Test-retest reliability of resting-state cerebral blood flow quantification using pulsed Arterial Spin Labeling (PASL) over 3 weeks vs 8 weeks in healthy controls.

Arterial Spin Labeling is a valuable functional imaging tool for both clinical and research purposes. However, little is known about the test-retest reliability of cerebral blood flow measurements over longer periods. In this study, we investigated the reliability of pulsed Arterial Spin Labeling in assessing cerebral blood flow over a 3 (n = 28) vs 8 (n = 19) weeks interscan interval in 47 healthy participants. As a measure of cerebral blood flow reliability, we calculated voxel-wise, whole-brain, and regions of interest intraclass correlation coefficients. The whole-brain mean resting-state cerebral blood flow showed good to excellent reliability over time for both periods (intraclass correlation coefficients = 0.85 for the 3-week delay, intraclass correlation coefficients = 0.53 for the 8-week delay). However, the voxel-wise and regions of interest intraclass correlation coefficients fluctuated at 8-week compared to the 3-week interval, especially within cortical areas. These results confirmed previous findings that Arterial Spin Labeling could be used as a reliable method to assess brain perfusion. However, as the reliability seemed to decrease over time, caution is warranted when performing correlations with other variables, especially in clinical populations.

The pathobiology of psychomotor slowing in psychosis: altered cortical excitability and connectivity.

Psychomotor slowing is a frequent symptom of schizophrenia. Short-interval intracortical inhibition assessed by transcranial magnetic stimulation demonstrated inhibitory dysfunction in schizophrenia. The inhibitory deficit results from additional noise during information processing in the motor system in psychosis. Here, we tested whether cortical inhibitory dysfunction was linked to psychomotor slowing and motor network alterations. In this cross-sectional study, we included 60 patients with schizophrenia and psychomotor slowing determined by the Salpêtrière Retardation Rating Scale, 23 patients without slowing and 40 healthy control participants. We acquired single and double-pulse transcranial magnetic stimulation effects from the left primary motor cortex, resting-state functional connectivity and diffusion imaging on the same day. Groups were compared on resting motor threshold, amplitude of the motor evoked potentials, as well as short-interval intracortical inhibition. Regression analyses calculated the association between motor evoked potential amplitudes or cortical inhibition with seed-based resting-state functional connectivity from the left primary motor cortex and fractional anisotropy at whole brain level and within major motor tracts. In patients with schizophrenia and psychomotor slowing, we observed lower amplitudes of motor evoked potentials, while the short-interval intracortical inhibition/motor evoked potentials amplitude ratio was higher than in healthy controls, suggesting lower cortical inhibition in these patients. Patients without slowing also had lower amplitudes of motor evoked potentials. Across the combined patient sample, cortical inhibition deficits were linked to more motor coordination impairments. In patients with schizophrenia and psychomotor slowing, lower amplitudes of motor evoked potentials were associated with lower fractional anisotropy in motor tracts. Moreover, resting-state functional connectivity between the primary motor cortex, the anterior cingulate cortex and the cerebellum increased with stronger cortical inhibition. In contrast, in healthy controls and patients without slowing, stronger cortical inhibition was linked to lower resting-state functional connectivity between the left primary motor cortex and premotor or parietal cortices. Psychomotor slowing in psychosis is linked to less cortical inhibition and aberrant functional connectivity of the primary motor cortex. Higher neural noise in the motor system may drive psychomotor slowing and thus may become a treatment target.

Psychomotor Slowing in Psychosis and Inhibitory Repetitive Transcranial Magnetic Stimulation: A Randomized Clinical Trial.

