Neurocomputational model of compulsivity: deviating from an uncertain goal-directed system.

Despite a theory that an imbalance in goal-directed versus habitual systems serve as building blocks of compulsions, research has yet to delineate how this occurs during arbitration between the two systems in obsessive-compulsive disorder. Inspired by a brain model in which the inferior frontal cortex selectively gates the putamen to guide goal-directed or habitual actions, this study aimed to examine whether disruptions in the arbitration process via the fronto-striatal circuit would underlie imbalanced decision-making and compulsions in patients. Thirty patients with obsessive-compulsive disorder [mean (standard deviation) age = 26.93 (6.23) years, 12 females (40%)] and 30 healthy controls [mean (standard deviation) age = 24.97 (4.72) years, 17 females (57%)] underwent functional MRI scans while performing the two-step Markov decision task, which was designed to dissociate goal-directed behaviour from habitual behaviour. We employed a neurocomputational model to account for an uncertainty-based arbitration process, in which a prefrontal arbitrator (i.e. inferior frontal gyrus) allocates behavioural control to a more reliable strategy by selectively gating the putamen. We analysed group differences in the neural estimates of uncertainty of each strategy. We also compared the psychophysiological interaction effects of system preference (goal-directed versus habitual) on fronto-striatal coupling between groups. We examined the correlation between compulsivity score and the neural activity and connectivity involved in the arbitration process. The computational model captured the subjects' preferences between the strategies. Compared with healthy controls, patients had a stronger preference for the habitual system (t = -2.88, P = 0.006), which was attributed to a more uncertain goal-directed system (t = 2.72, P = 0.009). Before the allocation of controls, patients exhibited hypoactivity in the inferior frontal gyrus compared with healthy controls when this region tracked the inverse of uncertainty (i.e. reliability) of goal-directed behaviour (P = 0.001, family-wise error rate corrected). When reorienting behaviours to reach specific goals, patients exhibited weaker right ipsilateral ventrolateral prefronto-putamen coupling than healthy controls (P = 0.001, family-wise error rate corrected). This hypoconnectivity was correlated with more severe compulsivity (r = -0.57, P = 0.002). Our findings suggest that the attenuated top-down control of the putamen by the prefrontal arbitrator underlies compulsivity in obsessive-compulsive disorder. Enhancing fronto-striatal connectivity may be a potential neurotherapeutic approach for compulsivity and adaptive decision-making.

Psychometrics of the Korean Version of the screen for adult anxiety related disorders (SCAARED).

BACKGROUND: For enhanced management of anxiety disorders, early screening and accurate diagnostic differentiation are essential. The Screen for Adult Anxiety Related Disorders (SCAARED) has been developed to identify and categorize anxiety disorders, thereby facilitating timely and appropriate interventions. In line with this, we aimed to translate and validate the Korean version of the SCAARED questionnaire for the Korean population. METHODS: The original SCAARED was translated into Korean and administered to community adult population (N = 119) ages 18-45 years old in South Korea. The internal consistency and test-retest reliability of the SCAARED were evaluated. In addition, its factor structure was examined using confirmatory and exploratory factor analysis. Concurrent validity was evaluated by comparing SCAARED with the Depression, Anxiety and Stress Scale-21 (DASS), the Beck's Anxiety Inventory (BAI) and the State-Trait Anxiety Inventory (STAI). Test-retest reliability was evaluated one week after the first assessment. RESULTS: The SCAARED showed good internal consistency (Cronbach's α = 0.945) and test-retest reliability (γ = 0.883). The SCAARED had significant correlation with DASS-21 subscales (γ = 0.655-0.701), BAI (γ = 0.788) and STAI subscales (γ = 0.548-0.736), confirming good concurrent validity. The results of the Exploratory Factor Analysis showed four factors comparable to the original SCAARED (Generalized anxiety, Somatic/Panic/Agoraphobia, Social anxiety, and Separation anxiety). The area under the curve of the receiver operating characteristic of total and each of the factor scores ranged from 0.724 to 0.942. CONCLUSIONS: The Korean version of the SCAARED is a reliable and valid instrument to screen for anxiety disorders in the Korean adult populations.

