Duration and not strength of activation in temporo-parietal cortex positively correlates with schizotypy

Impaired self- and own body processing in patients with schizophrenia and individuals along the schizophrenia spectrum have been associated with dysfunctional cortical activation at the temporo-parietal junction. Here we investigated whether strength or duration of temporo-parietal junction activation during an own body processing task correlates with level of abnormal self-processing in healthy subjects as measured by the frequency of spontaneously experienced schizotypal body schema alterations (perceptual aberrations) and dissociative experiences. Participants carried out a mental imagery task with respect to their own body. Behavioral data and high density EEG were measured. EEG data were analyzed using evoked potential mapping and electrical neuroimaging. Participants completed two validated self-report questionnaires, one asking about perceptual aberration and one about dissociative experiences. The own body transformation task activated the right temporo-parietal junction at 310-390 ms. Participants' reaction times and duration of activation at the right temporo-parietal junction, but not its strength, were found to correlate positively with perceptual aberration scores. No relationship was found with dissociative experiences scores. Brain activations proceeding and following activation of the right temporo-parietal junction did not correlate with scores on either scale. The positive correlation between performance and right temporo-parietal activation in an own body transformation task with perceptual aberrations scores in our healthy population suggests that disturbances in self- and body processing in individuals along the schizophrenia spectrum might be due to prolonged, rather than stronger activation of the right temporo-parietal junction. We argue that this might reflect local pathology, pathologies in cortico-cortical connections and/or re-entry of top-down processing

Schizotypal Perceptual Aberrations of Time: Correlation between Score, Behavior and Brain Activity

A fundamental trait of the human self is its continuum experience of space and time. Perceptual aberrations of this spatial and temporal continuity is a major characteristic of schizophrenia spectrum disturbances – including schizophrenia, schizotypal personality disorder and schizotypy. We have previously found the classical Perceptual Aberration Scale (PAS) scores, related to body and space, to be positively correlated with both behavior and temporo-parietal activation in healthy participants performing a task involving self-projection in space. However, not much is known about the relationship between temporal perceptual aberration, behavior and brain activity. To this aim, we composed a temporal Perceptual Aberration Scale (tPAS) similar to the traditional PAS. Testing on 170 participants suggested similar performance for PAS and tPAS. We then correlated tPAS and PAS scores to participants' performance and neural activity in a task of self-projection in time. tPAS scores correlated positively with reaction times across task conditions, as did PAS scores. Evoked potential mapping and electrical neuroimaging showed self-projection in time to recruit a network of brain regions at the left anterior temporal cortex, right temporo-parietal junction, and occipito-temporal cortex, and duration of activation in this network positively correlated with tPAS and PAS scores. These data demonstrate that schizotypal perceptual aberrations of both time and space, as reflected by tPAS and PAS scores, are positively correlated with performance and brain activation during self-projection in time in healthy individuals along the schizophrenia spectrum

Disturbances in Body Ownership in Schizophrenia: Evidence from the Rubber Hand Illusion and Case Study of a Spontaneous Out-of-Body Experience

A weakened sense of self may contribute to psychotic experiences. Body ownership, one component of self-awareness, can be studied with the rubber hand illusion (RHI). Watching a rubber hand being stroked while one's unseen hand is stroked synchronously can lead to a sense of ownership over the rubber hand, a shift in perceived position of the real hand, and a limb-specific drop in stimulated hand temperature. We aimed to assess the RHI in schizophrenia using quantifiable measures: proprioceptive drift and stimulation-dependent changes in hand temperature.The RHI was elicited in 24 schizophrenia patients and 21 matched controls by placing their unseen hand adjacent to a visible rubber hand and brushing real and rubber hands synchronously or asynchronously. Perceived finger location was measured before and after stimulation. Hand temperature was taken before and during stimulation. Subjective strength of the illusion was assessed by a questionnaire.Across groups, the RHI was stronger during synchronous stimulation, indicated by self-report and proprioceptive drift. Patients reported a stronger RHI than controls. Self-reported strength of RHI was associated with schizotypy in controls Proprioceptive drift was larger in patients, but only following synchronous stimulation. Further, we observed stimulation-dependent changes in skin temperature. During right hand stimulation, temperature dropped in the stimulated hand and rose in the unstimulated hand. Interestingly, induction of RHI led to an out-of-body experience in one patient, linking body disownership and psychotic experiences.The RHI is quantitatively and qualitatively stronger in schizophrenia. These findings suggest that patients have a more flexible body representation and weakened sense of self, and potentially indicate abnormalities in temporo-parietal networks implicated in body ownership. Further, results suggest that these body ownership disturbances might be at the heart of a subset of the pathognomonic delusions of passivity

