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.

Isolation of Distinct Networks Driving Action and Cognition in Psychomotor Processes.

BACKGROUND: Psychomotor disturbances are observed across psychiatric disorders and often manifest as psychomotor slowing, agitation, disorganized behavior, or catatonia. Psychomotor function includes both cognitive and motor components, but the neural circuits driving these subprocesses and how they relate to symptoms have remained elusive for centuries. METHODS: We analyzed data from the HCP-EP (Human Connectome Project for Early Psychosis), a multisite study of 125 participants with early psychosis and 58 healthy participants with resting-state functional magnetic resonance imaging and clinical characterization. Psychomotor function was assessed using the 9-hole pegboard task, a timed motor task that engages mechanical and psychomotor components of action, and tasks assessing processing speed and task switching. We used multivariate pattern analysis of whole-connectome data to identify brain correlates of psychomotor function. RESULTS: We identified discrete brain circuits driving the cognitive and motor components of psychomotor function. In our combined sample of participants with psychosis (n = 89) and healthy control participants (n = 52), the strongest correlates of psychomotor function (pegboard performance) (p < .005) were between a midline cerebellar region and left frontal region and presupplementary motor area. Psychomotor function was correlated with both cerebellar-frontal connectivity (r = 0.33) and cerebellar-presupplementary motor area connectivity (r = 0.27). However, the cognitive component of psychomotor performance (task switching) was correlated only with cerebellar-frontal connectivity (r = 0.19), whereas the motor component (processing speed) was correlated only with cerebellar-presupplementary motor area connectivity (r = 0.15), suggesting distinct circuits driving unique subprocesses of psychomotor function. CONCLUSIONS: We identified cerebellar-cortical circuits that drive distinct subprocesses of psychomotor function. Future studies should probe relationships between cerebellar connectivity and psychomotor performance using neuromodulation.

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.

Physical and mental health in adolescence: novel insights from a transdiagnostic examination of FitBit data in the ABCD study.

Adolescence is among the most vulnerable period for the emergence of serious mental illnesses. Addressing this vulnerability has generated interest in identifying markers of risk for symptoms and opportunities for early intervention. Physical fitness has been linked to psychopathology and may be a useful risk marker and target for early intervention. New wearable technology has made assessing fitness behavior more practical while avoiding recall and self-report bias. Still, questions remain regarding the clinical utility of physical fitness metrics for mental health, both transdiagnostically and along specific symptom dimensions. The current study includes 5007 adolescents (ages 10-13) who participated in the Adolescent Brain Cognitive Development (ABCD) study and additional sub-study that collected fitness data from wearable technology and clinical symptom measures. Physical fitness metrics included resting heart rate (RHR- an index of cardiovascular health), time spent sedentary (associated with increased inflammation and cardiovascular disease), and time spent in moderate physical activity (associated with increased neurogenesis, neuroplasticity, and healthy neurodevelopment). Self-report clinical symptoms included measures of psychosis-like experiences (PLE), internalizing symptoms, and externalizing symptoms. Increased RHR- lower cardiovascular fitness- related only to greater internalizing symptoms (t = 3.63). More sedentary behavior related to elevated PLE severity (t = 5.49). More moderate activity related to lower PLE (t = -2.69) and internalizing (t = -6.29) symptom severity. Wearable technology fitness metrics linked physical health to specific mental health dimensions, which emphasizes the utility of detailed digital health data as a marker for risk and the need for precision in targeting physical health behaviors to benefit symptoms of psychopathology.

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.

Non-invasive neuromodulation of the right temporoparietal junction using theta-burst stimulation in functional neurological disorder.

