Effects of Personalized Transcranial Magnetic Stimulation on Social Cognitive Network Functional Connectivity in Schizophrenia Spectrum Disorders: A Double-Blind, Randomized, Sham-Controlled Target Engagement Trial.
Schizophrenia spectrum disorders (SSDs) often feature debilitating social cognitive impairments, with limited treatment options. This study used a target engagement approach to examine the effects of individually-targeted repetitive transcranial magnetic stimulation (rTMS) to the dorsomedial prefrontal cortex (DMPFC) on social cognitive network functional connectivity (i.e., mentalizing and simulation networks) in individuals with SSDs.
We conducted a double-blind, randomized, sham-controlled trial in adults with SSDs (NCT04418011). Participants received two weeks of DMPFC stimulation with 10 Hz rTMS, intermittent theta burst stimulation (iTBS), or sham stimulation. They completed pre- and post-treatment functional magnetic resonance imaging, including a social processing task. Treatment was personalized using functional connectivity mapping and electric field modelling. Primary outcomes were changes in individualized within-mentalizing and between mentalizing-simulation network functional connectivity after active stimulation versus sham, compared using effect sizes. Secondary outcomes were safety and tolerability.
Analyses included 46 participants who completed treatment (10 Hz rTMS: n=15; iTBS: n=15; sham: n=16). iTBS produced a significantly greater increase in within-mentalizing network connectivity, with a large effect size, while 10 Hz rTMS did not differ from sham. Effects on between-network connectivity were negligible-to-small for both active conditions. Participants receiving iTBS reported higher pain ratings, but adverse event and discontinuation rates did not differ across groups.
Individualized DMPFC-targeted iTBS demonstrated target engagement via increased mentalizing network connectivity relative to sham, and was feasible, safe, and well-tolerated in adults with SSDs. A larger and longer clinical trial powered to assess change in social cognitive outcomes is ongoing (NCT06118268).
We conducted a double-blind, randomized, sham-controlled trial in adults with SSDs (NCT04418011). Participants received two weeks of DMPFC stimulation with 10 Hz rTMS, intermittent theta burst stimulation (iTBS), or sham stimulation. They completed pre- and post-treatment functional magnetic resonance imaging, including a social processing task. Treatment was personalized using functional connectivity mapping and electric field modelling. Primary outcomes were changes in individualized within-mentalizing and between mentalizing-simulation network functional connectivity after active stimulation versus sham, compared using effect sizes. Secondary outcomes were safety and tolerability.
Analyses included 46 participants who completed treatment (10 Hz rTMS: n=15; iTBS: n=15; sham: n=16). iTBS produced a significantly greater increase in within-mentalizing network connectivity, with a large effect size, while 10 Hz rTMS did not differ from sham. Effects on between-network connectivity were negligible-to-small for both active conditions. Participants receiving iTBS reported higher pain ratings, but adverse event and discontinuation rates did not differ across groups.
Individualized DMPFC-targeted iTBS demonstrated target engagement via increased mentalizing network connectivity relative to sham, and was feasible, safe, and well-tolerated in adults with SSDs. A larger and longer clinical trial powered to assess change in social cognitive outcomes is ongoing (NCT06118268).
Authors
Oliver Oliver, Blumberger Blumberger, Deng Deng, Hawco Hawco, Dickie Dickie, Gallucci Gallucci, Jeyachandra Jeyachandra, Mansour Mansour, Hare Hare, Gold Gold, Foussias Foussias, Argyelan Argyelan, Daskalakis Daskalakis, Buchanan Buchanan, Malhotra Malhotra, Voineskos Voineskos
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