 163–169. York, NY: The Guilford Press), attentional training. Exp. Brain Res. Legrand, D., and Ruby, P. (2009). What Lutz, A., Dunne, J. D., and Davidson, 186–203. 188, 317–322. is self-specific? Theoretical investi- R. J. (2007). “Meditation and Milad, M. R., Quinn, B. T., Pitman, R. Khalsa, S. S., Rudrauf, D., Damasio, A. gation and critical review of neu- the neuroscience of conscious- K.,Orr,S.P.,Fischl,B.,andRauch, R., Davidson, R. J., Lutz, A., and roimaging results. Psychol. Rev. 116, ness,” in Cambridge Handbook of S. L. (2005). Thickness of ventrome- Tranel, D. (2008). Interoceptive 252–282. Consciousness,eds.P.Zelazo,M. dial prefrontal cortex in humans is awareness in experienced med- Lenggenhager, B., Mouthon, M., Moscovitch and E. Thompson (New correlated with extinction memory. itators. Psychophysiology 45, and Blanke, O. (2009). Spatial York, NY: Cambridge University Proc. Natl. Acad. Sci. U.S.A. 102, 671–677. aspects of bodily self-consciousness. Press), 499–555. 10706–10711. Kilpatrick, L. A., Suyenobu, B. Conscious. Cogn. 18, 110–117. Lutz, A., Greischar, L. L., Perlman, D. Milad, M. R., Wright, C. I., Orr, S. Y., Smith, S. R., Bueller, J. A., Levenson,R.W.,Ekman,P.,andRicard, M., and Davidson, R. J. (2009). P.,Pitman,R.K.,Quirk,G.J., Goodman, T., Creswell, J. D., et al. M. (2012). Meditation and the star- BOLD signal in insula is differ- and Rauch, S. L. (2007). Recall of (2011). Impact of mindfulness- tle response: a case study. Emotion entially related to cardiac function fear extinction in humans activates based stress reduction training 12, 650–658. during compassion meditation in the ventromedial prefrontal cortex on intrinsic brain connectivity. Liao, W., Mantini, D., Zhang, Z., Pan, experts vs. novices. Neuroimage 47, and hippocampus in concert. Biol. Neuroimage 56, 290–298. Z., Ding, J., Gong, Q., et al. (2010). 1038–1046. Psychiatry 62, 446–454. Kjaer,T.W.,Bertelsen,C.,Piccini,P., Evaluating the effective connectiv- Lyubomirsky, S., King, L., and Diener, Modinos, G., Ormel, J., and Aleman, Brooks, D., Alving, J., and Lou, H. ity of resting state networks using E. (2005). The benefits of frequent A. (2010). Individual differences in

Frontiers in Human Neuroscience www.frontiersin.org October 2012 | Volume 6 | Article 296 | 28 Vago and Silbersweig S-ART: Mechanisms of mindfulness

dispositional mindfulness and brain responses to psychosocial stress Posner, M. I., and Rothbart, M. K. motivation, and self-regulated activity involved in reappraisal of do not predict subsequent com- (2009). Toward a physical basis of learning in contemplative per- emotion. Soc. Cogn. Affect. Neurosci. passion meditation practice time. attention and self regulation. Phys. spective. Educ. Psychol. 44, 5, 369–377. Psychoneuroendocrinology 35, Life Rev. 6, 103–120. 119–136. Mogg, K., and Bradley, B. P. (1998). 310–315. Quirk, G. J., and Mueller, D. (2008). Rothbart, M. K., and Ahadi, S. A. A cognitive-motivational analysis Pagnoni, G., and Cekic, M. (2007). Neural mechanisms of extinc- (1994). Temperament and the of anxiety. Behav. Res. Ther. 36, Age effects on gray matter vol- tion learning and retrieval. development of personality. J. 809–848. ume and attentional performance Neuropsychopharmacology 33, Abnorm. Psychol. 103, 55–66. Mogg, K., Bradley, B. P., and Williams, in Zen meditation. Neurobiol. Aging 56–72. Rothman, A. J., Baldwin, A. S., Hertel, R. (1995). Attentional bias in anx- 28, 1623–1627. Quirk, G. J., Pare, D., Richardson, R., A. W., and Fuglestad, P. T. (2011). iety and depression: the role of Pagnoni, G., Cekic, M., and Guo, Herry, C., Monfils, M. H., Schiller, “Self-regulation and behavioral awareness. Br. J. Clin. Psychol. 