The neural mechanisms of social reward in early psychosis.

In chronic psychosis, reduced trust is associated with a neural insensitivity to social reward and reduced theory of mind (ToM). Here we investigate whether these mechanisms could underlie emerging social impairments in early psychosis. Twenty-two participants with early psychosis and 25 controls (male, 13-19 years) participated in two interactive trust games against a cooperative and unfair partner. Region of interest neuroimaging analyses included right caudate, medial prefrontal cortex (mPFC) and right temporoparietal junction (rTPJ), involved in reward and ToM processing. Both groups showed similar levels of trust (i.e. investments). However, individuals with psychosis failed to activate the caudate differentially in response to cooperation and unfairness while making decisions to trust. During cooperative returns, patients showed reduced and controls increased caudate activation. Patients demonstrated greater rTPJ activation than controls, possibly pointing towards compensatory mechanisms. Effects were associated with Wechsler Abbreviated Scale of Intelligence vocabulary scores. No group differences emerged in mPFC activation. Early psychosis is associated with an aberrant neural sensitivity to social reward. This could foster reduced social motivation and social isolation. Absent behavioural differences in early, relative to chronic psychosis could indicate that trust is achieved through increased compensatory demand on ToM.

Neural correlates of reward processing in healthy siblings of patients with schizophrenia.

Deficits in motivational behavior and psychotic symptoms often observed in schizophrenia (SZ) may be driven by dysfunctional reward processing (RP). RP can be divided in two different stages; reward anticipation and reward consumption. Aberrant processing during reward anticipation seems to be related to SZ. Studies in patients with SZ have found less activation in the ventral striatum (VS) during anticipation of reward, but these findings do not provide information on effect of the genetic load on reward processing. Therefore, this study investigated RP in healthy first-degree relatives of SZ patients. The sample consisted of 94 healthy siblings of SZ patients and 57 healthy controls. Participants completed a classic RP task, the Monetary Incentive Delay task, during functional magnetic resonance imaging (fMRI). As expected, there were no behavioral differences between groups. In contrast to our expectations, we found no differences in any of the anticipatory reward related brain areas (region of interest analyses). Whole-brain analyses did reveal group differences during both reward anticipation and reward consumption; during reward anticipation siblings showed less deactivation in the insula, posterior cingulate cortex (PCC) and medial frontal gyrus (MFG) than controls. During reward consumption siblings showed less deactivation in the PCC and the right MFG compared to controls and activation in contrast to deactivation in controls in the precuneus and the left MFG. Exclusively in siblings, MFG activity correlated positively with subclinical negative symptoms. These regions are typically associated with the default mode network (DMN), which normally shows decreases in activation during task-related cognitive processes. Thus, in contrast to prior literature in patients with SZ, the results do not point to altered brain activity in classical RP brain areas, such as the VS. However, the weaker deactivation found outside the reward-related network in siblings could indicate reduced task-related suppression (i.e., hyperactivation) of the DMN. The presence of DMN hyperactivation during reward anticipation and reward consumption might indicate that siblings of patients with SZ have a higher baseline level of DMN activation and possible abnormal network functioning.

Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia.

BACKGROUND: Grey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies. METHODS: We compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (< 30 yr), genetic loading and subclinical psychotic symptoms to examine whether this would lead to different results. RESULTS: We included 89 siblings and 69 controls in our study. The results showed that siblings and controls did not differ significantly on grey matter volume or concentration. Furthermore, specifically selecting participants based on age, genetic loading or subclinical psychotic symptoms did not alter these findings. LIMITATIONS: The main limitation was that subdividing the sample resulted in smaller samples for the subanalyses. Furthermore, we used MRI data from 2 different scanner sites. CONCLUSION: These results indicate that grey matter measured through VBM might not be a suitable endophenotype for schizophrenia.

Alexithymia influences brain activation during emotion perception but not regulation.

