(ClinicalTrials.gov Identifier: NCT03921450)
Background In addition to symptoms such as hallucinations, delusions, and thought disorder, patients with schizophrenia frequently suffer from motor abnormalities. One of these motor abnormalities is psychomotor slowing (PS), which may affect both gross and fine motor behavior. Motor abnormalities are associated with abnormal functional and structural connectivity within the cerebral motor network. While PS causes significant distress and predicts poor outcome, researchers are just starting to understand its pathobiology. Recent studies suggested increased neural activity in the premotor cortex to underlie severe motor inhibition. Thus, a possible way to ameliorate PS is repetitive transcranial magnetic stimulation (rTMS), which may temporarily alter brain activity. This project will combine a motor battery, advanced neuroimaging, and rTMS to probe the cerebral motor network contributions to PS.
Hypothesis We hypothesize that (1) PS would be linked to increased functional connectivity in the motor network, (2) inhibitory rTMS to the premotor cortex will alleviate PS by reducing motor network functional connectivity, (3) patients responding to rTMS treatment of PS will have superior clinical and functional outcomes at 6-month follow-up.
Design of the study 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
Preliminary Data The pilot data on this study design (See Walther et al.2020, https://doi.org/10.1093/schizbullopen/sgaa020) suggest that three weeks of daily inhibitory rTMS over the premotor cortex might improve psychomotor slowing in schizophrenia.
Funding http://p3.snf.ch/project-182469
Study team Collaborators
Niluja Nadesalingam Prof. Roland Wiest, Institute of Diagnostic and
Stephanie Lefebvre, PhD Interventional Neuroradiology
Danai Alexaki, MD Prof. Jessica Bernard, Texas A & M University
Daniel Baumann, MD Prof. Roger Kalla, Dept. of Neurology, Bern
Sebastian Walther, MD Prof. Andrea Federspiel, Translational Research Center