Salience and Motivated Behaviour in Schizophrenia
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Dopamine Neurons Mediate a Fast Excitatory Signal Via Their Glutamatergic Synapses
972 • The Journal of Neuroscience, January 28, 2004 • 24(4):972–981 Cellular/Molecular Dopamine Neurons Mediate a Fast Excitatory Signal via Their Glutamatergic Synapses Nao Chuhma,1,6 Hui Zhang,2 Justine Masson,1,6 Xiaoxi Zhuang,7 David Sulzer,1,2,6 Rene´ Hen,3,5 and Stephen Rayport1,4,5,6 Departments of 1Psychiatry, 2Neurology, 3Pharmacology, and 4Anatomy and Cell Biology, and 5Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, 6Department of Neuroscience, New York State Psychiatric Institute, New York, New York 10032, and 7Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, Illinois 60637 Dopamine neurons are thought to convey a fast, incentive salience signal, faster than can be mediated by dopamine. A resolution of this paradox may be that midbrain dopamine neurons exert fast excitatory actions. Using transgenic mice with fluorescent dopamine neurons, in which the axonal projections of the neurons are visible, we made horizontal brain slices encompassing the mesoaccumbens dopamine projection. Focal extracellular stimulation of dopamine neurons in the ventral tegmental area evoked dopamine release and early monosynaptic and late polysynaptic excitatory responses in postsynaptic nucleus accumbens neurons. Local superfusion of the ventral tegmental area with glutamate, which should activate dopamine neurons selectively, produced an increase in excitatory synaptic events. Local superfusion of the ventral tegmental area with the D2 agonist quinpirole, which should increase the threshold for dopamine neuron activation, inhibited the early response. So dopamine neurons make glutamatergic synaptic connections to accumbens neurons. We propose that dopamine neuron glutamatergic transmission may be the initial component of the incentive salience signal. -
Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: a Central Pathway in Psychiatric Disease and Treatment
REVIEW published: 27 December 2016 doi: 10.3389/fnsys.2016.00104 Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment Sarah K. Peters 1, Katharine Dunlop 1 and Jonathan Downar 1,2,3,4* 1Institute of Medical Science, University of Toronto, Toronto, ON, Canada, 2Krembil Research Institute, University Health Network, Toronto, ON, Canada, 3Department of Psychiatry, University of Toronto, Toronto, ON, Canada, 4MRI-Guided rTMS Clinic, University Health Network, Toronto, ON, Canada The salience network (SN) plays a central role in cognitive control by integrating sensory input to guide attention, attend to motivationally salient stimuli and recruit appropriate functional brain-behavior networks to modulate behavior. Mounting evidence suggests that disturbances in SN function underlie abnormalities in cognitive control and may be a common etiology underlying many psychiatric disorders. Such functional and anatomical abnormalities have been recently apparent in studies and meta-analyses of psychiatric illness using functional magnetic resonance imaging (fMRI) and voxel- based morphometry (VBM). Of particular importance, abnormal structure and function in major cortical nodes of the SN, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been observed as a common neurobiological substrate across a broad spectrum of psychiatric disorders. In addition to cortical nodes of the SN, the network’s associated subcortical structures, including the dorsal striatum, mediodorsal thalamus and dopaminergic brainstem nuclei, comprise a discrete regulatory loop circuit. Edited by: The SN’s cortico-striato-thalamo-cortical loop increasingly appears to be central to Avishek Adhikari, mechanisms of cognitive control, as well as to a broad spectrum of psychiatric illnesses Stanford University, USA and their available treatments. -
Brain Responses to Different Types of Salience in Antipsychotic Naïve First Episode Psychosis: an Fmri Study