34(Pt Y. (2008). “Thinking about not- D., et al. (2010). Erasing fear mem- change,” in Handbook of self- 1), 17–36. thinking”: neural correlates of con- ories with extinction training. J. regulation, eds K. Vohs and R. Morgan, M. A., and Ledoux, J. E. ceptual processing during Zen med- Neurosci. 30, 14993–14997. Baumeister (New York, NY: The (1999). Contribution of ventrolat- itation. PLoS ONE 3:e3083. doi: Raffone, A., and Pantani, M. (2010). Guilford Press), 106–122. eral prefrontal cortex to the acqui- 10.1371/journal.pone.0003083 A global workspace model for phe- Roy, M., Shohamy, D., and Wager, T. sition and extinction of conditioned Parkinson, B., and Totterdell, P. (1999). nomenal and access consciousness. D. (2012). Ventromedial prefrontal- fear in rats. Neurobiol. Learn. Mem. Classifying affect-regulation strate- Conscious. Cogn. 19, 580–596. subcortical systems and the gener- 72, 244–251. gies. Cogn. Emot. 13, 277–303. Raffone, A., and Srinivasan, N. (2010). ation of affective meaning. Trends Nader, K., Schafe, G. E., and Ledoux, Paul, N., Stanton, S., Greeson, J., The exploration of meditation in Cogn. Sci. 16, 147–156. J. E. (2000). The labile nature Smoski, M., and Wang, L. (2012). the neuroscience of attention and Rubia, K. (2009). The neurobiology of of consolidation theory. Nat. Rev. Psychological and neural mecha- consciousness. Cogn. Process. 11, Meditation and its clinical effective- Neurosci. 1, 216–219. nisms of trait mindfulness in reduc- 1–7. ness in psychiatric disorders. Biol. Newberg,A.B.,Wintering,N., ing depression vulnerability. Soc. Rahula, W. (1974). What the Buddha Psychol. 82, 1–11. Waldman, M. R., Amen, D., Khalsa, Cogn.Affect.Neurosci.doi: 10.1093/ Taught. New York, NY: Grove Press. Ruby, P., and Decety, J. (2001). Effect of D. S., and Alavi, A. (2010). Cerebral scan/nss070. [Epub ahead of print]. Ramel, W., Goldin, P. R., Carmona, P. subjective perspective taking during blood flow differences between Pessoa, L. (2005). To what extent are E., and McQuaid, J. R. (2004). The simulation of action: a PET inves- long-term meditators and non- emotional visual stimuli processed effects of mindfulness meditation tigation of agency. Nat. Neurosci. 4, meditators. Conscious. Cogn. 19, without attention and awareness? on cognitive processes and affect in 546–550. 899–905. Curr. Opin. Neurobiol. 15, 188–196. patients with past depression. Cogn. Ryan, R. M., and Deci, E. L. (2000). Nielsen, L., and Kaszniak, A. W. (2006). Peters, J., Daum, I., Gizewski, E., Ther. Res. 28, 433–455. Self-determination theory and the Awareness of subtle emotional Forsting,M.,andSuchan,B. Raz, A., and Buhle, J. (2006). facilitation of intrinsic motivation, feelings: a comparison of long-term (2009). Associations evoked dur- Typologies of attentional networks. social development, and well-being. meditators and nonmeditators. ing memory encoding recruit the Nat. Rev. Neurosci. 7, 367–379. Am. Psychol. 55, 68–78. Emotion 6, 392–405. context-network. Hippocampus 19, Ricard, M. (2003). Happiness.New Safran, J. D., and Segal, Z. V. (1990). Northoff, G. (2005). Is emotion regu- 141–151. York, NY: Little, Brown and Interpersonal Process in Cognitive lation self-regulation? Trends Cogn. Phelps, E. A., Delgado, M. R., Nearing, Company. Therapy. New York, NY: Random Sci. 9, 408–409; author reply 409– K. I., and Ledoux, J. E. (2004). Ridderinkhof, K. R., Van Den House. 410. Extinction learning in humans: Wildenberg, W. P., Segalowitz, Sahdra,B.K.,Shaver,P.R.,andBrown, Northoff, G., and Bermpohl, F. (2004). role of the amygdala and vmPFC. S. J., and Carter, C. S. (2004). K. W. (2010). A scale to measure Cortical midline structures and the Neuron 43, 897–905. Neurocognitive mechanisms of nonattachment: a buddhist comple- self. Trends Cogn. Sci. 8, 102–107. Phillips, M. L., Ladouceur, C. D., cognitive control: the role of pre- ment to western research on attach- Northoff, G., and Panksepp, J. (2008). and Drevets, W. C. (2008). A frontal cortex in action selection, ment and adaptive functioning. J. The trans-species concept of self neural model of voluntary and response inhibition, performance Pers. Assess. 