Alexithymia is a psychological construct that can be divided into a cognitive and affective dimension. The cognitive dimension is characterized by difficulties in identifying, verbalizing and analysing feelings. The affective dimension comprises reduced levels of emotional experience and imagination. Alexithymia is widely regarded to arise from an impairment of emotion regulation. This is the first functional magnetic resonance imaging (fMRI) study to critically evaluate this by investigating the neural correlates of emotion regulation as a function of alexithymia levels. The aim of the current study was to investigate the neural correlates underlying the two alexithymia dimensions during emotion perception and emotion regulation. Using fMRI, we scanned 51 healthy subjects while viewing, reappraising or suppressing negative emotional pictures. The results support the idea that cognitive alexithymia, but not affective alexithymia, is associated with lower activation in emotional attention and recognition networks during emotion perception. However, in contrast with several theories, no alexithymia-related differences were found during emotion regulation (neither reappraisal nor suppression). These findings suggest that alexithymia may result from an early emotion processing deficit rather than compromised frontal circuits subserving higher-order emotion regulation processes.

Dissociable morphometric profiles of the affective and cognitive dimensions of alexithymia.

Alexithymia ("no words for feelings") is a psychological construct that can be divided in a cognitive and affective dimension. The cognitive dimension reflects the ability to identify, verbalize and analyze feelings, whereas the affective dimension reflects the degree to which individuals get aroused by emotional stimuli and their ability to fantasize. These two alexithymia dimensions may differentially put individuals at risk to develop psychopathology. However, their neural correlates have rarely been investigated. The aim of the current study was to investigate whether the cognitive and affective alexithymia dimension are associated with unique anatomical profiles. Structural MRI scans of 57 participants (29 males; mean age: 34) were processed using a voxel-based morphometry (VBM) - Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra (DARTEL) approach. Multiple regression analyses were performed to examine the common and specific associations between gray and white matter volume and alexithymia subdimensions. The results revealed that the cognitive dimension was related to lower dorsal anterior cingulate volume. In contrast, the affective alexithymia was associated with lower gray matter volume in the medial orbitofrontal cortex (OFC) and lower white matter volume in the superior longitudinal fasciculus (SLF) near the angular gyrus. No relationship between corpus callosum volume and alexithymia was observed. These results are consistent with the idea that there are two separable neural systems underlying alexithymia. This finding might encourage future research into the link between specific alexithymia subtypes and the development of psychopathology.

Trust and social reciprocity in adolescence--a matter of perspective-taking.

Changes in social behaviour from childhood to adulthood have been suggested to be driven by an increased sensitivity to others' perspectives. Yet, the link between perspective-taking and social processes, such as trust and reciprocity, has rarely been investigated during adolescence. Using two trust games with a cooperative and an unfair counterpart and an online perspective-taking task with 50 adolescents, we show that those with a higher perspective-taking tendency demonstrate greater trust towards others and higher levels of trust during cooperative interactions. Both low and high perspective-takers adapted their levels of trust in response to unfair behaviour. However, high perspective-takers reduced their trust more drastically and showed more malevolent and less benevolent tit-for-tat when they were treated unfairly by their counterpart. The findings suggest that a higher perspective-taking tendency in adolescence is associated with specific mechanisms of trust and reciprocity, as opposed to undifferentiated increases in positive social behaviour towards others.

Default distrust? An fMRI investigation of the neural development of trust and cooperation.

The tendency to trust and to cooperate increases from adolescence to adulthood. This social development has been associated with improved mentalizing and age-related changes in brain function. Thus far, there is limited imaging data investigating these associations. We used two trust games with a trustworthy and an unfair partner to explore the brain mechanisms underlying trust and cooperation in subjects ranging from adolescence to mid-adulthood. Increasing age was associated with higher trust at the onset of social interactions, increased levels of trust during interactions with a trustworthy partner and a stronger decline in trust during interactions with an unfair partner. Our findings demonstrate a behavioural shift towards higher trust and an age-related increase in the sensitivity to others' negative social signals. Increased brain activation in mentalizing regions, i.e. temporo-parietal junction, posterior cingulate and precuneus, supported the behavioural change. Additionally, age was associated with reduced activation in the reward-related orbitofrontal cortex and caudate nucleus during interactions with a trustworthy partner, possibly reflecting stronger expectations of trustworthiness. During unfair interactions, age-related increases in anterior cingulate activation, an area implicated in conflict monitoring, may mirror the necessity to inhibit pro-social tendencies in the face of the partner's actual levels of cooperation.

