Patients with schizophrenia show specific abnormalities in visual perception, and patients with bipolar disorder may have related perceptual deficits. During tasks that highlight perceptual dysfunction, patients with schizophrenia show abnormal activity in visual brain areas, including the lateral occipital complex (LOC) and early retinotopic cortex. It is unclear whether the anatomical structure of those visual areas is atypical in schizophrenia and bipolar disorder. In members of those two patient groups and healthy controls, we localized LOC and early retinotopic cortex individually for each participant using functional magnetic resonance imaging (MRI), then measured the thickness of those regions of interest using structural MRI scans. In both regions, patients with schizophrenia had the thinnest cortex, controls had the thickest cortex, and bipolar patients had intermediate cortical thickness. A control region, motor cortex, did not show this pattern of group differences. The thickness of each visual region of interest was significantly correlated with performance on a visual object masking task, but only in schizophrenia patients. These findings suggest an anatomical substrate for visual processing abnormalities that have been found with both neural and behavioral measures in schizophrenia and other severe mental illnesses.

Background

Human beings find social stimuli rewarding, which is thought to facilitate efficient social functioning. Although reward processing has been extensively studied in schizophrenia, a few studies have examined neural processes specifically involved in social reward processing. This study examined neural sensitivity to social and nonsocial rewards in schizophrenia.

Methods

Twenty-seven patients with schizophrenia and 25 community controls completed a One-Armed Bandit Task, an implicit reinforcement learning task, in the scanner. There were 2 conditions with an identical trial structure, one with social rewards and the other with nonsocial rewards. The data were analyzed using a region of interest (ROI) approach, focusing on the ventral striatum, ventromedial prefrontal cortex, and anterior cingulate cortex.

Results

Across all 3 ROIs, patients showed reduced activation for social rewards compared to controls. However, the 2 groups showed comparable levels of activation for nonsocial rewards. Within the patient group, levels of neural activation in these ROIs during the social reward condition were associated with better performance.

Conclusions

This study found reduced neural sensitivity in patients with schizophrenia in key reward-processing regions for social but not for nonsocial rewards. These findings suggest a relatively specific social reward-processing deficit in schizophrenia during an implicit reinforcement learning task.

Social cognitive skills training interventions for psychotic disorders have shown improvement in social cognitive performance tasks, but little was known about brain-based biomarkers linked to treatment effects. In this pilot study, we examined whether social cognitive skills training could modulate extrinsic and intrinsic functional connectivity in psychosis using functional magnetic resonance imaging (fMRI). Twenty-six chronic outpatients with psychotic disorders were recruited from either a Social Cognitive Skills Training (SCST) or an activity- and time-matched control intervention. At baseline and the end of intervention (12 weeks), participants completed two social cognitive tasks: a Facial Affect Matching task and a Mental State Attribution Task, as well as resting-state fMRI (rs-fMRI). Extrinsic functional connectivity was assessed using psychophysiological interaction (PPI) with amygdala and temporo-parietal junction as a seed region for the Facial Affect Matching Task and the Mental State Attribution task, respectively. Intrinsic functional connectivity was assessed with independent component analysis on rs-fMRI, with a focus on the default mode network (DMN). During the Facial Affect Matching task, we observed stronger PPI connectivity in the SCST group after intervention (compared to baseline), but no treatment-related change in the Control group. Neither group showed treatment-related changes in PPI connectivity during the Mental State Attribution task. During rs-fMRI, we found treatment-related changes in the DMN in the SCST group, but not in Control group. This study found that social cognitive skills training modulated both extrinsic and intrinsic functional connectivity in individuals with psychotic disorders after a 12-week intervention. These findings suggest treatment-related changes in functional connectivity as a potential brain-based biomarker of social cognitive skills training.

Individuals with schizophrenia demonstrate difficulties in attending to important stimuli (e.g., targets) and ignoring distractors (e.g., non-targets). We used a visual oddball task during fMRI to examine functional connectivity within and between the ventral and dorsal attention networks to determine the relative contribution of each network to detection of rare visual targets in schizophrenia. The sample comprised 25 schizophrenia patients and 27 healthy controls. Psychophysiological interaction analysis was used to examine whole-brain functional connectivity in response to targets. We used the right temporo parietal junction (TPJ) as the seed region for the ventral network and the right medial intraparietal sulcus (IPS) as the seed region for the dorsal network. We found that connectivity between right IPS and right anterior insula (AI; a component of the ventral network) was significantly greater in controls than patients. Expected patterns of within- and between-network connectivity for right TPJ were observed in controls, and not significantly different in patients. These findings indicate functional connectivity deficits between the dorsal and ventral attention networks in schizophrenia that may create problems in processing relevant versus irrelevant stimuli. Understanding the nature of network disruptions underlying cognitive deficits of schizophrenia may help shed light on the pathophysiology of this disorder.

