Neuroimaging Mechanisms of Therapeutic Transcranial Magnetic Stimulation for Major Depressive Disorder

Abstract

Research into therapeutic transcranial magnetic stimulation (TMS) for major depression has dramatically increased in the last decade. Understanding the mechanism of action of TMS is crucial to improve efficacy and develop the next generation of therapeutic stimulation. Early imaging research provided initial data supportive of widely held assumptions about hypothesized inhibitory or excitatory consequences of stimulation. Early work also indicated that while TMS modulated brain activity under the stimulation site, effects at deeper regions, in particular, the subgenual anterior cingulate cortex, were associated with clinical improvement. Concordant with earlier findings, functional connectivity studies also demonstrated that clinical improvements were related to changes distal, rather than proximal, to the site of stimulation. Moreover, recent work suggests that TMS modulates and potentially normalizes functional relationships between neural networks. An important observation that emerged from this review is that similar patterns of connectivity changes are observed across studies regardless of TMS parameters. Though promising, we stress that these imaging findings must be evaluated cautiously given the widespread reliance on modest sample sizes and little implementation of statistical validation. Additional limitations included use of imaging before and after a course of TMS, which provided little insight into changes that might occur during the weeks of stimulation. Furthermore, as studies to date have focused on depression, it is unclear whether our observations were related to mechanisms of action of TMS for depression or represented broader patterns of functional brain changes associated with clinical improvement.

Superior temporal sulcus hypoperfusion in children with autism spectrum disorder: an arterial spin-labeling magnetic resonance study

“…Firstly, identifying a core dysfunctional region in ASD bears direct implications to the development of novel therapeutic interventions. For example, in depression disorder, classical rest functional abnormalities in frontal regions have been the ground to development of transcranial magnetic stimulation (TMS) protocols applied to this region, with significant clinical improvements [40,41]. Results presented here suggest that STS could become an interesting target for this type of intervention in ASD.…”

Intrinsic connectivity of the prefrontal cortex and striato-limbic system respectively differentiate Major Depressive from Generalized Anxiety Disorder

“…Focal brain stimulation has been associated with changes that spread through the intrinsic networks of the brain and which outlast the actual stimulation period [17], including stimulation of the dorsolateral prefrontal cortex (DLPFC) which represents the primary and currently most effective target for non-invasive brain modulation in both MDD and GAD [18,19]. In line with these findings the anti-depressive treatment efficacy of non-invasive transcranial DLPFC stimulation has been associated with effects in distal brain regions and reorganization of multiple intrinsic brain networks, suggesting an important role of network level effects for therapeutic efficacy [20]. The most efficient stimulation targets across invasive and non-invasive targets are linked by shared intrinsic networks, further emphasizing the therapeutic and mechanistic importance of network level effects [21].…”

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

“…In PTSD+MDD, stronger amygdala‐to‐medial prefrontal cortex (MPFC) functional connectivity at baseline predicted superior improvement (Philip et al, ). Other studies have found predictive differences in pre‐TMS DLPFC‐striatum connectivity (Avissar et al, ; Kang et al, ), as well as between CEN and salience processing regions (Philip, Barredo, Aiken, & Carpenter, ).…”