Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate.
BACKGROUND
Transcranial magnetic stimulation (TMS) to the left dorsolateral prefrontal cortex (DLPFC) is used clinically for the treatment of depression. However, the antidepressant mechanism remains unknown and its therapeutic efficacy remains limited. Recent data suggest that some left DLPFC targets are more effective than others; however, the reasons for this heterogeneity and how to capitalize on this information remain unclear.


METHODS
Intrinsic (resting state) functional magnetic resonance imaging data from 98 normal subjects were used to compute functional connectivity with various left DLPFC TMS targets employed in the literature. Differences in functional connectivity related to differences in previously reported clinical efficacy were identified. This information was translated into a connectivity-based targeting strategy to identify optimized left DLPFC TMS coordinates. Results in normal subjects were tested for reproducibility in an independent cohort of 13 patients with depression.


RESULTS
Differences in functional connectivity were related to previously reported differences in clinical efficacy across a distributed set of cortical and limbic regions. Dorsolateral prefrontal cortex TMS sites with better clinical efficacy were more negatively correlated (anticorrelated) with the subgenual cingulate. Optimum connectivity-based stimulation coordinates were identified in Brodmann area 46. Results were reproducible in patients with depression.


CONCLUSIONS
Reported antidepressant efficacy of different left DLPFC TMS sites is related to the anticorrelation of each site with the subgenual cingulate, potentially lending insight into the antidepressant mechanism of TMS and suggesting a role for intrinsically anticorrelated networks in depression. These results can be translated into a connectivity-based targeting strategy for focal brain stimulation that might be used to optimize clinical response.
Partners Neurology, Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. foxmdphd@gmail.com
Michael D
MD
Fox
Randy L
RL
Buckner
Matthew P
MP
White
Michael D
MD
Greicius
Alvaro
A
Pascual-Leone
D000328:Adult; D001931:Brain Mapping; D003865:Major Depressive Disorder / Q000473:pathology* / Q000628:therapy*; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000098:blood supply*; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000098:blood supply* / Q000473:pathology; D011569:Psychiatric Status Rating Scales; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult
D010100:Oxygen