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provided by AIR Universita degli studi di Milano Opinion Article published: 31 January 2012 PSYCHIATRY doi: 10.3389/fpsyt.2012.00003 The dreaming brain/mind: a role in understanding complex mental disorders?

Armando D’Agostino1,2*, Ivan Limosani 2 and Silvio Scarone1,2

1 Department of Medicine, Surgery and Dentistry, Università degli Studi di Milano, Milan, Italy 2 Department of Mental Health, San Paolo Hospital, Milan, Italy *Correspondence: [email protected]

Abnormalities in the /wake cycle and few contemporary researchers to bind these enology, bursts of “covert” REM sleep have within sleep itself have extensively been complex phenomena, with electrophysi- been hypothesized to underlie mental studied in a broad range of psychiatric ological, neurochemical, and cerebrofunc- activity during other stages. This observa- and neurodegenerative disorders. Despite tional data now pointing to shared patterns tion is based on the correlation between increasing evidence for a mechanistic across dreaming and psychotic experiences hallucinatory subjective experiences and overlap between the disruptions of circa- (Hobson, 2004; Gottesmann, 2006). EEG configurations containing elements dian timing control and neuropathology, One relevant issue in the scientific study of both REM and NREM. Moreover, the the relationship remains unclear (Wulff of is bound to the limits of our cur- most vivid NREM mentation reports have et al., 2010). One possible way to address rent understanding of cerebral activation been collected when transient EMG sup- this problem from a psychiatric perspec- patterns across different stages of sleep. pressions and phasic muscle twitches, which tive is to compare the phenomenological Despite early observations binding dreams are typical of REM sleep, were recorded dur- correlate of sleep with the waking menta- to REM sleep physiology, it is now widely ing sleep onset (Nielsen, 2000). tion observed in patients. Indeed, so-called accepted that dreams occur across all stages Prefrontal hypometabolism and limbic/ “positive” symptoms such as abnormal (Nir and Tononi, 2010). However, mental paralimbic hypermetabolism have been senso-perceptual experiences or thought activity across sleep does differ, ranging reported in both waking schizophrenic processes ranging from ideas of reference to from simple thought-like experiences to and manic psychotic subjects (Molina et al., highly structured delusions, share substan- full-blown hallucinoid dreams, which 2005; Minzenberg et al., 2009; Brooks III tial similarities with phenomenol- have been shown to be underpinned by et al., 2010). On the neurochemical level, ogy. The same process by which psychotic NREM and REM polysomnographic pat- positive symptoms have been hypoth- patients progress from salience attributed to terns respectively (McNamara et al., 2010). esized to result from abnormal regulation irrelevant stimuli to a new, highly relevant Although a direct correlation between of NMDA-dependent synaptic plasticity meaning, appears to occur in dreams, where dreaming and underlying neurofunctional by transmitters like dopamine, acetylcho- a single hallucinatory image can convey “an modifications remains a challenge for line and serotonin (Stephan et al., 2009). immediate emotionally compelling mean- sleep/dream researchers, some studies have Long-term potentiation (LTP), a key ing that is not related to the image in any shown a relative hyperactivation of cerebral mechanism of synaptic consolidation, is obvious way” (Feinberg, 2011). With the regions related to emotional and affective similarly thought to rely on glutamatergic exception of the rare experience of lucid- life (i.e., amygdala and anterior cingulate transmission, with sleep spindles having ity, the dreamer has no recognition of cortex) and a relative hypoactivation of the been recognized as a possible neurophysio- his objective status, i.e., being asleep and frontal cortex, mainly in its dorsolateral logical correlate of the consolidation dialog vastly detached from the external environ- prefrontal regions, during REM sleep (Nir between the hippocampus and neocorti- ment; dream images produced uniquely by and Tononi, 2010). This functional condi- cal structures during sleep (Diekelmann endogenous neural activity are interpreted tion of the brain is mediated by