MEG-Derived Symptom-Sensitive Biomarkers with Long-Term Test-Retest Reliability

Neuroelectric measures derived from human magnetoencephalographic (MEG) recordings hold promise as aides to diagnosis and treatment monitoring and targeting for chronic sequelae of traumatic brain injury (TBI). This study tests novel MEG-derived regional brain measures of tonic neuroelectric activation for long-term test-retest reliability and sensitivity to symptoms. Resting state MEG recordings were obtained from a normative cohort (CamCAN, baseline: n = 613; mean 16-month follow-up: n = 245) and a chronic symptomatic TBI cohort (TEAM-TBI, baseline: n = 62; mean 6-month follow-up: n = 40). The MEG-derived neuroelectric measures were corrected for the empty-room contribution using a random forest classifier. The mean 16-month correlation between baseline and 16-month follow-up CamCAN measures was 0.67; test-retest reliability was markedly improved in this study compared with previous work. The TEAM-TBI cohort was screened for depression, somatization, and anxiety with the Brief Symptom Inventory and for insomnia with the Insomnia Severity Index and was assessed via adjudication for six clinical syndromes: chronic pain, psychological health, and oculomotor, vestibular, cognitive, and sleep dysfunction. Linear classifiers constructed from the 136 regional measures from each TEAM-TBI cohort member distinguished those with and without each symptom, p < 0.0003 for each, i.e., the tonic regional neuroelectric measures of activation are sensitive to the presence/absence of these symptoms and clinical syndromes. The novel regional MEG-derived neuroelectric measures obtained and tested in this study demonstrate the necessary and sufficient properties to be clinically useful, i.e., good test-retest reliability, sensitivity to symptoms in each individual, and obtainable using automatic processing without human judgement or intervention.