White matter integrity and functional predictors of response to repetitive transcranial magnetic stimulation for posttraumatic stress disorder and major depression

Abstract

Background: Recent evidence suggests that therapeutic repetitive transcranial magnetic stimulation (TMS) is an effective treatment for pharmacoresistant posttraumatic stress disorder (PTSD) and comorbid major depressive disorder (MDD). We recently demonstrated that response to 5 Hz TMS administered to the dorsolateral prefrontal cortex was predicted by functional connectivity of the medial prefrontal (MPFC) and subgenual anterior cingulate cortex (sgACC). This functionallydefined circuit is a novel target for treatment optimization research, however, our limited knowledge of the structural pathways that underlie this functional predisposition is a barrier to target engagement research.Methods: To investigate underlying structural elements of our previous functional connectivity findings, we submitted pre-TMS diffusion-weighted imaging data from 20 patients with PTSD and MDD to anatomically constrained tract-based probabilistic tractography (FreeSurfer's TRActs Constrained by UnderLying Anatomy). Averaged pathway fractional anisotropy (FA) was extracted from four frontal white matter tracts: the forceps minor, cingulum, anterior thalamic radiations (ATRs), and uncinate fasciculi. Tract FA statistics were treated as explanatory variables in backward regressions testing the relationship between tract integrity and functional connectivity coefficients from MPFC and sgACC predictors of symptom improvement after TMS.Results: FA in the ATRs was consistently associated with symptom improvement in PTSD and MDD (Bonferroni-corrected p < .05). Conclusion:We found that structural characteristics of the ATR account for significant variance in individual-level functional predictors of post-TMS improvement. TMS optimization studies should target this circuit either in stand-alone or successive TMS stimulation protocols. K E Y W O R D S diffusion magnetic resonance imaging, major depressive disorder, posttraumatic stress disorders, transcranial magnetic stimulation, white matter

Revisiting Hemispheric Asymmetry in Mood Regulation: Implications for rTMS for Major Depressive Disorder

“…Importantly, rTMS has demonstrated an ability to affect white matter tracts within the stimulated hemisphere [ 121 , 122 ]. Recent studies have demonstrated hemispheric differences in white matter topography underlying key cortical areas involved in mood and anxiety regulation [ 123 , 124 , 125 ], further suggesting that differences in structural connectivity between the left and right hemispheres in MDD likely have bearing on the efficacy of rTMS. This may be especially true in older adults, where it has been proposed that MDD is the result of age related degradation of white matter tracts [ 126 ].…”

The Effects of Repetitive Transcranial Magnetic Stimulation on Cognitive Impairment and the Brain Lipidome in a Cuprizone-Induced Mouse Model of Demyelination

“…Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive intervention widely used to treat several psychiatric disorders, such as major depressive disorder (MDD) ( Miron et al, 2019 ), posttraumatic stress disorder (PTSD) ( Philip et al, 2019 ) and schizophrenia ( Jiang et al, 2019 ). White matter integrity and function is a predictor for the treatment response of rTMS for PTSD and MDD ( Barredo et al, 2019 ), and low-intensity TMS promote the survival and maturation of newborn oligodendrocytes in the adult mouse brain ( Cullen et al, 2019 ). Moreover, rTMS has also been shown to be beneficial in treating demyelinating disorders, such as Alzheimer’s disease and multiple sclerosis ( San et al, 2019 ; Chou et al, 2020 ); thus, the protective effects of myelin might be involved in the beneficial effects of rTMS.…”

Treatment of major depressive disorder with bilateral theta burst stimulation: study protocol for a randomized, double-blind, placebo-controlled multicenter trial (TBS-D)

“…Recent results indicate that both structural [ 53 ] and functional connectivity MRI parameters [ 54 ] may contain relevant information concerning TBS treatment responses in depression. Regarding the understanding of mechanisms and response predictors of TBS therapy, there is no doubt that individual network structure and activity [ 55 , 56 ] as well as the genetic and epigenetic make-up [ 57 ] critically interacts with the clinical effect of TBS in depression.…”