Variability of white matter anatomy in the subcallosal cingulate area

• Published in: Human brain mapping Vol. 42; no. 7; pp. 2005 - 2017
• Main Authors: Tsolaki, Evangelia, Sheth, Sameer A., Pouratian, Nader
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.05.2021
• Subjects: Adult; Anatomy; Brain; Cingulum; Corpus Callosum - anatomy & histology; Corpus Callosum - diagnostic imaging; Cortex (cingulate); Cortex (temporal); Deep brain stimulation; depression; Depressive Disorder, Major - diagnostic imaging; Depressive Disorder, Major - pathology; Diffusion Tensor Imaging - methods; Gyrus Cinguli - anatomy & histology; Gyrus Cinguli - diagnostic imaging; Humans; Medical instruments; Mental depression; Neostriatum; Nerve Net - anatomy & histology; Nerve Net - diagnostic imaging; Neural networks; Prefrontal cortex; Prefrontal Cortex - anatomy & histology; Prefrontal Cortex - diagnostic imaging; probabilistic Tractography; Seeds; subcallosal cingulate; Substantia alba; Therapeutic targets; Variability; Ventral Striatum - anatomy & histology; Ventral Striatum - diagnostic imaging; White Matter - anatomy & histology; White Matter - diagnostic imaging; depression; anatomy; probabilistic Tractography; subcallosal cingulate
• ISSN: 1065-9471; 1097-0193; 1097-0193
• DOI: 10.1002/hbm.25341

The subcallosal cingulate (SCC) area is a putative hub in the brain network underlying depression. Deep brain stimulation (DBS) targeting a particular subregion of SCC, identified as the intersection of forceps minor (FM), uncinate fasciculus (UCF), cingulum and fronto‐striatal fiber bundles, may be critical to a therapeutic response in patients with severe, treatment‐resistant forms of major depressive disorder (MDD). The pattern and variability of the white matter anatomy and organization within SCC has not been extensively characterized across individuals. The goal of this study is to investigate the variability of white matter bundles within the SCC that structurally connect this region with critical nodes in the depression network. Structural and diffusion data from 100 healthy subjects from the Human Connectome Project database were analyzed. Anatomically defined SCC regions were used as seeds to perform probabilistic tractography and to estimate the connectivity from the SCC to subject‐specific target areas believed to be involved in the pathology of MDD including ventral striatum (VS), UCF, anterior cingulate cortex (ACC), and medial prefrontal cortex (mPFC). Four distinct areas of connectivity were identified within SCC across subjects: (a) postero‐lateral SCC connectivity to medial temporal regions via UCF, (b) postero‐medial connectivity to VS, (c) superior‐medial connectivity to ACC via cingulum bundle, and (d) antero‐lateral connectivity to mPFC regions via forceps minor. Assuming white matter connectivity is critical to therapeutic response, the improved anatomic understanding of SCC as well as an appreciation of the intersubject variability are critical to developing optimized therapeutic targeting for SCC DBS. The SCC demonstrates consistent connectivity across subjects to brain regions critical in mood regulation. Tractography‐based parcellation demonstrates a relative consistent pattern of white matter bundle organization within SCC. Despite relative consistency, variability in white matter anatomy within SCC was still significant. Understanding the pattern and variability of white matter organization within SCC across individuals may have significant implications for DBS targeting in future clinical trials.