92, 116–127. and the subcortical-cortical mid- automatic emotion regulation: monitoring, and reward-based Salzberg, S. (2011). Mindfulness line system. Trends Cogn. Sci. 12, implications for understanding the learning. Brain Cogn. 56, 129–140. and loving-kindness. Contemp. 259–264. pathophysiology and neurodevel- Rimes, K. A., and Watkins, E. (2005). Buddhism 12, 177–182. Ochsner, K. N., and Gross, J. J. (2005). opment of bipolar disorder. Mol. The effects of self-focused rumi- Salzberg, S., and Bush, M. (1999). The cognitive control of emotion. Psychiatry 13, 829, 833–857. nation on global negative self- Voices of Insight.Boston,MA: Trends Cogn. Sci. 9, 242–249. Pollak, D. D., Rogan, M. T., Egner, T., judgements in depression. Behav. Shambala Publications, Inc. Ott, U., Holzel, B. K., and Vaitl, Perez, D. L., Yanagihara, T. K., and Res. Ther. 43, 1673–1681. Sapolsky, R. M. (2003). Stress and D. (2010a). “Brain structure Hirsch, J. (2010). A translational Rinpoche, T. U., Kunsang, E. P., plasticity in the limbic system. and meditation. how spiritual bridge between mouse and human and Schmidt, M. B. (2006). Neurochem. Res. 28, 1735–1742. practice shapes the brain,” in models of learned safety. Ann. Med. Quintessential Dzogchen: Confusion Schmitz, T. W., and Johnson, S. C. Neuroscience, Consciousness and 42, 115–122. Dawns as Wisdom. Hong Kong: (2007). Relevance to self: a brief Spirituality: Proceedings of the Porges, S. W. (1995). Orienting in Rangjung Yeshe Publications. review and framework of neural Expert Meeting, ed H. W. S. Schmidt a defensive world: mammalian Ritskes, R., Ritskes-Hoitinga, systems underlying appraisal. (Freiburg/Breisgau: Springer). modifications of our evolution- M., Stodkilde-Jorgensen, H., Neurosci. Biobehav. Rev. 31, Ott, U., Walter, B., Gebhardt, H., ary heritage. A polyvagal theory. Baerentsen, K., and Hartman, T. 585–596. Stark, R., and Vaitl, D. (2010b). Psychophysiology 32, 301–318. (2003). MRI scanning during Zen Seeley, W. W., Menon, V., Schatzberg, “Inhibition of default mode net- Posner, M. I., and Petersen, S. E. meditation: the picture of enlight- A. F., Keller, J., Glover, G. H., work activity during mindfulness (1990). The attention system of the enment? Constructivism Hum. Sci. Kenna, H., et al. (2007). Dissociable meditation,” in 16th Annual Meeting human brain. Annu. Rev. Neurosci. 8, 85–90. intrinsic connectivity networks for of the Organization of Human Brain 13, 25–42. Robbins, T. W., and Everitt, B. J. (1996). salience processing and executive Mapping. (Barcelona, Spain). Posner, M. I., and Rothbart, M. K. Neurobehavioural mechanisms of control. J. Neurosci. 27, 2349–2356. Pace, T. W., Negi, L. T., Sivilli, T. I., (1998). Attention, self-regulation reward and motivation. Curr. Opin. Segal, Z. V., Williams, J. M. G., and Issa,M.J.,Cole,S.P.,Adame,D. and consciousness. Philos. Trans. Neurobiol. 6, 228–236. Teasdale, J. D. (2002). Mindfulness- D., et al. (2010). Innate immune, R.Soc.Lond.BBiol.Sci.353, Roeser, R. W., and Peck, S. C. (2009). based Cognitive Therapy for neuroendocrine and behavioral 1915–1927. An education in awareness: self, Depression: A New Approach to