bioRxiv preprint doi: https://doi.org/10.1101/263020; this version posted September 3, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Brain responses to different types of salience in antipsychotic naïve first episode psychosis: An fMRI study Franziska Knolle1,3*, Anna O Ermakova2*, Azucena Justicia2,4, Paul C Fletcher2,5,6, Nico Bunzeck7, Emrah Düzel8,9, Graham K Murray2,3,5 Running title: Salience signals in antipsychotic naïve first episode psychosis *joint first author with equal contribution to the work Affiliations 1 Department of Psychiatry, University of Cambridge, Cambridge, UK 2 Unit for Social & Community Psychiatry, WHO Collaborating Centre for Mental Health Services Development, East London NHS Foundation Trust 3 Behavioural and Clinical Neuroscience Institute, University of Cambridge 4 IMIM (Hospital del Mar Medical Research Institute). Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain. 5 Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK 6 Institute of Metabolic Science, University of Cambridge 7 Institute of Psychology, University of Lübeck, Lübeck, Germany 8 Otto-von-Guericke University Magdeburg, Institute of Cognitive Neurology and Dementia Research, Magdeburg, Germany 9 German Centre for Neurodegenerative Diseases (DZNE), Magdeburg, Germany 1 bioRxiv preprint doi: https://doi.org/10.1101/263020; this version posted September 3, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Abnormal salience processing has been suggested to contribute to the formation of positive psychotic symptoms in schizophrenia and related conditions. -
Cannabidiol Attenuates Insular Dysfunction During Motivational Salience Processing in Subjects at Clinical High Risk for Psychosis Robin Wilson1, Matthijs G
Wilson et al. Translational Psychiatry (2019) 9:203 https://doi.org/10.1038/s41398-019-0534-2 Translational Psychiatry ARTICLE Open Access Cannabidiol attenuates insular dysfunction during motivational salience processing in subjects at clinical high risk for psychosis Robin Wilson1, Matthijs G. Bossong1,2, Elizabeth Appiah-Kusi1, Natalia Petros 1, Michael Brammer1,3,JesusPerez4, Paul Allen1,5, Philip McGuire1 and Sagnik Bhattacharyya 1 Abstract Accumulating evidence points towards the antipsychotic potential of cannabidiol. However, the neurocognitive mechanisms underlying the antipsychotic effect of cannabidiol remain unclear. We investigated this in a double-blind, placebo-controlled, parallel-arm study. We investigated 33 antipsychotic-naïve subjects at clinical high risk for psychosis (CHR) randomised to 600 mg oral cannabidiol or placebo and compared them with 19 healthy controls. We used the monetary incentive delay task while participants underwent fMRI to study reward processing, known to be abnormal in psychosis. Reward and loss anticipation phases were combined to examine a motivational salience condition and compared with neutral condition. We observed abnormal activation in the left insula/parietal operculum in CHR participants given placebo compared to healthy controls associated with premature action initiation. Insular activation correlated with both positive psychotic symptoms and salience perception, as indexed by difference in reaction time between salient and neutral stimuli conditions. CBD attenuated the increased -
Attention Or Salience?
Attention and inference Attention or salience? Thomas Parr1, Karl J Friston1 1 Wellcome Centre for Human Neuroimaging, Institute of Neurology, University College London, WC1N 3BG, UK. [email protected], [email protected] Correspondence: Thomas Parr The Wellcome Centre for Human Neuroimaging Institute of Neurology 12 Queen Square, London, UK WC1N 3BG [email protected] Abstract While attention is widely recognised as central to perception, the term is often used to mean very different things. Prominent theories of attention – notably the premotor theory – relate it to planned or executed eye movements. This contrasts with the notion of attention as a gain control process that weights the information carried by different sensory channels. We draw upon recent advances in theoretical neurobiology to argue for a distinction between attentional gain mechanisms and salience attribution. The former depends upon estimating the precision of sensory data, while the latter is a consequence of the need to actively engage with the sensorium. Having established this distinction, we consider the intimate relationship between attention and salience. Keywords: Attention; Salience; Bayesian; Active inference; Precision; Active vision Introduction Optimal interaction with the world around us requires that we attend to those sources of information that help us form accurate beliefs about states of affairs in the world (and our body). This statement may be interpreted in two very different ways. The first interpretation is that we (covertly) select from multiple sensory channels (either within or between modalities) and ascribe greater weight to those sensory streams that convey the most reliable information about states of the world [1]. -
Dopaminergic Basis of Salience Dysregulation in Psychosis
