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McGregor, H. R.

Publications and source records attributed to McGregor, H. R..

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Artificial Gravity During a Spaceflight Analog Alters Brain Sensory Connectivity

Spaceflight has numerous untoward effects on human physiology. Various countermeasures are under investigation including artificial gravity (AG). Here, we investigated whether AG alters resting-state brain functional connectivity changes during head-down tilt bed rest (HDBR), a spaceflight analog. Participants underwent 60 days of HDBR. Two groups received daily AG administered either continuously (cAG) or intermittently (iAG). A control group received no AG. We assessed resting-state functional connectivity before, during, and after HDBR. We also measured balance and mobility changes from pre-to post-HDBR. We examined how functional connectivity changes throughout HDBR and whether AG is associated with differential effects. We found differential connectivity changes by group between posterior parietal cortex and multiple somatosensory regions. The control group exhibited increased functional connectivity between these regions throughout HDBR whereas the cAG group showed decreased functional connectivity. This finding suggests that AG alters somatosensory reweighting during HDBR. We also observed brain-behavioral correlations that differed significantly by group. Control group participants who showed increased connectivity between the putamen and somatosensory cortex exhibited greater mobility declines post-HDBR. For the cAG group, increased connectivity between these regions was associated with little to no mobility declines post-HDBR. This suggests that when somatosensory stimulation is provided via AG, functional connectivity increases between the putamen and somatosensory cortex are compensatory in nature, resulting in reduced mobility declines. Given these findings, AG may be an effective countermeasure for the reduced somatosensory stimulation that occurs in both microgravity and HDBR.

neuroscience↗

Impacts of Spaceflight Experience on Human Brain Structure

Spaceflight induces widespread changes in human brain morphology. It is unclear if these brain changes differ with varying mission durations or ones history of spaceflight experience (e.g., number of prior missions, time between missions). Here we addressed this issue by quantifying voxelwise post-flight changes in gray matter volume, white matter microstructure, extracellular free water (FW), and ventricular volume in a sample of 28 astronauts. We found that longer missions induced greater ventricular expansion and larger FW displacement at the top of the brain. A greater number of prior missions was associated with white matter microstructure declines in a tract supporting voluntary leg movement. Longer inter-mission intervals were associated with greater ventricle expansion, with compensatory ventricular expansion observed only in those crewmembers with inter-missions intervals of 3 years or longer. Longer missions therefore induce more extensive brain fluid shifts, and the ventricles may require at least 3 years to recover post-flight.

neuroscience↗

Sensory system-specific associations between brain structure and balance

Nearly 75% of older adults in the United States report balance problems. Balance difficulties are more pronounced during sensory feedback perturbation (e.g., standing with the eyes closed or on foam). Although it is known that aging results in widespread brain atrophy, less is known about how brain structure relates to balance performance under varied sensory conditions in older age. We measured postural sway of 36 young (18-34 years) and 22 older (66-84 years) adults during four conditions: eyes open, eyes closed, eyes open on foam, and eyes closed on foam. We calculated three summary measures indicating visual, proprioceptive, and vestibular contributions to balance. We also collected T 1-weighted and diffusion-weighted anatomical MRI scans. We aimed to: 1) test for age group differences in brain structure-balance relationships across a range of structural brain measures (i.e., volumetric, surface, and white matter microstructure); and 2) assess how brain structure measures relate to balance, regardless of age. Across both age groups, thinner cortex in multisensory integration regions was associated with greater reliance on visual inputs for balance. Greater gyrification within sensorimotor and parietal cortices was associated with greater reliance on proprioceptive inputs for balance. Poorer vestibular function was correlated with thinner vestibular cortex, greater gyrification within sensorimotor, parietal, and frontal cortices, and lower free water-corrected axial diffusivity in the superior-posterior corona radiata and across the corpus callosum. These results contribute to our scientific understanding of how individual differences in brain structure relate to balance. This has implications for developing brain stimulation interventions to improve balance. Significance StatementOlder age is associated with greater postural sway, particularly when sensory information is perturbed (e.g., by closing ones eyes). Our work contributes to the field by identifying how individual differences in regional brain structure relate to balance under varying sensory conditions in young and older adults. Across both age groups, lower cortical thickness in sensory integration and vestibular regions, greater gyrification within sensorimotor, parietal, and temporal regions, and lower free water-corrected axial diffusivity in the corpus callosum and corona radiata were related to individual differences in balance scores. We identified brain structures that are associated with specific sensory balance scores; therefore, these results have implications for which brain regions to target in future interventions for different populations.

