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Neuroanatomical correlates of attention and working memory deficits following traumatic brain injury

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thesis
posted on 14.03.2017, 06:04 authored by Jacqueline Owens
Attention and working memory deficits are frequent following moderate to severe traumatic brain injury (TBI), and can greatly impact everyday functioning. The mechanisms underpinning these deficits, however, are poorly understood. Identification of potential neuroanatomical markers that are associated with attentional impairment may help to inform targeted treatments, such as pharmacological interventions.
   The aims of the current studies were to investigate the association between attention and working memory deficits and TBI related brain changes, specially: (1) whole brain white matter microstructure; (2) white matter microstructure of the supero-lateral branch of the medial forebrain bundle (slMFB), a pathway rich in catecholamine; and (3) functional connectivity between the ventral tegmental area (VTA) (a brain region containing a large proportion of dopamine (DA) cell bodies) and the default mode network (DMN) – a resting-state network highly implicated in attention function.
   Twenty participants with a history of moderate to severe TBI and 20 demographically matched control participants were included in the study. White matter microstructure and functional connectivity between the VTA and DMN nodes were investigated using diffusion tensor imaging (DTI), and resting state functional magnetic resonance imaging (rs-fMRI), respectively. Participants also underwent neuropsychological assessment of attention and working memory.
   Participants with TBI demonstrated significantly slower performances on the Trail Making Task, Hayling, Selective Attention Task, n-back, and Symbol Digit Modalities Test (p < 0.001), when compared to controls. No impairments were identified in working memory or executive control of attention.
   The majority of white matter tracts within the brain were found to be altered following TBI, as indicated by lower FA (p < 0.001) and higher MD (p < 0.001). Correlation analysis revealed slowed information processing speed post-TBI was associated with lower FA  values in the corpus callosum, superior longitudinal fasciculus, cingulum, inferior fronto-occipital fasciculi, corona radiata, and cerebral white matter, when controlling for age and estimated pre-morbid intelligence.
   Alterations within the slMFB were also identified post-TBI. Participants with TBI demonstrated significantly lower FA (M = .32, SD = .03, p < 0.001) and higher MD (M = 7.43, SD = .46, p < 0.001) within the slMFB when compared to controls. No associations were found between slMFB white matter microstructure and attentional performance.
   Finally, the VTA was found to be functionally connected to the angular gyrus and precuneus (p < 0.05) for the control group only. Between-group differences were, however, not statistically significant. Individual variability in damage caused by TBI likely accounted for the lack of significant findings in this cohort. Given no significant alterations were identified, the correlation analysis with attention tasks was not undertaken. Findings from the control group suggest the VTA may influence the DMN via dopaminergic input into key DMN nodes.
   This thesis highlights the association between widespread white matter damage and slowed information processing speed following TBI. Additionally, it demonstrates both structural and functional changes to the DA system following TBI. Investigating dysfunction of catecholamine systems such as the DA system is promising as currently many therapeutic pharmacological agents are available. However, the current thesis did not provide substantial evidence for the role of DA disruption in attentional deficits following TBI.

History

Principal supervisor

Catherine Willmott

Additional supervisor 1

Jennie Ponsford

Year of Award

2017

Department, School or Centre

Psychological Sciences

Campus location

Australia

Course

Doctorate of Psychology (Clinical Neuropsychology)

Degree Type

DOCTORATE

Faculty

Faculty of Medicine Nursing and Health Sciences