The role of the hippocampo-prefrontal cortex system in phencyclidine-induced psychosis: A model for schizophrenia

Phencyclidine (PCP) is a psychotomimetic drug that induces schizophrenia-like symptoms in healthy individuals and exacerbates pre-existing symptoms in patients with schizophrenia. PCP also induces behavioral and cognitive abnormalities in non-human animals, and PCP-treated animals are considered a reliable pharmacological model of schizophrenia. However, the exact neural mechanisms by which PCP modulates behavior are not known. During the last decade several studies have indicated that disturbed activity of the prefrontal cortex (PFC) may be closely related to PCP-induced psychosis. Systemic administration of PCP produces long-lasting activation of medial PFC (mPFC) neurons in rats, almost in parallel with augmentation of locomotor activity and behavioral stereotypies. Later studies have showed that such PCP-induced behavioral abnormalities are ameliorated by prior administration of drugs that normalize or inhibit excess excitability of PFC neurons. Similar activation of mPFC neurons is not induced by systemic injection of a typical psychostimulant such as methamphetamine, even though behavioral hyperactivity is induced to almost the same level. This suggests that the neural circuits mediating PCP-induced psychosis are different to those mediating methamphetamine-induced psychosis. Locally applied PCP does not induce excitation of mPFC neurons, indicating that PCP-induced tonic excitation of mPFC neurons is mediated by inputs from regions outside the mPFC. This hypothesis is strongly supported by experimental results showing that local perfusion of PCP in the ventral hippocampus, which has dense fiber projections to the mPFC, induces tonic activation of mPFC neurons with accompanying augmentation of behavioral abnormalities. In this review we summarize current knowledge on the neural mechanisms underlying PCP-induced psychosis and highlight a possible involvement of the PFC and the hippocampus in PCP-induced psychosis.     

Childhood Emotional Maltreatment Severity Is Associated with Dorsal Medial Prefrontal Cortex Responsivity to Social Exclusion in Young Adults

Children who have experienced chronic parental rejection and exclusion during childhood, as is the case in childhood emotional maltreatment, may become especially sensitive to social exclusion. This study investigated the neural and emotional responses to social exclusion (with the Cyberball task) in young adults reporting childhood emotional maltreatment. Using functional magnetic resonance imaging, we investigated brain responses and self-reported distress to social exclusion in 46 young adult patients and healthy controls (mean age = 19.2±2.16) reporting low to extreme childhood emotional maltreatment. Consistent with prior studies, social exclusion was associated with activity in the ventral medial prefrontal cortex and posterior cingulate cortex. In addition, severity of childhood emotional maltreatment was positively associated with increased dorsal medial prefrontal cortex responsivity to social exclusion. The dorsal medial prefrontal cortex plays a crucial role in self-and other-referential processing, suggesting that the more individuals have been rejected and maltreated in childhood, the more self- and other- processing is elicited by social exclusion in adulthood. Negative self-referential thinking, in itself, enhances cognitive vulnerability for the development of psychiatric disorders. Therefore, our findings may underlie the emotional and behavioural difficulties that have been reported in adults reporting childhood emotional maltreatment.     

Nonlinear Complexity Analysis of Brain fMRI Signals in Schizophrenia

We investigated the differences in brain fMRI signal complexity in patients with schizophrenia while performing the Cyberball social exclusion task, using measures of Sample entropy and Hurst exponent (H). 13 patients meeting diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM IV) criteria for schizophrenia and 16 healthy controls underwent fMRI scanning at 1.5 T. The fMRI data of both groups of participants were pre-processed, the entropy characterized and the Hurst exponent extracted. Whole brain entropy and H maps of the groups were generated and analysed. The results after adjusting for age and sex differences together show that patients with schizophrenia exhibited higher complexity than healthy controls, at mean whole brain and regional levels. Also, both Sample entropy and Hurst exponent agree that patients with schizophrenia have more complex fMRI signals than healthy controls. These results suggest that schizophrenia is associated with more complex signal patterns when compared to healthy controls, supporting the increase in complexity hypothesis, where system complexity increases with age or disease, and also consistent with the notion that schizophrenia is characterised by a dysregulation of the nonlinear dynamics of underlying neuronal systems.     

