Application of Tractography-Guided Deep Brain Stimulation

Application of Tractography-Guided Deep Brain Stimulation to Treatment-Resistant Major Depressive Disorder INTRODUCTION Major Depressive Disorder (MDD): a neuropsychiatric disorder characterized by persistent feelings of sadness and/or hopelessness RESULTS Figure 1 (Subject 100307, left cingulate gyrus mask only) DISCUSSION & CONCLUSIONS Limitations: • Feasibility as a long-term, non-recurrent treatment • Degree of precision required • Generalizability of brain circuitry associated with depression • Ability to determine whether or not a patient will respond to DBS Strengths: Mayberg, Lozano et al, Neuron 2005 (MDD patient) Treatment-Resistant Depression (TRD): depression that fails to respond to typical treatments (e.g. antidepressants) Figure 2 (Subject 101410, whole cingulate gyrus) • Circumvents side-effects associated with antidepressant use, particularly as the brain is adjusting to said medication. Additionally, it avoids the addiction/dependency development on pharmaceuticals. • An estimated 1/3 of MDD patients are affected by TRD Subcallosal Cingulate Gyrus (SCG): an area in the limbic system which regulates emotional behavior, specifically sadness ● ● Hyperactivity in this region correlates with symptoms of MDD By stimulating the SCG, hyperactivity can be modulated Tractography: a 3D modeling technique used to represent neural nerve tracts Deep Brain Stimulation (DBS): a surgical procedure which entails the insertion of electrodes in the brain of a patient to stimulate an area, thereby neuromodulating hyperactivity METHODS 1. Analyzed existing literature and selected the cingulate gyrus as the region of focus based on evidence of its association with depression and common use as a target of DBS targeting TRD. 2. Obtained subject bedpostX data (for subjects 100307, 101410, and 102614) from the Human Connectome Project. ○ bedpostX (Bayesian Estimation of Diffusion Parameters Obtained using Sampling Techniques) is processed subject data that models crossing fibres within each voxel of the brain. Used as input in the generation of probabilistic tractography models 3. Used the JHU White Matter Tractography Atlas to create anatomically based seed masks from the left and right cingulate gyrus 4. Used the PROBTRACKX tool (contained with FMRIB's Diffusion Toolbox, which is part of FSL - FMRIB's Software Library). Input the cingulate gyrus seed masks. ○ PROBTRACKX uses each voxel located in the seed masks to generate probabilistic tracts (in our subject data, PROBTRACKX generated 7.4-7.5 million tracts per subject) 5. Visualized these probabilistic tracts through the fsleyes viewer ○ Set the overlay type of the probabilistic tracts to maximum intensity projection and added the subject’s brain mask to see the tract’s location in the brain and filter out noise 6. Noted the most likely tracts (and therefore the optimal pathways to target for deep brain stimulation) based on the intensity of the tracts generated ○ In our probabilistic tractography models, the tracts that are less faint have a higher probability of being anatomically correct • Offers treatment to those who otherwise would have no alternative option • Augments our understanding of MDD circuitry on an electrical, as opposed to chemical, level Figure 3 (102614, whole cingulate gyrus) Interpreting Figures: ● PROBTRACKX displays the most probable tracts to be followed when a region is stimulated by calculating the connectivity distribution of each voxel. Voxels with a higher connectivity (i.e. more streamlines go through the voxel) appear darker in the masks generated above. FUTURE WORK Due to time constraints, precision calculations have not been made as of yet. ● In the future, we will be adapting the methodology of Raslan, Ahmed, Lee, Albert, & Burchiel, Kim (2013) to determine precision in application to DBS of the SCG to ameliorate TRD MDD symptoms. Similar to this study, we will be calculating the correlation between vector error and trajectory deviation error; however, measurements will be extracted from FSL by stimulating surrounding voxels to determine the degree of precision required to consistently generate pathways, as opposed to actual electrode placements in patients. ● In addition to hyperactivity in the SCG, TRD MDD is characterized by lower levels of activity in the regions depicted in blue from the Mayberg, Lozano et al, Neuron 2005 figure. Past studies suggest connectivity (both anatomical and functional) exists between these regions and the SCG. We will be targeting these regions of interest to measure the connectivity between them in FSL. Scan to view results produced after poster-printing!