Ventral tegmental area fiber tracts implicated in various DBS targets for neuropsychiatric disease.

Introduction: We recently characterized the connectivity of the Ventral tegmental area (VTA) with the raphe nuclei, hypothalamus, mammillary bodies, fornix, septal nuclei, bed nucleus of the stria terminalis (BNST), nucleus basalis of Meynert (NBM), caudate, putamen, globus pallidus, insula, amygdala, dorsal hippocampus/dentate gyrus, nucleus accumbens (NAc), entorhinal cortex, BA10, BA11, and BA12. Given the abundance of connections between the VTA and basal forebrain structures, we hypothesize that the VTA network is implicated in DBS of the midbrain and diencephalon.

Methods: We analyzed previously reported targeted hotspots and coordinates on the efficacy of ventral tegmentum and diencephalon DBS in the treatment of various neurological and psychiatric diseases. To identify relevant data, we conducted a comprehensive literature review. AC-PC coordinates were converted into MNI coordinates as described previously and visualized as electrode trajectories in Lead-DBS. The characterized VTA fiber tracts were reconstructed in Lead-DBS in MNI space. Using Lead-DBS software, we evaluated the relationship between lead trajectories and the identified VTA tracts.

Results: We successfully reconstructed electrode trajectories and our characterized VTA tracts in MNI space by utilizing our fiber tractography data and previously reported DBS data. VTA fiber tracts exhibited very close anatomical relationship and/or overlap with VTA, GP, inferior thalamic peduncle, BNST, fornix, posterior hypothalamus, ventral capsule/ventral striatum, and NAc, DBS targets utilized for the treatment of Obsessive-Compulsive Disorder, Major Depression, cluster headaches, aggression, and Alzheimer’s Disease.

Conclusion : Reconstruction of the lead trajectories and characterized tracts using Lead-DBS software allowed us to evaluate their relationship. DBS treatment effects and stimulation related complications can be now studied under the lens of the recently characterized VTA circuitry. The VTA is a hub that might provide an effective DBS target for neuropsychiatric disease with fewer side effects and should be further assessed through future studies.