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From target definition to TMS response predictors in drug-resistant hallucinators: first-evidence from the MULTIMODHAL trial
Low-frequency rTMS has been proposed as an efficient add-on treatment for refractory hallucinations in schizophrenia. However, the exact molecular mechanism of rTMS stays poorly understood, notably at distance of the stimulation site. Here, we considered the striatum as a highly probable final pathway for schizophrenia and proposed to compare striatal GABA and Glx changes in responders vs non-responders to rTMS. GABA/Cr and Glx/Cr were measured using MEGAPRESS Magnetic Resonance Spectroscopy (MRS) before and after rTMS targeted based on per-hallucinatory fMRI capture. Positive response was considered for a >25% decrease at (t+1 month) on hallucinations severity scores. 30 patients (15 responders and 15 non-responders) were included. Mean striatal GABA/Cr changes were found significantly different in responders (mean evolution = + 19.13 %) vs non-responders (mean evolution = + 1.12 %), pcorr = 0.04. No change was evidenced in the Glx/Cr striatal ratio of rTMS responders, but we found a correlation between positive PANSS score and glx/Cr changes (r = 0.43 ; p = 0.02). These preliminary results support specific changes in striatal GABAergic concentrations in hallucinated patients who positively respond to rTMS treatment. MRS of GABA and Glx concentrations could constitute promising predictors of the clinical response to neuromodulation.