Importance: Psychomotor slowing is a frequent symptom of psychosis, impairing gross and fine motor behavior. It is associated with poor outcomes and functioning, and no treatment is available. Objective: To investigate whether 15 sessions of inhibitory repetitive transcranial magnetic stimulation (rTMS) may reduce psychomotor slowing. Design, Setting, and Participants: This was a 4-arm, double-blind, randomized, sham-controlled trial at a university hospital in Switzerland. Enrollment took place from March 2019 to August 2022. Adults aged 18 to 60 years with schizophrenia spectrum disorders and severe psychomotor slowing were eligible. All patients continued existing medications, including antipsychotics and benzodiazepines. Those with substance misuse (other than nicotine), conditions associated with impaired or aberrant movement, convulsions, history of hearing problems, other conditions typically excluded from magnetic resonance imaging or TMS, any TMS treatment in the past 3 months, or those who were pregnant or breastfeeding were excluded. Of 615 patients screened for eligibility, 103 were randomized and 88 received at least 1 session of rTMS: 22 were assigned to 1-Hz rTMS, 22 to iTBS, 22 to sham, and 22 to the waiting group. Follow-up was conducted at 6 weeks and 24 weeks following the week 3 assessments including clinical, functional, and motor measures. Interventions: Fifteen sessions of rTMS in 3 weeks over the supplementary motor area: 1-Hz rTMS, iTBS, sham, or no treatment (waiting). After 3 weeks, the waiting group received 15 sessions of 1-Hz rTMS over the supplementary motor area. Main Outcomes and Measures: The main outcome was the proportion of responders at week 3 in the Salpêtrière Retardation Rating Scale (SRRS) defined as a 30% or greater reduction from baseline (last-observation-carried-forward). The SRRS has 15 items and a maximum total score of 60. Results: Of the 88 participants analyzed, 45 were men and 43 were women. The mean (SD) age was 36.3 (12.4) years and the mean (SD) SRRS score was 24.0 (5.9). A total of 69 participants completed the study. At week 3, response rates differed between groups: 15 of 22 (68%) in the 1-Hz rTMS group, 8 of 22 (36%) in the iTBS group, 7 of 22 (32%) in the sham group, and 4 of 22 (18%) in the waiting group (χ23 = 12.1; P = .007). The 1-Hz rTMS group had more responders than sham (odds ratio [OR], 0.13; 95% CI, 0.02-0.65; P = .03), iTBS (OR, 0.12; 95% CI, 0.02-0.61; P = .02), and waiting (OR, 0.04; 95% CI, 0.01-0.22; P = .003). In the waiting group, 10 of 16 participants (63%) responded after receiving 15 sessions of 1-Hz rTMS. No serious adverse events occurred. Conclusions and Relevance: In this study, inhibitory add-on rTMS safely alleviated psychomotor slowing in psychosis compared with iTBS, sham, and no treatment. The treatment was also effective with delayed onset. Future studies need to explore the neural changes associated with supplementary motor area rTMS in psychosis. Trial Registration: ClinicalTrials.gov Identifier: NCT03921450.

External Validation of the SMART Medical Clearance Form for Emergency Patients With Psychiatric Manifestations.

BACKGROUND: The SMART Medical Clearance Form, developed in the USA, is used to standardize the medical evaluation of emergency patients with primarily psychiatric manifestations. The goal of this study was external validation of the use of this form. METHODS: Data were collected retrospectively on emergency patients with psychiatric manifestations. The combined primary clinical endpoint consisted of hospitalization, repeated presentation to the emergency room, and/or death within 30 days. RESULTS: From September 2019 to June 2022, 2404 patients presented with psychiatric manifestations to the emergency room of the Cantonal Hospital of Lucerne, Switzerland, of whom 674 were included in the study. 134 did not satisfy any of the parameters of the SMART Medical Clearance Form (the nSMART group), while 540 satisfied at least one parameter (the pSMART group). In the nSMART group, there were no hospitalizations for a medical indication, no repeated presentations for medical reasons, and no deaths within 30 days. In the pSMART group, there were 90 hospitalizations, 4 repeated presentations, and 4 deaths within 30 days. Although 44% of the patients in the nSMART group underwent further diagnostic studies, such as imaging or laboratory tests, none of these studies led to any change in these patients' further clinical management. CONCLUSION: Use of the SMART Medical Clearance Form apparently enables safe standardized processing of patients with psychiatric manifestations in the emergency room.

