Individualizing rTMS in treatment-resistant depression from patient-specific perfusion abnormalities a proof-of-concept randomized trial in comparison to standard rTMS and tDCS.

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Title: Individualizing rTMS in treatment-resistant depression from patient-specific perfusion abnormalities a proof-of-concept randomized trial in comparison to standard rTMS and tDCS.
Authors: Dormegny-Jeanjean, Ludovic C. (AUTHOR), de Crespin de Billy, Clément (AUTHOR), Pierrat, Camille (AUTHOR), Mainberger, Olivier (AUTHOR), Schorr, Benoit (AUTHOR), Obrecht, Alexandre (AUTHOR), Arcay, Hippolyte (AUTHOR), Moreau, Augustin (AUTHOR), Humbert, Ilia (AUTHOR), Scarlatti, Francesco (AUTHOR), Bertschy, Gilles (AUTHOR), de Sousa, Paulo Loureiro (AUTHOR), Lamy, Julien (AUTHOR), Weibel, Sebastien (AUTHOR), Landré, Lionel (AUTHOR), Foucher, Jack R. (AUTHOR)
Source: European Archives of Psychiatry & Clinical Neuroscience. Sep2025, Vol. 275 Issue 6, p1809-1825. 17p.
Subjects: Transcranial magnetic stimulation, Perfusion magnetic resonance imaging, Mental depression, Individualized medicine, Clinical trials, Brain imaging, Multiple human abnormalities, Cerebral circulation
Abstract: Background: Studies examining treatment-resistant depression (TRD) as a group implicitly assume that these conditions share similar pathophysiological features, like left prefrontal hypoactivity, and should respond to standardized treatments like repetitive transcranial magnetic stimulation (S-rTMS) or transcranial direct current stimulation (tDCS). Recent advances in arterial spin labeling functional MRI (ASL-fMRI) revealed that subject-specific perfusion abnormalities may be more heterogeneous than expected. Individualized rTMS protocols (I-rTMS) could alleviate such abnormalities and establish their relevance. Methods: iADAPT was a randomized, cross-over trial comparing I-rTMS with active comparators (S-rTMS and tDCS) on brain perfusion, assessed with ASL-fMRI, and single blind clinical evaluation. Patient-specific abnormalities were determined from three ASL-fMRI sessions. I-rTMS multi-target interventions targeted all reachable bi-frontal abnormalities, upregulating hypoperfusions and downregulating hyperperfusions. S-rTMS and tDCS were placed on F3. rTMS interventions used neuronavigation and a robotic targeting device. Each arm included 20 sessions over two weeks. Results: Twenty-two patients with TRD were included and analyzed. While at the group level they presented subgenual cingulate hyperperfusion, they presented heterogeneous prefrontal perfusion abnormalities individually. I-rTMS was the only intervention to have specific effects on brain perfusion, showing perfusion reductions compatible with the disengagement of negative emotional systems, e.g. subgenual cingulate, anterior insula. Conclusions: Paradoxically, I-rTMS induced more reproducible remote effects on cerebral perfusion than S-rTMS, while the I-rTMS protocol differed considerably between participants. These results suggest that the heterogeneities observed in ASL-MRI at the individual level are significant and may have the potential to inform individualized treatment. Clinicaltrials.gov no NCT02863380, registered on 2016-08-05. [ABSTRACT FROM AUTHOR]
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Database: Psychology and Behavioral Sciences Collection
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