Functional connectivity of the left DLPFC to striatum predicts treatment response of depression to TMS

Abstract

Background Repetitive transcranial magnetic stimulation (TMS) is a non-invasive, safe, and efficacious treatment for depression. TMS has been shown to normalize abnormal functional connectivity of cortico-cortical circuits in depression and baseline functional connectivity of these circuits predicts treatment response. Less is known about the relationship between functional connectivity of frontostriatal circuits and treatment response. Objective/Hypothesis We investigated whether baseline functional connectivity of distinct frontostriatal circuits predicted response to TMS. Methods Resting-state fMRI (rsfMRI) was acquired in 27 currently depressed subjects with treatment resistant depression and 27 healthy controls. Depressed subjects were treated with 5 weeks of daily TMS over the left dorsolateral prefrontal cortex (DLPFC). The functional connectivity between limbic, executive, rostral motor, and caudal motor regions of frontal cortex and their corresponding striatal targets were determined at baseline using an existing atlas based on diffusion tensor imaging. TMS treatment response was measured by percent reduction in the 24-item Hamilton Depression Rating Scale (HAMD24). In an exploratory analysis, correlations were determined between baseline functional connectivity and TMS treatment response. Results Seven cortical clusters belonging to the executive and rostral motor frontostriatal projections had reduced functional connectivity in depression compared to healthy controls. No frontostriatal projections showed increased functional connectivity in depression (voxel-wise p < 0.01, familywise α < 0.01). Only baseline functional connectivity between the left DLPFC and the striatum predicted TMS response. Higher baseline functional connectivity correlated with greater reductions in HAMD24 (Pearson’s R = 0.58, p = 0.002). Conclusion(s) In an exploratory analysis, higher functional connectivity between the DLPFC and striatum predicted better treatment response. Our findings suggest that the antidepressant mechanism of action of TMS may require connectivity from cortex proximal to the stimulation site to the striatum.

Nicotine normalizes cortico-striatal connectivity in non-smoking individuals with major depressive disorder

“…There also is evidence that MDD is characterized by disruptions in other cortico-striatal paths including increased connectivity between the dorsal striatum (DS) and dorsolateral prefrontal cortex (DLPFC) [5], particularly with greater disease severity [17]. Enhanced baseline DS-DLPFC connectivity predicted favorable response to transcranial magnetic stimulation (TMS) [18]. Treatment response was associated with a trend level decrease in DS-DLPFC connectivity, suggesting that reduced DS-DLPFC connectivity correlates with MDD symptom reduction.…”

Repetitive transcranial magnetic stimulation in the treatment of depression

“…Depression is associated with dysfunctional connectivity in these networks, and successful rTMS treatment is associated with normalisation of these abnormalities. [11][12][13][14] Current evidence 18 The Canadian authors 18 found that rTMS (both high and low frequency) is suitable as first-line treatment for treatmentresistant MDD, grading the evidence as 'Level I'. The European authors 16 gave rTMS (both high and low frequency) a 'Level A recommendation' and reported 'definite efficacy'.…”

A Double-Blind Pilot Dosing Study of Low Field Magnetic Stimulation (LFMS) for Treatment-Resistant Depression (TRD)

“…In addition to optimizing the dosing protocol and testing the durability of the mood improvments, we need to better characterize the subgroup of patients who respond to LFMS. Using functional neuroimaging to understand the circuit abnormalities that are predictive of treatment response has shown great promise for TMS [32][33][34][35][36][37][38]. Mapping these abnormalities in LFMS responders could eventually help match the treatment to depressed patients most likely to benefit and will guide advancements in LFMS coil design to optimize treatment [39,40].…”