Fatigue after traumatic brain injury is linked to altered striato-thalamic-cortical functioning

• Mental fatigue is a common symptom in the chronic phase of traumatic brain injury. Despite its high prevalence, no treatmentis available for this disabling symptom, and the mechanisms underlying fatigue are poorly understood. Some studies have suggested that fatigue in traumatic brain injury and other neurological disorders might reflect dysfunction within striato-thalamic-cortical loops. In the present study, we investigated whether functional magnetic resonance imaging(fMRI) can be used to detect chronic fatigue after traumatic brain injury (TBI), with emphasis on the striato-thalamic cortical-loops. We included patients who had suffered traumatic brain injury (n = 57, age range 20–64 years) and experienced mental fatigue > 1 year post injury (mean = 8.79 years, SD = 7.35), and age- and sex-matched healthycontrols (n = 27, age range 25–65 years). All participants completed self-assessment scales of fatigue and other symptoms, underwent an extensive neuropsychological test battery and performed a fatiguing 27-minute attention task (the modified Symbol Digit Modalities Test) during fMRI. Accuracy did not differ between groups, but reaction times were slower in the traumatic brain injury group (p < 0.001). Patients showed a greater increase in fatigue than controls from before to after task completion (p < 0.001). Patients showed less fMRI blood oxygen level–dependent activity in several a priori hypothesized regions (family-wise error corrected,p < 0.05), including the bilateral caudate, thalamus and anterior insula. Using the left caudate as a region of interest and testing for sensitivity and specificity, we identified 91% of patients and 81% of controls. As expected, controls showed decreased activation over time in regions of interest—the bilateral caudate and anterior thalamus (p < 0.002, uncorrected)—whereas patients showed no corresponding activity decrease. These results suggest that chronic fatigue after TBI is linked to altered striato-thalamic-cortical functioning. The high precision of fMRI for the detection of fatigue is of great clinical interest, given the lack of objective measures for the diagnosis of fatigue.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

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art (subject category)