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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p> <p>Clinicaltrials.gov no NCT02863380, registered on 2016-08-05.</p> Graphical abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2025年6月14日

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  • Ludovic C. Dormegny-Jeanjean,
  • Clément de Crespin de Billy,
  • Camille Pierrat,
  • Olivier Mainberger,
  • Benoit Schorr,
  • Alexandre Obrecht,
  • Hippolyte Arcay,
  • Augustin Moreau,
  • Ilia Humbert,
  • Francesco Scarlatti,
  • Gilles Bertschy,
  • Paulo Loureiro de Sousa,
  • Julien Lamy,
  • Sebastien Weibel,
  • Lionel Landré,
  • Jack R. Foucher

摘要

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.

Graphical abstract