Neural Effects of Auditory Distraction on Visual Attention in Schizophrenia

Sensory flooding, particularly during auditory stimulation, is a common problem for patients with schizophrenia. The functional consequences of this impairment during cross-modal attention tasks, however, are unclear. The purpose of this study was to examine how auditory distraction differentially affects task-associated response during visual attention in patients and healthy controls. To that end, 21 outpatients with schizophrenia and 23 healthy comparison subjects performed a visual attention task in the presence or absence of distracting, environmentally relevant “urban” noise while undergoing functional magnetic resonance imaging at 3T. The task had two conditions (difficult and easy); task-related neural activity was defined as difficult – easy. During task performance, a significant distraction (noise or silence) by group (patient or control) interaction was observed in the left dorsolateral prefrontal cortex, right hippocampus, left temporoparietal junction, and right fusiform gyrus, with patients showing relative hypoactivation during noise compared to controls. In patients, the ability to recruit the dorsolateral prefrontal cortex during the task in noise was negatively correlated with the effect of noise on reaction time. Clinically, the ability to recruit the fusiform gyrus during the task in noise was negatively correlated with SANS affective flattening score, and hippocampal recruitment during the task in noise was positively correlated with global functioning. In conclusion, schizophrenia may be associated with abnormalities in neural response during visual attention tasks in the presence of cross-modal noise distraction. These response differences may predict global functioning in the illness, and may serve as a biomarker for therapeutic development.     

Aberrant Interference of Auditory Negative Words on Attention in Patients with Schizophrenia

Previous research suggests that deficits in attention-emotion interaction are implicated in schizophrenia symptoms. Although disruption in auditory processing is crucial in the pathophysiology of schizophrenia, deficits in interaction between emotional processing of auditorily presented language stimuli and auditory attention have not yet been clarified. To address this issue, the current study used a dichotic listening task to examine 22 patients with schizophrenia and 24 age-, sex-, parental socioeconomic background-, handedness-, dexterous ear-, and intelligence quotient-matched healthy controls. The participants completed a word recognition task on the attended side in which a word with emotionally valenced content (negative/positive/neutral) was presented to one ear and a different neutral word was presented to the other ear. Participants selectively attended to either ear. In the control subjects, presentation of negative but not positive word stimuli provoked a significantly prolonged reaction time compared with presentation of neutral word stimuli. This interference effect for negative words existed whether or not subjects directed attention to the negative words. This interference effect was significantly smaller in the patients with schizophrenia than in the healthy controls. Furthermore, the smaller interference effect was significantly correlated with severe positive symptoms and delusional behavior in the patients with schizophrenia. The present findings suggest that aberrant interaction between semantic processing of negative emotional content and auditory attention plays a role in production of positive symptoms in schizophrenia. (224 words)     

Pavlovian reward prediction and receipt in schizophrenia: relationship to anhedonia

Reward processing abnormalities have been implicated in the pathophysiology of negative symptoms such as anhedonia and avolition in schizophrenia. However, studies examining neural responses to reward anticipation and receipt have largely relied on instrumental tasks, which may confound reward processing abnormalities with deficits in response selection and execution. 25 chronic, medicated outpatients with schizophrenia and 20 healthy controls underwent functional magnetic resonance imaging using a pavlovian reward prediction paradigm with no response requirements. Subjects passively viewed cues that predicted subsequent receipt of monetary reward or non-reward, and blood-oxygen-level-dependent signal was measured at the time of cue presentation and receipt. At the group level, neural responses to both reward anticipation and receipt were largely similar between groups. At the time of cue presentation, striatal anticipatory responses did not differ between patients and controls. Right anterior insula demonstrated greater activation for nonreward than reward cues in controls, and for reward than nonreward cues in patients. At the time of receipt, robust responses to receipt of reward vs. nonreward were seen in striatum, midbrain, and frontal cortex in both groups. Furthermore, both groups demonstrated responses to unexpected versus expected outcomes in cortical areas including bilateral dorsolateral prefrontal cortex. Individual difference analyses in patients revealed an association between physical anhedonia and activity in ventral striatum and ventromedial prefrontal cortex during anticipation of reward, in which greater anhedonia severity was associated with reduced activation to money versus no-money cues. In ventromedial prefrontal cortex, this relationship held among both controls and patients, suggesting a relationship between anticipatory activity and anhedonia irrespective of diagnosis. These findings suggest that in the absence of response requirements, brain responses to reward receipt are largely intact in medicated individuals with chronic schizophrenia, while reward anticipation responses in left ventral striatum are reduced in those patients with greater anhedonia severity.     