The neural signature of psychomotor disturbance in depression.

Up to 70% of patients with major depressive disorder present with psychomotor disturbance (PmD), but at the present time understanding of its pathophysiology is limited. In this study, we capitalized on a large sample of patients to examine the neural correlates of PmD in depression. This study included 820 healthy participants and 699 patients with remitted (n = 402) or current (n = 297) depression. Patients were further categorized as having psychomotor retardation, agitation, or no PmD. We compared resting-state functional connectivity (ROI-to-ROI) between nodes of the cerebral motor network between the groups, including primary motor cortex, supplementary motor area, sensory cortex, superior parietal lobe, caudate, putamen, pallidum, thalamus, and cerebellum. Additionally, we examined network topology of the motor network using graph theory. Among the currently depressed 55% had PmD (15% agitation, 29% retardation, and 11% concurrent agitation and retardation), while 16% of the remitted patients had PmD (8% retardation and 8% agitation). When compared with controls, currently depressed patients with PmD showed higher thalamo-cortical and pallido-cortical connectivity, but no network topology alterations. Currently depressed patients with retardation only had higher thalamo-cortical connectivity, while those with agitation had predominant higher pallido-cortical connectivity. Currently depressed patients without PmD showed higher thalamo-cortical, pallido-cortical, and cortico-cortical connectivity, as well as altered network topology compared to healthy controls. Remitted patients with PmD showed no differences in single connections but altered network topology, while remitted patients without PmD did not differ from healthy controls in any measure. We found evidence for compensatory increased cortico-cortical resting-state functional connectivity that may prevent psychomotor disturbance in current depression, but may perturb network topology. Agitation and retardation show specific connectivity signatures. Motor network topology is slightly altered in remitted patients arguing for persistent changes in depression. These alterations in functional connectivity may be addressed with non-invasive brain stimulation.

Neural Correlates of Formal Thought Disorder Dimensions in Psychosis.

BACKGROUND AND HYPOTHESIS: Formal thought disorder (FTD) is a core symptom of psychosis, but its neural correlates remain poorly understood. This study tested whether four FTD dimensions differ in their association with brain perfusion and brain structure. STUDY DESIGN: This cross-sectional study investigated 110 patients with schizophrenia spectrum disorders using 3T magnetic resonance imaging (MRI). The Thought and Language Disorder scale (TALD) was utilized, which comprises four subscales: Objective Positive (OP), Objective Negative (ON), Subjective Positive (SP), and Subjective Negative (SN). Resting-state cerebral blood flow (rsCBF), cortical thickness (CortTh), gray matter volume (GMV), and diffusion MRI tractography were tested for associations with TALD subscales controlling for age, medication, total intracranial volume, and for variance of the 3 other TALD subscales. STUDY RESULTS: Following Bonferroni correction, the FTD dimensions presented distinct neural correlates. OP scores were associated with increased rsCBF and increased GMV in the right cerebellum lingual gyrus. Higher SP scores were linked to increased GMV in bilateral prefrontal cortex. In contrast, ON was associated with increased GMV in the right premotor cortex. At more liberal statistical thresholds, higher SP was associated with increased CortTh in the right inferior frontal gyrus, whereas SN scores were linked to decreased GMV in the right prefrontal lobe, the left inferior temporal gyrus, and the left supplementary motor area. Unadjusted analyses mostly corroborated these findings. CONCLUSION: These findings stress the heterogeneity in FTD, suggesting distinct neural patterns for specific FTD experiences. In sum, FTD in psychosis may require distinct treatment strategies and further mechanistic investigations on single-item levels.

Test-retest reliability of a finger-tapping fMRI task in a healthy population.

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. Thirty-one 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. Although caution is warranted in interpreting correlations of activations with other variables, identification of activated regions in response to a task and their between-group comparisons are still valid and important modes of analysis in neuroimaging to find population tendencies and differences.

The Behavioral Mapping of Psychomotor Slowing in Psychosis Demonstrates Heterogeneity Among Patients Suggesting Distinct Pathobiology.