neuroscience↗

Differential relationships between brain structure and dual task walking in young and older adults

Almost 25% of all older adults experience difficulty walking. Mobility difficulties for older adults are more pronounced when performing a simultaneous cognitive task while walking (i.e., dual task walking). Although it is known that aging results in widespread brain atrophy, few studies have integrated across more than one neuroimaging modality to comprehensively examine the structural neural correlates that may underly dual task walking in older age. We collected spatiotemporal gait data during single and dual task walking for 37 young (18-34 years) and 23 older adults (66-86 years). We also collected T1-weighted and diffusion-weighted MRI scans to determine how brain structure differs in older age and relates to dual task walking. We addressed two aims: 1) to characterize age differences in brain structure across a range of metrics including volumetric, surface, and white matter microstructure; and 2) to test for age group differences in the relationship between brain structure and the dual task cost (DTcost) of gait speed and variability. Key findings included widespread brain atrophy for the older adults, with the most pronounced age differences in brain regions related to sensorimotor processing. We also found multiple associations between regional brain atrophy and greater DTcost of gait speed and variability for the older adults. The older adults showed a relationship of both thinner temporal cortex and shallower sulcal depth in the frontal, sensorimotor, and parietal cortices with greater DTcost of gait. Additionally, the older adults showed a relationship of ventricular volume and superior longitudinal fasciculus free-water corrected axial and radial diffusivity with greater DTcost of gait. These relationships were not present for the young adults. Stepwise multiple regression found sulcal depth in the left precentral gyrus, axial diffusivity in the superior longitudinal fasciculus, and sex to best predict DTcost of gait speed, and cortical thickness in the superior temporal gyrus to best predict DTcost of gait variability for older adults. These results contribute to scientific understanding of how individual variations in brain structure are associated with mobility function in aging. This has implications for uncovering mechanisms of brain aging and for identifying target regions for mobility interventions for aging populations. CONTRIBUTION TO THE FIELDOlder age is associated with poorer mobility, including difficulties in performing a cognitive task while walking (i.e., dual task walking). Our work contributes to the field by examining multimodal structural neuroimaging data to characterize how brain structure relates to dual task walking in young versus older adults. We extracted multiple indices from T1-weighted and diffusion-weighted magnetic resonance imaging (MRI) scans that describe morphological characteristics of brain gray matter, white matter, and cerebrospinal fluid. We analyzed MRI and gait data from 37 young (18-34 years) and 23 older (66-86 years) adults. We identified multiple relationships between regional brain atrophy and greater dual task costs (DTcosts) to gait, i.e., greater slowing of gait speed and greater increases in gait variability from single to dual task walking. Specifically, for the older adults only, thinner temporal cortex and shallower sulcal depth in the frontal, sensorimotor, and parietal cortices were associated with larger DTcosts to walking. Additionally, for the older adults only, ventricular volume and superior longitudinal fasciculus free-water corrected axial and radial diffusivity were associated with larger DTcosts. These findings illustrate that temporal, frontoparietal and sensorimotor brain structures are associated with walking DTcosts in older adults, highlighting potential targets for interventions.

neuroscience↗

The role of dopamine in reward-based motor adaptation, savings, and interference

Dopamine signaling is thought to mediate reward-based learning. We tested for a role of dopamine in motor adaptation by administering the dopamine precursor levodopa to healthy participants in two experiments involving reaching movements. Levodopa has been shown to impair reward-based learning in cognitive tasks. Thus, we hypothesized that levodopa would selectively impair aspects of motor adaptation that depend on reinforcement of rewarding actions. In the first experiment, participants performed two separate tasks in which adaptation was driven either by visual error-based feedback of the hand position or binary reward feedback. We used EEG to measure event-related potentials evoked by task feedback. We hypothesized that levodopa would specifically diminish adaptation and the neural responses to feedback in the reward learning task. However, levodopa did not affect motor adaptation in either task nor did it diminish event-related potentials elicited by reward outcomes. In the second experiment, participants learned to compensate for mechanical force field perturbations applied to the hand during reaching. Previous exposure to a particular force field can result in savings during subsequent adaptation to the same force field or interference during adaptation to an opposite force field. We hypothesized that levodopa would diminish savings and anterograde interference, as previous work suggests that these phenomena result from a reinforcement learning process. However, we found no reliable effects of levodopa. These results suggest that reward-based motor adaptation, savings, and interference may not depend on the same dopaminergic mechanisms that have been shown to be disrupted by levodopa during various cognitive tasks. New and NoteworthyMotor adaptation relies on multiple processes including reinforcement of successful actions. Cognitive reinforcement learning is impaired by levodopa-induced disruption of dopamine function. We administered levodopa to healthy adults who participated in multiple motor adaptation tasks. We found no effects of levodopa on any component of motor adaptation. This suggests that motor adaptation may not depend on the same dopaminergic mechanisms as cognitive forms or reinforcement learning that have been shown to be impaired by levodopa.