Background: Disrupted sense of agency (SoA)-the sense of being the agent of one's own actions-has been demonstrated in patients with functional neurological disorder (FND), and a key area of the corresponding neuronal network is the right temporoparietal junction (rTPJ). Several functional MRI (fMRI) studies have found hypoactivation as well as hyperactivation of the rTPJ in FND. In a proof-of-concept study, we tested whether repetitive transcranial magnetic stimulation (rTMS) over the rTPJ could restore this aberrant activity. Methods: In a randomised, crossover, single-blinded, sham-controlled study design, theta-burst stimulation (tb-rTMS) was applied over the rTPJ in 23 patients with FND and 19 healthy controls (HC), with each participant undergoing three stimulatory visits (inhibitory continuous TBS (cTBS), excitatory intermittent TBS (iTBS) and sham). During fMRI, participants played a visuomotor task artificially reducing their SoA (manipulated agency, MA), repeated after each neurostimulation. We compared brain activity and behavioural SoA as primary outcomes before and after tb-rTMS and investigated the feasibility of tb-rTMS over the rTPJ in FND as secondary outcome. Results: At baseline, patients showed decreased accuracy in detecting reduced agency compared with controls (p<0.001), paralleled by lower brain activation in the rTPJ during MA (p=0.037, volume of interest). A region of interest analysis on the rTPJ showed no effect of the sham condition in FND or HC (p=0.917; p=0.375) but revealed a significant effect of stimulation protocol (cTBS/iTBS, p=0.037) in patients with FND, with the excitatory protocol increasing the blood-oxygen-level-dependent (BOLD) signal, whereas this effect was not found in HC. In neither group, a behavioural effect of tb-rTMS was observed. Conclusion: Aberrant processing of agency in FND was confirmed at baseline, reflected in behavioural outcome and reduced activity in the rTPJ. Tb-rTMS over this key region elicited neuronal changes in patients, paving ways for future studies exploring TMS as neurobiologically informed intervention to restore SoA in FND. We critically discuss methodological intricacies and outline further steps in this research line.

From one to many: Hypertonia in schizophrenia spectrum psychosis an integrative review and adversarial collaboration report.

Different types of resistance to passive movement, i.e. hypertonia, were described in schizophrenia spectrum disorders (SSD) long before the introduction of antipsychotics. While these have been rediscovered in antipsychotic-naïve patients and their non-affected relatives, the existence of intrinsic hypertonia vs drug-induced parkinsonism (DIP) in treated SSD remains controversial. This integrative review seeks to develop a commonly accepted framework to specify the putative clinical phenomena, highlight conflicting issues and discuss ways to challenge each hypothesis and model through adversarial collaboration. The authors agreed on a common framework inspired from systems neuroscience. Specification of DIP, locomotor paratonia (LMP) and psychomotor paratonia (PMP) identified points of disagreement. Some viewed parkinsonian rigidity to be sufficient for diagnosing DIP, while others viewed DIP as a syndrome that should include bradykinesia. Sensitivity of DIP to anticholinergic drugs and the nature of LPM and PMP were the most debated issues. It was agreed that treated SSD should be investigated first. Clinical features of the phenomena at issue could be confirmed by torque, EMG and joint angle measures that could help in challenging the selectivity of DIP to anticholinergics. LMP was modeled as the release of the reticular formation from the control of the supplementary motor area (SMA), which could be challenged by the tonic vibration reflex or acoustic startle. PMP was modeled as the release of primary motor cortex from the control of the SMA and may be informed by subclinical echopraxia. If these challenges are not met, this would put new constraints on the models and have clinical and therapeutic implications.

Linking connectivity of deep brain stimulation of nucleus accumbens area with clinical depression improvements: a retrospective longitudinal case series.

Treatment-resistant depression is a severe form of major depressive disorder and deep brain stimulation is currently an investigational treatment. The stimulation's therapeutic effect may be explained through the functional and structural connectivities between the stimulated area and other brain regions, or to depression-associated networks. In this longitudinal, retrospective study, four female patients with treatment-resistant depression were implanted for stimulation in the nucleus accumbens area at our center. We analyzed the structural and functional connectivity of the stimulation area: the structural connectivity was investigated with probabilistic tractography; the functional connectivity was estimated by combining patient-specific stimulation volumes and a normative functional connectome. These structural and functional connectivity profiles were then related to four clinical outcome scores. At 1-year follow-up, the remission rate was 66%. We observed a consistent structural connectivity to Brodmann area 25 in the patient with the longest remission phase. The functional connectivity analysis resulted in patient-specific R-maps describing brain areas significantly correlated with symptom improvement in this patient, notably the prefrontal cortex. But the connectivity analysis was mixed across patients, calling for confirmation in a larger cohort and over longer time periods.

