Elucidating Brainstem Contributions to Visceral and Somatic Motor Dysfunction after mTBI

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PROJECT SUMMARY/ABSTRACT Rehabilitation and medical management for those with mild traumatic brain injury (mTBI) is often guided by classifying people into subtypes based on self-reported symptoms and clinical signs. However, common motor signs and symptoms are not easily parsed into subtype classifications, and the underlying pathophysiology of motor symptoms remains unclear. Our long-term goal is to improve clinical care of mTBI by directing patients to treatment that targets the key underlying dysfunction based on objective and quantifiable markers. Common symptoms, such as headache and dizziness, and clinical signs, such as cardiovascular instability and postural imbalance, relate to key visceral motor (autonomic) and somatic motor (balance and gait) function that may share a common neuroanatomical origin within the brainstem. Yet, the brainstem has received little attention in people with mTBI, and no research has examined whether visceral (autonomic) and somatic (balance and gait) motor dysfunction share a common neuroanatomical origin. This exploratory project will examine structural and functional manifestations of brainstem injury in people with mTBI through novel neuroimaging and objective assessments of somatic motor and visceral motor function. Our central hypothesis is that mTBI creates distinct abnormalities in motor (visceral and somatic) function that have a common neuroanatomical origin within the brainstem. Our first Specific Aim will determine differences between people with mTBI and healthy controls in brainstem integrity, as assessed structurally by neuroimaging and functionally by quantitative assessment of somatic and visceral motor function. Brainstem integrity will be determined from fractional anisotropy (FA) of white matter tracts imaged using high density fiber tractography. Somatic and visceral motor function will be assess using objective, instrumented mobility tests and cardiovascular autonomic measures of baroreceptor function, respectively. Specific Aim II will explore the relationship between acute brainstem integrity and the longitudinal recovery of objective motor function and self-reported symptoms. Brainstem FA values will be compared to objective measures of visceral motor and somatic motor function and to self-reported symptoms. We will also compare the extent to which structural integrity of the brainstem, quantified using FA, can predict recovery of objective motor function and self-reported symptoms over 3 months. This innovative study will be the first of its kind to collect objective measures of somatic and visceral motor function in conjunction with novel neuroimaging in people with mTBI. This study will establish the foundation for a future proposal seeking to characterize the response of structural integrity of the brainstem, motor function, and self-reported symptoms to targeted rehabilitation treatments after mTBI. Ultimately, this significant study may shift the paradigm of mTBI management by revealing the origin of motor dysfunction and providing physiological and structural neural markers that complement clinical classifications to guide treatment for those with mTBI.