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.

Psychomotor slowing alters gait velocity, cadence, and stride length and indicates negative symptom severity in psychosis.

Schizophrenia is a severe mental disorder, in which 50% of the patients present with motor abnormalities such as psychomotor slowing. Slow spontaneous gait has been reported in schizophrenia. However, comprehensive objective instrumental assessments of multiple gait conditions are missing. Finally, the specific gait patterns of subjects with psychomotor slowing are still unknown. Therefore, this study aimed to objectively assess multiple gait parameters at different walking conditions in patients with schizophrenia with and without psychomotor slowing. Also, we hypothesised gait impairments to correlate with expert ratings of hypokinetic movement disorders and negative symptoms. We collected gait data (GAITRite®) in 70 patients with psychomotor slowing (SRRS (Salpetriere retardation rating scale) ≥15), 22 non-psychomotor slowed patients (SRRS < 15), and 42 healthy controls. Participants performed four walking conditions (self-selected speed, maximum speed, head reclined, and eyes closed) and six gait parameters were extracted (velocity, cadence, stride length, functional ambulation profile (FAP), and variance of stride length and time). Patients with psychomotor slowing presented slower velocity, lower cadence, and shorter stride length in all walking conditions compared to healthy controls, with the non-slowed patients in an intermediate position (all F > 16.18, all p < 0.001). Secondly, slower velocity was associated with more severe hypokinetic movement disorders and negative symptoms. In conclusion, gait impairments exist in a spectrum with healthy controls on one end and patients with psychomotor slowing on the other end. Patients with psychomotor slowing are specifically impaired when an adaptation of gait patterns is required, contributing to the deleterious effects of sedentary behaviours.

Structural alterations of the motor cortex and higher order cortical areas suggest early neurodevelopmental origin of catatonia in schizophrenia.

The neurobiology of catatonia is still poorly understood. Particularly structural MRI studies yielded conflicting results. Heterogeneity of findings was suggested to stem from specifics of different rating scales. This study sought to test grey matter differences between patients with catatonia, patients without catatonia, and healthy controls using the two main instruments of catatonia rating. We included 98 patients with schizophrenia spectrum disorders and 42 healthy controls. Catatonia was measured using the Bush Francis Catatonia Rating Scale and the Northoff Catatonia Rating Scale. According to these scales, patients were classified into those with and those without catatonia. We tested whole brain grey matter volume, cortical thickness, and local gyrification across groups. Both catatonia rating scales correlated at tau = 0.65 but failed to classify identical subjects as catatonia patients. However, group differences in grey matter parameters were broadly similar with either rating scale to identify catatonia cases. Catatonia patients had reduced grey matter volume compared to controls in a large network including orbitofrontal cortex, cingulate, thalamus, and amygdala. While there was no group difference in cortical thickness, catatonia patients had increased local gyrification in premotor, motor, and parietal cortices compared to controls. Hypergyrification of the motor cortex and higher order cortical areas was found in catatonia patients compared to patients without catatonia. Both catatonia rating scales find similar symptom severity and group differences in grey matter indices. Catatonia is linked to reduced grey matter volume and increased local gyrification, suggesting some impact of early neurodevelopmental insults.

Actigraphically measured psychomotor slowing in depression: systematic review and meta-analysis.

