Inter- and Intra-Subject Variability of White Matter Activation Pathways in SCC DBS for Depression

18 

Abstract Submission 

Ha Neul Song¹, Helen Mayberg¹, Ki Sueng Choi¹

¹Icahn School of Medicine at Mount Sinai, New York, NY

Ha Neul Song  
Icahn School of Medicine at Mount Sinai
New York, NY

Helen Mayberg  
Icahn School of Medicine at Mount Sinai
New York, NY

Ki Sueng Choi  
Icahn School of Medicine at Mount Sinai
New York, NY

Deep brain stimulation (DBS) of the subcallosal cingulate cortex (SCC) has shown efficacy in treating treatment-resistant depression (TRD). Recent advancements in targeting have shifted the focus from a focal target to a multi-node network target within the SCC. The SCC's interconnectedness with other brain regions through white matter (WM) bundles underscores the necessity of stimulating all connections for a clinical response. Surgical targeting relies on individual structural connectivity analysis to maximize the activation of critical WM bundles including the cingulum bundle, forceps minor, and subcortical junction. Due to the limitations of many clinics to collect high spatial and angular diffusion-weighted data, use of normative connectome data might be a suitable substitute to identify patient-specific targets for SCC DBS surgery because of its high signal-to-noise ratio and test-retest reliability. Applying normative data to define an SCC target, predefined by connectome data, is also more convenient than a personalized SCC target, which necessitates individual diffusion data for each case. We explored inter- and intra-subject variabilities of WM activation pathways in known SCC targets using available human connectome data to investigate connectome-based targeting accuracy.

We approximated bilateral volumes of tissue activated (VTAs) in 143 TRD patients based on their known DBS stimulation settings (amplitude and contact configuration) using Lead DBS software. For each hemisphere, a probabilistic stimulation map (PSM) was derived using VTAs, and one SCC target was defined by maximum value of PSM (x = ±7, y = 24, z = -8). Whole brain tractography was performed on the Human Connectome Database (HCP; n = 1,000) using this target as the identical center of seed (radius = 3 mm). The inter-subject similarity in each critical WM bundle was measured using correlation coefficient values. Moreover, intra-subject similarity (spatial similarity) was measured in each critical WM bundle while the seed was moved 3 mm in (1) superior-inferior, (2) anterior-posterior, and (3) medial-lateral directions.

The findings revealed low inter-subject similarity in general (0.53 ± 0.07 out of 1.00), with distinct dissimilarity patterns within the left and right hemispheres. Notably, the cingulum bundle and subcortical junction exhibited significantly lower inter-subject similarity on the left side than right (p < 0.001). Intra-subject similarity analysis demonstrated a low similarity in the left hemisphere when the seed was moved in the superior-inferior or medial-lateral axis (0.56 ± 0.14), whereas high similarity was observed with movement in the anterior-posterior axis (0.84 ± 0.11; p < 0.001).

The predefined SCC targets, which can be optimal for SCC-DBS in normative data, induced high variability of WM activation in individual subjects. Our findings suggest that identifying SCC targets using normative data may compromise treatment efficacy due to low inter-subject similarity. Moreover, spatial similarity results emphasize the necessity of delivering a precise target identification due to the large variability of WM activation pathways in inferior-superior and medial-lateral directions. This study further validates the importance of patient-specific targeting using individual connectivity profiles.

Deep Brain Stimulation ¹

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ²

White Matter Anatomy, Fiber Pathways and Connectivity

MRI

Psychiatric Disorders

White Matter

Other - Deep Brain Stimulation; Depression