Trust versus paranoia: abnormal response to social reward in psychotic illness.

Psychosis is characterized by an elementary lack of trust in others. Trust is an inherently rewarding aspect of successful social interactions and can be examined using neuroeconomic paradigms. This study was aimed at investigating the underlying neural basis of diminished trust in psychosis. Functional magnetic resonance imaging data were acquired from 20 patients with psychosis and 20 healthy control subjects during two multiple-round trust games; one with a cooperative and the other with a deceptive counterpart. An a priori region of interest analysis of the right caudate nucleus, right temporo-parietal junction and medial prefrontal cortex was performed focusing on the repayment phase of the games. For regions with group differences, correlations were calculated between the haemodynamic signal change, behavioural outcomes and patients' symptoms. Patients demonstrated reduced levels of baseline trust, indicated by smaller initial investments. For the caudate nucleus, there was a significant game × group interaction, with controls showing stronger activation for the cooperative game than patients, and no differences for the deceptive game. The temporo-parietal junction was significantly more activated in control subjects than in patients during cooperative and deceptive repayments. There were no significant group differences for the medial prefrontal cortex. Patients' reduced activation within the caudate nucleus correlated negatively with paranoia scores. The temporo-parietal junction signal was positively correlated with positive symptom scores during deceptive repayments. Reduced sensitivity to social reward may explain the basic loss of trust in psychosis, mediated by aberrant activation of the caudate nucleus and the temporo-parietal junction.

Examining frontotemporal connectivity and rTMS in healthy controls: implications for auditory hallucinations in schizophrenia.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has been shown to have clinically beneficial effects in altering the perception of auditory hallucinations (AH) in patients with schizophrenia. However, the mode of action is not clear. Recent neuroimaging findings indicate that rTMS has the potential to induce not only local effects but also changes in remote, functionally connected brain regions. Frontotemporal dysconnectivity has been proposed as a mechanism leading to psychotic symptoms in schizophrenia. The current study examines functional connectivity between temporal and frontal brain regions after rTMS and the implications for AH in schizophrenia. METHOD: A connectivity analysis was conducted on the fMRI data of 11 healthy controls receiving rTMS, compared with 11 matched subjects receiving sham TMS, to the temporoparietal junction, before engaging in a task associated with robust frontotemporal activation. RESULTS: Compared to the control group, the rTMS group showed an altered frontotemporal connectivity with stronger connectivity between the right temporoparietal cortex and the dorsolateral prefrontal cortex and the angular gyrus. CONCLUSION: This finding provides preliminary evidence for the hypothesis that normalizing the functional connectivity between the temporoparietal and frontal brain regions may underlie the therapeutic effect of rTMS on AH in schizophrenia.

To trust or not to trust: the dynamics of social interaction in psychosis.

Psychotic illness is a disorder of social interaction unique to humans. However, up to now research has failed to pin down the exact determinants of the complex and interactive processes associated with the development of trust and reciprocity in psychosis. Utilizing a novel multi-round version of an interactive trust game experiment, we show that patients with psychosis and healthy relatives with a heightened risk for the illness exhibit lower baseline levels of trust compared with healthy controls. This effect partly overlapped with a reduced general intelligence. Furthermore, patients were unable to modify their trusting behaviour neither in response to information about the general trustworthiness of their interaction partner, nor in response to their partners' specific direct behavioural feedback. Relatives, in contrast, modified their trusting behaviour towards similar levels as healthy subjects in response to both. The results show that behavioural flexibility in response to socially relevant information is a critical determinant of success in the instantiation and maintenance of social relationships. A lack thereof may drive social dysfunction and the progression from subclinical symptoms to a full-blown psychosis. This offers a testable mechanistic hypothesis for progression from prodrome to psychotic illness, and may provide a therapeutic avenue to grapple the psychotic symptoms of social dysfunction.