Review Dopaminergic basis of salience dysregulation in psychosis 1* 1,2* 3 Toby T. Winton-Brown , Paolo Fusar-Poli , Mark A. Ungless , and 1,3 Oliver D. Howes 1 Department of Psychosis Studies, Institute of Psychiatry, King’s College London, De Crespigny Park, SE58AF London, UK 2 OASIS Prodromal Service, South London and Maudsley (SLaM) National Health Service (NHS) Foundation Trust, London, UK 3 Medical Research Council Clinical Sciences Centre, Imperial College London, London, UK Disrupted salience processing is proposed as central in In recent years, there have been attempts to bridge this linking dysregulated dopamine function with psychotic gap. We will critically review here the evidence for the symptoms. Several strands of evidence are now converg- recent interpretation of dopaminergic dysfunction in psy- ing in support of this model. Animal studies show that chosis, according to which delusions emerge as an individ- midbrain dopamine neurons are activated by unexpected ual’s own explanation of the experience of aberrant salient events. In psychotic patients, neurochemical stud- salience. We start by examining normal aspects of salience ies have confirmed subcortical striatal dysregulation of and salience processing and how these relate to dopamine dopaminergic neurotransmission, whereas functional function in the human brain. We then describe the experi- magnetic resonance imaging (fMRI) studies of salience ence of aberrant salience in those experiencing early symp- tasks have located alterations in prefrontal and striatal toms of psychosis, before examining experimental evidence dopaminergic projection fields. At the clinical level, this of aberrant salience from animal studies and from neuro- may account for the altered sense of meaning and signifi- imaging studies in humans. -
Aberrant Salience Is Related to Reduced Reinforcement Learning Signals and Elevated Dopamine Synthesis Capacity in Healthy Adults
The Journal of Neuroscience, July 15, 2015 • 35(28):10103–10111 • 10103 Behavioral/Cognitive Aberrant Salience Is Related to Reduced Reinforcement Learning Signals and Elevated Dopamine Synthesis Capacity in Healthy Adults Rebecca Boehme,1 XLorenz Deserno,1,2,3 XTobias Gleich,1 Teresa Katthagen,1 Anne Pankow,1 Joachim Behr,1,4,5 Ralph Buchert,1 XJonathan P. Roiser,6 Andreas Heinz,1 and Florian Schlagenhauf1,2 1Department of Psychiatry and Psychotherapy, Charite´ Universita¨tsmedizin, 10117 Berlin, Germany, 2Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany, 3Department of Neurology, Otto-von-Guericke University, 39106 Magdeburg, Germany, 4Institute of Neurophysiology, Charite´ Universita¨tsmedizin, 10117 Berlin, Germany, 5Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School Brandenburg, 16816 Neuruppin, Germany, and 6Institute of Cognitive Neuroscience, University College London, WC1N 3AR London, United Kingdom The striatum is known to play a key role in reinforcement learning, specifically in the encoding of teaching signals such as reward prediction errors (RPEs). It has been proposed that aberrant salience attribution is associated with impaired coding of RPE and height- ened dopamine turnover in the striatum, and might be linked to the development of psychotic symptoms. However, the relationship of aberrant salience attribution, RPE coding, and dopamine synthesis capacity has not been directly investigated. Here we assessed the association between a behavioral measure of aberrant salience attribution, the salience attribution test, to neural correlates of RPEs measured via functional magnetic resonance imaging while healthy participants (n ϭ 58) performed an instrumental learning task. A 18 subset of participants (n ϭ 27) also underwent positron emission tomography with the radiotracer [ F]fluoro-L-DOPA to quantify striatal presynaptic dopamine synthesis capacity. -
A Single Dose of Nicotine Enhances Reward Responsiveness in Nonsmokers: Implications for Development of Dependence Ruth S
