BACKGROUND Transcranial magnetic stimulation (TMS) to the left dorsal-lateral 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 suggests 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) fMRI 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. DLPFC TMS sites with better clinical efficacy were more negatively correlated (anticorrelated) with the subgenual cingulate. Optimum connectivity-based stimulation coordinates were identified in BA46. 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.

Hypnosis has proven clinical utility, yet changes in brain activity underlying the hypnotic state have not yet been fully identified. Previous research suggests that hypnosis is associated with decreased default mode network (DMN) activity and that high hypnotizability is associated with greater functional connectivity between the executive control network (ECN) and the salience network (SN). We used functional magnetic resonance imaging to investigate activity and functional connectivity among these three networks in hypnosis. We selected 57 of 545 healthy subjects with very high or low hypnotizability using two hypnotizability scales. All subjects underwent four conditions in the scanner: rest, memory retrieval, and two different hypnosis experiences guided by standard pre-recorded instructions in counterbalanced order. Seeds for the ECN, SN, and DMN were left and right dorsolateral prefrontal cortex, dorsal anterior cingulate cortex (dACC), and posterior cingulate cortex (PCC), respectively. During hypnosis there was reduced activity in the dACC, increased functional connectivity between the dorsolateral prefrontal cortex (DLPFC;ECN) and the insula in the SN, and reduced connectivity between the ECN (DLPFC) and the DMN (PCC). These changes in neural activity underlie the focused attention, enhanced somatic and emotional control, and lack of self-consciousness that characterizes hypnosis.

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This small open-label study suggests that aripiprazole is a promising treatment for the treatment of trichotillomania. Larger double-blind, placebo-controlled studies are needed to follow up on these findings.