Identifying altered sensorimotor pathways and their role in motor impairment post-stroke

Karbasforoushan, Haleh

doi:https://doi.org/10.21985/n2-efe8-8e17

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Identifying altered sensorimotor pathways and their role in motor impairment post-stroke

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Stroke is the leading cause of permanent adult disability. Subcortical unilateral (hemiparetic) stroke affecting the internal capsule or basal ganglia is the most common of all strokes and usually results in hemiparesis of the contralateral arm and leg. About 80% of the individuals with a moderate to severe hemiparetic stroke suffer from upper limb motor impairment, particularly in the wrist and fingers, as the most disabling, which limits the basic activities of daily life like dressing, eating, and grooming. The wrist/finger weakness in these individuals is greater for extensors than flexors, causing difficulty in hand opening, and leading to a dysfunctional wrist/fingers flexed posture. Previous neuroimaging studies of hemiparetic stroke over the past two decades, trying to understand the underlying neural mechanism of hand impairment, have frequently reported increased neural activity in motor cortices of both lesioned and non-lesioned hemispheres in individuals with stroke, during their attempt to move their affected upper extremity. It is also known that the more severe the stroke, the greater activity in the contralesional (non-lesioned) hemisphere than ipsilesional (lesioned) hemisphere. However, it is still unclear what descending motor pathways allow the non-lesioned hemisphere to control the ipsilateral paretic arm, although one proposed idea from animal studies suggests the brainstem ipsilaterally projecting motor pathways to play this role. Damage to the corticospinal tract and its role in motor impairment post unilateral subcortical stroke is widely studied, however less is known about changes to other sensorimotor pathways. One reason for this lack of knowledge is that a majority of previous studies have only investigated the morphological changes in the brain, where the main descending and ascending brain pathways (e.g. corticospinal, cortico-bulbospinal, dorsal column medial lemniscal tracts) mostly overlap and are not distinguishable with currently available imaging techniques. Sensorimotor pathways, in fact, delineate from each other in the brainstem and continue travelling through separate regions in the spinal cord. To this end, the goal of this dissertation is to use a combination of advanced anatomical and functional MRI methods to identify all altered sensorimotor pathways and their role in motor impairment post stroke. More specifically, we first used high resolution and advanced structural MRI of brainstem and cervical spinal cord to identify sensorimotor pathways with microstructural changes in individuals with stroke compared to controls. Furthermore, we used functional MRI (fMRI) of the brainstem to examine the activity in nuclei of brainstem descending motor pathways in individuals with chronic stroke and age-match gender-match controls, while they attempt to close their paretic hand. The results from our morphological investigations in brainstem and cervical spinal cord indicated a significant decrease of white matter integrity in corticospinal tract, lateral and medial reticulospinal tracts, descending medial longitudinal fasciculus, tectospinal tract and cuneate and gracile fasciculi related to the lesioned hemisphere. Furthermore, the results from brainstem and cervical spinal cord DTI analyses indicate a significant increase in the white matter integrity of medial reticulospinal tract at the side of contralesional hemisphere which projects ipsilaterally to the paretic (contralesional) limbs. When testing the correlation between these morphological changes and impairment severity in individuals with stroke, we found the decreased white matter integrity of ipsi-lesional corticospinal tract and increased white matter integrity of contra-lesional medial reticulospinal tract are correlated with upper limb impairment severity in these stroke participants. The results of our investigation of functional activity in brainstem during squeezing a pressure ball indicated significant activity in medial reticulospinal tract nuclei in all severely and moderately impaired individuals with stroke, as well as, a less intense activity in lateral reticulospinal tract nuclei, medial vestibulospinal tract nuclei, and pontine nuclei of motor cortex-ponto-cerebellum pathway in some individuals with stroke. Interestingly, mildly impaired stroke subjects, as well as, healthy controls did not show any activation in nuclei of brainstem descending pathways, suggesting that they continue to use the main motor pathway - corticospinal tract - during the hand closing task. These results for the first time identify all altered sensorimotor pathways post unilateral subcortical stroke and their correlation with upper extremity motor impairment in these individuals. Furthermore, this work directly suggests the brainstem ipsilaterally projecting pathways to facilitate the hand closing post stroke. It is also noteworthy to mention that these results demonstrate a correlation between impairment severity and greater reliance on reticulospinal tract, but not a causation. These findings suggest that the excessive flexor hypertonicity in elbow, wrist and fingers, as well as, the flexion synergy impairment observed in individuals post stroke to be a result of increased reliance on reticulospinal tract post stroke (due to flexor-biased nature of this pathway). However, it still remains unclear that what the impact of these alternative pathways projecting from non-lesioned hemisphere is during motor recovery in severely impaired individuals and how much movement control they could gain without the help of these alternative motor pathways. Further longitudinal investigations with targeted interventions in a large group of individuals with acute stroke should help us better understand how these pathways affect recovery after stroke. This will allow us to optimize rehabilitation strategies that take into account the innate capabilities of these pathways.

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