Psychomotor slowing is a key feature of depressive disorders. Despite its great clinical importance, the pathophysiology and prevalence across different diagnoses and mood states are still poorly understood. Actigraphy allows unbiased, objective, and naturalistic assessment of physical activity as a marker of psychomotor slowing. Yet, the true effect-sizes remain unclear as recent, large systematic reviews are missing. We conducted a novel meta-analysis on actigraphically measured slowing in depression with strict inclusion and exclusion criteria for diagnosis ascertainment and sample duplications. Medline/PubMed and Web-of-Science were searched with terms combining mood-keywords and actigraphy-keywords until September 2021. Original research measuring actigraphy for ⩾24 h in at least two groups of depressed, remitted, or healthy participants and applying operationalized diagnosis was included. Studies in somatically ill patients, N < 10 participants/group, and studies using consumer-devices were excluded. Activity-levels between groups were compared using random-effects models with standardized-mean-differences and several moderators were examined. In total, 34 studies (n = 1804 patients) were included. Patients had lower activity than controls [standardized mean difference (s.m.d.) = -0.78, 95% confidence interval (CI) -0.99 to -0.57]. Compared to controls, patients with unipolar and bipolar disorder had lower activity than controls whether in depressed (unipolar: s.m.d. = -0.82, 95% CI -1.07 to -0.56; bipolar: s.m.d. = -0.94, 95% CI -1.41 to -0.46), or remitted/euthymic mood (unipolar: s.m.d. = -0.28, 95% CI -0.56 to 0.0; bipolar: s.m.d. = -0.92, 95% CI -1.36 to -0.47). None of the examined moderators had any significant effect. To date, this is the largest meta-analysis on actigraphically measured slowing in mood disorders. They are associated with lower activity, even in the remitted/euthymic mood-state. Studying objective motor behavior via actigraphy holds promise for informing screening and staging of affective disorders.

Motor abnormalities are associated with poor social and functional outcomes in schizophrenia.

BACKGROUND: Up to 50% of patients with schizophrenia are suffering from motor abnormalities, which may contribute to decreased quality of life, impaired work capacity, and a reduced life expectancy by 10-20 years. However, the effect of motor abnormalities on social and global functioning, as well as, functional capacity is not clear. We hypothesized, that the presence of motor abnormalities is associated with poorer functional outcomes in patients with schizophrenia. METHODS: We collected data on 5 different motor abnormalities in 156 patients suffering from schizophrenia spectrum disorders: parkinsonism, catatonia, dyskinesia, neurological soft signs and psychomotor slowing (PS). Additionally, we used three different scales to evaluate the functional outcomes in these patients: the Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS) which use clinicians' judgment; and one using a performance-based measure of functional capacity, the brief version of the UCSD Performance-based Skills Assessment (UPSA-B). RESULTS: Our analysis demonstrated that patients with catatonia (all F > 4.5; p < 0.035) and parkinsonism (all F > 4.9; p < 0.027) scored lower on GAF and SOFAS compared to patients without catatonia and parkinsonism. In contrast, no significant difference on functional outcomes between patients with dyskinesia versus without dyskinesia exist in our study. Furthermore, there are statistically significant negative correlations for parkinsonism and PS with GAF, SOFAS and UPSA-B (all tau are at least -0.152, p-value <0.036). We also found significant negative correlations between catatonia and both GAF & SOFAS (all tau are at least -0.203, p-value<0.001) and between NES and SOFAS (tau = -0.137, p-value = 0.033). CONCLUSION: Here, we showed that four of the most common motor abnormalities observed in schizophrenia were associated with at least one of the patients' functional outcomes. The stronger the motor impairment was the worse the global and social functioning. Future studies need to test, whether amelioration of motor abnormalities is linked to improved community functioning.

Limbic links to paranoia: increased resting-state functional connectivity between amygdala, hippocampus and orbitofrontal cortex in schizophrenia patients with paranoia.

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.

Altered central pain processing in fibromyalgia-A multimodal neuroimaging case-control study using arterial spin labelling.