Impairments of social motor coordination in schizophrenia

It has been demonstrated that motor coordination of interacting people plays a crucial role in the success of social exchanges. Abnormal movements have been reported during interpersonal interactions of patients suffering from schizophrenia and a motor coordination breakdown could explain this social interaction deficit, which is one of the main and earliest features of the illness. Using the dynamical systems framework, the goal of the current study was (i) to investigate whether social motor coordination is impaired in schizophrenia and (ii) to determine the underlying perceptual or cognitive processes that may be affected. We examined intentional and unintentional social motor coordination in participants oscillating hand-held pendulums from the wrist. The control group consisted of twenty healthy participant pairs while the experimental group consisted of twenty participant pairs that included one participant suffering from schizophrenia. The results showed that unintentional social motor coordination was preserved while intentional social motor coordination was impaired. In intentional coordination, the schizophrenia group displayed coordination patterns that had lower stability and in which the patient never led the coordination. A coupled oscillator model suggests that the schizophrenia group coordination pattern was due to a decrease in the amount of available information together with a delay in information transmission. Our study thus identified relational motor signatures of schizophrenia and opens new perspectives for detecting the illness and improving social interactions of patients.     

Neural Correlates of Belief and Emotion Attribution in Schizophrenia

Impaired mental state attribution is a core social cognitive deficit in schizophrenia. With functional magnetic resonance imaging (fMRI), this study examined the extent to which the core neural system of mental state attribution is involved in mental state attribution, focusing on belief attribution and emotion attribution. Fifteen schizophrenia outpatients and 14 healthy controls performed two mental state attribution tasks in the scanner. In a Belief Attribution Task, after reading a short vignette, participants were asked infer either the belief of a character (a false belief condition) or a physical state of an affair (a false photograph condition). In an Emotion Attribution Task, participants were asked either to judge whether character(s) in pictures felt unpleasant, pleasant, or neutral emotion (other condition) or to look at pictures that did not have any human characters (view condition). fMRI data were analyzing focusing on a priori regions of interest (ROIs) of the core neural systems of mental state attribution: the medial prefrontal cortex (mPFC), temporoparietal junction (TPJ) and precuneus. An exploratory whole brain analysis was also performed. Both patients and controls showed greater activation in all four ROIs during the Belief Attribution Task than the Emotion Attribution Task. Patients also showed less activation in the precuneus and left TPJ compared to controls during the Belief Attribution Task. No significant group difference was found during the Emotion Attribution Task in any of ROIs. An exploratory whole brain analysis showed a similar pattern of neural activations. These findings suggest that while schizophrenia patients rely on the same neural network as controls do when attributing beliefs of others, patients did not show reduced activation in the key regions such as the TPJ. Further, this study did not find evidence for aberrant neural activation during emotion attribution or recruitment of compensatory brain regions in schizophrenia.     

Increased Intra-Individual Variability of Cognitive Processing in Subjects at Risk Mental State and Schizophrenia Patients

Intra-individual variability (IIV) has received recent attention as an indicator of the stability of cognitive functioning that may outperform mean performance in reflecting putative neurobiological abnormalities. Increased IIV is regarded as a core deficit in schizophrenia patients; however, whether this deficit is present in the prodromal phase before the onset of schizophrenia has not been well established. In the present study, we investigated IIV using the stop-signal paradigm in at-risk mental state (ARMS) individuals and in schizophrenia patients. The study included 27 ARMS subjects, 37 schizophrenia patients, and 38 normal controls. The stop-signal task was administered to assess IIV and response inhibition. IIV was estimated by calculating the standard deviation across sub-blocks for the three groups. We observed increased IIV in ARMS subjects and schizophrenia patients compared with normal controls in both the “stop” and the “go” processes even though the mean response inhibition performances were not impaired in the ARMS group. Schizophrenia patients showed impaired response inhibition that was associated with the severity of negative symptoms. Our findings suggest that the analysis of IIV may identify cognitive and clinical features of ARMS that are not detectable by conventional mean performance analysis. The unstable response patterns associated with ARMS may originate from abnormal processing in neural systems caused by alterations in the integrity of functional brain networks and dopamine neuromodulation.     

Computerized cognitive training restores neural activity within the reality monitoring network in schizophrenia

Schizophrenia patients suffer from severe cognitive deficits, such as impaired reality monitoring. Reality monitoring is the ability to distinguish the source of internal experiences from outside reality. During reality monitoring tasks, schizophrenia patients make errors identifying "I made it up" items, and even during accurate performance, they show abnormally low activation of the medial prefrontal cortex (mPFC), a region that supports self-referential cognition. We administered 80 hr of computerized training of cognitive processes to schizophrenia patients and found improvement in reality monitoring that correlated with increased mPFC activity. In contrast, patients in a computer games control condition did not show any behavioral or neural improvements. Notably, recovery in mPFC activity after training was associated with improved social functioning 6 months later. These findings demonstrate that a serious behavioral deficit in schizophrenia, and its underlying neural dysfunction, can be improved by well-designed computerized cognitive training, resulting in better quality of life.     

