Katharine N. Thakkar

BackgroundSocial dysfunction is widespread across psychiatric disorders, but treatments remain limited. Identifying underlying mechanisms could inform novel treatment approaches that meaningfully improve clinical outcomes. We previously showed that basic visual processing deficits cascade through gaze perception and emotion recognition to impair theory of mind. Here, we test an extended model assessing whether this cascade ultimately predicts real-world social dysfunction via theory of mind in an expanded sample.MethodsA combined sample of 202 psychiatric patients with varying levels of social dysfunction and healthy individuals completed basic visual processing tasks, a multi-level social cognition battery that included measures of gaze perception, emotion recognition, and theory of mind, and clinical assessments of social functioning. A five-level path model evaluated the sequential cascade from visual processing to gaze perception, emotion recognition, theory of mind, and social functioning.ResultsThe extended five-level path model demonstrated good fit to the data. Poorer basic visual processing sequentially predicted deficits across intermediate social cognitive domains, culminating in theory of mind, which directly predicted worse social functioning.ConclusionThese findings indicate that basic visual deficits cascade through social cognitive steps to impair everyday social functioning. As a candidate shared mechanism contributing to social dysfunction, basic visual processing represents a promising target for psychiatric interventions.

Background. Psychosis, social anxiety, and autism are clinical constructs that share important phenotypic features, particularly social dysfunction. A critical determinant of social functioning is an individual’s ability to recognize when social cues, like eye gaze, are meant for them. Emerging computational modeling data in psychosis suggest that altered perception of gaze direction stems from deficits in evidence accumulation – the process of gathering and integrating information – when processing social cues. Here, we investigated whether aberrant evidence accumulation during eye gaze processing are associated with social functioning or, as a secondary aim, with other measures of psychopathology, in a transdiagnostic sample enriched for psychotic, socially anxious, or autistic characteristics.Methods. We examined gaze perception in a sample of 111 adolescents and young adults (ages 14-30) with varying levels of social dysfunction and enriched for psychosis proneness, social anxiety, and autistic traits. We used drift diffusion models (DDM) to characterize key processes driving perceptual judgements in a self-directed gaze discrimination task, including the efficiency of evidence accumulation. We tested whether evidence accumulation was associated with social functioning, social cognition, and these different psychopathology dimensions.Results. Impaired evidence accumulation during gaze processing showed strong associations with impaired social cognition and modest associations with diminished social functioning and elevated psychosis and social anxiety symptoms. However, evidence accumulation sensitivity was not associated with autism traits.Conclusions. Evidence accumulation for subtle social cues relates to social cognition—a key determinant of social functioning. It may also be relevant to real-world social functioning and multiple psychopathology dimensions, including psychosis and social anxiety. Therefore, evidence accumulation should be investigated as a mechanism supporting social difficulties and related psychopathology.

Background: Social cognitive deficits are common across many psychiatric conditions and contribute to broader social dysfunction. One hypothesized mechanism involves altered basic visual processing, which may disrupt the perception of low-level social cues and, in turn, compromise broader social cognitive processes. Here, we examined relations between basic visual processing and different levels of social cognition in a transdiagnostic youth sample. Methods: A sample of 148 youth, ranging from healthy individuals to individuals with neuropsychiatric diagnoses and significant social dysfunction, completed two measures of basic visual processing (contrast sensitivity and visual integration) and a battery of social cognition tasks spanning lower-level (gaze perception) to mid-level (emotion recognition) to higher-level (theory of mind) social cognition. We used a four-level path model to test whether basic visual processing predicts gaze perception, which in turn predicts emotion recognition, which predicts theory of mind. Results: Poorer contrast sensitivity and visual integration were associated with less precise gaze perception, which was, in turn, associated with worse emotion recognition, which was associated with worse theory of mind. This four-level path model demonstrated good fit and showed superior fit compared to alternative models. Conclusions: These findings suggest that basic visual processing influences the perception of basic social cues (e.g. gaze direction), which subsequently impairs more complex social perception and inference. Notably, this study extends prior observations from individuals with chronic schizophrenia to a transdiagnostic youth sample, indicating that altered basic visual processing may be a shared mechanism contributing to social cognitive deficits across psychiatric disorders and illness stages.

