Presented By: Department of Psychology
CCN Forum - Transcranial magnetic stimulation and intrinsic connectivity networks in depression
Stephan F. Taylor, Professor of Psychiatry, Associate Chair, MSA Institution Review Board, Medical School and Psychiatry Department
Abstract
Repetitive transcranial magnetic stimulation (rTMS) is an effective therapy for major depressive disorder (MDD), with unknown mechanisms of action. Specific theories have hypothesized that indirect effects on the subgenual anterior cingulate cortex (sgACC), a structure strongly implicated in the treatment of depression, may mediate effective treatment by TMS.
We sought to test this hypothesis in the framework of intrinsic connectivity networks (ICN), by examining using functional MRI to probe ICNs before and after rTMS therapy. We studied 32 patients with major depressive disorder in a sham-controlled, double-blinded, randomized trial of rTMS to the left dorsolateral prefrontal cortex (dlFPC). Seed voxels were used to identify the affective network (subgenual anterior cingulate cortex [sgACC], amygdala), default mode network (DMN; posterior cingulate cortex [PCC]), salience network (dorsal anterior cingulate cortex) and the fronto-parietal network (FP; dlPFC stimulation site).
Analysis of the effect of rTMS (sham vs active) on connectivity revealed no significant change in connectivity. However, sgACC connectivity was reduced with the limbic, DMN and FP networks. To identify neural predictors of treatment response, we analyzed the relationship between baseline ICN activity and treatment response including subjects who started with sham but went on to active treatment (13 responders, 14 non-responders; 5 placebo responders excluded). This analysis found that greater DMN (PCC seed) positive connectivity to the anterior insula (aIns -- normal DMN connectivity is negative) was associated with a poorer treatment response.
These results provide additional support for the importance of sgACC in reducing depressive symptoms. However, the data do not support the conclusion that sgACC connectivity changes mediate the effect of TMS. Altered connectivity of DMN with aIns, a node of the salience network involved in integration of internal states and behavioral control, may reflect a type of patient less likely to respond to dlPFC rTMS therapy. Overall, the results, while preliminary, illustrate specific ICN changes in the relief of depressive symptoms.
Repetitive transcranial magnetic stimulation (rTMS) is an effective therapy for major depressive disorder (MDD), with unknown mechanisms of action. Specific theories have hypothesized that indirect effects on the subgenual anterior cingulate cortex (sgACC), a structure strongly implicated in the treatment of depression, may mediate effective treatment by TMS.
We sought to test this hypothesis in the framework of intrinsic connectivity networks (ICN), by examining using functional MRI to probe ICNs before and after rTMS therapy. We studied 32 patients with major depressive disorder in a sham-controlled, double-blinded, randomized trial of rTMS to the left dorsolateral prefrontal cortex (dlFPC). Seed voxels were used to identify the affective network (subgenual anterior cingulate cortex [sgACC], amygdala), default mode network (DMN; posterior cingulate cortex [PCC]), salience network (dorsal anterior cingulate cortex) and the fronto-parietal network (FP; dlPFC stimulation site).
Analysis of the effect of rTMS (sham vs active) on connectivity revealed no significant change in connectivity. However, sgACC connectivity was reduced with the limbic, DMN and FP networks. To identify neural predictors of treatment response, we analyzed the relationship between baseline ICN activity and treatment response including subjects who started with sham but went on to active treatment (13 responders, 14 non-responders; 5 placebo responders excluded). This analysis found that greater DMN (PCC seed) positive connectivity to the anterior insula (aIns -- normal DMN connectivity is negative) was associated with a poorer treatment response.
These results provide additional support for the importance of sgACC in reducing depressive symptoms. However, the data do not support the conclusion that sgACC connectivity changes mediate the effect of TMS. Altered connectivity of DMN with aIns, a node of the salience network involved in integration of internal states and behavioral control, may reflect a type of patient less likely to respond to dlPFC rTMS therapy. Overall, the results, while preliminary, illustrate specific ICN changes in the relief of depressive symptoms.
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