Structural Thalamofrontal Hypoconnectivity Is Related to Oculomotor Corollary Discharge Dysfunction in Schizophrenia.

By predicting sensory consequences of actions, humans can distinguish self-generated sensory inputs from those that are elicited externally. This is one mechanism by which we achieve a subjective sense of agency over our actions. Corollary discharge (CD) signals-"copies" of motor signals sent to sensory areas-permit such predictions, and CD abnormalities are a hypothesized mechanism for the agency disruptions in schizophrenia that characterize a subset of symptoms. Indeed, behavioral evidence of altered CD, including in the oculomotor system, has been observed in schizophrenia patients. A pathway projecting from the superior colliculus to the frontal eye fields (FEFs) via the mediodorsal thalamus (MD) conveys oculomotor CD associated with saccadic eye movements in nonhuman primates. This animal work provides a promising translational framework in which to investigate CD abnormalities in clinical populations. In the current study, we examined whether structural connectivity of this MD-FEF pathway relates to oculomotor CD functioning in schizophrenia. Twenty-two schizophrenia patients and 24 healthy control participants of both sexes underwent diffusion tensor imaging, and a large subset performed a trans-saccadic perceptual task that yields measures of CD. Using probabilistic tractography, we identified anatomical connections between FEF and MD and extracted indices of microstructural integrity. Patients exhibited compromised microstructural integrity in the MD-FEF pathway, which was correlated with greater oculomotor CD abnormalities and more severe psychotic symptoms. These data reinforce the role of the MD-FEF pathway in transmitting oculomotor CD signals and suggest that disturbances in this pathway may relate to psychotic symptom manifestation in patients.SIGNIFICANCE STATEMENT People with schizophrenia sometimes experience abnormalities in a sense of agency, which may stem from abnormal sensory predictions about their own actions. Consistent with this notion, the current study found reduced structural connectivity in patients with schizophrenia in a specific brain pathway found to transmit such sensorimotor prediction signals in nonhuman primates. Reduced structural connectivity was correlated with behavioral evidence for impaired sensorimotor predictions and psychotic symptoms.

Stronger tilt aftereffects in persons with schizophrenia.

Individuals with schizophrenia may fail to appropriately use temporal context and apply past environmental regularities to the interpretation of incoming sensory information. Here we use the visual system as a test bed for investigating how prior experience shapes perception in individuals with schizophrenia. Specifically, we use visual aftereffects, illusory percepts resulting from prior exposure to visual input, to measure the influence of prior events on current processing. At a neural level, visual aftereffects arise due to attenuation in the responses of neurons that code the features of the prior stimulus (neuronal adaptation) and subsequent disinhibition of neurons signaling activity at the opposite end of the feature dimension. In the current study, we measured tilt aftereffects and negative afterimages, 2 types of aftereffects that reflect, respectively, adaptation of cortical orientation-coding neurons and adaptation of subcortical and retinal luminance-coding cells in persons with schizophrenia (PSZ; n = 36) and demographically matched healthy controls (HC; n = 22). We observed stronger tilt aftereffects in PSZ compared to HC, but no difference in negative afterimages. Stronger tilt aftereffects were related to more severe negative symptoms. These data suggest oversensitivity to recent regularities, in the form of stronger visual adaptation, at cortical, but not subcortical, levels in schizophrenia. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Social vs. non-social measures of learning potential for predicting community functioning across phase of illness in schizophrenia.

Studies demonstrate that dynamic assessment (i.e., learning potential) improves the prediction of response to rehabilitation over static measures in individuals with schizophrenia. Learning potential is most commonly assessed using neuropsychological tests under a test-train-test paradigm to examine change in performance. Novel learning potential approaches using social cognitive tasks may have added value, particularly for the prediction of social functioning, but this area is unexplored. The present study is the first to investigate whether patients with schizophrenia demonstrate social cognitive learning potential across phase of illness. This study included 43 participants at clinical high risk (CHR), 63 first-episode, and 36 chronic schizophrenia patients. Assessment of learning potential involved test-train-test versions of the Wisconsin Card Sorting Test (non-social cognitive learning potential) and the Facial Emotion Identification Test (social cognitive learning potential). Non-social and social cognition pre-training scores (static scores) uniquely predicted concurrent community functioning in patients with schizophrenia, but not in CHR participants. Learning potential showed no incremental explanation of variance beyond static scores. First-episode patients showed larger non-social cognitive learning potential than CHR participants and were similar to chronic patients; chronic patients and CHR participants were similar. Group differences across phase of illness were not observed for social cognitive learning potential. Subsequent research could explore whether non-social and social cognitive learning potential relate differentially to non-social versus social types of training and rehabilitation.

