An agile, data-driven approach for target selection in rTMS therapy for anxiety symptoms: Proof of concept and preliminary data for two novel targets.

INTRODUCTION: Data-driven approaches to transcranial magnetic stimulation (TMS) might yield more consistent and symptom-specific results based on individualized functional connectivity analyses compared to previous traditional approaches due to more precise targeting. We provide a proof of concept for an agile target selection paradigm based on using connectomic methods that can be used to detect patient-specific abnormal functional connectivity, guide treatment aimed at the most abnormal regions, and optimize the rapid development of new hypotheses for future study. METHODS: We used the resting-state functional MRI data of 28 patients with medically refractory generalized anxiety disorder to perform agile target selection based on abnormal functional connectivity patterns between the Default Mode Network (DMN) and Central Executive Network (CEN). The most abnormal areas of connectivity within these regions were selected for subsequent targeted TMS treatment by a machine learning based on an anomalous functional connectivity detection matrix. Areas with mostly hyperconnectivity were stimulated with continuous theta burst stimulation and the converse with intermittent theta burst stimulation. An image-guided accelerated theta burst stimulation paradigm was used for treatment. RESULTS: Areas 8Av and PGs demonstrated consistent abnormalities, particularly in the left hemisphere. Significant improvements were demonstrated in anxiety symptoms, and few, minor complications were reported (fatigue (n = 2) and headache (n = 1)). CONCLUSIONS: Our study suggests that a left-lateralized DMN is likely the primary functional network disturbed in anxiety-related disorders, which can be improved by identifying and targeting abnormal regions with a rapid, data-driven, agile aTBS treatment on an individualized basis.

Real world demonstration of hand motor mapping using the structural connectivity atlas.

BACKGROUND: Locating the hand-motor-cortex (HMC) is an essential component within many neurosurgeries. Despite advancements in these localization methods there are still downfalls for each. Additionally, the importance of presurgical planning calls for increasingly accurate and efficient methods of locating specific cortical regions. OBJECTIVE: In this study we aimed to test the ability of the Structural Connectivity Atlas (SCA), a machine-learning based method to parcellate the human cortex, to locate the HMC in a small cohort study. METHODS: Using MRI and DTI images obtained from adult subjects (n = 11), personalized brain maps were created for each individual based on a SCA paired with the Brainnetome region for the HMC. Subjects received single pulse TMS, over the HMC region through the use of a neuronavigation system. If they responded with motor movement, this was recorded. The SCA identified HMC region was compared to the visual-determined HMC through identifying the Omega fold on the Precentral Gyrus, which was completed by a trained neuroanatomist. A Kendall's Tau B correlation was conducted between anatomical match and visual movement. RESULTS: This study concluded that the SCA was capable of locating the HMC in healthy and distorted brains. Overall, the SCA defined the anatomical area of the HMC in 90 % of subjects and triggered a motor response in 61 %. CONCLUSION: The SCA could be suitable for incorporation into presurgical planning practices due to its ability to map anatomically abnormal brains. Further studies on larger cohorts and targeting different areas of cortex could be beneficial.

Anatomy and White Matter Connections of the Superior Parietal Lobule.

BACKGROUND: The superior parietal lobule (SPL) is involved in somatosensory and visuospatial integration with additional roles in attention, written language, and working memory. A detailed understanding of the exact location and nature of associated white matter tracts could improve surgical decisions and subsequent postoperative morbidity related to surgery in and around this gyrus. OBJECTIVE: To characterize the fiber tracts of the SPL based on relationships to other well-known neuroanatomic structures through diffusion spectrum imaging (DSI)-based fiber tracking validated by gross anatomical dissection as ground truth. METHODS: Neuroimaging data of 10 healthy, adult control subjects was obtained from a publicly accessible database published in Human Connectome Project for subsequent tractographic analyses. White matter tracts were mapped between both cerebral hemispheres, and a lateralization index was calculated based on resultant tract volumes. Post-mortem dissections of 10 cadavers identified the location of major tracts and validated our tractography results based on qualitative visual agreement. RESULTS: We identified 9 major connections of the SPL: U-fiber, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, middle longitudinal fasciculus, extreme capsule, vertical occipital fasciculus, cingulum, and corpus callosum. There was no significant fiber lateralization detected. CONCLUSION: The SPL is an important region implicated in a variety of tasks involving visuomotor and visuospatial integration. Improved understanding of the fiber bundle anatomy elucidated in this study can provide invaluable information for surgical treatment decisions related to this region.

Anatomy and White Matter Connections of the Parahippocampal Gyrus.

BACKGROUND: The parahippocampal gyrus is understood to have a role in high cognitive functions including memory encoding and retrieval and visuospatial processing. A detailed understanding of the exact location and nature of associated white tracts could significantly improve postoperative morbidity related to declining capacity. Through diffusion tensor imaging-based fiber tracking validated by gross anatomic dissection as ground truth, we have characterized these connections based on relationships to other well-known structures. METHODS: Diffusion imaging from the Human Connectome Project for 10 healthy adult controls was used for tractography analysis. We evaluated the parahippocampal gyrus as a whole based on connectivity with other regions. All parahippocampal gyrus tracts were mapped in both hemispheres, and a lateralization index was calculated with resultant tract volumes. RESULTS: We identified 2 connections of the parahippocampal gyrus: inferior longitudinal fasciculus and cingulum. Lateralization of the cingulum was detected (P < 0.05). CONCLUSIONS: The parahippocampal gyrus is an important center for memory processing. Subtle differences in executive functioning following surgery for limbic tumors may be better understood in the context of the fiber-bundle anatomy highlighted by this study.