THE ROLE OF PARACINGULATE SULCAL MORPHOLOGY IN AFFECTIVE NETWORK CONNECTIVITY

PROJECT SUMMARY The cingulum bundle (CB) is a major white matter fiber system mediating connectivity of the affective network. As mood monitoring and regulation are controlled by the affective network, the CB is often investigated in relation to the pathophysiology and treatment interventions for mood disorders. Several efforts have attempted

to characterize the CB relative to mood disorders, however, previous approaches have overlooked consideration of interindividual variability in local anatomy. The most common anatomical variation in the cingulate region is the presence or absence of paracingulate sulcus (PCS) morphological pattern. Despite 70%

of the population exhibiting a distinct PCS in at least one cerebral hemisphere, and its presence inducing known reorganization and connectivity changes in cingulate gray matter, its influence on white matter remains unknown. Interindividual variability in paracingulate sulcus (PCS) morphology may alter local white matter

organization, specifically the cingulum bundle (CB) fiber system. Given the importance of the CB in mediating affective network connectivity implicated in mood disorders and treatment efforts, characterization of structural and functional implications of PCS variability is necessary. The goal of this project is to identify CB connectivity

alterations across PCS morphology and characterize ill-defined PCS-related white matter with respect to the cingulum fiber system. I hypothesize that PCS morphology will influence CB connectivity with affective network regions and that the PCS-related white matter, termed paracingulate white matter (pcWM), will

demonstrate affective network connectivity. I will evaluate these central hypotheses in the following two Specific Aims. Aim 1. To use high-resolution diffusion-based probabilistic tractography to determine the impact of PCS morphology on CB structural connectivity and characterize pcWM. Aim 2. To employ human

intracranial single pulse stimulation directed to the CB to determine the effect of PCS morphology on electrographically-defined effective connectivity of the CB. Completion of these Aims will provide novel insight into the relationship between white matter organization and sulcation pattern. Further, elucidating the influence

of PCS pattern on connectivity perturbation of the CB is necessary for informing and optimizing treatment intervention for mood disorders like depression. More than 30% of patients with Major Depressive Disorder (MDD) suffer from suboptimal responses and are diagnosed with Treatment Resistant Depression (TRD). With

a continued lack of response to other methods, patients may undergo an invasive surgical approach called deep brain stimulation (DBS) for depression treatment. DBS for TRD traditionally targets a confluence of white matter paths, and despite inconsistent response, CB engagement is the primary predictor of optimal patient

response. Parsing the correspondence of PCS pattern and the connectivity of the CB may reveal a contributing factor to response inconsistency, thereby informing neurosurgical planning and improving the capacity for predicting treatment response in TRD for DBS.