a complex and Born, 2010; Fogel and Smith, 2011). as coming from the external world; height- and interactive neurochemical pathway In this regard, it seems interesting to note ened and often incongruous emotions are within which a strong increase of cholin- that sleep spindle density has been found coupled with a decrease in ego functions ergic activity is coupled with the reduction to be reduced in schizophrenic subjects which ultimately leads to instinctual behav- of serotonergic and noradrenergic firing (Ferrarelli et al., 2007). Indeed, procedural iors and severe impairment in reality test- rates. Mesolimbic dopaminergic activa- and declarative memory consolidation ing (Hobson, 2009). The striking similarity tion has also been hypothesized to occur impairment has been correlated to sleep between these aspects of dreaming and psy- in dream sleep in absence of serotonergic disturbances in these patients (Manoach chosis has been observed by most of the inhibition (Gottesmann, 2002). Indeed, a et al., 2010; Seeck-Hirschner et al., 2010). funding pioneers of the modern approach raise in cortical dopamine activity has been The mixed findings that have historically to psychopathology. Indeed, it is largely causally linked to the generation of night- emerged from sleep studies in this popu- unknown that Emil Kraepelin extensively mares, possibly implying an intensification lation could at least in part be attributed studied his own dreams with the aim of pro- of cholinergically driven characteristics of to the complex nosographical boundaries gressing his understanding of schizophrenic REM sleep-related dream mentation. In of the disorder. In our view, abnormalities (Engels et al., 2003). order to account for the relevant findings in sleep-dependent consolidation mecha- Recent advances in neuroscience have led which link REM sleep to dream phenom- nisms should be considered in ­relationship

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to positive symptoms rather than to the activity in posterior brain structures” (Voss environmentally predisposed subjects. broader concept of , and one et al., 2009). In other words, reactivation of Similarities and differences in brain func- recent study seems to suggest that neuro- frontal lobes within REM sleep appears to tion will have to be addressed directly in the cognitive deficits do correlate with sleep underlie awareness within the hallucinatory future by binding sleep and dream research spindle density in a population of psychotic nature of one’s experience. Although the with research in psychotic disorders within patients belonging to several different diag- multidimensional construct of insight has the same experimental framework. nostic categories (Keshavan et al., 2011). been shown to reflect a vast and complex Sleep-dependent processing of memory neural circuitry in psychotic patients, fron- References may be viewed as a continuous adaptation tal lobe processing is thought to play a criti- Antonius, D., Prudent, V., Rebani, Y., D’Angelo, D., of the brain to the external environment, of cal role (Antonius et al., 2011). Disruption Ardekani, B. A., Malaspina, D., and Hoptman, M. J. which dreaming constitutes the subjective of synaptic plasticity in the prefrontal cor- (2011). White matter integrity and lack of insight in schizophrenia and schizoaffective disorder. Schizophr. epiphenomenon. In this perspective, posi- tex has been confirmed in rodent models of Res. 128, 76–82. tive psychotic symptoms may be considered schizophrenia and available antipsychotic Brooks, J. O. III, Hoblyn, J. C., and Ketter, T. A. (2010). the subjective correlate of aberrant underly- medications are known to modulate LTP Metabolic evidence of corticolimbic dysregulation in ing consolidation processes. Indeed, several in this area (Goto et al., 2010). The atypical bipolar mania. Psychiatry Res. 181, 136–140. neurobiological findings seem to support antipsychotic clozapine appears to improve Corlett, P. R., Frith, C. D., and Fletcher, P. C. (2009). From drugs to deprivation: a Bayesian framework for under- the view that delusions occur when con- insight phenomenologically and is often standing models of psychosis. Psychopharmacology solidation of prior beliefs is driven above referred to as the most effective antipsy- (Berl.) 206, 515–530. new extinction learning by dopaminergic chotic in clinical practice (Tiihonen et al., Diekelmann, S., and Born, J. (2010). The memory func- hyperactivity (Corlett et al., 2009). The neu- 2009). Clozapine, which produces funda- tion of sleep. Nat. Rev. Neurosci. 