A putative implication for fronto-parietal connectivity in out-of-body experiences

Self-processing has been related to the prefrontal cortex (PFC) and the temporo-parietal junction (TPJ) as well as to their connectivity. So far, out-of-body experiences (OBEs), impressive transient deviations of intact bodily self-integration, could be associated with the TPJ, but the mediation by the frontal lobe, and thus fronto-parietal connectivity, is yet unknown. Thus, we assessed switching performance to assess fronto-parietal connectivity when healthy participants [11 reported previous OBEs (OBE-individuals); 36 reported no previous OBEs (nOBE-individuals)] performed two different mental own body imagery tasks. By using the same stimuli of a front-facing and back-facing human figure, a cue simultaneously presented with the target indicated to participants whether they had to take the position of the depicted human figure (disembodied self-location mimicking an OBE) or had to imagine that the figure was their own reflection in a mirror (embodied Self-location). By repeating trials of the same task instruction for a differing number of trials (2-6 trials), we could assess switch costs when alternating between these two task instructions with switch costs being considered to be a behavioural indicator of fronto-parietal connectivity. Results showed that OBE-individuals performed worse than nOBE-individuals in switch trials, but not in trials in which the same task instruction was repeated. Moreover, this reduced performance was specific to body positions that are normally considered easier (front-facing in the mirror condition; back-facing in the OBE mimicking condition). These findings suggest that a fronto-parietal network might be implicated in OBEs, and that the flexible and spontaneous egocentric perspective taking of self-congruent body representations is hampered in individuals with previous OBEs

Schizotypy: environmental risk, genetic vulnerability, and neural correlates

Schizotypy is a unifying construct that draws a continuum between subclinical and clinical symptoms of psychotic disorders, reflected in commonly occurring cognitive, behavioural, and personality features. This thesis aims to carry out a holistic investigation of the genetic, neurocognitive, and environmental contributions to schizotypy in cohort of healthy individuals and those diagnosed with schizophrenia and bipolar disorder, to benefit from exploring the full range of schizotypal expressions. The main empirical chapters examine the impact of environmental factors and genetic vulnerability for schizophrenia on schizotypy and its component dimensions, with the final empirical chapter focused on the functional neural correlates of schizotypy during specific cognitive task. Participants for these studies were drawn from a cohort of 245 adults (mean age=38.58, sd=11.83, range=18.26 to 60.52), comprising 79 healthy controls, 86 individuals diagnosed with bipolar disorder, and 80 individuals diagnosed with schizophrenia. Study 1 reports positive associations between childhood trauma and schizotypy, while demonstrating the role of sociodemographic disadvantage as partial mediator of these associations. Study 2 reports that associations between childhood trauma and schizotypy are moderated by polygenic risk score for schizophrenia. Study 3 consisted of a systematic review of the available literature on structural and functional neural correlates of schizotypy. The high degree of methodological and conceptual heterogeneity across studies precluded the identification of a distinct pattern of schizotypy-associated brain alterations. Finally, Study 4 investigated the associations between schizotypy and brain activity during facial emotion processing using a data-driven approach. Overall, the findings from this thesis emphasised the relevance of investigating schizotypy in psychotic disorders, not restricted to schizophrenia, as well as the complex interaction between genetic and environmental risk factors in association with higher levels of schizotypy. Future research of schizotypy would be enhanced with utilization of longitudinal designs, with repeated measures of schizotypy over time, while incorporating data on exposure to childhood and adulthood environmental risk variables and genetic vulnerability. In addition, neuroimaging studies of schizotypy would benefit from multimodal, data-driven approaches, as well as being informed by environmental risk factors

What influences the neural correlates of social cognition? Studies from a microscopic and macroscopic perspective