BackgroundSocial cognitive deficits are common across many psychiatric conditions and contribute to broader social dysfunction. One hypothesized mechanism involves altered basic visual processing, which may disrupt the perception of low-level social cues and, in turn, compromise broader social cognitive processes. Here, we examined relations between basic visual processing and different levels of social cognition in a transdiagnostic youth sample.MethodsA sample of 148 youth, ranging from healthy individuals to individuals with neuropsychiatric diagnoses and significant social dysfunction, completed two measures of basic visual processing (contrast sensitivity and visual integration) and a battery of social cognition tasks spanning lower-level (gaze perception) to mid-level (emotion recognition) to higher-level (theory of mind) social cognition. We used a four-level path model to test whether basic visual processing predicts gaze perception, which in turn predicts emotion recognition, which predicts theory of mind.ResultsPoorer contrast sensitivity and visual integration were associated with less precise gaze perception, which was, in turn, associated with worse emotion recognition, which was associated with worse theory of mind. This four-level path model demonstrated good fit and showed superior fit compared to alternative models.ConclusionThese findings suggest that basic visual processing influences the perception of basic social cues (e.g., gaze direction), which subsequently impairs more complex social perception and inference. Notably, this study extends prior observations from individuals with chronic schizophrenia to a transdiagnostic youth sample, indicating that altered basic visual processing may be a shared mechanism contributing to social cognitive deficits across psychiatric disorders and illness stages.

Background and Hypothesis: Perception integrates sensory input with prior knowledge. Alterations in how both information sources are combined may lead to the departures from consensus reality that characterize schizophrenia (SZ). One source of prior knowledge is recent experience. Visual aftereffects—perceptions of the “opposite” of previously viewed stimulus—are driven by neuronal adaptation and demonstrate how recent experience influences perception. Our recent work revealed stronger tilt (orientation) aftereffects, but not negative afterimages (luminance aftereffects) in people with SZ relating to negative symptom severity, suggesting altered adaptation is more prominent in cortical than subcortical visual systems and may be an important illness mechanism. Because different aftereffects depend differentially on adaptation at different levels of the visual hierarchy, we sought to extend findings and probe where in the cortical hierarchy neuronal adaptation is most pronounced in SZ. Study Design: Two types of motion aftereffects were measured in SZ (n = 55) and healthy controls (HC; n = 43): “first-order” aftereffects caused by luminance-defined motion that elicits strong adaptation in early visual cortex, and “higher-order” aftereffects caused by non-luminance-feature-defined motion (eg, texture) that is primarily represented in extrastriate motion-sensitive areas. Study Results: Relative to HC, SZ showed stronger first-order but not higher-order motion aftereffects. Differences were not explained by task sensitivity, response bias, visual acuity, blinks, or fixation deviations. Conclusions: Altered neuronal adaptation in SZ is likely more pronounced at earlier (eg, V1) versus later (eg, V5/MT) stages of the visual hierarchy. Consequently, findings potentially implicate early visual cortical processing alterations in illness pathophysiology and/or clinical presentation.

Subjective visual disturbances and objective visual deficits are common across the psychosis spectrum. Few investigations have tested them in the same sample to ask whether subjective disturbances may arise from low-level visual processing deficits. This study assessed whether reduced contrast sensitivity (CS), a low-level visual processing deficit in people with schizophrenia (PSZ), may contribute to subjective visual disturbances across the psychosis spectrum. PSZ (n = 54) and controls (n = 54) matched for gender, age, and race/ethnicity, together with High PLE (n = 55) and Low PLE (n = 45) matched for gender, age, race/ethnicity, education, and IQ completed a CS task and the Bonn Scale, a structured interview assessing visual distortions. Group differences in CS and Bonn scores as well as their correlations with social risk factors were evaluated. In addition, the Bonn Scale's factor structure was examined. PSZ and High PLE endorsed more distortions than controls. In PSZ, distortion severity, but not CS, correlated with social risk factors and clinical symptoms. Only PSZ showed reduced CS, and no associations between distortions and CS were observed. Findings do not support a bottom-up account of visual distortions; instead, they may arise from higher-order processes.