11, 114–126. ral plasticity which underlies continuous mental changes in prefrontal cortex func- Dresler, M., Koch, S. P., Wehrle, R., Spoormaker, V. I., Holsboer, F., Steiger, A., Samann, P. G., Obrig, H., and integration of information could be abnor- tioning in schizophrenic patients (Pallanti Czisch, M. (2011). Dreamed movement elicits activa- mal in several clinical conditions, leading to et al., 1999), has been shown to enhance tion in the sensorimotor cortex. Curr. Biol. 21, 1–5. a phenomenological overlap between sleep LTP induction (Matsumoto et al., 2008) Dupin, N., Mailliet, F., Rocher, C., Kessal, K., Spedding, and waking mentation. This conceptualiza- and to reverse stress-induced impairments M., and Jay, T. M. (2006). Common efficacy of psycho- tion may be of use in explaining the broad tropic drugs in restoring stress-induced impairment of LTP induction in the hippocampus–PFC of prefrontal plasticity. Neurotox. Res. 10, 193–198. variety of disorders within which psychotic pathway (Dupin et al., 2006). Alongside Engels, H., Heynick, F., and van der Staak, C. (2003). Emil symptoms occur, and the high correla- pharmacological interventions, Cognitive Kraepelin’s dream speech: a psychoanalytic interpre- tion found between these symptoms and Remediation Therapy has been shown to tation. Int. J. Psychoanal. 84, 1281–1294. chronobiological disruptions. From a phe- enhance activity in the prefrontal cortex of Feinberg, I. (2011). Corollary discharge, hallucinations, and dreaming. Schizophr. Bull. 37, 1–3. nomenological point of view, the waking schizophrenic patients (Wexler and Bell, Ferrarelli, F., Huber, R., Peterson, M. J., Massimini, M., cognition of acutely psychotic subjects has 2005). This type of treatment may also Murphy, M., Riedner, B. A., Watson, A., Bria, P., and been shown by our group to share similarly contribute to the reduction of psychotic Tononi, G. (2007). Reduced sleep spindle activity elevated levels of cognitive bizarreness with symptoms, suggesting a relationship with in schizophrenia patients. Am. J. Psychiatry 164, their own dream reports and those of a con- the increase of synaptic plasticity in frontal 483–492. Fogel, S. M., and Smith, C. T. (2011). The function of the trol population independent of diagnostic structures obtained through cognitive skills sleep spindle: a physiological index of intelligence and categorizations (Limosani et al., 2011). training (Lecardeur et al., 2009). a mechanism for sleep-dependent memory consolida- The key similarity between dreams Future directions for research may involve tion. Neurosci. Biobehav. Rev. 35, 1154–1165. and psychosis evolves around the subject’s low-intensity scalp stimulation techniques Goto, Y., Yang, C. R., and Otani, S. (2010). Functional inability to discern external reality from that have been shown to modulate neuronal and dysfunctional synaptic plasticity in prefrontal cortex: roles in psychiatric disorders. Biol. Psychiatry internally generated stimuli that arise to con- excitability. In a recent review, transcranial 67, 199–207. sciousness. Severe impairment of cognitive direct current stimulation (tDCS) in the Gottesmann, C. (2002). The neurochemistry of wak- processes such as self-reflective awareness, DLPFC was reported to improve cognition ing and sleeping mental activity: the disinhibition- abstract thinking and metacognition justify in schizophrenic patients (Minzenberg and dopamine hypothesis. Psychiatry Clin. Neurosci. 56, the impaired reality testing found in both 345–354. Carter, 2012). Gottesmann, C. (2006). The dreaming sleep stage: a new mental states, converging on the crucial role Although interest in the relation- neurobiological model of schizophrenia? Neuroscience of frontal regions. Promising findings have ship between dreams and psychosis has 140, 1105–1115. recently emerged from research into the refluorished in recent research (Scarone Hobson, A. (2004). A model for madness? Nature 430, 21. neurobiological substrates of - et al., 2008; Lusignan et al., 2009; Yu, 2009; Hobson, J. A. (2009). REM sleep and dreaming: towards a theory of protoconsciousness. Nat. Rev. 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