Structural plasticity following deep brain stimulation of the internal capsule in treatment resistant depression

Objective Deep brain stimulation (DBS) targeting the ventral anterior limb of the internal capsule (vALIC) shows potential as treatment for treatment resistant depression (TRD). While DBS alters brain function, it is not yet known whether it also induces anatomical alterations. Here we investigated the long-term effects of vALIC DBS on brain structure using structural magnetic resonance imaging. Methods We included data from twelve patients with TRD before DBS surgery and after DBS parameter optimization, and from sixteen matched healthy controls at a comparable time interval to control for test-retest effects. To investigate the short-term effects of DBS deactivation after parameter optimization, thirteen patients were additionally scanned after double-blind periods of active and sham stimulation. Voxel-based morphometry analysis was used to identify volumetric differences. Result The group x time interaction showed significant changes in anterior thalamic gray matter volume, with a relative reduction in TRD patients compared to controls. Follow-up analysis suggested that this was related to larger thalamic volume at baseline in DBS non-responders. A direct comparison between responders and non-responders showed an additional interaction in the posterior thalamus and hippocampus, which was also related to larger volumes at baseline in non-responders. The comparison between active and sham stimulation during the crossover phase did not show significant differences. Conclusion These results show that long-term vALIC DBS is associated with a reduction in thalamic volume compared to healthy controls, suggesting that long-term DBS induces focal structural plasticity.