Abstract
ObjectivesAbnormal activity of the subgenual anterior cingulate cortex (sACC) is implicated in depression, suggesting the sACC as a potentially effective target for therapeutic modulation in cases resistant to conventional treatments (treatment-resistant depression, TRD). We hypothesized that areas in the prefrontal cortex (PFC) with direct fiber connections to the sACC may be particularly effective sites for treatment using transcranial magnetic stimulation (TMS). The aim of this study was to identify PFC sites most strongly connected to the sACC.MethodsTwo neuroimaging data sets were used to construct anatomic and functional connectivity maps using sACC as the seed region. Data set 1 included magnetic resonance (MR) images from 20 healthy controls and Data set 2 included MR images from 15 TRD patients and 15 additional healthy controls. PFC voxels with maximum values in the mean anatomic connection probability maps were identified as optimal sites for TMS.ResultsBoth right and left PFC contained sites strongly connected to the sACC, but the coordinates (in Montreal Neurological Institute space) of peak anatomic connectivity differed slightly between hemispheres. The left PFC site connected directly to the sACC both anatomically and functionally, while the right PFC site was functionally connected to the posterior cingulate cortex (PCC).ConclusionsBoth left and right PFC are functionally connected to regions implicated in depression, the sACC and PCC, respectively. These bilateral PFC sites may be effective TMS targets to treat TRD.
Highlights
Major depressive disorder (MDD) can be effectively treated in the majority of cases by medication, psychotherapy, or a combination of both, but more than one third of patients fail to respond to these standard interventions and other treatments, termed treatment-resistant depression or TRD cases [1]
A probability connectivity map was derived for both hemispheres of each subject and mean probability connectivity maps obtained (Figure 1), yielded bilateral maximum probability coordination (x-y-z in Montreal Neurological Institute (MNI) space) as potential Transcranial magnetic stimulation (TMS) sites
Potential prefrontal cortex (PFC) stimulation sites were identified as voxels with the highest probability of connectivity to the subgenual anterior cingulate cortex (sACC) (Supplementary Figure 2)
Summary
Major depressive disorder (MDD) can be effectively treated in the majority of cases by medication, psychotherapy, or a combination of both, but more than one third of patients fail to respond to these standard interventions and other treatments, termed treatment-resistant depression or TRD cases [1]. Transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS) exert antidepressant effects by modulating activity within specific neural networks associated with emotional regulation and cognition [2,3,4,5]. Vagus nerve stimulation has been approved by the United States Food and Drug Administration (FDA) for TRD treatment, not for management of acute illness [6]. While TMS has been approved by the FDA for TRD, its effect size is generally modest compared to DBS [6]. This lower efficacy may result from uncertainty regarding therapeutic mechanisms and the optimal regimens and target sites. While the prefrontal cortex (PFC) is widely regarded as an effective stimulation site, the precise subregions of left and right PFC evoking the optimal therapeutic response are unclear [11,12,13]
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