Association Between Failures in Perceptual Updating and the Severity of Psychosis in Schizophrenia.

Importance: Recent accounts suggest that delusions and hallucinations may result from alterations in how prior knowledge is integrated with new information, but experimental evidence supporting this idea has been complex and inconsistent. Evidence from a simpler perceptual task would make clear whether psychotic symptoms are associated with overreliance on prior information and impaired updating. Objective: To investigate whether individuals with schizophrenia or schizoaffective disorder (PSZ) and healthy control individuals (HCs) differ in the ability to update their beliefs based on evidence in a relatively simple perceptual paradigm. Design, Setting, and Participants: This case-control study included individuals who met DSM-IV criteria for PSZ and matched HC participants in 2 independent samples. The PSZ group was recruited from the Maryland Psychiatric Research Center, Yale University, and community clinics, and the HC group was recruited from the community. To test perceptual updating, a random dot kinematogram paradigm was implemented in which dots moving coherently in a single direction were mixed with randomly moving dots. On 50% of trials, the direction of coherent motion changed by 90° midway through the trial. Participants were asked to report the direction perceived at the end of the trial. The Peters Delusions Inventory and Brief Psychiatric Rating Scale (BPRS) were used to quantify the severity of positive symptoms. Data were collected from September 2018 to March 2020 and were analyzed from approximately March 2020 to March 2021. Main Outcomes and Measures: Critical measures included the proportion of responses centered around the initial direction vs the subsequent changed direction and the overall precision of motion perception and reaction times. Results: A total of 48 participants were included in the PSZ group (31 [65%] male; mean [SD] age, 36.56 [9.76] years) and 36 in the HC group (22 [61%] male; mean [SD] age, 35.67 [10.74] years) in the original sample. An independent replication sample included 42 participants in the PSZ group (29 [69%] male; mean [SD] age, 33.98 [11.03] years) and 34 in the HC group (20 [59%] male; mean [SD] age, 34.29 [10.44] years). In line with previous research, patients with PSZ were less precise and had slower reaction times overall. The key finding was that patients with PSZ were significantly more likely (original sample: mean, 27.88 [95% CI, 24.19-31.57]; replication sample: mean, 26.70 [95% CI, 23.53-29.87]) than HC participants (original sample: mean, 18.86 [95% CI, 16.56-21.16]; replication sample: mean, 15.67 [95% CI, 12.61-18.73]) to report the initial motion direction rather than the final one. Moreover, the tendency to report the direction of initial motion correlated with the degree of conviction on the Peters Delusions Inventory (original sample: r = 0.32 [P = .05]; replication sample: r = 0.30 [P = .05]) and the Brief Psychiatric Rating Scale Reality Distortion score (original sample: r = 0.55 [P = .001]; replication sample: r = 0.35 [P = .03]) and severity of hallucinations (original sample: r = 0.39 [P = .02]; replication sample: r = 0.30 [P = .05]). Conclusions and Relevance: The findings of this case-control study suggest that the severity of psychotic symptoms is associated with a tendency to overweight initial information over incoming sensory evidence. These results are consistent with predictive coding accounts of the origins of positive symptoms and suggest that deficits in very elementary perceptual updating may be a critical mechanism in psychosis.

Global prefrontal and fronto-amygdala dysconnectivity in bipolar I disorder with psychosis history.

BACKGROUND: Pathophysiological models of bipolar disorder postulate that mood dysregulation arises from fronto-limbic dysfunction, marked by reduced prefrontal cortex (PFC) inhibitory control. This might occur due to both disruptions within PFC networks and abnormal inhibition over subcortical structures involved in emotional processing. However, no study has examined global PFC dysconnectivity in bipolar disorder and tested whether regions with within-PFC dysconnectivity also exhibit fronto-limbic connectivity deficits. Furthermore, no study has investigated whether such connectivity disruptions differ for bipolar patients with psychosis history, who might exhibit a more severe clinical course. METHODS: We collected resting-state functional magnetic resonance imaging at 3T in 68 remitted bipolar I patients (34 with psychosis history) and 51 demographically matched healthy participants. We employed a recently developed global brain connectivity method, restricted to PFC (rGBC). We also independently tested connectivity between anatomically defined amygdala and PFC. RESULTS: Bipolar patients exhibited reduced medial prefrontal cortex (mPFC) rGBC, increased amygdala-mPFC connectivity, and reduced connectivity between amygdala and dorsolateral PFC. All effects were driven by psychosis history. Moreover, the magnitude of observed effects was significantly associated with lifetime psychotic symptom severity. CONCLUSIONS: This convergence between rGBC, seed-based amygdala findings, and symptom severity analyses highlights that mPFC, a core emotion regulation region, exhibits both within-PFC dysconnectivity and connectivity abnormalities with limbic structures in bipolar illness. Furthermore, lateral PFC dysconnectivity in patients with psychosis history converges with published work in schizophrenia, indicating possible shared risk factors. Observed dysconnectivity in remitted patients suggests a bipolar trait characteristic and might constitute a risk factor for phasic features of the disorder.