neuroscience↗

Brain Connectivity and Behavioral Changes in aSpaceflight Analog Environment with Elevated CO2

Astronauts are exposed to microgravity and elevated CO2 levels onboard the International Space Station. Little is known about how microgravity and elevated CO2 combine to affect the brain and sensorimotor performance during and after spaceflight. Here we examined changes in resting-state functional connectivity (FC) and sensorimotor behavior associated with a spaceflight analog environment. Participants underwent 30 days of strict 6{degrees} head-down tilt bed rest with elevated ambient CO2 (HDBR+CO2). Resting-state functional magnetic resonance imaging and sensorimotor assessments were collected 13 and 7 days prior to bed rest, on days 7 and 29 of bed rest, and 0, 5, 12, and 13 days following bed rest. We assessed the time course of FC changes from before, during, to after HDBR+CO2. We then compared the observed connectivity changes with those of a HDBR control group, which underwent HDBR in standard ambient air. Moreover, we assessed associations between post-HDBR+CO2 FC changes and alterations in sensorimotor performance. HDBR+CO2 was associated with significant changes in functional connectivity between vestibular, visual, somatosensory and motor brain areas. Several of these sensory and motor regions showed post-HDBR+CO2 FC changes that were significantly associated with alterations in sensorimotor performance. We propose that these FC changes reflect multisensory reweighting associated with adaptation to the HDBR+CO2 microgravity analog environment. This knowledge will further improve HDBR as a model of microgravity exposure and contribute to our knowledge of brain and performance changes during and after spaceflight.

neuroscience↗

Reversal of visual feedback modulates somatosensory plasticity

Reversed visual feedback during unimanual training increases transfer of skills to the opposite untrained hand and modulates plasticity in motor areas of the brain. However, it is unclear if unimanual training with reversed visual feedback also affects somatosensory areas. Here we manipulated visual input during unimanual training using left-right optical reversing spectacles and tested whether unimanual training with reversed vision modulates somatosensory cortical excitability to facilitate motor performance. Thirty participants practiced a unimanual ball-rotation task using the right hand with either left-right reversed vision (incongruent visual and somatosensory feedback) or direct vision (congruent feedback) of the moving hand. We estimated cortical excitability in primary somatosensory cortex (S1) before and after unimanual training by measuring somatosensory evoked potentials (SEPs). This was done by electrically stimulating the median nerve in the wrist while participants rested, and recording potentials over both hemispheres using electroencephalography. Performance of the ball-rotation task improved for both the right (trained) and left (untrained) hand after training across both direct and reversed vision conditions. Participants with direct vision of the right hand during training showed SEPs amplitudes increased bilaterally. In contrast, participants in the reversed visual condition showed attenuated SEPs following training. The results suggest that cortical suppression of S1 activity supports skilled motor performance after unimanual training with reversed vision, presumably by sensory gating of afferent signals from the movement. This finding provides insight into the mechanisms by which visual input interacts with the sensorimotor system and induces neuroplastic changes in S1 to support skilled motor performance.

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Ophthalmic Changes in a Spaceflight Analog Are Associated with Brain Functional Reorganization

