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

TitleFunctional connectivity of the left DLPFC to striatum predicts treatment response of depression to TMS.
Publication TypeJournal Article
Year of Publication2017
AuthorsAvissar M, Powell F, Ilieva I, Respino M, Gunning FM, Liston C, Dubin MJ
JournalBrain Stimul
Date Published2017 Sep - Oct
KeywordsAdult, Depressive Disorder, Treatment-Resistant, Diffusion Tensor Imaging, Female, Frontal Lobe, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neostriatum, Nerve Net, Predictive Value of Tests, Transcranial Magnetic Stimulation, Treatment Outcome

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, family-wise 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 HAMD (Pearson's R = 0.58, p = 0.002).

CONCLUSION(S): In an exploratory analysis, higher functional connectivity between the left 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.

Alternate JournalBrain Stimul
PubMed ID28747260
PubMed Central IDPMC5568496
Grant ListT32 MH018870 / MH / NIMH NIH HHS / United States
R00 MH097822 / MH / NIMH NIH HHS / United States
R01 MH097735 / MH / NIMH NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
K99 MH097822 / MH / NIMH NIH HHS / United States