A Single Dose of Nicotine Enhances Reward Responsiveness in Nonsmokers: Implications for Development of Dependence Ruth S. Barr, Diego A. Pizzagalli, Melissa A. Culhane, Donald C. Goff, and A. Eden Evins Background: Tobacco smoking, driven by the addictive properties of nicotine, is the most prevalent preventable cause of death in the Western world. Accumulated evidence suggests that nicotine may increase appetitive responding for nondrug incentives in the environment. Methods: To test this hypothesis, we conducted a randomized, double-blind, placebo-controlled, crossover study of the effect of a single dose of transdermal nicotine on reward responsiveness in 30 psychiatrically healthy nonsmokers. A novel signal detection task in which correct responses were differentially rewarded in a 3:1 ratio was used to assess the extent to which participants modulated their behavior as a function of reward. Results: Despite expected adverse effects such as nausea, nicotine significantly increased response bias toward the more frequently rewarded condition, at the expense of accuracy, independent of effects on attention or overall vigilance. Additionally, response bias on placebo was greater in participants who received nicotine in the first session, indicating that an effect of nicotine on reward responsiveness or reward-based learning persisted for at least 1 week. Conclusions: These findings suggest that a single dose of nicotine enhances response to non-drug-related rewards in the environment, with lasting effects. This effect may contribute to reinforcement of early smoking behavior and development of nicotine dependence. Key Words: Anhedonia, drug addiction, nicotine, nonsmokers, re- ducted in conjunction with a larger study of the effect of nicotine ward, reward responsiveness on cognitive performance in nonsmokers (7). -
Neurobiological Basis of Vulnerability in Adolescence to Drug
REVIEW ARTICLE Neurobiological Basis of Vulnerability in Adolescence to Drug Use SUNITA MANCHANDA1 From 1Max Hospital Gurugram, Haryana Correspondence to: Dr Sunita Manchanda, Max Hospital, Gurugram,122001, Haryana, India [email protected] In adolescence, there is heightened susceptibility to drugs. Neurobiology of addiction is based on the working of four neural networks: (a) reward (b) memory and learning (c) motivation/drive (d) control. Knowledge of neurobiological vulnerabilities is essential for prevention and treatment interventions. Key words : Substance abuse, Neurobiological basis, Drug addiction Adolescence is a critical period of life in which the developing [4]. The progression from initial drug use to addiction may brain is highly vulnerable to the impact of life experiences. It is involve repeated activation of the mesolimbic pathway which also a time of heightened susceptibility to the effects of addictive increases the motivational salience (a form of attention that drugs.Various factors have been associated with increased risk of motivates toward a behavior) of the drug. As contextual cues substance use during this period. Epidemiological evidence become associated and strengthened with repetitive drug suggests that substance use disorders (SUDs) are more likely to administration, a process initially under the purview of the develop in people who begin experimenting with drugs early mesolimbic dopaminergic system progressively incorporates the during their adolescence, but this correlation does not guarantee neurocircuitory involved in emotional, memory, obsessive causation.The neurobiological mechanisms underlying thoughts, stress response, decision making, and behavioral vulnerability to drug addiction are poorly understood and are inhibition, into the drug experience [4]. Even in the absence of likely to involve a balance between factors that confer ongoing drug use these neuro-adaptive responses remain vulnerability and those that protect against it. -
An Investigation of Behavioural Response to Natural Rewards and Drug Cues
Psychiatry Research 215 (2014) 522–527 Contents lists available at ScienceDirect Psychiatry Research journal homepage: www.elsevier.com/locate/psychres Do motivation deficits in schizophrenia-spectrum disorders promote cannabis use? An investigation of behavioural response to natural rewards and drug cues Clifford M. Cassidy, Martin Lepage, Ashok Malla n McGill University, Douglas Mental Health University Institute, 6875 Boul., Lasalle, Montreal, Qc, Canada H4H 1R3 article info abstract Article history: Deficits in incentive motivation are often present in both Schizophrenia Spectrum Disorders (SSD) and Received 13 June 2013 substance-use disorders. The current study aims to test whether the presence of such deficits confers Received in revised form vulnerability to cannabis use in individuals with SSD. SSD patients (n¼35) and healthy controls (n¼35) were 3 December 2013 each divided into a group with (n¼20)andagroupwithout(n¼15) current cannabis use disorder. Subjects Accepted 14 December 2013 performed a behavioural task designed for schizophrenia patients in which they could seek exposure to Available online 21 December 2013 pleasant and cannabis visual stimuli on the basis of internal representations of these stimuli. Intensity of Keywords: cannabis use was assessed by self-report. SSD patients were significantly less likely than controls to exert effort Psychosis to try to re-view pleasant stimuli but were not significantly less likely to work to avoid unpleasant stimuli. Lack Reward of response to re-view pleasant stimuli significantly predicted higher subsequent cannabis self-administration Substance use in patients but not controls, after controlling for degree of prior exposure to cannabis. Deficits in incentive Addiction motivation may be an aspect of SSD which promotes cannabis use in this population. -
