Altered Resting State Cortico-Striatal Connectivity in Mild to Moderate Stage Parkinson's Disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by dopamine depletion in the striatum. One consistent pathophysiological hallmark of PD is an increase in spontaneous oscillatory activity in the basal ganglia thalamocortical networks. We evaluated these effects using resting state functional connectivity MRI in mild to moderate stage Parkinson's patients on and off l-DOPA and age-matched controls using six different striatal seed regions. We observed an overall increase in the strength of cortico-striatal functional connectivity in PD patients off l-DOPA compared to controls. This enhanced connectivity was down-regulated by l-DOPA as shown by an overall decrease in connectivity strength, particularly within motor cortical regions. We also performed a frequency content analysis of the BOLD signal time course extracted from the six striatal seed regions. PD off l-DOPA exhibited increased power in the frequency band 0.02–0.05 Hz compared to controls and to PD on l-DOPA. The l-DOPA associated decrease in the power of this frequency range modulated the l-DOPA associated decrease in connectivity strength between striatal seeds and the thalamus. In addition, the l-DOPA associated decrease in power in this frequency band correlated with the l-DOPA associated improvement in cognitive performance. Our results demonstrate that PD and l-DOPA modulate striatal resting state BOLD signal oscillations and cortico-striatal network coherence

Cerebellar contributions to visuomotor adaptation and motor sequence learning: an ALE meta-analysis

Cerebellar contributions to motor learning are well-documented. For example, under some conditions, patients with cerebellar damage are impaired at visuomotor adaptation and at acquiring new action sequences. Moreover, cerebellar activation has been observed in functional MRI (fMRI) investigations of various motor learning tasks. The early phases of motor learning are cognitively demanding, relying on processes such as working memory, which have been linked to the cerebellum as well. Here, we investigated cerebellar contributions to motor learning using activation likelihood estimation (ALE) meta-analysis. This allowed us to determine, across studies and tasks, whether or not the location of cerebellar activation is constant across differing motor learning tasks, and whether or not cerebellar activation in early learning overlaps with that observed for working memory. We found that different regions of the anterior cerebellum are engaged for implicit and explicit sequence learning and visuomotor adaptation, providing additional evidence for the modularity of cerebellar function. Furthermore, we found that lobule VI of the cerebellum, which has been implicated in working memory, is activated during the early stages of explicit motor sequence learning. This provides evidence for a potential role for the cerebellum in the cognitive processing associated with motor learning. However, though lobule VI was activated across both early explicit sequence learning and working memory studies, there was no spatial overlap between these two regions. Together, our results support the idea of modularity in the formation of internal representations of new motor tasks in the cerebellum, and highlight the cognitive processing relied upon during the early phases of motor skill learning

Impulsivity in Parkinson’s disease is associated with alterations in affective and sensorimotor striatal networks

A subset of patients with Parkinson’s disease (PD) experiences problems with impulse control, characterized by a loss of voluntary control over impulses, drives, or temptations regarding excessive hedonic behavior. The present study aimed to better understand the neural basis of such impulse control disorders (ICDs) in PD. We collected resting-state functional connectivity and structural MRI data from 21 PD patients with ICDs and 30 patients without such disorders. To assess impulsivity, all patients completed the Barratt Impulsiveness Scale and performed an information-gathering task. MRI results demonstrated substantial differences in neural characteristics between PD patients with and without ICDs. Results showed that impulsivity was linked to alterations in affective basal ganglia circuitries. Specifically, reduced frontal–striatal connectivity and GPe volume were associated with more impulsivity. We suggest that these changes affect decision making and result in a preference for risky or inappropriate actions. Results further showed that impulsivity was linked to alterations in sensorimotor striatal networks. Enhanced connectivity within this network and larger putamen volume were associated with more impulsivity. We propose that these changes affect sensorimotor processing such that patients have a greater propensity to act. Our findings suggest that the two mechanisms jointly contribute to impulsive behaviors in PD

The Effects of Long Duration Head Down Tilt Bed Rest on Neurocognitive Performance: Extent, Longevity, & Neural Bases

No abstract availabl

Fractional Anisotropy in Selected, Motor-Related White Matter Tracts and Its Cross-Sectional and Longitudinal Associations With Motor Function in Healthy Older Adults

Background: While it is well-known that deficits in motor performance and brain structural connectivity occur in the course of healthy aging, it is still unclear if and how these changes are related to each other. While some cross-sectional studies suggest that white matter (WM) microstructure is positively associated with motor function in healthy older adults, more evidence is needed. Moreover, longitudinal data is required to estimate whether similar associations can be found between trajectories of change in WM microstructure and motor function. The current study addresses this gap by investigating age-associations and longitudinal changes in WM microstructure and motor function, and the cross-sectional (level-level) and longitudinal (level-change, change-change) association between these two domains. Method: We used multiple-occasion data (covering 4 years) from a large sample (N = 231) of healthy older adults from the Longitudinal Healthy Aging Brain (LHAB) database. To measure WM microstructure, we used diffusion-weighted imaging data to compute mean FA in three selected WM tracts [forceps minor (FMIN); superior longitudinal fasciculus (SLF); corticospinal tract (CST)]. Motor function was measured via two motor speed tests (grooved pegboard, finger tapping) and one motor strength test (grip force test), separately for the left and the right hand. The statistical analysis was conducted with longitudinal growth curve models in the structural equation modeling framework. Results: The results revealed longitudinal decline and negative cross-sectional age-associations for mean WM FA in the FMIN and SLF, and for motor function in all tests, with a higher vulnerability for left than right hand motor performance. Regarding cross-domain associations, we found a significant positive level-level correlation among mean WM FA in the FMIN with motor speed. Mean FA in SLF and CST was not correlated with motor performance measures, and none of the level-change or change-change associations were significant. Overall, our results (a) provide important insights into aging-related changes of fine motor abilities and FA in selected white matter tracts associated with motor control, (b) support previous cross-sectional work showing that neural control of movement in older adults also involves brain structures outside the core motor system and (c) align with the idea that, in healthy aging, compensatory mechanisms may be in place and longer time delays may be needed to reveal level-change or change-change associations

