Transcranial Magnetic Stimulation to Improve Gesture Control (GestTMS)

Repetitive Transcranial Magnetic Stimulation (rTMS) to Improve Gesture Control in Schizophrenia: A Randomised, Placebo-controlled, Double-blind Crossover Trial

The majority of schizophrenia patients is impaired in hand gesture performance, which contributes to poor functional outcome and poor communication skills. The left inferior frontal gyrus (IFG) and the left inferior parietal lobe (IPL) are key nodes of the gesture network, which is less active in patients with schizophrenia. Here, the investigators test single sessions of rTMS/TBS known to either enhance or inhibit local brain activity for app. 1 hour. The investigators aim to determine, which protocol may improve gesture performance in patients and healthy controls. This is a randomized, double-blind, cross-over, placebo-controlled single-center trial in 20 patients with schizophrenia spectrum disorders and 20 healthy controls. Gesture performance will be tested immediately after each TMS session, which are separated by 48 hours. Results of this study will inform larger interventional trials comparing 2 TMS protocols with repeated administration.

Schizophrenia is associated with poor social functioning, which is perturbed by deficits in social interaction including nonverbal communication. The use of hand gestures is critical for nonverbal communication, but the majority of schizophrenia patients has severe gesture impairments. Today no intervention may ameliorate gesture impairments. Patients with gesture impairments have altered structure and function of the gesture network, particularly the left inferior frontal gyrus (IFG) and also the left inferior parietal lobe (IPL). Noninvasive brain stimulation techniques may alter local brain function. Repetitive transcranial magnetic stimulation (rTMS) and particularly theta burst stimulation (TBS) for a few mins is a very safe method to alter brain states locally for approximately 1 hour. Indeed, facilitatory stimulation of the left frontal cortex by transcranial direct current stimulation (tDCS) demonstrated improved gesture perception and interpretation in healthy subjects. In addition, inhibitory stimulation with continuous theta burst stimulation (cTBS) over left IFG may perturb gesture performance in healthy subjects. Thus, the investigators hypothesize that local changes of brain activity within the gesture network would change gesture performance. Particularly, facilitatory intermittent theta burst stimulation (iTBS) of the left IFG would improve gesture performance. The investigators will test single sessions of rTMS in healthy subjects and schizophrenia patients. If one of the protocols proves to have superior effects, this result will help to plan interventional trials targeting social interaction deficits in schizophrenia. The aim of the study is to determine the effect of one session of iTBS over the left IFG on gesture performance compared to cTBS over the right IPL (active comparator) and one placebo rTMS sessions. This is a randomized, double-blind, cross-over, placebo-controlled single-center trial in 20 patients with schizophrenia spectrum disorders and 20 healthy controls. After baseline assessment of gesture performance, participants will receive one rTMS protocol at each time point, immediately followed by assessments of gesture performance and dexterity. rTMS sessions will be separated by 48 hours. Gesture performance will be measured with video recorded Test of Upper Limb Apraxia, which is rated blindly according to a manual.

participants, outcome assessors and raters are blinded. rTMS application is performed by an unblinded investigator

15 daily sessions of intermittent theta burst stimulation at 80% resting motor threshold, total duration of 190 s, localization using EEG 10/20 system at F3/F4

15 daily sessions of continuous theta burst stimulation at 100% resting motor threshold, total duration of 45 s, localization using EEG 10/20 system at F3/F4

rTMS with a placebo coil that looks identical and makes identical noises for 180 s, localization over left IPL

Standardized gesture performance test, video recorded and rated according to manual by a rater blind to treatment and group

Standardized gesture performance test, video recorded and rated according to manual by a rater blind to treatment

Standardized gesture performance test, video recorded and rated according to manual by a rater blind to treatment

Standardized gesture performance test, video recorded and rated according to manual by a rater blind to treatment

Test of dexterity, 3 trials of 10s to rotate a .5 Swiss Francs (SFr) coin between thumb, index and middle finger, video recorded, rated blindly according to number of coin half turns

Test of dexterity, 3 trials of 10s to rotate a .5 SFr coin between thumb, index and middle finger, video recorded, rated blindly according to number of coin half turns

Test of dexterity, 3 trials of 10s to rotate a .5 SFr coin between thumb, index and middle finger, video recorded, rated blindly according to number of coin half turns

Test of dexterity, 3 trials of 10s to rotate a .5 SFr coin between thumb, index and middle finger, video recorded, rated blindly according to number of coin half turns

Inclusion Criteria: Right handed according to the Edinburgh Handedness Inventory Ability and willingness to participate in the study Ability to provide written informed consent Informed Consent as documented by signature (Appendix Informed Consent Form) Spent majority of childhood/adolescence in Switzerland Patients: schizophrenia spectrum disorder according to Diagnostic and Statistical Manual version 5 (DSM-5) Exclusion Criteria: Women who are pregnant or breast feeding Metal objects on or in the body (e.g. grenade splinter, cardiac pacemaker, vessel clips, metal prostheses, contraceptive coil, cochlear implants, hearing aid, tooth implant) History of neurosurgery, any severe head wounds, history of neurologic disorders impacting gesture, e.g. Parkinson's disease, stroke, multiple sclerosis sclerosis and epilepsy, convulsion or seizure History of any hearing problems or ringing in the ears. Active drug addiction except nicotine Controls: first-degree relatives with schizophrenia spectrum disorders

The investigators do not plan to share the data, because they cannot anonymize the video data sufficiently