Abstract

Deriving Candidate TMS Targets for Bipolar Disorder with Brain Lesions Causing Mania or Depression

Taylor J, Frandsen S, Anand A, Gunning F, Silbersweig D, Burdick K, Brodtmann A, Corbetta M, Cotovio G, Egorova N, Gozzi S, Grafman J, Naidech A, Oliveira-Maia A, Phan T, Voss J, Fox M, Siddiqi S
61st Annual Meeting of the American College of Neuropsychopharmacology. 2022.

Abstract

Background: Patients with bipolar disorder need better treatments. Transcranial magnetic stimulation (TMS) shows promise, but the optimal brain regions to stimulate are unknown. In this study, we derived a map that is causally implicated in mood valence based on the functional connectivity of brain lesions causing mania versus depression.

Methods: We combined seven independent lesion datasets for mania and depression into a single model. First, we estimated the connectivity of each lesion location using a normative connectome (n = 1000). Second, we created a mood valence map from the differential functional connectivity patterns of mania versus depression lesions. Third, we used permutation testing to determine whether the absolute mean voxel value in the mood valence map was stronger than chance (10,000 permutations). Fourth, we assessed specificity of the mood valence map with control lesions not associated with mood disturbance. Finally, we assessed whether the average coordinates of common TMS targets (i.e., bilateral 5 cm, anti-subgenual, dorsomedial) were preferentially connected to the mood valence map.

Results: Mania is more likely to be associated with lesions functionally connected to right prefrontal cortex, and depression is more likely to be associated with lesions functionally connected to left prefrontal cortex. This mood valence map was stronger than expected by chance (p < 0.05) and did not change when multiple control lesions were added into the model (spatial correlation r > 0.99). The left anti-subgenual TMS target was preferentially connected to the negative valence map (p < 0.01), and the right dorsomedial prefrontal cortex was preferentially connected to the positive valence map (p < 0.005).

Conclusions: Mood valence shows left-right frontal lobe asymmetry, consistent with existing literature. However, the topography of this asymmetry could guide optimization of TMS treatment targets for bipolar depression versus mania. Future analyses will search for a candidate treatment target functionally connected to both mania and depression lesions, which may be relevant for mood stabilization.