Table 1.

Assessment of concussion across scales.

Level	What is measured?	Assessment methods	Challenges
Cellular	Structure and function of neurons, glia, vasculature, and cytoarchitecture; biomarkers of tissue damage	Proteomics (e.g., glial fibrillary acidic protein); blood serum biomarkers (e.g., hemosiderin and SB-100); animal models for brain injury (e.g., LFPI and various impact models); and postmortem histological analyses	Limited translation from animal models; lack of non-invasive in vivo human data; and no successful Phase 3 clinical trials
Network	Connectivity, timing, and functioning of brain networks	Neuroimaging (e.g., diffusion tensor imaging, magnetic resonance imaging, fMRI, MRS PET, MEG, event-related potentials, and quantitative EEG); eye tracking; reaction time measures; balance and gait measures; neurological assessments; and sleep assessments	Neurodiagnostic limitations (feasibility and resource requirements; prohibitive cost in clinical settings); lack of baseline or matched control scans
Experiential	Symptoms; deficits in cognitive, psychological, and emotional functioning	Neuropsychological assessments; self-reported symptom logs and health history; gait and balance tests; and psychophysics (light or sound sensitivity)	Reliability and accuracy of self-report; current neuropsychological assessments not designed for concussion; and variability in self-awareness and symptom expression
Social	Signs; strength of social relationships and social functioning	Medical evaluations; informant reports; and information about context of injury	Detection accuracy; reliability of informant reports; and differential access to health care