Social interaction is impaired in schizophrenia, including the use of hand gestures, which is linked to poor social perception and outcome. Brain imaging suggests reduced neural activity in a left-lateralized frontoparietal network during gesture preparation; therefore, gesturing might be improved through facilitation of left hemispheric brain areas or via disruption of interhemispheric inhibition from the right homolog. This study tested whether repetitive transcranial magnetic stimulation (rTMS) protocols would improve gesture performance in schizophrenia. This randomized, placebo-controlled, double-blind, crossover trial applied 3 different protocols of rTMS separated by 48 h. Twenty right-handed schizophrenia patients and 20 matched healthy controls received facilitatory intermittent theta burst stimulation (iTBS) over the left inferior frontal gyrus (IFG), inhibitory continuous theta burst stimulation (cTBS) over right inferior parietal lobe (IPL), and placebo over left IPL in randomized order. Primary outcome was change in the test of upper limb apraxia (TULIA), rated from video recordings of hand gesture performance. Secondary outcome was change in manual dexterity using the coin rotation task. Participants improved on both tasks following rTMS compared with baseline. Only patients improved gesture performance following right IPL cTBS compared with placebo (P = .013). The results of the coin rotation parallel those of the TULIA, with improvements following right IPL cTBS in patients (P = .001). Single sessions of cTBS on the right IPL substantially improved both gesture performance accuracy and manual dexterity. The findings point toward an inhibition of interhemispheric rivalry as a potential mechanism of action.

Paranoia is a frequent and highly distressing experience in psychosis. Models of paranoia suggest limbic circuit pathology. Here, we tested whether resting-state functional connectivity (rs-fc) in the limbic circuit was altered in schizophrenia patients with current paranoia. We collected MRI scans in 165 subjects including 89 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, brief psychotic disorder, schizophreniform disorder) and 76 healthy controls. Paranoia was assessed using a Positive And Negative Syndrome Scale composite score. We tested rs-fc between bilateral nucleus accumbens, hippocampus, amygdala and orbitofrontal cortex between groups and as a function of paranoia severity. Patients with paranoia had increased connectivity between hippocampus and amygdala compared to patients without paranoia. Likewise, paranoia severity was linked to increased connectivity between hippocampus and amygdala. Furthermore, paranoia was associated with increased connectivity between orbitofrontal and medial prefrontal cortex. In addition, patients with paranoia had increased functional connectivity within the frontal hubs of the default mode network compared to healthy controls. These results demonstrate that current paranoia is linked to aberrant connectivity within the core limbic circuit and prefrontal cortex reflecting amplified threat processing and impaired emotion regulation. Future studies will need to explore the association between limbic hyperactivity, paranoid ideation and perceived stress.

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Objectives Psychomotor slowing (PS) occurs in up to half of schizophrenia patients and is linked to poorer outcomes. As standard treatment fails to improve PS, novel approaches are needed. Here, we applied the RDoC framework using 3 units of analysis, ie, behavior, self-report, and physiology to test, whether patients with PS are different from patients without PS and controls. Methods Motor behavior was compared between 71 schizophrenia patients with PS, 25 without PS, and 42 healthy controls (HC) using 5 different measures: (1) for behavior, an expert rating scale: Motor score of the Salpêtrière Retardation Rating Scale, (2) for self-report, the International Physical Activity Questionnaire; and for physiology, (3) Actigraphy, which accounts for gross motor behavior, (4) Gait velocity, and (5) coin rotation task to assess manual dexterity. Results The ANCOVAs comparing the 3 groups revealed differences between patients with PS and HC in expert ratings, self-report, and instrumental measures (all P ≤ .001). Patients with PS also scored higher in expert ratings and had lower instrumental activity levels compared to patients without PS (all P ≤ .045). Instrumental activity levels correlated with an expert rating of PS (rho = −0.51, P-fdr corrected <.001) and classified similarly at 72% accuracy. Conclusions PS is characterized by slower gait, lower activity levels, and slower finger movements compared to HC. However, only actigraphy and observer ratings enable to clearly disentangle PS from non-PS patients. Actigraphy may become the standard assessment of PS in neuroimaging studies and clinical trials.

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ObjectiveCatatonia is a neuropsychiatric syndrome, with important psychomotor features, associated with schizophrenia and other psychiatric disorders. The syndrome comprises multiple symptoms including abnormal motor control, behaviors, volition, and autonomic regulation. Catatonia assessment relies on clinical rating scales and clinicians familiar with the catatonia exam. However, objective instrumentation may aid the detection of catatonia. We aimed to investigate the relationship between movement parameters derived from actigraphy and expert ratings of catatonia symptoms measured by the Bush Francis Catatonia Rating Scale (BFCRS) and the Northoff Catatonia scale (NCS).MethodsEighty-six acutely ill inpatients with schizophrenia spectrum disorders were assessed with the BFCRS, the NCS, and 24 h continuous actigraphy. Non-wear and sleep periods were removed from the actigraphy data prior to analysis. Associations between total catatonia scores, derived from both BFCRS and NCS, and actigraphy parameters as well as between single BFCRS items and actigraphy parameters were calculated using Spearman's rank correlation and non-parametric ANCOVAs (Quade's ANCOVAs), respectively.ResultsBoth higher BFCRS total scores (r = 0.369, p = 0.006) and NCS total scores (r = 0.384, p = 0.004) were associated with lower activity levels (AL). Higher scores on single BFCRS items such as immobility/stupor or staring were linked to lower AL (immobility/stupor: F = 17.388, p < 0.001, η2 = 0.175; staring: F = 7.849, p = 0.001, η2 = 0.162) and lower metabolic equivalents of task (MET).ConclusionSpecific catatonia symptoms such as immobility/stupor and staring can be measured with actigraphy. This may aid the detection, staging, and monitoring of catatonia in clinical settings.

Measuring brain activity during functional MRI (fMRI) tasks is one of the main tools to identify brain biomarkers of disease or neural substrates associated with specific symptoms. However, identifying correct biomarkers relies on reliable measures. Recently, poor reliability was reported for task-based fMRI measures. The present study aimed to demonstrate the reliability of a finger-tapping fMRI task across two sessions in healthy participants. Thirtyone right-handed healthy participants aged 18-60 years took part in two MRI sessions 3 weeks apart during which we acquired finger-tapping task-fMRI.We examined the overlap of activations between sessions using Dice similarity coefficients, assessing their location and extent. Then, we compared amplitudes calculating intraclass correlation coefficients (ICCs) in three sets of regions of interest (ROIs) in the motor network: literature-based ROIs (10-mm-radius spheres centred on peaks of an activation likelihood estimation), anatomical ROIs (regions as defined in an atlas) and ROIs based on conjunction analyses (superthreshold voxels in both sessions). Finger tapping consistently activated expected regions, for example, left primary sensorimotor cortices, premotor area and right cerebellum. We found good-to-excellent overlap of activations for most contrasts (Dice coefficients: .54-.82). Across time, ICCs showed large variability in all ROI sets (.04-.91). However, ICCs in most ROIs indicated fair-to-good reliability (mean = .52). The least specific contrast consistently yielded the best reliability. Overall, the finger-tapping task showed good spatial overlap and fair reliability of amplitudes on group level.