Anodal Transcranial Direct Current Stimulation Over Prefrontal Cortex Slows Sequence Learning in Older Adults

Aging is associated with declines in sensorimotor function. Several studies have demonstrated that transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, can be combined with training to mitigate age-related cognitive and motor declines. However, in some cases, the application of tDCS disrupts performance and learning. Here, we applied anodal tDCS either over the left prefrontal cortex (PFC), right PFC, supplementary motor complex (SMC), the left M1, or in a sham condition while older adults (n = 63) practiced a Discrete Sequence Production (DSP), an explicit motor sequence, task across 3 days. We hypothesized that stimulation to either the right or left PFC would enhance motor learning for older adults, based on the extensive literature showing increased prefrontal cortical activity during motor task performance in older adults. Contrary to our predictions, stimulation to the right and left PFC resulted in slowed motor learning, as evidenced by a slower reduction rate of reduction of reaction time and the number of sequence chunks across trials relative to sham in session one and session two, respectively. These findings suggest an integral role of the right PFC early in sequence learning and a role of the left PFC in chunking in older adults, and contribute to mounting evidence of the difficultly of using tDCS in an aging population

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

Head Down Tilt Bed Rest Plus Elevated CO2 as a Spaceflight Analog: Effects on Cognitive and Sensorimotor Performance

Long duration head down tilt bed rest (HDBR) has been widely used as a spaceflight analog environment to understand the effects of microgravity on human physiology and performance. Reports have indicated that crewmembers onboard the International Space Station (ISS) experience symptoms of elevated CO2 such as headaches at lower levels of CO2 than levels at which symptoms begin to appear on Earth. This suggests there may be combinatorial effects of elevated CO2 and the other physiological effects of microgravity including headward fluid shifts and body unloading. The purpose of the current study was to investigate these effects by evaluating the impact of 30 days of 6◦ HDBR and 0.5% CO2 (HDBR C CO2) on mission relevant cognitive and sensorimotor performance. We found a facilitation of processing speed and a decrement in functional mobility for subjects undergoing HDBR C CO2 relative to our previous study of HDBR in ambient air. In addition, nearly half of the participants in this study developed signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), a constellation of ocular structural and functional changes seen in approximately one third of long duration astronauts. This allowed us the unique opportunity to compare the two subgroups. We found that participants who exhibited signs of SANS became more visually dependent and shifted their speed-accuracy tradeoff, such that they were slower but more accurate than those that did not incur ocular changes. These small subgroup findings suggest that SANS may have an impact on mission relevant performance inflight via sensory reweighting. NEW AND NOTEWORTHY We examined the effects of long duration head down tilt bed rest coupled with elevated CO2 as a spaceflight analog environment on human cognitive and sensorimotor performance. We found enhancements in processing speed and declines in functional Frontiers in Human Neuroscience | www.frontiersin.org 1 October 2019 | Volume 13 | Article 355Lee et al. Spaceflight Analog Effects on Behavior mobility. A subset of participants exhibited signs of Spaceflight Associated Neuroocular Syndrome (SANS), which affects approximately one in three astronauts. These individuals increased their visual reliance throughout the intervention in comparison to participants who did not show signs of SAN

Fractional Anisotropy in Selected, Motor-Related White Matter Tracts and Its Cross-Sectional and Longitudinal Associations With Motor Function in Healthy Older Adults

BackgroundWhile it is well-known that deficits in motor performance and brain structural connectivity occur in the course of healthy aging, it is still unclear if and how these changes are related to each other. While some cross-sectional studies suggest that white matter (WM) microstructure is positively associated with motor function in healthy older adults, more evidence is needed. Moreover, longitudinal data is required to estimate whether similar associations can be found between trajectories of change in WM microstructure and motor function. The current study addresses this gap by investigating age-associations and longitudinal changes in WM microstructure and motor function, and the cross-sectional (level-level) and longitudinal (level-change, change-change) association between these two domains.MethodWe used multiple-occasion data (covering 4 years) from a large sample (N = 231) of healthy older adults from the Longitudinal Healthy Aging Brain (LHAB) database. To measure WM microstructure, we used diffusion-weighted imaging data to compute mean FA in three selected WM tracts [forceps minor (FMIN); superior longitudinal fasciculus (SLF); corticospinal tract (CST)]. Motor function was measured via two motor speed tests (grooved pegboard, finger tapping) and one motor strength test (grip force test), separately for the left and the right hand. The statistical analysis was conducted with longitudinal growth curve models in the structural equation modeling framework.ResultsThe results revealed longitudinal decline and negative cross-sectional age-associations for mean WM FA in the FMIN and SLF, and for motor function in all tests, with a higher vulnerability for left than right hand motor performance. Regarding cross-domain associations, we found a significant positive level-level correlation among mean WM FA in the FMIN with motor speed. Mean FA in SLF and CST was not correlated with motor performance measures, and none of the level-change or change-change associations were significant. Overall, our results (a) provide important insights into aging-related changes of fine motor abilities and FA in selected white matter tracts associated with motor control, (b) support previous cross-sectional work showing that neural control of movement in older adults also involves brain structures outside the core motor system and (c) align with the idea that, in healthy aging, compensatory mechanisms may be in place and longer time delays may be needed to reveal level-change or change-change associations