Differential Contributions of Transcallosal Sensorimotor Fiber Tract Structure and Neurophysiologic Function to Manual Motor Control in Young and Older Adults.

Consider tying your shoes, one of the most automatic movements an adult performs. Each hand works independently during this task to accomplish a unified goal. With advanced age comes a decline in motor control affecting the ability of older adults to perform such activities of daily living. Specifically, older adults show pronounced deficits in the ability to perform tasks with both hands. I investigated whether age-related declines in callosal microstructural integrity and inhibitory function contribute to age differences in the ability to perform such tasks. In the first study I determined the relationship between corpus callosum microstructural integrity and interhemispheric inhibition in young adults. I found a positive relationship between interhemispheric inhibition and microstructure of interhemispheric fibers that was specific to tracts connecting the primary motor cortices. My second study revealed that young adults with greater interhemispheric inhibition had reduced motor overflow during a unimanual force production task; however these same individuals had the poorest performance during a bimanual independent force production task. I suggest that a high capacity for interhemispheric inhibition from one motor cortex to another can effectively prevent motor overflow during unimanual tasks, however it also limits the ability for optimal control during independent bimanual tasks, possibly due to a reduced capability for interhemispheric cooperation. My third study determined whether age reductions in callosal structure and inhibitory function underlie impairments in independent bimanual control. I found that better microstructure of callosal tracts connecting the two primary motor cortices was positively related to bimanual task performance in older adults, but negatively related to performance in young adults. Further, increased interhemispheric inhibition was related to poorer bimanual task performance in older adults across all tasks, whereas this relationship was only observed in young adults for the independent bimanual task. Collectively, the results of my dissertation have identified age reductions in callosal structure and their resultant impact on neurophysiological function and manual motor control. These studies provide a mechanistic understanding that can be leveraged for the design of targeted training interventions that will allow individuals with dysfunction of interhemispheric inhibition, to maintain independence and improve their quality of life.Ph.D.KinesiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/89624/1/bfling_1.pd

Gait Asymmetry in People With Parkinson’s Disease Is Linked to Reduced Integrity of Callosal Sensorimotor Regions

Background: Individuals with Parkinson’s disease (PD) often manifest significant temporal and spatial asymmetries of the lower extremities during gait, which significantly contribute to mobility impairments. While the neural mechanisms underlying mobility asymmetries within this population remain poorly understood, recent evidence points to altered microstructural integrity of white matter fiber tracts within the corpus callosum as potentially playing a substantial role. Objectives: The purpose of this study was to quantify spatial and temporal gait asymmetries as well as transcallosal microstructural integrity of white matter fiber tracts connecting the primary and secondary sensorimotor cortices in people with PD and age-matched control participants. Methods: Spatial and temporal gait asymmetry in the levodopa off state was assessed using an instrumented walkway. On the next day, diffusion-weighted images were collected to assess white matter microstructural integrity in transcallosal fibers connecting the homologous sensorimotor cortical regions. Results: People with PD exhibited significantly more temporal and spatial gait asymmetry than healthy control subjects. Furthermore, people with PD had significantly reduced white matter microstructural integrity of transcallosal fibers connecting homologous regions of the pre-supplementary motor and supplementary motor areas (SMAs), but not the primary motor or somatosensory cortices. Finally, reduced transcallosal fiber tract integrity of the pre-SMA and S1 was associated with greater step length asymmetry in people with PD. Conclusion: People with PD showed increased step length asymmetries and decreased microstructural integrity of callosal white matter tracts connecting the higher-order sensorimotor cortices (pre-SMA and SMA). The strong association between gait asymmetries and corpus collosum integrity, supports the hypothesis that reduced transcallosal structural connectivity is a significant mechanism underlying gait asymmetries in people with PD

Freezing of gait associated with a corpus callosum lesion

Freezing of gait (FoG) is a debilitating feature of Parkinson’s disease and other parkinsonian disorders. This case demonstrates a variant of freezing of gait in a non-parkinsonian patient with a lesion of the anterior corpus callosum. The freezing improved with increased upper extremity sensory input, suggesting that compensatory circuits for use of somatosensory inputs from the arms to postural and locomotor centers were intact