Mapping Psychomotor Behavior in the Brain.

This Viewpoint describes a new conception of brain regions that may be associated with abnormal psychomotor behaviors in psychotic and mood disorders.

The Effect of Electroconvulsive Therapy on Specific Catatonia Symptoms and Predictors of Late Response.

INTRODUCTION: Electroconvulsive therapy (ECT) is known to be effective in the treatment of catatonia, reaching response rates of about 80 to 100%. It is indicated in cases of treatment resistance to benzodiazepines and in life-threatening conditions such as malignant catatonia. Beneficial effects on specific symptoms or predictors of response are less clear. The objective of this retrospective study is to examine the ECT effect on specific catatonia symptoms in the acute phase of the illness and to identify predictors of response. METHODS: A retrospective study examined data from 20 patients with catatonia, 18 associated with schizophrenia and 2 with bipolar disorder, who underwent ECT from 2008 to 2021. Ten subjects had more than one ECT-series, resulting in a total of 31 ECT-series. Catatonia symptom severity was assessed with the Bush Francis Catatonia Rating Scale (BFCRS). RESULTS: ECT yielded excellent response. Nineteen of 20 patients and 30 of 31 ECT-series achieved response. The mean number of ECT sessions to response was 4.2. Response to ECT was more pronounced for motor inhibition symptoms such as stupor and mutism, while echophenomena, dyskinesia, stereotypy and perseveration responded less well. A predictor of late response was the presence of grasp reflex. DISCUSSION: The present study corroborates the high and rapid effectiveness of ECT in the treatment of catatonia. Focus on single catatonia signs may help to identify those who are most likely to achieve remission quickly, as well as those who might need longer ECT-series.

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.

Physical and Mental Health in Adolescence: Novel Insights from a transdiagnostic examination of FitBit data in the ABCD Study.

Adolescence is among the most vulnerable period for the emergence of serious mental illnesses. Addressing this vulnerability has generated interest in identifying markers of risk for symptoms and opportunities for early intervention. Physical fitness has been linked to psychopathology and may be a useful risk marker and target for early intervention. New wearable technology has made assessing fitness behavior more practical while avoiding recall and self-report bias. Still, questions remain regarding the clinical utility of physical fitness metrics for mental health, both transdiagnostically and along specific symptom dimensions. The current study includes 5007 adolescents (ages 10 to 13) who participated in the Adolescent Brain Cognitive Development (ABCD) study and additional sub-study that collected fitness data from wearable technology and clinical symptom measures. Physical fitness metrics included resting heart rate (RHR- an index of cardiovascular health), time spent sedentary (associated with increased inflammation and cardiovascular disease), and time spent in moderate physical activity (associated with increased neurogenesis, neuroplasticity, and healthy neurodevelopment). Self-report clinical symptoms included measures of internalizing symptoms, externalizing symptoms, and psychosis-like experiences - PLE). Increased RHR- lower cardiovascular fitness- related only to greater internalizing symptoms (t = 3.63). More sedentary behavior related to elevated PLE severity (t = 5.49). More moderate activity related to lower PLE (t=-2.69) and internalizing (t=-6.29) symptom severity. Wearable technology fitness metrics linked physical health to specific mental health dimensions, which emphasizes the utility of detailed digital health data as a marker for risk and the need for precision in targeting physical health behaviors to benefit symptoms of psychopathology.

Modelling the overlap and divergence of autistic and schizotypal traits on hippocampal subfield volumes and regional cerebral blood flow.

