دور از خانه: مغز سرگردان از ذهن به عنوان یک مدل برای اسکیزوفرنی

The notion that schizophrenia patients' (SZ) sense of being detached from external reality is a core feature of the disorder has existed since the early days of its recognition and is still largely emphasized in first person accounts of SZs; however, its etiology, neurophysiological mechanism, and significance for clinical symptoms are unclear. Mind-wandering is a ubiquitous experience of being detached from reality, the underlying neural mechanism of which closely resembles the brain in a resting-state. Methods The resting-state functional magnetic resonance imaging data of 33 SZs and 33 matched healthy controls (CNT) were acquired. All subjects answered the mind-wandering subscale of the Imaginal Processing Inventory Questionnaire. Functional connectivity maps were constructed using 82 regions of interest comprising default-mode, salience, and frontoparietal networks. Results SZs exhibit significantly higher mind-wandering frequency relative to CNT. The elevated mind-wandering frequency in SZs significantly correlated with positive and general symptom severity. The mind-wandering frequency was inversely correlated with connectivity degree in the right ventromedial prefrontal cortex, the brain region involved in self-experience in SZs. Conclusions Our results suggest that self-disturbances in SZs can explain SZs' disconnection to the external world, leading to the manifestation of positive psychotic symptoms. This study demonstrates strong preliminary evidence that contributes significantly to resolve the complex relationship between self, world, and the brain of SZs, which may lie at the “core” of psychotic experiences.

People with schizophrenia (SZ) commonly feel “detached from [commonly shared] reality” and “away from home”(Stanghellini and Ballerini, 2007). In a recent first-person account of psychosis, Kean describes the overwhelming sense of being disconnected and disintegrated from external reality that lies behind the psychotic symptoms, but psychiatrists tend to see nothing but the symptoms alone (Kean, 2009). This notion is not new. In the 19th century, Eugene Bleuler also conceptualized SZs' psychotic despairs as mostly brought on by a lack of vital contact with reality and a withdrawal into a private world (Scarone et al., 2003 and Parnas, 2011). Both in classical and modern psychiatric literatures, this trait has been considered to be the core gestalt of SZ (Parnas, 2011). The importance of the core phenomenology of psychotic experience also has been largely emphasized by recent first-person accounts of psychosis (Kean, 2009, Johnson, 2012, Payne, 2012 and Humpston, 2014). Despite the fact that current diagnostic criteria revolve around the presence of psychotic symptoms (Keefe and Fenton, 2007 and McGuire et al., 2008), this core phenomenology of SZs has largely escaped the mainstream topic of research (Humpston, 2014). A lack of vital studies on the phenomenology of SZs which lie beyond classical diagnosis may hinder progress in our understanding of the disorder and our ability to find adequate treatment. Mind-wandering is a shift in attention from external circumstances toward one's personal thoughts and feelings (Smallwood et al., 2007a and Smallwood et al., 2007b). As humans, our minds often wander from the task at hand without intention or even awareness (Giambra, 1995, Schooler, 2002 and Smallwood et al., 2007b). During mind-wandering, our conscious attention is decoupled from reality and online sensory information, and focused on one's inner mental activities (Smallwood and Schooler, 2006, Kam et al., 2011 and Schooler et al., 2011). It is the ubiquitous experience of being ‘detached from reality,’ which shares an emphasis processing information beyond the here and now (Smallwood et al., 2007b). In the brain, a set of cortical regions that increase activity during rest and reflection—the default-mode network (DMN)—were believed to underlie one's state of mind-wandering (Mason et al., 2007). More recently, Hasenkamp and colleagues explored the brains of people experiencing mind-wandering and proposed dissociable association of the DMN, frontoparietal (FPN), and salience networks (SN) in each cognitive element of mind-wandering (Hasenkamp et al., 2012). While possible connections between mind-wandering and resting-state brain activity were suggested in previous literature (Smallwood and Schooler, 2006 and Gruberger et al., 2011), these have only lately started to be studied systematically, as one recently published study has demonstrated (Kucyi et al., 2013). More recently, a well-known disconnection hypothesis about SZs (Friston and Frith, 1995) proposes that SZ symptomology arises from the anomalous integration of a distributed network of brain regions or a misconnection of neural circuitry (Kim et al., 2003 and Rubinov et al., 2009). Advances in functional connectivity analysis of resting-state functional magnetic resonance imaging (rs-fMRI) facilitate the measurement of functional integrity within and between brain networks (Rubinov et al., 2009). Using the spontaneous resting-state neural activity, inferred on the basis of blood oxygen level dependence (BOLD) response time-series data, studies have found spatially segregated functional connectivity networks in the human brain (Fox et al., 2005). SZs' distinct symptomology is understood through impairments in fundamental resting activities of the brain regions and connections (Bassett et al., 2012, Jung et al., 2012 and Kuhn and Gallinat, 2013). Specifically, SZs showed hypoactivation in the ventromedial prefrontal cortex (vmPFC), the posterior cingulated cortex (PCC), and the precuneus at rest (Kuhn and Gallinat, 2013). These brain regions have been demonstrated substantially for their anatomical deviations as well that the paralimbic system are lateralized in SZ (Honea et al., 2005 and Crow et al., 2013). In the network level, SZ was associated with enhanced resting-state connectivity in DMN and reduced connectivity within SN, FPN and between SN and DMN (Lawrie et al., 2002, Whitfield-Gabrieli et al., 2009, White et al., 2010, Pu et al., 2012 and Tu et al., 2012). While abnormalities in DMN and vmPFC, which are involved in self-referential and introspective processing, in SZs (Whitfield-Gabrieli et al., 2009 and van Buuren et al., 2012) support the assumption that the fundamental disturbance causing psychotic symptoms is disorder of the self, a deviance in one's subjective self-experience and the external reality, it is unclear how SZs' disconnection to the world is related to their disconnectivity in the brain. Thus, we sought to examine the brain in the state of detached-from-reality mentation as neurophenomenological model for psychosis. This may provide valuable information for identifying the clinical core of SZ and its neural system that contributes to impairments that cut across traditional diagnostic boundaries.