Associations between Proprioceptive Neural Pathway Structural Connectivity and Balance in People with Multiple Sclerosis

Mobility and balance impairments are a hallmark of multiple sclerosis (MS), affecting nearly half of patients at presentation and resulting in decreased activity and participation, falls, injuries, and reduced quality of life. A growing body of work suggests that balance impairments in people with mild MS are primarily the result of deficits in proprioception, the ability to determine body position in space in the absence of vision. A better understanding of the pathophysiology of balance disturbances in MS is needed to develop evidence-based rehabilitation approaches. The purpose of the current study was to (1) map the cortical proprioceptive pathway in vivo using diffusion-weighted imaging and (2) assess associations between proprioceptive pathway white matter microstructural integrity and performance on clinical and behavioral balance tasks. We hypothesized that people with MS (PwMS) would have reduced integrity of cerebral proprioceptive pathways, and that reduced white matter microstructure within these tracts would be strongly related to proprioceptive-based balance deficits. We found poorer balance control on proprioceptive-based tasks and reduced white matter microstructural integrity of the cortical proprioceptive tracts in PwMS compared with age-matched healthy controls (HC). Microstructural integrity of this pathway in the right hemisphere was also strongly associated with proprioceptive-based balance control in PwMS and controls. Conversely, while white matter integrity of the right hemisphere’s proprioceptive pathway was significantly correlated with overall balance performance in HC, there was no such relationship in PwMS. These results augment existing literature suggesting that balance control in PwMS may become more dependent upon (1) cerebellar-regulated proprioceptive control, (2) the vestibular system, and/or (3) the visual system

Age Differences in Interhemispheric Interactions: Callosal Structure, Physiological Function, and Behavior

There is a fundamental gap in understanding how brain structural and functional network connectivity are interrelated, how they change with age, and how such changes contribute to older adults’ sensorimotor deficits. Recent neuroimaging approaches including resting state functional connectivity MRI (fcMRI) and diffusion tensor imaging (DTI) have been used to assess brain functional (fcMRI) and structural (DTI) network connectivity, allowing for more integrative assessments of distributed neural systems than in the past. Declines in corpus callosum size and microstructure with advancing age have been well documented, but their contributions to age deficits in unimanual and bimanual function are not well defined. Our recent work implicates age-related declines in callosal size and integrity as a key contributor to unimanual and bimanual control deficits. Moreover, our data provide evidence for a fundamental shift in the balance of excitatory and inhibitory interhemispheric processes that occurs with age, resulting in age differences in the relationship between functional and structural network connectivity. Training studies suggest that the balance of interhemispheric interactions can be shifted with experience, making this a viable target for future interventions

Associations between mobility, cognition and callosal integrity in people with parkinsonism

Falls in people with parkinsonism are likely related to both motor and cognitive impairments. In addition to idiopathic Parkinson\u27s disease (PD), some older adults have lower body parkinsonism (a frontal gait disorder), characterized by impaired lower extremity balance and gait as well as cognition, but without tremor or rigidity. Neuroimaging during virtual gait suggests that interhemispheric, prefrontal cortex communication may be involved in locomotion, but contributions of neuroanatomy connecting these regions to objective measures of gait in people with parkinsonism remains unknown. Our objectives were to compare the integrity of fiber tracts connecting prefrontal and sensorimotor cortical regions via the corpus callosum in people with two types of parkinsonism and an age-matched control group and to relate integrity of these callosal fibers with clinical and objective measures of mobility and cognition. We recruited 10 patients with frontal gait disorders, 10 patients with idiopathic PD and 10 age-matched healthy control participants. Participants underwent cognitive and mobility testing as well as diffusion weighted magnetic resonance imaging to quantify white matter microstructural integrity of interhemispheric fiber tracts. People with frontal gait disorders displayed poorer cognitive performance and a slower, wider-based gait compared to subjects with PD and age-matched control subjects. Despite a widespread network of reduced white matter integrity in people with frontal gait disorders, gait and cognitive deficits were solely related to interhemispheric circuitry employing the genu of the corpus callosum. Current results highlight the importance of prefrontal interhemispheric communication for lower extremity control in neurological patients with cognitive dysfunction

