Cortical and subcortical connections change after repetitive transcranial magnetic stimulation therapy in cocaine use disorder and predict clinical outcome

BackgroundCocaine use disorder (CUD) is a worldwide public health condition which is suggested to induce pathological changes in macro- and microstructure. Repetitive transcranial magnetic stimulation (rTMS) has gained attention to induce a reduction in CUD symptoms. Here, we sought to elucidate whether rTMS induces changes on white-matter (WM) microstructure in frontostriatal circuits after two weeks of therapy in patients with CUD, and to test whether baseline WM microstructure of the same circuits has an effect on clinical improvement. This study consisted of a 2-week, parallel group, double-blind, randomized controlled clinical trial (acute phase) (sham [n=23] and active [n=27]), in which patients received two daily sessions of rTMS on the left dorsolateral prefrontal cortex (lDLPFC) as an add-on treatment. T1-weighted and HARDI-DWI at baseline and two weeks after served to evaluate WM microstructure. After active rTMS, results showed a significant increase in neurite density compared to sham rTMS in WM-tracts connecting left DLPFC with left and right vmPFC. Similarly, rTMS showed reduction in orientation dispersion in WM tracts connecting left DLPFC with left caudate nucleus, left thalamus and left vmPFC. Results also showed a greater reduction in craving VAS after rTMS when baseline ICVF was low in WM tracts connecting left caudate nucleus with substantia nigra, left pallidum, and left thalamus with substantia nigra and left pallidum. Our results evidence rTMS-induced WM microstructural changes in fronto-striato-thalamic circuits and support its efficacy as a therapeutic tool in the treatment of CUD. Further, individual clinical improvement may rely on the patients individual structural connectivity integrity. HighlightsO_LIWhite matter microstructural changes between fronto-striato-thalamic regions after 2 weeks of rTMS. C_LIO_LIWhether rTMS would induce microstructural changes may depend on the baseline integrity of the connections between the striatum, thalamus, and the substantia nigra. C_LIO_LIOur results highlight rTMS as a potential therapeutic tool in the treatment of CUD, due to its ability to modulate altered brain microstructure. C_LI