Neural Correlates of Emotional Interference in Social Anxiety Disorder

Disorder-relevant but task-unrelated stimuli impair cognitive performance in social anxiety disorder (SAD); however, time course and neural correlates of emotional interference are unknown. The present study investigated time course and neural basis of emotional interference in SAD using event-related functional magnetic resonance imaging (fMRI). Patients with SAD and healthy controls performed an emotional stroop task which allowed examining interference effects on the current and the succeeding trial. Reaction time data showed an emotional interference effect in the current trial, but not the succeeding trial, specifically in SAD. FMRI data showed greater activation in the left amygdala, bilateral insula, medial prefrontal cortex (mPFC), dorsal anterior cingulate cortex (ACC), and left opercular part of the inferior frontal gyrus during emotional interference of the current trial in SAD patients. Furthermore, we found a positive correlation between patients’ interference scores and activation in the mPFC, dorsal ACC and left angular/supramarginal gyrus. Taken together, results indicate a network of brain regions comprising amygdala, insula, mPFC, ACC, and areas strongly involved in language processing during the processing of task-unrelated threat in SAD. However, specifically the activation in mPFC, dorsal ACC, and left angular/supramarginal gyrus is associated with the strength of the interference effect, suggesting a cognitive network model of attentional bias in SAD. This probably comprises exceeded allocation of attentional resources to disorder-related information of the presented stimuli and increased self-referential and semantic processing of threat words in SAD.     

Altered Neural Basis of the Reality Processing and Its Relation to Cognitive Insight in Schizophrenia

It has been reported that reality evaluation and recognition are impaired in patients with schizophrenia and these impairments are related to the severity of psychotic symptoms. The current study aimed to investigate the neural basis of impairments in reality evaluation and recognition and their relationships with cognitive insight in schizophrenia. During functional magnetic resonance imaging, 20 patients with schizophrenia and 20 healthy controls performed a set of reality evaluation and recognition tasks, in which subjects judged whether scenes in a series of drawings were real or unreal and whether they were familiar or novel. During reality evaluation, patients showed decreased activity in various regions including the inferior parietal lobule, retrosplenial cortex and parahippocampal gyrus, compared with controls. Particularly, parahippocampal gyrus activity was correlated with the severity of positive symptoms in patients. During recognition, patients also exhibited decreased activity in various regions, including the dorsolateral prefrontal cortex, inferior parietal lobule and posterior cingulate cortex. Particularly, inferior parietal lobule activity and posterior cingulate cortex activity were correlated with cognitive insight in patients. These findings provide evidence that neural impairments in reality evaluation and recognition are related to psychotic symptoms. Anomalous appraisal of context by dysfunctions in the context network may contribute to impairments in the reality processing in schizophrenia, and abnormal declarative memory processes may be involved in cognitive insight in patients with schizophrenia.     

Stronger Neural Modulation by Visual Motion Intensity in Autism Spectrum Disorders

Theories of autism spectrum disorders (ASD) have focused on altered perceptual integration of sensory features as a possible core deficit. Yet, there is little understanding of the neuronal processing of elementary sensory features in ASD. For typically developed individuals, we previously established a direct link between frequency-specific neural activity and the intensity of a specific sensory feature: Gamma-band activity in the visual cortex increased approximately linearly with the strength of visual motion. Using magnetoencephalography (MEG), we investigated whether in individuals with ASD neural activity reflect the coherence, and thus intensity, of visual motion in a similar fashion. Thirteen adult participants with ASD and 14 control participants performed a motion direction discrimination task with increasing levels of motion coherence. A polynomial regression analysis revealed that gamma-band power increased significantly stronger with motion coherence in ASD compared to controls, suggesting excessive visual activation with increasing stimulus intensity originating from motion-responsive visual areas V3, V6 and hMT/V5. Enhanced neural responses with increasing stimulus intensity suggest an enhanced response gain in ASD. Response gain is controlled by excitatory-inhibitory interactions, which also drive high-frequency oscillations in the gamma-band. Thus, our data suggest that a disturbed excitatory-inhibitory balance underlies enhanced neural responses to coherent motion in ASD.     