Following long-duration spaceflight, some astronauts exhibit ophthalmic structural changes referred to as Spaceflight Associated Neuro-ocular Syndrome (SANS). Optic disc edema is a common sign of SANS. The origin and effects of SANS are not understood as signs of SANS have not manifested in previous spaceflight analog studies. In the current spaceflight analog study, eleven subjects underwent 30 days of strict head down-tilt bed rest in elevated ambient carbon dioxide (HDBR+CO2). Using functional magnetic resonance imaging (fMRI), we acquired resting-state fMRI data at 6 time points: before (2), during (2), and after (2) the HDBR+CO2 intervention. Five participants developed optic disc edema during the intervention (SANS subgroup) and 6 did not (NoSANS group). This occurrence allowed us to explore whether development of signs of SANS during the spaceflight analog impacted resting-state functional connectivity during HDBR+CO2. In light of previous work identifying genetic and biochemical predictors of SANS, we further assessed whether the SANS and NoSANS subgroups exhibited differential patterns of resting-state functional connectivity prior to the HDBR+CO2 intervention. We found that the SANS and NoSANS subgroups exhibited distinct patterns of resting-state functional connectivity changes during HDBR+CO2 within visual and vestibular-related brain networks. The SANS and NoSANS subgroups also exhibited different resting-state functional connectivity prior to HDBR+CO2 within a visual cortical network and within a large-scale network of brain areas involved in multisensory integration. We further present associations between functional connectivity within the identified networks and previously identified genetic and biochemical predictors of SANS. Subgroup differences in resting-state functional connectivity changes may reflect differential patterns of visual and vestibular reweighting as optic disc edema develops during the spaceflight analog. This finding suggests that SANS impacts not only neuro-ocular structures, but also functional brain organization. Future prospective investigations incorporating sensory assessments are required to determine the functional significance of the observed connectivity differences. HIGHLIGHTSWe investigated resting-state functional connectivity (FC) during a spaceflight analog with elevated CO2 (HDBR+CO2). During the HDBR+CO2 intervention, a subset of participants developed optic disc edema, a sign of spaceflight-associated neuro-ocular syndrome (SANS). Participants with signs of SANS exhibited a distinct pattern of resting-state functional connectivity changes within visual and vestibular-related networks during HDBR+CO2. Participants who developed optic disc edema exhibited different FC prior to the spaceflight analog within a visual cortical network and within a large-scale network of brain areas involved in multisensory integration.

neuroscience↗

Changes in corticospinal excitability associated with motor learning by observing

While many of our motor skills are acquired through physical practice, we can also learn how to make movements by observing others. For example, individuals can learn how to reach in novel dynamical environments ( force fields, FF) by observing the movements of a tutor. Previous neurophysiology and neuroimaging studies in humans suggest a role for the motor system in motor learning by observing. Here we tested the role of primary motor cortex (M1) in motor learning by observing. We used single-pulse transcranial magnetic stimulation (TMS) to elicit motor evoked potentials (MEPs) in right hand muscles at rest. MEPs were elicited before and after participants observed either a video adapting her reaches to a FF or a control video showing a tutor performing reaches in an unlearnable FF. We predicted that observing motor learning would increase M1 excitability to a greater extent than observing movements that did not involve learning. We found that observing FF learning increased MEP amplitudes recorded from right first dorsal interosseous (FDI) and right abductor pollicis brevis (APB) muscles. There were no changes in MEP amplitudes for control participants who observed a tutor performing reaches in an unlearnable, randomly varying FF. The observed MEP changes can thus be specifically linked to observing motor learning. These results are consistent with the idea that observing motor learning produces functional changes in M1, or corticospinal networks or both.

neuroscience↗

Functional Connectivity Between Somatosensory and Motor Brain Areas Predicts Individual Differences in Motor Learning by Observing

Action observation can facilitate the acquisition of novel motor skills, however, there is considerable individual variability in the extent to which observation promotes motor learning. Here we tested the hypothesis that individual differences in brain function or structure can predict subsequent observation-related gains in motor learning. Subjects underwent an anatomical MRI scan and resting-state fMRI scans to assess pre-observation grey matter volume and pre-observation resting-state functional connectivity (FC), respectively. On the following day, subjects observed a video of a tutor adapting her reaches to a novel force field. After observation, subjects performed reaches in a force field as a behavioral assessment of gains in motor learning resulting from observation. We found that individual differences in resting-state FC, but not grey matter volume, predicted post-observation gains in motor learning. Pre-observation resting-state FC between left S1 and bilateral PMd, M1, S1 and left SPL was positively correlated with behavioral measures of post-observation motor learning. Sensory-motor resting-state FC can thus predict the extent to which observation will promote subsequent motor learning.\n\nNew & NoteworthyWe show that individual differences in pre-observation brain function can predict subsequent observation-related gains in motor learning. Pre-observation resting-state functional connectivity within a sensory-motor network may be used as a biomarker for the extent to which observation promotes motor learning. This kind of information may be useful if observation is to be used as a way to boost neuroplasticity and sensory motor recovery for patients undergoing rehabilitation for diseases that impair movement such as stroke.

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