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Overcoming psychomotor slowing in psychosis - a combined neuroimaging and transcranial magnetic stimulation study on the pathophysiology of motor slowing

English title Overcoming psychomotor slowing in psychosis - a combined neuroimaging and transcranial magnetic stimulation study on the pathophysiology of motor slowing
Applicant Walther Sebastian
Number 182469
Funding scheme Project funding (Div. I-III)
Research institution Psychiatrische Poliklinik Universitätsklinik für Psychiatrie Universität Bern
Institution of higher education University of Berne - BE
Main discipline Neurology, Psychiatry
Start/End 01.03.2019 - 28.02.2023
Approved amount 479'611.00
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Keywords (4)

psychomotor slowing; schizophrenia; noninvasive brain stimulation; psychmotor retardation

Lay Summary (German)

Lead
Psychomotorische Verlangsamung kann unter anderem bei Erkrankungen des Schizophrenie-Spektrums vorkommen. Dieses Projekt wird testen, ob durch nicht-invasive Hirnstimulation dieses Symptom behoben werden kann.
Lay summary
Die Verlangsamung von Fein- und Grobmotorischen Bewegungen kommt bei verschiedenen psychiatrischen Erkrankungen, z.B. bei Schizophrenie vor. Bei Schizophreniekranken führt die Verlangsamung zu einem schlechteren Krankheitsverlauf und Problemen bei der sozialen Wiedereingliederung. Wir wissen inzwischen, welche Hirnveränderungen bei der Entstehung von Verlangsamung beteiligt sind. Allerdings gibt es heute keine Möglichkeit, dieses Symptom wirksam zu bekämpfen.
Dieses Projekt wird versuchen, mittels transkranieller Magnetstimulation die Hirnfunktion der betroffenen Regionen zu verändern, um dadurch die psychomotorische Verlangsamung der Betroffenen zu vermindern. Betroffene werden zufällig einer von drei möglichen Behandlungsformen zugeteilt. Vor und nach der Magnetstimulation werden verschiedene Hirnfunktionen geprüft. Wir möchten herausfinden, ob in der motorischen Hirnrinde eine Veränderung bei den Betroffenen möglich ist, und ob sie zu einer mittelfristigen Verbesserung der Verlangsamung führen kann. Wir prüfen dazu Bewegungskoordination, Feinmotorik und Grobmotorik. Insgesamt sollen 88 Patienten untersucht werden. Die Studie wird helfen, die Problematik von psychomotorischer Verlangsamung bei Schizophrenie besser zu verstehen und im besten Fall eine neue Behandlungsmethode für die Betroffenen erschliessen.
Direct link to Lay Summary Last update: 01.10.2018

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Associated projects

Number Title Start Funding scheme
152619 Gesture deficits in Schizophrenia: A combined functional MRI and diffusion tensor imaging study of disconnectivity to investigate the neural basis of limb praxis 01.06.2014 Project funding (Div. I-III)
184717 Combined social cognitive remediation and neurostimulation to improve nonverbal communication in Schizophrenia: a longitudinal study on neurobiology, functional capacity, and social outcome 01.10.2019 Project funding (Div. I-III)
144797 Associations of motor performance and white matter microstructure of the motor system in healthy subjects and in high performing cricket players 01.03.2013 Fellowships for prospective researchers

Abstract

Schizophrenia is a chronic disorder causing tremendous burden to the patients, families and society. Besides prominent symptoms such as hallucinations, delusions, and thought disorder, the majority of patients also experiences motor abnormalities. Converging evidence links aberrant structure and function of the cerebral motor network to schizophrenia pathology, particularly to motor abnormalities. One of the most frequent motor abnormalities is psychomotor slowing (PS), which may impact both gross and fine motor behavior. While PS causes significant distress and predicts poor outcome, researchers are just starting to understand its pathobiology. First evidence points to aberrant functional and structural connectivity within the cerebral motor network in schizophrenia patients with PS, particularly in connections between premotor/motor cortex and thalamus, as well as between motor cortex and cerebellum. In addition, severe motor inhibition was linked to increased neural activity in the premotor cortex. Repetitive transcranial magnetic stimulation (rTMS) may temporarily alter brain activity. Pilot data from an ongoing double blind RCT indicate that 15 sessions of inhibitory rTMS on the premotor cortex alleviate PS. The pathobiology of PS, however, is still unknown. This project will combine a motor battery, advanced neuroimaging, and rTMS to probe the cerebral motor network contributions to PS. The aims of the proposed project are (1) to characterize neural correlates of psychomotor slowing (PS) on the network level, (2) to investigate neural changes following 3 weeks of rTMS treatment (inhibitory, facilitatory or sham), (3) to explore short term changes of PS by testing a waiting list cohort, and (4) to test the clinical outcome of rTMS for PS at 6-month follow-up. To reach these aims, we plan to investigate four groups of schizophrenia patients (total 88) in a randomized, double blind, 3-arm sham-controlled trial of 15 rTMS sessions in 3 weeks with pre and post intervention MRI scans and a clinical follow-up at 6 months. One group will first be kept on a 3 week waiting list and then enter the study. Longitudinal MRI scans and motor tests separated by 3 weeks will also be applied to a control group of 40 healthy subjects for comparisons with the patient groups. We hypothesize that (1) PS would be linked to increased functional connectivity in motor cortical-basal ganglia loops as well as motor cortical-cerebellar loops, (2) inhibitory rTMS to the premotor cortex will reduce motor network functional connectivity and thus alleviate PS, (3) patients on the waiting list may experience stable PS severity, and finally, (4) patients responding to rTMS treatment of PS will have superior clinical and functional outcomes at 6-month follow-up. Thus, the study will substantially contribute to the understanding of PS by describing and probing the neural alterations in the motor network in schizophrenia associated with behavioral PS. Therefore, the study will impact future treatment strategies for PS and inform on the causal network pathology in schizophrenia. The project has great potential to improve clinical care in a difficult population, aiding families and caregivers. Ultimately, the results will help improving real world functioning and quality of life in patients.
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