Social cognition, as of the fundament of social interaction, is central to our daily social life. Although the past two decades have witnessed a huge increase in academic interest in social cognition, knowledge of the neural correlates of social cognition is still limited. With a growing number of studies investigating social cognition with a neuroscientific approach, a well-framed structure based on systematic perspectives to understand social cognition is urgently needed. The present dissertation attempted to investigate social cognition from two domains based on the idea what influences social cognition, the so-called microscopic perspective on the individual and the macroscopic perspective on the culture. From the microscopic perspective, the effects of schizophrenia risk factors (including schizotypy and rs1344706 SNP) on neural correlates of social cognition were investigated in a healthy German sample. The results show associations between schizotypy, as well as the risk allele of the rs1344706 SNP and posterior superior temporal sulcus (pSTS) activation in response to neutral facial stimuli, suggesting right pSTS dysfunction in response to neural social stimuli might present an endophenotype for schizophrenia. Furthermore, these findings give evidence on the microscopic perspective proposed above that neural correlates of social cognition can be influenced by risk factors for mental illnesses in healthy participants. Regarding the macroscopic perspective, the cultural effects on neural responses to different facets of social categorization were investigated with participants from different ethnicities. During the ethnicitybased categorization, the Chinese group showed higher ventral medial prefrontal cortex (MFC) activation for categorizing in-ethnicity versus out-ethnicity faces than the German group, even inethnicity bias was not observed in the Chinese group on the behavioral level. Since ventral MFC is welldocumented to be associated with representing the preference of stimuli even in an unconscious or automatic fashion, the increased ventral MFC activation in the Chinese group may indicate that they present higher in-ethnicity preference than the German group. Further, increased dorsal MFC activation in response to in-team versus out-team faces was found in both ethnic groups during team-basedcategorization, inferring that the dorsal MFC might be a generalized neural code for encoding in-team members across ethnicities. In addition, by comparing the contrasts of in-team versus in-ethnicity and out-team versus out-ethnicity, the results suggest that ethnicity-based and team-based categorization probably presenting different dimensions of social categorization (such as perceptual- and knowledgebased categorization). To summarize, the present dissertation aimed to advance the understanding of social cognition from microscopic and macroscopic perspectives. Such an approach might transfer to the clinical and psychotherapeutic field for developing more generalized interventions and treatments across ethnicities to prevent people from mental disorders or to optimize interventions for people with mental illnesses

Schizotypy as An Organizing Framework for Social and Affective Sciences

Schizotypy, defined in terms of commonly occurring personality traits related to the schizophrenia spectrum, has been an important construct for understanding the neurodevelopment and stress-diathesis of schizophrenia. However, as schizotypy nears its sixth decade of application, it is important to acknowledge its impressively rich literature accumulating outside of schizophrenia research. In this article, we make the case that schizotypy has considerable potential as a conceptual framework for understanding individual differences in affective and social functions beyond those directly involved in schizophrenia spectrum pathology. This case is predicated on (a) a burgeoning literature noting anomalies in a wide range of social functioning, affiliative, positive and negative emotional, expressive, and social cognitive systems, (b) practical and methodological features associated with schizotypy research that help facilitate empirical investigation, and (c) close ties to theoretical constructs of central importance to affective and social science (eg, stress diathesis, neural compensation). We highlight recent schizotypy research, ie providing insight into the nature of affective and social systems more generally. This includes current efforts to clarify the neurodevelopmental, neurobiological, and psychological underpinnings of affiliative drives, hedonic capacity, social cognition, and stress responsivity systems. Additionally, we discuss neural compensatory and resilience factors that may mitigate the expression of stress-diathesis and functional outcome, and highlight schizotypy's potential role for understanding cultural determinants of social and affective function

An exploration of functional connectivity and GABA in schizophrenia and related conditions

Schizophrenia is a severe and enduring mental illness with psychopathology including positive symptoms, negative symptoms and cognitive impairment. It has been hypothesised that such symptoms represent a loss of integration within and between brain regions. This is known as the dysconnectivity hypothesis and integrates with other neurochemical hypotheses of the disorder. In this thesis, I sought to explore the dysconnectivity hypothesis using amplitude envelope correlation in MEG, firstly in two groups of individuals with schizophrenia. I then sought to address the continuum model of schizophrenia through exploring functional connectivity in two groups with high schizotypy. Next, I explored dysconnectivity in schizophrenia in more depth by looking separately at individuals with recent onset psychosis and those with established schizophrenia. I then went on to look at connectivity following ketamine administration thus seeking to link this model of schizophrenia with my findings in those with schizophrenia. Finally, I explored the GABA hypothesis of schizophrenia using MRS, again in two groups of individuals with schizophrenia, at different stages of illness and linked this with connectivity. Overall, this work supports the dysconnectivity hypothesis of schizophrenia, finding reduced connectivity in schizophrenia. Such changes are found predominantly in the later stages of the disorder suggesting the possibility of progressive changes in connectivity throughout its course. I found increased connectivity following ketamine administration in the same frequency band and region suggesting the drug does not model later stages of the disorder well (where I predominantly found hypo-connectivity). In addition, I found reduced GABA iv in later stages of schizophrenia but not in early stages, again suggesting progressive changes throughout the course of the disorder. Finally, I also found hypo-connectivity in healthy volunteers with high schizotypy scores suggesting biological continuity between subclinical symptoms and diagnosable schizophrenia. Overall, these results add support to the dysconnectivity hypothesis, the GABA/glutamate hypothesis and the continuum hypothesis of schizophrenia