Date of Degree

9-2022

Document Type

Dissertation

Degree Name

Ph.D.

Program

Psychology

Advisor

Junghoon Kim

Committee Members

Ze Wang

Tony Ro

Jacek Dmochowski

Prin Amorapanth

Subject Categories

Biological Psychology

Keywords

neuroimaging, neuroscience, traumatic brain injury

Abstract

The main purpose of this dissertation is to characterize noninvasive neuroimaging biomarkers of neurovascular injury in moderate-severe traumatic brain injury (msTBI) as potential treatment targets for neuromodulation therapy. In Chapter 1, I aim to introduce msTBI and two known sequelae of neurovascular damage in msTBI: reduced cerebral blood flow (Ware et al., 2020; Julliene et al., 2016) and altered low frequency fluctuations in blood oxygen level-dependent signal (Zhou et al., 2021; Palacios et al., 2013). Chapter 2 aims to identify the regional pattern of altered resting cerebral blood flow from a cohort of 29 patients with msTBI assessed at 3, 6, and 12 months post-injury.

Chapter 3 aims to identify the regional pattern of MRI indices of spontaneous neural activity derived from resting blood oxygen level-dependent signal in the same patients: amplitude of low frequency fluctuations (ALFF) and fractional amplitude of low frequency fluctuations (fALFF). I have analyzed both the cerebral blood flow and BOLD signal data and have explored the relationship of the change in hemodynamics over time with the improvement/decline in cognition (measured by executive functioning, processing speed, and verbal learning) from 3 to 6 and 6 to 12 months post-injury. I also tested the relationship of these measures with injury severity and other clinical and demographic variables. Further, this chapter aims to determine the extent that the alterations of proxy measures of spontaneous neural activity co-localize with deficits in perfusion in traumatic brain injury patients.

Chapter 4 aims to spatially correlate the perfusion measures from Chapter 2 and proxy measures of spontaneous neural activity using a more direct method than co-localization method presented in Chapter 3; the working term for this correlation is MRI biomarkers of neurovascular coupling. There has been much evidence of a tight relationship between cerebral blood flow and neural activity (Girouard et al., 2006; Armstead, 2016). While neurovascular coupling is maintained in healthy adults (Liang et al., 2013), it is weakened in multiple populations (Zhu et al., 2017; Phillips et al., 2016). However, the extent and pattern of disruption of this relationship have yet to be explored in TBI. In this chapter, I related cerebral blood flow to fALFF (voxel-wise) at 3, 6, and 12 months post-injury. Similar to previous chapters, I measured the relationship of CBF-fMRI fluctuation coupling to both injury severity and cognition during the first year post-injury. With this data, I have determined a ‘profile’ (or spatial map) from the pattern of coupling deficits. I determined regions of MRI biomarkers of coupling deficit that can be potential treatment targets for noninvasive brain stimulation that is better described using individual-specific analysis. In Chapter 5, I will write up concluding remarks.

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