Psychiatric disorders show high co-morbidity, including co-morbid expressions of subclinical psychopathology across multiple disease spectra. Given the limitations of classical case-control designs in elucidating this overlap, new approaches are needed to identify biological underpinnings of spectra and their interaction. We assessed autistic-like traits (using the Autism Quotient, AQ) and schizotypy - as models of subclinical expressions of disease phenotypes and examined their association with volumes and regional cerebral blood flow (rCBF) of anterior, mid- and posterior hippocampus segments from  structural MRI scans in 318 and arterial spin labelling (ASL) in 346 nonclinical subjects, which overlapped with the structural imaging sample (N = 298). We demonstrate significant interactive effects of positive schizotypy and AQ social skills as well as of positive schizotypy and AQ imagination on hippocampal subfield volume variation. Moreover, we show that AQ attention switching modulated hippocampal head rCBF, while positive schizotypy by AQ attention to detail interactions modulated hippocampal tail rCBF. In addition, we show significant correlation of hippocampal volume and rCBF in both region-of-interest and voxel-wise analyses, which were robust after removal of variance related to schizotypy and autistic traits. These findings provide empirical evidence for both the modulation of hippocampal subfield structure and function through subclinical traits, and in particular how only the interaction of phenotype facets leads to significant reductions or variations in these parameters. This makes a case for considering the synergistic impact of different (subclinical) disease spectra on transdiagnostic biological parameters in psychiatry.

Associations of resting-state perfusion and auditory verbal hallucinations with and without emotional content in schizophrenia.

Auditory Verbal Hallucinations (AVH) are highly prevalent in patients with schizophrenia. AVH with high emotional content lead to particularly poor functional outcome. Increasing evidence shows that AVH are associated with alterations in structure and function in language and memory related brain regions. However, neural correlates of AVH with emotional content remain unclear. In our study (n = 91), we related resting-state cerebral perfusion to AVH and emotional content, comparing four groups: patients with AVH with emotional content (n = 13), without emotional content (n = 14), without hallucinations (n = 20) and healthy controls (n = 44). Patients with AVH and emotional content presented with increased perfusion within the amygdala and the ventromedial and dorsomedial prefrontal cortex (vmPFC/ dmPFC) compared to patients with AVH without emotional content. In addition, patients with any AVH showed hyperperfusion within the anterior cingulate gyrus, the vmPFC/dmPFC, the right hippocampus, and the left pre- and postcentral gyrus compared to patients without AVH. Our results indicate metabolic alterations in brain areas critical for the processing of emotions as key for the pathophysiology of AVH with emotional content. Particularly, hyperperfusion of the amygdala may reflect and even trigger emotional content of AVH, while hyperperfusion of the vmPFC/dmPFC cluster may indicate insufficient top-down amygdala regulation in patients with schizophrenia.

Case report: Psychosis and catatonia in an adolescent patient with adipsic hypernatremia and autoantibodies against the subfornical organ.

This is the first description of a patient in which adipsic hypernatremia, a rare autoimmune encephalitis, presented in combination with complex psychiatric symptomatology, including psychosis and catatonia. Adipsic hypernatremia is characterized by autoantibodies against the thirst center of the brain. These autoantibodies cause inflammation and apoptosis in key regions of water homeostasis, leading to lack of thirst and highly increased serum sodium. To date, the symptoms of weakness, fatigue and drowsiness have been associated with adipsic hypernatremia, but no psychiatric symptomatology. Here, we showcase the first description of an adolescent patient, in which severe and complex psychiatric symptoms presented along with adipsic hypernatremia. The patient experienced delusion, hallucinations, restlessness and pronounced depression. Further, he showed ritualized, aggressive, disinhibited and sexualized behavior, as well as self-harm and psychomotor symptoms. Due to his severe condition, he was hospitalized on the emergency unit of the child and adolescent psychiatry for 8 months. Key symptoms of the presented clinical picture are: childhood-onset complex and treatment-resistant psychosis/catatonia, pronounced behavioral problems, fatigue, absent thirst perception, hypernatremia and elevated prolactin levels. This case report renders first evidence speaking for a causal link between the autoimmune adipsic hypernatremia and the psychotic disorder. Moreover, it sheds light on a new form of autoimmune psychosis.

Resting-state perfusion in motor and fronto-limbic areas is linked to diminished expression of emotion and speech in schizophrenia.