Alteration in left frontoparietal connectivity correlates with impaired cognitive reappraisal in early psychosis.

BACKGROUND: Impaired cognitive reappraisal is a notable symptom of early psychosis, but its neurobiological basis remains underexplored. We aimed to identify the underlying neurobiological mechanism of this impairment by using resting-state functional connectivity (FC) analyses focused on brain regions related to cognitive reappraisal. METHODS: Resting-state functional magnetic resonance images were collected from 36 first-episode psychosis (FEP) patients, 32 clinical high-risk (CHR) individuals, and 48 healthy controls (HCs). Whole-brain FC maps using seed regions associated with cognitive reappraisal were generated and compared across the FEP, CHR and HC groups. We assessed the correlation between resting-state FC, reappraisal success ratio, positive symptom severity and social functioning controlling for covariates. RESULTS: FEP patients showed higher FC between the left superior parietal lobe and left inferior frontal gyrus than HCs. Higher FC between the left superior parietal lobe and left inferior frontal gyrus negatively correlated with the reappraisal success ratio in the FEP group after controlling for covariates. Lower FC correlated with lower positive symptom severity and improved global functioning in the FEP group. CONCLUSIONS: Alteration in left frontoparietal connectivity reflects impaired cognitive reappraisal in early psychosis, and such alteration correlates with increased positive symptoms and decreased global functioning. These findings offer a potential path for interventions targeting newly emerging symptoms in the early stages of psychosis.

In Vivo Reactive Astrocyte Imaging in Patients With Schizophrenia Using Fluorine 18-Labeled THK5351.

Importance: In vivo imaging studies of reactive astrocytes are crucial for understanding the pathophysiology of schizophrenia because astrocytes play a critical role in glutamate imbalance and neuroinflammation. Objective: To investigate in vivo reactive astrocytes in patients with schizophrenia associated with positive symptoms using monoamine oxidase B (MAO-B)-binding fluorine 18 ([18F])-labeled THK5351 positron emission tomography (PET). Design, Setting, and Participants: In this case-control study, data were collected from October 1, 2021, to January 31, 2023, from the internet advertisement for the healthy control group and from the outpatient clinics of Seoul National University Hospital in Seoul, South Korea, for the schizophrenia group. Participants included patients with schizophrenia and age- and sex-matched healthy control individuals. Main Outcomes and Measures: Standardized uptake value ratios (SUVrs) of [18F]THK5351 in the anterior cingulate cortex (ACC) and hippocampus as primary regions of interest (ROIs), with other limbic regions as secondary ROIs, and the correlation between altered SUVrs and Positive and Negative Syndrome Scale (PANSS) positive symptom scores. Results: A total of 68 participants (mean [SD] age, 32.0 [7.0] years; 41 men [60.3%]) included 33 patients with schizophrenia (mean [SD] age, 32.3 [6.3] years; 22 men [66.7%]) and 35 healthy controls (mean [SD] age, 31.8 [7.6] years; 19 men [54.3%]) who underwent [18F]THK5351 PET scanning. Patients with schizophrenia showed significantly higher SUVrs in the bilateral ACC (left, F = 5.767 [false discovery rate (FDR)-corrected P = .04]; right, F = 5.977 [FDR-corrected P = .04]) and left hippocampus (F = 4.834 [FDR-corrected P = .04]) than healthy controls. Trend-level group differences between the groups in the SUVrs were found in the secondary ROIs (eg, right parahippocampal gyrus, F = 3.387 [P = .07]). There were positive correlations between the SUVrs in the bilateral ACC and the PANSS positive symptom scores (left, r = 0.423 [FDR-corrected P = .03]; right, r = 0.406 [FDR-corrected P = .03]) in patients with schizophrenia. Conclusions and Relevance: This case-control study provides novel in vivo imaging evidence of reactive astrocyte involvement in the pathophysiology of schizophrenia. Reactive astrocytes in the ACC may be a future target for the treatment of symptoms of schizophrenia, especially positive symptoms.