Social perceptual deficits in schizophrenia are well established. Recent work suggests that the ability to extract social information from bodily cues is reduced in patients. However, little is known about the neurobiological mechanisms underlying this deficit. In the current study, 20 schizophrenia patients and 16 controls completed two tasks using point-light animations during fMRI: a basic biological motion task and an emotion in biological motion task. The basic biological motion task was used to localize activity in posterior superior temporal sulcus (pSTS), a critical region for biological motion perception. During the emotion in biological motion task, participants viewed brief videos depicting happiness, fear, anger, or neutral emotions and were asked to decide which emotion was portrayed. Activity in pSTS and amygdala was interrogated during this task. Results indicated that patients showed overall reduced activation compared to controls in pSTS and at a trend level in amygdala across emotions, despite similar task performance. Further, a functional connectivity analysis revealed that controls, but not patients, showed significant positive connectivity between pSTS and left frontal regions as well as bilateral angular gyrus during the emotion in biological motion task. These findings indicate that schizophrenia patients show aberrant neural activity and functional connectivity when extracting complex social information from simple motion stimuli, which may contribute to social perception deficits in this disorder.

Although it has been proposed that schizophrenia is characterized by impaired empathy, several recent studies found intact neural responses on tasks measuring the affective subdomain of empathy. This study further examined affective empathy in 21 schizophrenia outpatients and 21 healthy controls using a validated pain empathy paradigm with two components: (i) observing videos of people described as medical patients who were receiving a painful sound stimulation treatment; (ii) listening to the painful sounds (to create regions of interest). The observing videos component incorporated experimental manipulations of perspective taking (instructions to imagine 'Self' vs 'Other' experiencing pain) and cognitive appraisal (information about whether treatment was 'Effective' vs 'Not Effective'). When considering activation across experimental conditions, both groups showed similar dorsal anterior cingulate cortex (dACC) and anterior insula (AI) activation while merely observing others in pain. However, there were group differences associated with perspective taking: controls showed relatively greater dACC and AI activation for the Self vs Other contrast whereas patients showed relatively greater activation in these and additional regions for the Other vs Self contrast. Although patients demonstrated grossly intact neural activity while observing others in pain, they showed more subtle abnormalities when required to toggle between imagining themselves vs others experiencing pain.

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.

Although it has been proposed that schizophrenia is characterized by impaired empathy, several recent studies found intact neural responses on tasks measuring the affective subdomain of empathy. This study further examined affective empathy in 21 schizophrenia outpatients and 21 healthy controls using a validated pain empathy paradigm with two components: (i) observing videos of people described as medical patients who were receiving a painful sound stimulation treatment; (ii) listening to the painful sounds (to create regions of interest). The observing videos component incorporated experimental manipulations of perspective taking (instructions to imagine 'Self' vs 'Other' experiencing pain) and cognitive appraisal (information about whether treatment was 'Effective' vs 'Not Effective'). When considering activation across experimental conditions, both groups showed similar dorsal anterior cingulate cortex (dACC) and anterior insula (AI) activation while merely observing others in pain. However, there were group differences associated with perspective taking: controls showed relatively greater dACC and AI activation for the Self vs Other contrast whereas patients showed relatively greater activation in these and additional regions for the Other vs Self contrast. Although patients demonstrated grossly intact neural activity while observing others in pain, they showed more subtle abnormalities when required to toggle between imagining themselves vs others experiencing pain.

Early visual perception and attention are impaired in schizophrenia, and these deficits can be observed on target detection tasks. These tasks activate distinct ventral and dorsal brain networks which support stimulus-driven and goal-directed attention, respectively. We used single and dual target rapid serial visual presentation (RSVP) tasks during fMRI with an ROI approach to examine regions within these networks associated with target detection and the attentional blink (AB) in 21 schizophrenia outpatients and 25 healthy controls. In both tasks, letters were targets and numbers were distractors. For the dual target task, the second target (T2) was presented at three different lags after the first target (T1) (lag1 = 100 ms, lag3 = 300 ms, lag7 = 700ms). For both single and dual target tasks, patients identified fewer targets than controls. For the dual target task, both groups showed the expected AB effect with poorer performance at lag 3 than at lags 1 or 7, and there was no group by lag interaction. During the single target task, patients showed abnormally increased deactivation of the temporo-parietal junction (TPJ), a key region of the ventral network. When attention demands were increased during the dual target task, patients showed overactivation of the posterior intraparietal cortex, a key dorsal network region, along with failure to deactivate TPJ. Results suggest inefficient and faulty suppression of salience-oriented processing regions, resulting in increased sensitivity to stimuli in general, and difficulty distinguishing targets from non-targets.

Schizophrenia patients have abnormal neural responses to salient, infrequent events. We integrated event-related potentials (ERP) and fMRI to examine the contributions of the ventral (salience) and dorsal (sustained) attention networks to this dysfunctional neural activation. Twenty-one schizophrenia patients and 22 healthy controls were assessed in separate sessions with ERP and fMRI during a visual oddball task. Visual P100, N100, and P300 ERP waveforms and fMRI activation were assessed. A joint independent components analysis (jICA) on the ERP and fMRI data were conducted. Patients exhibited reduced P300, but not P100 or N100, amplitudes to targets and reduced fMRI neural activation in both dorsal and ventral attentional networks compared with controls. However, the jICA revealed that the P300 was linked specifically to activation in the ventral (salience) network, including anterior cingulate, anterior insula, and temporal parietal junction, with patients exhibiting significantly lower activation. The P100 and N100 were linked to activation in the dorsal (sustained) network, with no group differences in level of activation. This joint analysis approach revealed the nature of target detection deficits that were not discernable by either imaging methodology alone, highlighting the utility of a multimodal fMRI and ERP approach to understand attentional network deficits in schizophrenia.