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Preventing Relapse.NewYork,NY: awareness: a neurocognitive Barendregt, H. P. (2010a). Greater processing of emotional informa- Guilford. hypothesis. Cogn. Process. 11, 9–20. efficiency in attentional processing tion. Cogn. Emot. 24, 3–47. Shapiro, S. L., Carlson, L. E., Astin, Tang,Y.Y.,Lu,Q.,Geng,X.,Stein, related to mindfulness meditation. Young, J. D., and Taylor, E. (1998). J. A., and Freedman, B. (2006). E.A.,Yang,Y.,andPosner,M. Q. J. Exp. Psychol. (Colchester) 63, Meditation as a voluntary Mechanisms of mindfulness. J. Clin. I. (2010). Short-term meditation 1168–1180. hypometabolic state of biologi- Psychol. 62, 373–386. induces white matter changes in the vandenHurk,P.A.M.,Janssen, cal activation. News Physiol. Sci. 13, Simons, D. J., and Levin, D. T. (1997). anterior cingulate. Proc. Natl. Acad. B. H., Giommi, F., Barendregt, 149–153. Change blindness. Trends Cogn. Sci. Sci. U.S.A. 107, 15649–15652. H. P., and Gielen, S. C. (2010b). Young, S. (2010). Working with 1, 261–267. Tang,Y.Y.,Ma,Y.,Fan,Y.,Feng,H., Mindfulness meditation associated Mental Images. Available online Sin, N. L., and Lyubomirsky, S. (2009). Wang, J., Feng, S., et al. (2009). with alterations in bottom-up at: http://shinzen.org/Articles/ Enhancing well-being and alleviat- Central and autonomic nervous sys- processing: psychophysiological artWorkWithImage.pdf (Accessed ing depressive symptoms with pos- tem interaction is altered by short- evidence for reduced reactivity. Int. 2011). itive psychology interventions: a term meditation. Proc. Natl. Acad. J. Psychophysiol. 78, 151–157. Zaki, J., and Ochsner, K. (2012). The practice-friendly meta-analysis. J. Sci. U.S.A. 106, 8865–8870. Varela, F. J., Thompson, E., and Rosch, neuroscience of empathy: progress, Clin. Psychol. 65, 467–487. Tang,Y.Y.,Ma,Y.,Wang,J.,Fan,Y., E. (1991). The Embodied Mind. pitfalls and promise. Nat. Neurosci. Singer, T., and Lamm, C. (2009). Feng, S., Lu, Q., et al. (2007). Short- Cambridge, MA: MIT Press. 15, 675–680. The social neuroscience of empathy. term meditation training improves Vestergaard-Poulsen, P., Van Beek, Zeidan, F., Gordon, N. S., Merchant, Ann. N.Y. Acad. Sci. 1156, 81–96. attention and self-regulation. M., Skewes, J., Bjarkam, C. R., J., and Goolkasian, P. (2010). The Slagter,H.A.,Lutz,A.,Greischar,L. Proc. Natl. Acad. Sci. U.S.A. 104, Stubberup, M., Bertelsen, J., et al. effects of brief mindfulness med- L.,Francis,A.D.,Nieuwenhuis, 17152–17156. (2009). Long-term meditation itation training on experimentally S., Davis, J. M., et al. (2007). Tankersley, D., Stowe, C. J., and Huettel, is associated with increased gray induced pain. J. Pain 11, 199–209. Mental training affects distribu- S. A. (2007). Altruism is associated matter density in the brain stem. Zeidan,F.,Martucci,K.T.,Kraft, tion of limited brain resources. with an increased neural response to Neuroreport 20, 170–174. R. A., Gordon, N. S., McHaffie, PLoS Biol. 5:e138. doi: 10.1371/jour- agency. Nat. Neurosci. 10, 150–151. Vincent, J. L., Kahn, I., Snyder, A. J. G., and Coghill, R. C. (2011). nal.pbio.0050138 Taylor, V. A., Daneault, V., Grant, J., Z., Raichle, M. E., and Buckner, Brain mechanisms support- Smith, J. C. (2004). Alterations in Scavone,G.,Breton,E.,Roffe-Vidal, R. L. (2008). Evidence for a ing the modulation of pain by brain and immune function pro- S., et al. (2012). Impact of medita- frontoparietal control system mindfulness meditation. J. Neurosci. duced by mindfulness meditation: tion training on the default mode revealed by intrinsic functional 31, 5540–5548. three caveats. Psychosom. Med. 66, network during a restful state. Soc. connectivity. J. Neurophysiol. 100, Zelazo, P. D., Gao, H. H., and Todd, 148–152; author reply 148–152. Cogn.Affect.Neurosci.doi: 10.1093/ 3328–3342. R. (2007). “The development of Smith, J. M., and Alloy, L. B. (2009). A scan/nsr087. [Epub ahead of print]. Waikar,S.V.,andCraske,M.G. consciousness,” in The Cambridge roadmap to rumination: a review of Thangru, R., and Johnson, C. (2004). (1997). Cognitive correlates of Handbook of Consciousness, 1st Edn., the definition, assessment, and con- Essentials of Mahamudra: Looking anxious and depressive symp- eds P. D. Zelazo, M. Moscovitch, ceptualization of this multifaceted directly at the mind.Boston,MA: tomatology: an examination of the and E. Thompson (Cambridge, construct. Clin.Psychol.Rev.29, Wisdom Publications. Helplessness/Hopelessness model. MA: Cambridge University Press), 116–128. Thera, N. (1962). The Heart of Buddhist J. Anxiety Disord. 