Aberrant Salience and Probabilistic Reasoning in Distressing Attenuated Positive Psychotic Symptoms: an Examination of a Two Factor Model
City University of New York (CUNY) CUNY Academic Works All Dissertations, Theses, and Capstone Projects Dissertations, Theses, and Capstone Projects 9-2017 Aberrant Salience and Probabilistic Reasoning in Distressing Attenuated Positive Psychotic Symptoms: An Examination of a Two Factor Model Huw Green The Graduate Center, City University of New York How does access to this work benefit ou?y Let us know! More information about this work at: https://academicworks.cuny.edu/gc_etds/2304 Discover additional works at: https://academicworks.cuny.edu This work is made publicly available by the City University of New York (CUNY). Contact: [email protected] Aberrant Salience and Probabilistic Reasoning in Distressing Attenuated Positive Psychotic Symptoms: An Examination of a Two Factor Model By Huw Green A dissertation submitted to the Graduate Faculty in Psychology in partial fulfillment of the requirements for the degree of Doctor of Philosophy. The City University of New York 2017 © 2017 Huw Green All Rights Reserved ii Aberrant Salience and Probabilistic Reasoning in Distressing Attenuated Positive Psychotic Symptoms: An Examination of a Two Factor Model Huw Green This manuscript has been read and accepted for the Graduate Faculty in Psychology to satisfy the dissertation requirement for the degree of Doctor of Philosophy. Deidre Anglin Date Chair of Examining Committee Richard Bonar Date Executive Officer Sarah O Neill Eric Fertuck Lissa Weinstein Supervisory Committee THE CITY UNIVERSITY OF NEW YORK iii Abstract Aberrant Salience and Probabilistic Reasoning in Distressing Attenuated Positive Psychotic Symptoms: An Examination of a Two Factor Model By Huw Green Advisor: Deidre Anglin Theoretical psychological models of positive psychotic symptoms have increasingly emphasized the interaction of multiple cognitive factors. -
Should Compulsive Sexual Behavior (CSB) Be Considered As a Behavioral Addiction? a Debate Paper Presenting the Opposing View
Should compulsive sexual behavior (CSB) be considered as a behavioral addiction? A debate paper presenting the opposing view Journal of Behavioral ELI SASSOVER1,2 and AVIV WEINSTEIN1* Addictions 1 Department of Behavioral Science, Ariel University, Science Park, Ariel, Israel 2 Department of Behavioral Science and Integrative Brain and Cognition Center, Ariel University, DOI: Ariel, Israel 10.1556/2006.2020.00055 © 2020 The Author(s) Received: February 6, 2020 • Revised manuscript received: June 18, 2020; July 12, 2020; August 16, 2020 • Accepted: August 18, 2020 DEBATE PAPER ABSTRACT Background and aims: Compulsive sexual behavior disorder (CSBD) has been a long debated issue. While formerly the discussion was about whether to regard CSBD as a distinctive disorder, the current debate is dealing with the classification of this phenomenon. One of the prominent voices in this field considers CSBD as a behavioral addiction and proposes CSBD to be called and diagnosed as sexual addiction (SA). This present debate paper will review the existing evidence supporting this view and it will argue against it. Results: We have found that a great deal of the current literature is anecdotal while empirical evidence is insufficient. First, the reports about the prevalence of CSBD are contradictory. Additionally, the field mainly suffers from inconsistent defining criteria of CSBD and a consensus which symptoms should be included. As a result, the empirical evidence that does exist is mostly about some symptoms individually and not on the disorder as a whole construct. Conclusions: We conclude that currently, there is not enough data supporting CSBD as a behavioral addiction. Further research has to be done, examining CSBD phenomenology as a whole construct and based on a homogeneous criterion.