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Shared Alterations in Thalamic Functional Architecture & Integration Across Neurologic Disorders

Monday, February 12, 2024

3:00 PM-5:00 PM

BIOMED PhD Research Proposal

Shared Alterations in Thalamic Functional Architecture and Integration Across Multiple Neurologic Disorders Could Improve Transdiagnostic Etiology

Stacy N. Hudgins, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Hasan Ayaz, PhD
Associate Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University
The human thalamus, a complex network of bilateral subcortical nuclei, plays a pivotal role in central nervous system connectivity. Despite its crucial function, the full extent of its involvement in integrating neural connections remains largely elusive. Research indicates that focal thalamic lesions have far-reaching consequences, disrupting the topographical organization of cortical functions. Emerging evidence suggests that the thalamus is intricately involved in the functional integration of diverse cortical networks, going beyond its conventional role of merely relaying sensory and motor processing. However, historically, thalamic functional subdivisions have primarily been examined through the lens of its histological organization. Understanding the functional network architecture of the thalamus, particularly in the context of shared clinical symptoms, can enhance our ability to assess and address various neurological disorders, transcending current diagnostic paradigms and improving therapeutic strategies.

In this thesis, we leverage functional magnetic resonance imaging (fMRI) whole-brain data, utilizing state-independent blood-oxygen-level-dependent (BOLD) signal from a total of 420 individuals (285 in the epilepsy studies and 135 in the psychiatric studies) to investigate the functional relationships intrinsic and extrinsic to the thalamic architecture across various neurologic disorders and neurotypical individuals. This non-invasive approach offers high spatial and temporal resolution, enabling precise visualization of neuronal activation in the context of a subject’s neurological state (neurotypical or aberrations associated with their disorder).

This research addresses a gap in the literature concerning the shared alterations in thalamic functional architecture and integration across multiple neurological disorders. Drawing from established anatomical network structures, such as the Default Mode Network (DMN), and Cortico-thalamo-cerebellar (CTC) circuit, as well as shared behavioral manifestations in task and task-free conditions, we seek to assess intrinsic and functional network connectivity by leveraging voxel- and cluster-based analyses, respectively. Specifically, we investigate whether distinct intrinsic functional networks emerge within thalamic regions in subtypes of temporal lobe epilepsy (TLE). Furthermore, we explore whether thalamic regions ipsilateral or contralateral to the ictal focus contribute to the architecture supporting seizure severity. By extending our analysis to subcortical regions, we compare these thalamic functional networks with those found ipsilateral or contralateral to the ictal focus, enhancing our understanding of their role in seizure severity. Our research also extends to other neurological disorders, such as schizophrenia, bipolar II, and attention deficit hyperactivity disorder (ADHD), examining whether thalamic regions form distinct functional networks sensitive to clinical assessments. The brain inherently operates through functional networks that closely correspond to context-specific regional co-activation. By associating clinical symptoms and traits with the degree of regional integration patterns, we aim to uncover transdiagnostic patterns related to neurological disorders.

This comprehensive investigation into thalamic functional architecture and its role in various neurological conditions holds the potential to significantly advance our understanding of the brain's intricate connectivity and its implications for clinical diagnosis and treatment.

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