11, 1–16. 404–430. Sperling, G. (1960). The information Meditation: A Handbook of Mental Walach, H., Buchheld, N., available in brief visual presenta- Training Based on the Buddha’s Way Buttenmuller, V., Kleinknecht, N., Conflict of Interest Statement: The tions. Psychol. Monogr. 74, 1–29. of Mindfulness. London: Rider and and Schmidt, S. (2006). Measuring authors declare that the research Spreng,R.N.,Mar,R.A.,andKim,A.S. Company. mindfulness - the freiburg mindful- was conducted in the absence of any (2009). The common neural basis of Todd, R. M., Cunningham, W. A., ness inventory (FMI). Pers. Individ. commercial or financial relationships autobiographical memory, prospec- Anderson, A. K., and Thompson, Dif. 40, 1543–1555. that could be construed as a potential tion, navigation, theory of mind, E. (2012). Affect-biased attention Wallace, B. A. (2006). The Attention conflict of interest. and the default mode: a quantitative as emotion regulation. Trends Cogn. Revlolution.Sommerville,MA: meta-analysis. J. Cogn. Neurosci. 21, Sci. 16, 365–372. Wisdom Publications, Inc. 489–510. Treanor, M. (2011). The potential Wallace, B. A. (2011). Minding Received: 01 November 2011; accepted: Srinivasan, N., and Baijal, S. (2007). impact of mindfulness on expo- Closely: The Four Applications of 05 October 2012; published online: 25 Concentrative meditation enhances sure and extinction learning in anx- Mindfulness. Ithaca, NY: Snow Lion October 2012. preattentive processing: a mismatch iety disorders. Clin. Psychol. Rev. 31, Publications. Citation: Vago DR and Silbersweig DA negativity study. Neuroreport 18, 617–625. Wallenstein,G.V.,Vago,D.R., (2012) Self-awareness, self-regulation, 1709–1712. Tsakiris, M., Longo, M. R., and and Walberer, A. M. (2002). and self-transcendence (S-ART): a Sterling, P., and Eyer, J. (1988). Haggard, P. (2010). Having a body Time-dependent involvement of framework for understanding the neu- “Allostasis: a new paradigm to versus moving your body: neural PKA/PKC in contextual memory robiological mechanisms of mindfulness. explain arousal pathology,” in signatures of agency and body- consolidation. Behav. Brain Res. Front. Hum. Neurosci. 6:296. doi: Handbook of Life Stress, Cognition, ownership. Neuropsychologia 48, 133, 159–164. 10.3389/fnhum.2012.00296 and Health, eds S. Fisher and J. 2740–2749. Wells, A., and Matthews, G. (1996). Copyright © 2012 Vago and Reason (New York, NY: Wiley), Vago, D. R., and Nakamura, Y. (2011). Modelling cognition in emotional Silbersweig. This is an open-access 629–649. Selective attentional bias towards disorder: the S-REF model. Behav. article distributed under the terms of the Sweatt, J. D. (2009). Experience- pain-related threat in fibromyal- Res. Ther. 34, 881–888. Creative Commons Attribution License, dependent epigenetic modifications gia: preliminary evidence for effects Williams, J. M. G. (2010). Mindfulness which permits use, distribution and in the central nervous system. Biol. of mindfulness meditation training. and psychological process. Emotion reproduction in other forums, provided Psychiatry 65, 191–197. Cogn. Ther. Res. 35, 581–594. 10, 1–7. the original authors and source are cred- Tagini, A., and Raffone, A. (2010). The vandenHurk,P.A.,Giommi,F., Yiend, J. (2010). The effects of emotion ited and subject to any copyright notices ‘I’ and the ‘Me’ in self-referential Gielen, S. C., Speckens, A. E., and on attention: a review of attentional concerning any third-party graphics etc.

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