Reduced pupil dilation during action preparation in schizophrenia.

Impairments in cognitive control-the ability to exert control over thoughts and actions and respond flexibly to the environment-are well-documented in schizophrenia. However, the degree to which experimental task performance reflects true cognitive control impairments or more general alterations in effort, arousal and/or task preparedness is unclear. Pupillary responses can provide insight into these latter factors, as the pupil dilates with degree of cognitive effort and response preparation. In the current study, 16 medicated outpatients with schizophrenia (SZP) and 18 healthy controls performed a task that measures the ability to reactively inhibit and modify a planned action-the double-step task. In this task, participants were required to make a saccade to a visual target. Infrequently, the target jumped to a new location and participants were instructed to rapidly inhibit and change their eye movement plan. Applying a race model of performance, we have previously shown that SZP require more time to inhibit a planned action. In the current analysis, we measured pupil dilation associated with task preparation and found that SZP had a shallower increase in pupil size prior to the onset of the trial. Additionally, reduced magnitude of the pupil response was associated with negative symptom severity in patients. Based on primate neurophysiology and cognitive neuroscience work, we suggest that this blunted pupillary response may reflect abnormalities in a general orienting response or reduced motivational significance of a cue signifying the onset of a preparatory period and that these abnormalities might share an autonomic basis with negative symptoms.

Episodic Memory for Dynamic Social Interaction Across Phase of Illness in Schizophrenia.

Although a number of studies examined recollection and familiarity memory in schizophrenia, most of studies have focused on nonsocial episodic memory. Little is known about how schizophrenia patients remember social information in everyday life and whether social episodic memory changes over the course of illness. This study aims to examine episodic memory for dynamic social interaction with multimodal social stimuli in schizophrenia across phase of illness. Within each phase of illness, probands and demographically matched controls participated: 51 probands at clinical high risk (CHR) for psychosis and 36 controls, 80 first-episode schizophrenia patients and 49 controls, and 50 chronic schizophrenia patients and 39 controls. The participants completed the Social Remember-Know Paradigm that assessed overall social episodic memory, social recollection and familiarity memory, and social context memory, in addition to social cognitive measures and measures on community functioning. Probands showed impairment for recollection but not in familiarity memory and this pattern was similar across phase of illness. In contrast, impaired social context memory was observed in the first-episode and chronic schizophrenia samples, but not in CHR samples. Social context memory was associated with community functioning only in the chronic sample. These findings suggest that an impaired recollection could be a vulnerability marker for schizophrenia whereas impaired social context memory could be a disease-related marker. Further, a pattern of impaired recollection with intact familiarity memory for social stimuli suggests that schizophrenia patients may have a different pattern of impaired episodic memory for social vs nonsocial stimuli.

Longitudinal stability of social cognition in schizophrenia: A 5-year follow-up of social perception and emotion processing.

BACKGROUND: Individuals with schizophrenia exhibit marked and disproportional impairment in social cognition, which is associated with their level of community functioning. However, it is unclear whether social cognitive impairment is stable over time, or if impairment worsens as a function of illness chronicity. Moreover, little is known about the longitudinal associations between social cognition and community functioning. METHOD: Forty-one outpatients with schizophrenia completed tests of emotion processing (Mayer-Salovey-Caruso Emotional Intelligence Test, MSCEIT) and social perception (Relationships Across Domains, RAD) at baseline and approximately five years later. Stability of performance was assessed using paired t-tests and correlations. Longitudinal associations between social cognition and community functioning (Role Functioning Scale, RFS) were assessed using cross-lagged panel correlation analysis. RESULTS: Performance on the two social cognition tasks were stable over follow-up. There were no significant mean differences between assessment points [p's≥0.20, Cohen'sd's≤|0.20|], and baseline performance was highly correlated with performance at follow-up [ρ's≥0.70, ICC≥0.83, p's<0.001]. The contemporaneous association between social cognition and community functioning was moderately large at follow-up [ρ=0.49, p=0.002]. However, baseline social cognition did not show a significant longitudinal influence on follow-up community functioning [z=0.31, p=0.76]. CONCLUSIONS: These data support trait-like stability of selected areas of social cognition in schizophrenia. Cross-lagged correlations did not reveal a significant unidirectional influence of baseline social cognition on community functioning five years later. However, consistent with the larger literature, a moderately large cross-sectional association between social cognition and community functioning was observed. Based on stability and cross-sectional associations, these results suggest that social cognition might have short-term implications for functional outcome rather than long-term consequences.