Reduced signal propagation elicited by frontal transcranial magnetic stimulation is associated with oligodendrocyte abnormalities in treatment-resistant depression

Abstract

Background:The efficacy of repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (dlPFC) has been established in patients with treatment-resistant depression (TRD), suggesting that alterations in signal propagation from the left dlPFC to other brain regions may be linked to the pathophysiology of TRD. Alterations at the cellular level, including dysfunction of oligodendrocytes, may contribute to these network abnormalities. The objectives of the present study were to compare signal propagation from the left dlPFC to other neural networks in patients with TRD and healthy controls. We used TMS combined with electroencephalography to explore links between cell-specific gene expression and signal propagation in TRD using a virtual-histology approach. Methods: We exam ined source-level estimated signal propagation from the left dlPFC to the 7 neural networks in 60 patients with TRD and 30 healthy controls. We also calculated correlations between the interregional profiles of altered signal propagation and gene expression for 9 neural cell types derived from the Allen Human Brain Atlas data set. Results: Signal propagation from the left dlPFC to the salience network was reduced in the θ and α bands in patients with TRD (p = 0.0055). Furthermore, this decreased signal propagation was correlated with cellspecific gene expression of oligodendrocytes (p < 0.000001). Limitations: These results show only part of the pathophysiology of TRD, because stimulation was limited to the left dlPFC. Conclusion: Reduced signal propagation from the left dlPFC to the salience network may represent a pathophysiological endophenotype of TRD; this finding may be associated with reduced expression of oligodendrocytes.Wada et al. E326

Neuroplasticity of the left dorsolateral prefrontal cortex in patients with treatment-resistant depression as indexed with paired associative stimulation: a TMS–EEG study

“…2019 ). In the present study, the ratio of the TRD group to the HC group was set to 2:1, in line with our previously published work ( Wada et al. 2022 ).…”

“…In TRD, the DLPFC is not only the hub of cognitive functions, including executive function and working memory in normal physiology, but abnormalities in networks originating from this region have also been identified as the pathological basis of depression ( Wada et al. 2022 ).…”

Sex Differences of the Functional Brain Activity in Treatment-Resistant Depression: A Resting-State Functional Magnetic Resonance Study

“…The DLPFC is responsible for top-down regulation of emotional processing, decision making, working memory, and attention processing, and is closely related to the onset of MDD [ 29 , 30 , 31 , 32 ]. DLPFC is an important target for repetitive transcranial magnetic stimulation in the treatment of TRD and is effective in preventing relapse in patients with TRD [ 33 , 34 ]. A study found that the male MDD patients had lower ALFF in the left superior frontal gyrus compared with female MDD patients, which supports the results of this study [ 17 ].…”

Development of Artificial Intelligence for Determining Major Depressive Disorder Based on Resting-State EEG and Single-Pulse Transcranial Magnetic Stimulation-Evoked EEG Indices

“…Here, the TMS coil was placed on the scalp at MNI coordinates [x = −38, y = 44, z = 26] at a 45 degree angle to the midline. Other details of the TMS-EEG experimental procedures have been reported in our previously published articles [16,17].…”