Brain-wide electrophysiological signatures of blast-induced traumatic brain injury
File(s)
Author(s)
Tsikonofilos, Konstantinos
Type
Thesis
Abstract
Traumatic Brain Injury (TBI) stands as a significant contributor to mortality and disability, imparting enduring repercussions that diminish one’s quality of life. Notably, it constitutes a
well-established occupational hazard for military personnel exposed to explosive blasts. Despite extensive research, our understanding of the impact of TBI on macroscopic brain circuitry and networks remains incomplete. Furthermore, TBI can disrupt sensory processing, most notably affecting auditory perception and consequently undermining everyday communication.
In this thesis, I employ a rodent model to investigate blast-induced TBI (bTBI). My approach involves assessing the temporal progression of injury through electrophysiological recordings
of brain activity, conducted at both acute and chronic post-injury intervals, during periods of rest and auditory stimulation. To discern distinct injury markers, I employ a spectrum of metrics encompassing power, functional connectivity, and characteristics of evoked potentials.
Additionally, I utilize graph-theoretical metrics and supplement these with computational models of brain activity. Regarding resting-state data, my analysis reveals an elevation in power alongside a shift towards lower-frequency activity—a hallmark of TBI. This is accompanied by a conspicuous hyperconnectivity effect in the gamma frequency band. Graph theoretical exploration of gamma-band networks reveals disparities in small-worldness and rich-club structure, indicating functional reorganization following bTBI. I further investigate the cost-efficiency trade-offs within these networks, with a proposed normalization procedure suggesting a metabolic rationale as the driving force behind this phenomenon. Complementing this view, I employ a computational model of brain-wide seizure dynamics to support the notion of reorganization as a homeostatic mechanism for activity level regulation. Furthermore, my findings indicate heightened sound-evoked response amplitudes, particularly at the cortical level, underscoring post-injury hyperexcitability...
well-established occupational hazard for military personnel exposed to explosive blasts. Despite extensive research, our understanding of the impact of TBI on macroscopic brain circuitry and networks remains incomplete. Furthermore, TBI can disrupt sensory processing, most notably affecting auditory perception and consequently undermining everyday communication.
In this thesis, I employ a rodent model to investigate blast-induced TBI (bTBI). My approach involves assessing the temporal progression of injury through electrophysiological recordings
of brain activity, conducted at both acute and chronic post-injury intervals, during periods of rest and auditory stimulation. To discern distinct injury markers, I employ a spectrum of metrics encompassing power, functional connectivity, and characteristics of evoked potentials.
Additionally, I utilize graph-theoretical metrics and supplement these with computational models of brain activity. Regarding resting-state data, my analysis reveals an elevation in power alongside a shift towards lower-frequency activity—a hallmark of TBI. This is accompanied by a conspicuous hyperconnectivity effect in the gamma frequency band. Graph theoretical exploration of gamma-band networks reveals disparities in small-worldness and rich-club structure, indicating functional reorganization following bTBI. I further investigate the cost-efficiency trade-offs within these networks, with a proposed normalization procedure suggesting a metabolic rationale as the driving force behind this phenomenon. Complementing this view, I employ a computational model of brain-wide seizure dynamics to support the notion of reorganization as a homeostatic mechanism for activity level regulation. Furthermore, my findings indicate heightened sound-evoked response amplitudes, particularly at the cortical level, underscoring post-injury hyperexcitability...
Version
Open Access
Date Issued
2023-10-21
Date Awarded
2024-02-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Kozlov, Andriy
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)