Table 1.

Hypothesized Findings and Recommendations for Future Research into the Development of Functional Neuroimaging Biomarkers Indicative of Accelerated Aging in Remote TBI

Neuroimaging method	Hypothesized findings and recommendations for future research
Functional Magnetic Resonance Imaging
A. Activation studies of cognitive control:	• Abnormal patterns and amount of brain activation with increasing task complexity and cognitive load • Determine whether increased activation is in fact compensatory
B. Network analysis of intrinsic connectivity:	I. Task-based connectivity • Abnormalities in task-based functional connectivity and brain dynamics  ○ Particularly in the default mode, salience, and executive control networks • Changes in the interaction within and between nodes of these networks • Relate changes in network dynamics to cognitive dysfunction II. Resting state connectivity • Identify abnormalities in resting state functional connectivity within specific nodes of resting state networks (e.g., default mode, salience, dorsal attention, and executive control networks) • Determine how abnormalities in connectivity between, and brain activation within, regions in these networks relate to cognitive dysfunction
C. Activation studies of episodic memory:	• Bilateral, and more widespread, activation patterns • Decreased activation in the hippocampus and medial temporal lobe structures • Impairments in repetition suppression in brain regions and networks associated with episodic memory deficits
Event-Related Potential	• Delayed P300 latency and attenuated amplitude • Identification of other ERP components sensitive to disease-specific changes  ○ Candidate components include: P50, N400, auditory mismatch negativity
Electrophysiology	• Decreases in alpha power • Increases in delta power • Determine which changes in power spectra best classify neurodegenerative disease • Identify disease-specific changes in the profile of the power spectrum
Magnetoencephalography	• Complexity analysis of brain noise using multiscale entropy measures • Abnormalities in theta, alpha, and delta band oscillations • Identify how changes in the power spectrum are related to cognitive function

TBI, traumatic brain injury; ERP, event-related potential.