Negative symptoms (NS) are a core component of schizophrenia affecting community functioning and quality of life. We tested neural correlates of NS considering NS factors and consensus subdomains. We assessed NS using the Clinical Assessment Interview for Negative Symptoms and the Scale for Assessment of Negative Symptoms. Arterial spin labeling was applied to measure resting-state cerebral blood flow (rCBF) in 47 schizophrenia patients and 44 healthy controls. Multiple regression analyses calculated the relationship between rCBF and NS severity. We found an association between diminished expression (DE) and brain perfusion within the cerebellar anterior lobe and vermis, and the pre-, and supplementary motor area. Blunted affect was linked to fusiform gyrus and alogia to fronto-striatal rCBF. In contrast, motivation and pleasure was not associated with rCBF. These results highlight the key role of motor areas for DE. Considering NS factors and consensus subdomains may help identifying specific pathophysiological pathways of NS.

Using virtual reality to assess gesture performance deficits in schizophrenia patients.

Introduction: Gesture performance deficits are prevalent in schizophrenia patients and are strongly associated with poor social communication skills and community functioning, affecting their overall quality of life. Currently, video-recording technology is widely used in clinical settings to assess gesture production deficits in schizophrenia patients. Nevertheless, the subjective evaluation of video-recordings can encumber task assessment. The present study will aim to use virtual reality to examine its potential use as an alternative tool to objectively measure gesture performance accuracy in schizophrenia patients and healthy controls. Methods: Gesture performance in the virtual reality setting will be based on the well-established Test of Upper Limb Apraxia. Participants will be immersed in a virtual environment where they will experience themselves being embodied in a collocated virtual body seen from a first-person perspective. Motion trackers will be placed on participants' hands and elbows to track upper body movements in real-time, and to record gesture movement for later analysis. Participants will see a virtual agent sitting across from them, with a virtual table in between. The agent will perform various types of gestures and the participants' task will be to imitate those gestures as accurately as possible. Measurements from the tracking devices will be stored and analyzed to address gesture performance accuracy across groups. Discussion: This study aims to provide objective measurements of gesture performance accuracy in schizophrenia patients. If successful, the results will provide new knowledge to the gesture literature and offer the potential for novel therapeutic interventions using virtual reality technologies. Such interventions can improve gesturing and thus advance social communication skills in schizophrenia patients.

Electroconvulsive therapy induces remodeling of hippocampal co-activation with the default mode network in patients with depression.

INTRODUCTION: Electroconvulsive therapy (ECT) is a highly efficient treatment for depression. Previous studies repeatedly reported an ECT-induced volume increase in the hippocampi. We assume that this also affects extended hippocampal networks. This study aims to investigate the structural and functional interplay between hippocampi, hippocampal pathways and core regions of the default mode network (DMN). Twenty patients with a current depressive episode receiving ECT-treatment and twenty age and sex matched healthy controls (HC) were included in the study. ECT-patients underwent multimodal magnetic resonance imaging (MRI)-scans (diffusion weighted imaging, resting state functional MRI) before and after an ECT-index series. HC were also scanned twice in a similar between-scan time-interval. Parahippocampal cingulum (PHC) and uncinate fasciculus (UF) were reconstructed for each participant using manual tractography. Fractional anisotropy (FA) was averaged across tracts. Furthermore, we investigated seed-based functional connectivity (FC) from bilateral hippocampi and from the PCC, a core region of the DMN. At baseline, FA in PHC and UF did not differ between groups. There was no baseline group difference of hippocampal-FC. PCC-FC was decreased in ECT-patients. ECT induced a decrease in FA in the left PHC in the ECT group. No longitudinal changes of FA were found in the UF. Furthermore, there was a decrease in hippocampal-PCC-FC, an increase in hippocampal-supplementary motor area-FC, and an increase in PCC-FC in the ECT-group, reversing group differences at baseline. Our findings suggest that ECT induces structural and functional remodeling of a hippocampal-DMN. Those changes may contribute to ECT-induced clinical response in patients with depression.