Discovery of Therapy-targeting Biomarkers for Post-Concussion Syndrome using Functional Neurocognitive Imaging

Abstract

Background: Post-concussion syndrome (PCS) occurs in a significant percentage of concussion patients. Functional MRI reveals irregular blood-oxygen level dependent signals in PCS patients. PCS biomarkers with functional predictive values have yet to be discovered and validated. Therefore, this study describes five PCS biomarkers and includes a description of their therapeutic application.Methods: A neurocognitive imaging protocol was developed and a group of healthy control patients was used to generate a normative reference atlas. Biomarker candidate search was performed using an initial sample of PCS patients. Sample validation was applied to each biomarker using a new sample of PCS patients to assess sensitivities/ specificities. A multivariate base rate analysis was performed using 132 new patients and a base rate cutoff matrix was constructed. An example of the biomarker's therapeutic application in a PCS patient is described. Results:The five functional biomarkers included: Frontal Attentional System hypoactivation, Subcortical System hypoactivation, Visual System hyperactivation, Verbal System hypoactivation, and Frontal/Parietal System hyperactivation. Individual biomarker sensitivities and specificities are reported. Collectively, using the base rate cutoff matrix, a threshold using 3/5 biomarkers below the 10 th percentile as the cutoff resulted in a suitable sensitivity (88%) and specificity (99%). The uses of these biomarkers were crucial in guiding the successful treatment of Patient A. Conclusion:We report the discovery of five functional PCS biomarkers. We show an example of the therapeutic application of the five biomarkers in the successful treatment of PCS. These neuroimaging biomarkers serve to advance diagnostic capabilities and subsequent PCS rehabilitation efforts.