Resting-State Cortico-Thalamic-Striatal Connectivity Predicts Response to Dorsomedial Prefrontal rTMS in Major Depressive Disorder

Abstract

Despite its high toll on society, there has been little recent improvement in treatment efficacy for major depressive disorder (MDD). The identification of biological markers of successful treatment response may allow for more personalized and effective treatment. Here we investigate whether resting-state functional connectivity predicted response to treatment with repetitive transcranial magnetic stimulation (rTMS) to dorsomedial prefrontal cortex (dmPFC). Twenty-five individuals with treatment-refractory MDD underwent a 4-week course of dmPFC-rTMS. Before and after treatment, subjects received resting-state functional MRI scans and assessments of depressive symptoms using the Hamilton Depresssion Rating Scale (HAMD17). We found that higher baseline cortico-cortical connectivity (dmPFC-subgenual cingulate and subgenual cingulate to dorsolateral PFC) and lower cortico-thalamic, cortico-striatal, and cortico-limbic connectivity were associated with better treatment outcomes. We also investigated how changes in connectivity over the course of treatment related to improvements in HAMD17 scores. We found that successful treatment was associated with increased dmPFC-thalamic connectivity and decreased subgenual cingulate cortex-caudate connectivity, Our findings provide insight into which individuals might respond to rTMS treatment and the mechanisms through which these treatments work.

Elevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy

“…6 The MPFC is overactive in individuals with MDD, 7 and functional connectivity between the DLPFC and MPFC predicts response to TMS. [8][9][10] Little is known about how connectivity between the DLPFC and MPFC gives rise to the antidepressant effect of TMS.…”

“…6 The MPFC is overactive in individuals with MDD,7 and functional connectivity between the DLPFC and MPFC predicts response to TMS. [8][9][10] Little is known about how connectivity between the DLPFC and MPFC gives rise to the antidepressant effect of TMS.Other antidepressants appear to act in part by modulating the excitability of cortical circuits. Levels of γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain, which are generally decreased in depressed individuals, 11 have been reported to increase after treatment with selective serotonin reuptake inhibitors (SSRIs) 12 and electroconvulsive therapy (ECT).…”

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

“…Additionally, graph theoretical measures such as betweenness centrality have been shown to differentiate dmPFC-rTMS responders and non-responders at baseline based on subscales for hedonic responses 23 . Neuroimaging also points to anterior mid-cingulate cortex and dorsomedial thalamic resting state functional connectivity change that correlates to treatment response 27 . In sum, functional neuroimaging may become a useful clinical tool as potential predictors and mechanisms of treatment response are identified.…”

“…Acquiring patient neuroimaging data before and after treatment allows for the identification of potential biological pre-treatment predictors and mechanisms of treatment response. Dorsomedial and subgenual cingulate resting-state functional connectivity have been identified as potential predictors to treatment response 27 . Additionally, graph theoretical measures such as betweenness centrality have been shown to differentiate dmPFC-rTMS responders and non-responders at baseline based on subscales for hedonic responses 23 .…”

Molecular, Functional, and Structural Imaging of Major Depressive Disorder

“…Interestingly, networks may show abnormal functional connectivity to the same brain nodes, which further adds our understanding of the concomitant symptoms of MDD patients. Meanwhile, altered functional connectivity values detected by resting-state fMRI have been used to evaluate the therapeutic effect of a diversity of treatments on MDD, such as specific pharmacological treatments, psychological treatment, transcranial magnetic stimulation, and electroconvulsive shock therapy [79][80][81][82][83][84][85][86]. To date, pharmacotherapy is still the dominant method for patients with MDD.…”