Fibromyalgia is characterized by chronic pain and a striking discrepancy between objective signs of tissue damage and severity of pain. Function and structural alterations in brain areas involved in pain processing may explain this feature. Previous case-control studies in fibromyalgia focused on acute pain processing using experimentally-evoked pain paradigms. Yet, these studies do not allow conclusions about chronic, stimulus-independent pain. Resting-state cerebral blood flow (rsCBF) acquired by arterial spin labelling (ASL) may be a more accurate marker for chronic pain. The objective was to integrate four different functional and structural neuroimaging markers to evaluate the neural correlate of chronic, stimulus-independent pain using a resting-state paradigm. In line with the pathophysiological concept of enhanced central pain processing we hypothesized that rsCBF is increased in fibromyalgia in areas involved in processing of acute pain. We performed an age matched case-control study of 32 female fibromyalgia patients and 32 pain-free controls and calculated group differences in rsCBF, resting state functional connectivity, grey matter volume and cortical thickness using whole-brain and region of interest analyses. We adjusted all analyses for depression and anxiety. As centrally acting drugs are likely to interfere with neuroimaging markers, we performed a subgroup analysis limited to patients not taking such drugs. We found no differences between cases and controls in rsCBF of the thalamus, the basal ganglia, the insula, the somatosensory cortex, the prefrontal cortex, the anterior cingulum and supplementary motor area as brain areas previously identified to be involved in acute processing in fibromyalgia. The results remained robust across all neuroimaging markers and when limiting the study population to patients not taking centrally acting drugs and matched controls. In conclusion, we found no evidence for functional or structural alterations in brain areas involved in acute pain processing in fibromyalgia that could reflect neural correlates of chronic stimulus-independent pain.

Nonverbal communication remains untouched: No beneficial effect of symptomatic improvement on poor gesture performance in schizophrenia.

BACKGROUND: Gestures are an important part of communication. Patients with schizophrenia present gesture deficits that tend to deteriorate in the course of the disease and hamper functional outcome. This gesture deficit has been associated with motor abnormalities, cognitive impairment, and psychotic symptoms. Unaffected, first-degree relatives of schizophrenia patients share some subclinical motor and cognitive abnormalities. We aimed to investigate, whether gesture performance changes with symptomatic improvement in patients, and to test the longitudinal performance in unaffected, first-degree relatives. METHODS: In this study, we measured gesture performance using a validated test in 33 patients, 29 first-degree relatives and 38 healthy controls. Measurements were completed shortly after admission and before discharge in patients. Performance was rated blindly by experts using video recordings of the gesture task. Additionally, we evaluated cognitive function and psychotic symptoms at both visits. RESULTS: Gesture performance was poorer in relatives compared to controls and poorer in patients compared to both relatives and controls. Patients showed an improvement in psychopathology but a significant decrease in gesture performance at follow-up, while performance in the other groups remained stable. Proportional change of gesture performance correlated with change of cognitive function in patients, whereas there were no correlations with change of cognitive function in the other groups. CONCLUSION: While symptom severity was reduced, the gesture deficit further deteriorated in schizophrenia. The finding argues for distinct processes contributing to poor nonverbal communication skills in patients, requiring novel alternative treatment efforts.

Dysbalanced Resting-State Functional Connectivity Within the Praxis Network Is Linked to Gesture Deficits in Schizophrenia.

Patients with schizophrenia frequently present deficits in gesture production and interpretation, greatly affecting their communication skills. As these gesture deficits can be found early in the course of illness and as they can predict later outcomes, exploring their neural basis may lead to a better understanding of schizophrenia. While gesturing has been reported to rely on a left lateralized network of brain regions, termed praxis network, in healthy subjects and lesioned patients, studies in patients with schizophrenia are sparse. It is currently unclear whether within-network connectivity at rest is linked to gesture deficit. Here, we compared the functional connectivity between regions of the praxis network at rest between 46 patients and 44 healthy controls. All participants completed a validated test of hand gesture performance before resting-state functional magnetic resonance imaging (fMRI) was acquired. Patients performed gestures poorer than controls in all categories and domains. In patients, we also found significantly higher resting-state functional connectivity between left precentral gyrus and bilateral superior and inferior parietal lobule. Likewise, patients had higher connectivity from right precentral gyrus to left inferior and bilateral superior parietal lobule (SPL). In contrast, they exhibited lower connectivity between bilateral superior temporal gyrus (STG). Connectivity between right precentral gyrus and left SPL, as well as connectivity between bilateral STG, correlated with gesture performance in healthy controls. We failed to detect similar correlations in patients. We suggest that altered resting-state functional connectivity within the praxis network perturbs correct gesture planning in patients, reflecting the gesture deficit often seen in schizophrenia.