No association of Disrupted-in-Schizophrenia-1 variation with prefrontal function in patients with schizophrenia and bipolar disorder

The Disrupted-in-Schizophrenia-1 (DISC1) gene has been implicated in both schizophrenia and bipolar disorder by linkage and genetic association studies. Altered prefrontal cortical function is a pathophysiological feature of both disorders, and we have recently shown that variation in DISC1 modulates prefrontal activation in healthy volunteers. Our goal was to examine the influence of the DISC1 polymorphism Cys704Ser on prefrontal function in schizophrenia and bipolar disorder. From 2004 to 2008, patients with schizophrenia (N = 44), patients with bipolar disorder (N = 35) and healthy volunteers (N = 53) were studied using functional magnetic resonance imaging while performing a verbal fluency task. The effect of Cys704Ser on cortical activation was compared between groups as Cys704 carriers vs. Ser704 homozygotes. In contrast to the significant effect on prefrontal activation we had previously found in healthy subjects, no significant effect of Cys704Ser was detected in this or any other region in either the schizophrenia or bipolar groups. When controls were compared with patients with schizophrenia, there was a diagnosis by genotype interaction in the left middle/superior frontal gyrus [family-wise error (FWE) P = 0.002]. In this region, Ser704/ser704 controls activated more than Cys704 carriers, and there was a trend in the opposite direction in schizophrenia patients. In contrast to its effect in healthy subjects, variation in DISC1 Cys704Ser704 genotype was not associated with altered prefrontal activation in patients with schizophrenia or bipolar disorder. The absence of an effect in patients may reflect interactions of the effects of DISC1 genotype with the effects of other genes associated with these disorders, and/or with the effects of the disorders on brain function.     

Impaired associative learning in schizophrenia: behavioral and computational studies

Associative learning is a central building block of human cognition and in large part depends on mechanisms of synaptic plasticity, memory capacity and fronto–hippocampal interactions. A disorder like schizophrenia is thought to be characterized by altered plasticity, and impaired frontal and hippocampal function. Understanding the expression of this dysfunction through appropriate experimental studies, and understanding the processes that may give rise to impaired behavior through biologically plausible computational models will help clarify the nature of these deficits. We present a preliminary computational model designed to capture learning dynamics in healthy control and schizophrenia subjects. Experimental data was collected on a spatial-object paired-associate learning task. The task evinces classic patterns of negatively accelerated learning in both healthy control subjects and patients, with patients demonstrating lower rates of learning than controls. Our rudimentary computational model of the task was based on biologically plausible assumptions, including the separation of dorsal/spatial and ventral/object visual streams, implementation of rules of learning, the explicit parameterization of learning rates (a plausible surrogate for synaptic plasticity), and learning capacity (a plausible surrogate for memory capacity). Reductions in learning dynamics in schizophrenia were well-modeled by reductions in learning rate and learning capacity. The synergy between experimental research and a detailed computational model of performance provides a framework within which to infer plausible biological bases of impaired learning dynamics in schizophrenia.     

Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia

Adolescence is a critical developmental period where the early symptoms of schizophrenia frequently emerge. First-degree relatives of people with schizophrenia who are at familial high risk (FHR) may show similar cognitive and emotional changes. However, the neurological changes underlying the emergence of these symptoms remain unclear. This study sought to identify differences in frontal, striatal, and limbic regions in children and adolescents with FHR using functional magnetic resonance imaging. Groups of 21 children and adolescents at FHR and 21 healthy controls completed an emotional oddball task that relied on selective attention and the suppression of task-irrelevant emotional information. The standard oddball task was modified to include aversive and neutral distractors in order to examine potential group differences in both emotional and executive processing. This task was designed specifically to allow for children and adolescents to complete by keeping the difficulty and emotional image content age-appropriate. Furthermore, we demonstrate a technique for suitable fMRI registration for children and adolescent participants. This paradigm may also be applied in future studies to measure changes in neural activity in other populations with hypothesized developmental changes in executive and emotional processing.     