Reduced Interhemispheric Functional Connectivity in the Motor Cortex during Rest in Limb-Onset Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of motor neurons that leads to paralysis and eventually death. There is evidence that atrophy occurs in the primary motor cortex (M1), but it is unclear how the disease affects the intrinsic connectivity of this structure. Thus, the goal of this study was to examine interhemispheric coupling of low frequency blood-oxygen-level dependent (BOLD) signal fluctuations in M1 using functional connectivity magnetic resonance imaging during rest. Because disease progression is rapid, high-functioning patients were recruited to assess neural changes in the relatively early stages of ALS. Twenty patients with limb-onset ALS participated in this study. A parceling technique was employed to segment both precentral gyri into multiple regions of interest (ROI), thus increasing sensitivity to detect changes that exist along discretely localized regions of the motor cortex. We report an overall systemic decrease in functional connectivity between right and left motor cortices in patients with limb-onset ALS. Additionally, we observed a pronounced disconnection between dorsal ROI pairs in the ALS group compared to the healthy control group. Furthermore, measures of limb functioning correlated with the connectivity data from dorsal ROI pairs in the ALS group, suggesting a symptomatic relationship with interhemispheric M1 connectivity

Gait Asymmetry in People With Parkinson’s Disease Is Linked to Reduced Integrity of Callosal Sensorimotor Regions

BackgroundIndividuals with Parkinson’s disease (PD) often manifest significant temporal and spatial asymmetries of the lower extremities during gait, which significantly contribute to mobility impairments. While the neural mechanisms underlying mobility asymmetries within this population remain poorly understood, recent evidence points to altered microstructural integrity of white matter fiber tracts within the corpus callosum as potentially playing a substantial role.ObjectivesThe purpose of this study was to quantify spatial and temporal gait asymmetries as well as transcallosal microstructural integrity of white matter fiber tracts connecting the primary and secondary sensorimotor cortices in people with PD and age-matched control participants.MethodsSpatial and temporal gait asymmetry in the levodopa off state was assessed using an instrumented walkway. On the next day, diffusion-weighted images were collected to assess white matter microstructural integrity in transcallosal fibers connecting the homologous sensorimotor cortical regions.ResultsPeople with PD exhibited significantly more temporal and spatial gait asymmetry than healthy control subjects. Furthermore, people with PD had significantly reduced white matter microstructural integrity of transcallosal fibers connecting homologous regions of the pre-supplementary motor and supplementary motor areas (SMAs), but not the primary motor or somatosensory cortices. Finally, reduced transcallosal fiber tract integrity of the pre-SMA and S1 was associated with greater step length asymmetry in people with PD.ConclusionPeople with PD showed increased step length asymmetries and decreased microstructural integrity of callosal white matter tracts connecting the higher-order sensorimotor cortices (pre-SMA and SMA). The strong association between gait asymmetries and corpus collosum integrity, supports the hypothesis that reduced transcallosal structural connectivity is a significant mechanism underlying gait asymmetries in people with PD

284 - Clayton W. Swanson

Includes bibliographical references.Motor cortex inhibition is significantly associated with complex bimanual control of the upper extremities. It remains unclear whether this same relationship exists for the lower extremities. We utilized transcranial magnetic stimulation to assess motor cortex inhibition and wireless, inertial sensors to quantify gait variables to assess how cortical inhibition contributes to the control of gait in healthy, young adults. Gait cycle duration variability was significantly correlated to right motor cortex inhibition. The results of this study indicate that motor cortex inhibition may be associated with complex components of gait in a similar fashion to its association with bimanual control