Background/Hypothesis: Unpacking the pathophysiological mechanisms of schizophrenia is necessary for advancing prediction, prevention, and treatment efforts. Mechanisms can be identified using easy-to-use and scalable clinical biomarkers which reflect illness processes. Pupillometry is one such biomarker. Blunted dilation related to cognitive demand has been interpreted as a metric of diminished effort in schizophrenia while blunted constriction to light has been interpreted as a metric of altered autonomic balance in schizophrenia. However, these two sets of findings may also reflect a common mechanism of schizophrenia. Therefore, this study aimed to explore the association between blunted cognitive dilation and blunted constriction to light to provide a parsimonious mechanism of autonomic and effort disturbances experienced by individuals with schizophrenia. Study Design: We assessed light-induced constriction and cognitive dilation during a double-step task in individuals with schizophrenia (n=84) and demographically matched healthy controls (n=69), compared these metrics between groups, and computed their correlation within each group. Study Results: Replicating prior findings, dilation and constriction were blunted in schizophrenia relative to healthy controls. Blunted constriction and dilation were positively correlated in schizophrenia but not healthy controls (although the two correlations did not differ significantly). Conclusions: Findings provide, for the first time, preliminary support of a common mechanism linking blunted pupil constriction to light and dilation to cognitive demands in schizophrenia. We propose that individuals with schizophrenia may exhibit impaired top-down modulation of autonomic control. Future studies are needed to validate this proposed mechanism.

Objective: Researchers are increasingly interested in exploring the role of the menopausal transition in eating disorder risk. We recently embarked on studies of this critical life phase and encountered significant challenges in assessing menopausal status that limited our ability to test study hypotheses. This Research Forum describes these challenges and presents descriptive data on staging accuracy as well as recommendations for improving assessments that can advance research in this critical area of women's health.Method: Data come from 207 women (ages 40–58) assessed in an ongoing study from the MSU Twin Registry. Menopausal status (premenopause, perimenopause, postmenopause) was measured with the Perimenopause Evaluation Questionnaire assessing women's self‐identified stage as well as the regularity of menstrual cycles and medical history. Staging accuracy was evaluated by comparing the self‐identified stage with results from individual case analyses of questionnaire responses.Results: Many more women self‐identified as premenopausal (62%), perimenopausal (27%), and postmenopausal (11%) than we identified in case analyses (20%, 7%, 8%, respectively). These discrepancies appeared to be due to women failing to account for medications or medical conditions that would cause premature cessation of menses and/or insufficient questionnaire items and information for staging women with complicated reproductive histories.Discussion: Findings highlight significant limitations of self‐identified status or questionnaire responses alone in determining menopausal status. We provide recommendations for improving stage assessments, drawn from the challenges and lessons learned in our own studies, thereby allowing others to better explore this critical stage and advance women's health in our field.

Background and Hypothesis: Sequential saccade planning requires corollary discharge (CD) signals that provide information about the planned landing location of an eye movement. These CD signals may be altered among individuals with schizophrenia (SZ), providing a potential mechanism to explain passivity and anomalous self-experiences broadly. In healthy controls (HC), a key oculomotor CD network transmits CD signals from the thalamus to the frontal eye fields (FEF) and the intraparietal sulcus (IPS) and also remaps signals from FEF to IPS. Study Design: Here, we modeled fMRI data using dynamic causal modeling (DCM) to examine patient-control differences in effective connectivity evoked by a double-step (DS) task (30 SZ, 29 HC). The interrogated network was formed from a combination of (1) functionally identified FEF and IPS regions that robustly responded on DS trials and (2) anatomically identified thalamic regions involved in CD transmission. We also examined the relationship between clinical symptoms and effective connectivity parameters associated with task modulation of network pathways. Study Results: Network connectivity was indeed modulated by the DS task, which involves CD transmission. More importantly, we found reduced effective connectivity from thalamus to IPS in SZ, which was further correlated with passivity symptom severity. Conclusions: These results reaffirm the importance of IPS and thalamocortical connections in oculomotor CD signaling and provide mechanistic insights into CD alterations and consequently agency disturbances in schizophrenia.