EEG Findings of Reduced Neural Synchronization during Visual Integration in Schizophrenia

Schizophrenia patients exhibit well-documented visual processing deficits. One area of disruption is visual integration, the ability to form global objects from local elements. However, most studies of visual integration in schizophrenia have been conducted in the context of an active attention task, which may influence the findings. In this study we examined visual integration using electroencephalography (EEG) in a passive task to elucidate neural mechanisms associated with poor visual integration. Forty-six schizophrenia patients and 30 healthy controls had EEG recorded while passively viewing figures comprised of real, illusory, or no contours. We examined visual P100, N100, and P200 event-related potential (ERP) components, as well as neural synchronization in the gamma (30-60 Hz) band assessed by the EEG phase locking factor (PLF). The N100 was significantly larger to illusory vs. no contour, and illusory vs. real contour stimuli while the P200 was larger only to real vs. illusory stimuli; there were no significant interactions with group. Compared to controls, patients failed to show increased phase locking to illusory versus no contours between 40-60 Hz. Also, controls, but not patients, had larger PLF between 30-40 Hz when viewing real vs. illusory contours. Finally, the positive symptom factor of the BPRS was negatively correlated with PLF values between 40-60 Hz to illusory stimuli, and with PLF between 30-40 Hz to real contour stimuli. These results suggest that the pattern of results across visual processing conditions is similar in patients and controls. However, patients have deficits in neural synchronization in the gamma range during basic processing of illusory contours when attentional demand is limited.     

Neural Correlates of the Preserved Inhibition of Return in Schizophrenia

Inhibition of return (IOR) is an attentional mechanism that previously has been reported to be either intact or blunted in subjects with schizophrenia (SCZ). In the present study, we explored the neural mechanism of IOR in SCZ by comparing the target-locked N1 and P1 activity evoked by valid-cued trials with that evoked by invalid-cued trials. Twenty-seven schizophrenia patients and nineteen healthy controls participated in a task involving covert orienting of attention with two stimulus onset asynchronies (SOAs: 700 ms and 1200 ms) during which 64-channel EEG data were recorded. Behavioral reaction times (RTs) were longer in response to valid-cued trials than to invalid-cued ones, suggesting an intact IOR in SCZ. However, reduced N1 amplitude elicited by valid-cued trials suggested a stronger inhibition of attention from being oriented to a previously cued location, and therefore a relative inhibition of perceptual processing at that location in SCZ. These results indicate that altered N1 activity is associated with the preservation of IOR in SCZ and could be a sensitive marker to track the IOR effect.     

The Roles of Reward,Default, and Executive Control Networks in Set-Shifting Impairments in Schizophrenia

Patients with schizophrenia (SZ) show deficits on tasks of rapid reinforcement learning, like probabilistic reversal learning (PRL), but the neural bases for those impairments are not known. Recent evidence of relatively intact sensitivity to negative outcomes in the ventral striatum (VS) in many SZ patients suggests that PRL deficits may be largely attributable to processes downstream from feedback processing, involving both the activation of executive control task regions and deactivation of default mode network (DMN) components. We analyzed data from 29 chronic SZ patients and 21 matched normal controls (NCs) performing a PRL task in an MRI scanner. Subjects were presented with eight pairs of fractal stimuli, for 50 trials each. For each pair, subjects learned to choose the more frequently-rewarded (better) stimulus. Each time a criterion was reached, the better stimulus became the worse one, and the worse became the better. Responses to feedback events were assessed through whole-brain and regions-of-interest (ROI) analyses in DMN. We also assessed correlations between BOLD signal contrasts and clinical measures in SZs. Relative to NCs, SZ patients showed comparable deactivation of VS in response to negative feedback, but reduced deactivation of DMN components including medial prefrontal cortex (mPFC). The magnitudes of patients'' punishment-evoked deactivations in VS and ventromedial PFC correlated significantly with clinical ratings for avolition/anhedonia. These findings suggest that schizophrenia is associated with a reduced ability to deactivate components of default mode networks, following the presentation of informative feedback and that motivational deficits in SZ relate closely to feedback-evoked activity in reward circuit components. These results also confirm a role for ventrolateral and dorsomedial PFC in the execution of response-set shifts.     

Peak alpha frequency and psychopathological symptoms in schizophrenia

Spectral characteristic of the alpha activity (frequency of the maximum spectral peak) were comparatively studied in schizophrenic patients with predominance of positive or negative symptoms and healthy subjects in the resting state and during cognitive task performance. In patients with negative symptoms, the spectral peak frequency of the alpha activity (8-13 Hz) was decreased at rest as compared to healthy subjects in all cortical areas. In patients with positive symptoms, the peak frequency of the alpha rhythm in the occipital cortical areas was higher than in healthy subjects. The performance-induced increase in the alpha-rhythm peak frequency during cognitive tasks was less expressed in schizophrenics than in healthy subjects. A correlation of these characteristics with psychopathological symptoms was revealed. The results suggest a difference in neurophysiological mechanisms underlying positive and negative symptoms in schizophrenia.