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Context: Chronic ankle instability (CAI) has been considered a neurophysiological condition, with dysfunctional somatosensory and motor system excitability. However, few researchers have explored the changes in cortical activation during balance tasks of patients with CAI., Objective: To compare the cortical activity during single-legged stance among CAI, copers, and uninjured control participants and to compare dynamic balance across groups., Design: Cross-sectional study., Setting: Biomechanics laboratory., Patients or Other Participants: A total of 22 participants with CAI (median [interquartile range]; age = 34.5 [11.0] years, height = 170.0 [15.8] cm, mass = 67.0 [16.2] kg), 17 copers (age = 27.0 [14.0] years, height = 170.0 [9.5] cm, mass = 66.5 [16.5] kg), and 21 uninjured control participants (age = 25.0 [10.5] years, height = 170.0 [11.0] cm, mass = 64.0 [16.5] kg)., Main Outcome Measure(s): Participants performed single-legged stance while cortical activation was tested with functional near-infrared spectroscopy. The peak oxyhemoglobin response of the activated cortex was calculated and compared across groups. The Y-Balance test outcomes and patient-reported outcomes were assessed and compared across groups., Results: The CAI group had worse Y-balance test and patient-reported outcomes than the coper and uninjured control groups. Differences in the peak oxyhemoglobin response were observed for the primary somatosensory cortex (S1; F2,57 = 4.347, P = .017, ηp2 = 0.132) and superior temporal gyrus (STG; F2,57 = 4.548, P = .015, ηp2 = 0.138). Specifically, copers demonstrated greater activation in S1 and STG than the CAI (d = 0.73, P = .034, and d = 0.69, P = .043, respectively) and uninjured control (d = 0.77, P = .036, and d = 0.88, P = .022, respectively) groups. No differences were found in the cortical activation between CAI and uninjured control participants., Conclusions: Copers displayed greater cortical activation in S1 and STG than CAI and uninjured control participants. Greater activation in S1 and STG suggested a better ability to perceive somatosensory stimuli and may represent a compensatory mechanism that allows copers to maintain good functional ability after the initial severe ankle sprain., (© by the National Athletic Trainers’ Association, Inc.)