(TBI) is one of the most common neurological disorders in the United States with the majority of the cases being classified as mild injury (GCS 13-15). Although diffuse axonal injury (DAI) may be present among such patients, it is often missed by CT and conventional MRI. This disruption of white matter connections between disperse regions of the brain will likely disrupt the large-scale neural networks supporting cognition. Therefore, in spite of being labeled as acquiring only mild injuries, many of these individuals suffer from cognitive symptoms, including memory complaints, as long-term sequelae from the injury. Functional MRI is a useful tool for assessing such disturbances in large-scale neural networks. Through resting state fMRI, groups have demonstrated a number of functionally connected neural networks including the default mode network (DMN) (TPN). During a working memory task, the DMN is suppressed while the TPN is activated. The Default Mode Interference Hypothesis suggests that the efficient switching between these two networks is required for peak cognitive performance. Further, if the TPN fails to adequately deactivate or suppress the activity of the DMN, there is an interference with goal directed behavior represented as a lapse in attention. This lapse in attention can be represented behaviorally by an increased reaction time or increased variability in reaction time throughout the duration of a task. The DMN and TPN are ideally anti-correlated as demonstrated by negative functional connectivity between the two networks. Due to the diffuse nature of the injuries associated with mTBI, we hypothesize that working memory deficits experienced after mTBI are associated with altered modulation of the interactions between the DMN and the TPN. A greater degree of disruption between these two networks will be associated with poorer performance on working memory tasks. I will test this hypothesis using fMRI of the N-back working memory paradigm in the sub-acute stage of mild TBI. I will assess patterns of neural activity in the DMN and the TPN during the working memory task. In addition, I will assess functional connectivity between the DMN and TPN during both rest and the working memory task. Results from this study will for the first time elucidate the neural correlates and mechanisms for lapses in working memory stemming from mild traumatic brain injury

Public Health Relevance

Mild traumatic brain injury (mTBI) is one of the most common neurological disorders in the United States affecting both military and civilian populations. Many patients suffer from cognitive symptoms including disturbances in memory for months following the injury in spite of demonstrating normal CT and conventional MR imaging. Significant challenges remain to understand disruptions in neural networks that are evident in a large number of mTBI patients who do not present with any structural or radiological deficits. Results from the proposed study may further advance our knowledge of why some mTBI patients have a poor cognitive and neuropsychological long-term outcome. An understanding of the disruption in the interaction between the DMN and the TPN may provide fundamental insights into the workings of the injured human brain during a working memory task. Furthermore, when the nature of injury if fully understood, this will allow investigators to look for ways to improve this imbalance including either pharmacological or behavioral interventions. This would help to improve the quality of life for these patients as well as minimiz losses in productivity. Finally, the possibility to link the results from task based fMRI and restig state fMRI in a mTBI population may have clinical implications. Resting state fMRI is more practicable in the clinical scenario especially at the acute stages of injury when task based fMRI may not be feasible due to the clinical condition of the patient.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-F01-F (20))
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Hicks, Ramona R
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University of Maryland Baltimore
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Sours, Chandler; Zhuo, Jiachen; Roys, Steven et al. (2015) Disruptions in Resting State Functional Connectivity and Cerebral Blood Flow in Mild Traumatic Brain Injury Patients. PLoS One 10:e0134019
Sours, Chandler; George, Elijah O; Zhuo, Jiachen et al. (2015) Hyper-connectivity of the thalamus during early stages following mild traumatic brain injury. Brain Imaging Behav 9:550-63
Sours, Chandler; Chen, Haoxing; Roys, Steven et al. (2015) Investigation of Multiple Frequency Ranges Using Discrete Wavelet Decomposition of Resting-State Functional Connectivity in Mild Traumatic Brain Injury Patients. Brain Connect 5:442-50
Sours, Chandler; Rosenberg, Joseph; Kane, Robert et al. (2015) Associations between interhemispheric functional connectivity and the Automated Neuropsychological Assessment Metrics (ANAM) in civilian mild TBI. Brain Imaging Behav 9:190-203
Sours, Chandler; Zhuo, Jiachen; Janowich, Jacqueline et al. (2013) Default mode network interference in mild traumatic brain injury - a pilot resting state study. Brain Res 1537:201-15