Daily artificial gravity is associated with greater neural efficiency during sensorimotor adaptation.

Altered vestibular signaling and body unloading in microgravity results in sensory reweighting and adaptation. Microgravity effects are well-replicated in head-down tilt bed rest (HDBR). Artificial gravity (AG) is a potential countermeasure to mitigate the effects of microgravity on human physiology and performance. We examined the effectiveness of daily AG for mitigating brain and/or behavioral changes in 60 days of HDBR. One group received AG for 30 minutes daily (AG; n = 16) and a control group spent the same time in HDBR but received no AG (CTRL; n = 8). All participants performed a sensorimotor adaptation task five times during fMRI scanning: twice prior to HDBR, twice during HDBR, and once following HDBR. The AG group showed similar behavioral adaptation effects compared with the CTRLs. We identified decreased brain activation in the AG group from pre to late HDBR in the cerebellum for the task baseline portion and in the thalamus, calcarine, cuneus, premotor cortices, and superior frontal gyrus in the AG group during the early adaptation phase. The two groups also exhibited differential brain-behavior correlations. Together, these results suggest that AG may result in a reduced recruitment of brain activity for basic motor processes and sensorimotor adaptation. These effects may stem from the somatosensory and vestibular stimulation that occur with AG.

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.

A table tennis serve versus rally hit elicits differential hemispheric electrocortical power fluctuations.

Human visuomotor control requires coordinated interhemispheric interactions to exploit the brain's functional lateralization. In right-handed individuals, the left hemisphere (right arm) is better for dynamic control and the right hemisphere (left arm) is better for impedance control. Table tennis is a game that requires precise movements of the paddle, whole body coordination, and cognitive engagement, providing an ecologically valid way to study visuomotor integration. The sport has many different types of strokes (e.g., serve, return, and rally shots), which should provide unique cortical dynamics given differences in the sensorimotor demands. The goal of this study was to determine the hemispheric specialization of table tennis serving - a sequential, self-paced, bimanual maneuver. We used time-frequency analysis, event-related potentials, and functional connectivity measures of source-localized electrocortical clusters and compared serves with other types of shots, which varied in the types of movement required, attentional focus, and other task demands. We found greater alpha (8-12 Hz) and beta (13-30 Hz) power in the right sensorimotor cortex than in the left sensorimotor cortex, and we found a greater magnitude of spectral power fluctuations in the right sensorimotor cortex for serve hits than return or rally hits, in all right-handed participants. Surprisingly, we did not find a difference in interhemispheric functional connectivity between a table tennis serve and return or rally hits, even though a serve could arguably be a more complex maneuver. Studying real-world brain dynamics of table tennis provides insight into bilateral sensorimotor integration.NEW & NOTEWORTHY We found different spectral power fluctuations in the left and right sensorimotor cortices during table tennis serves, returns, and rallies. Our findings contribute to the basic science understanding of hemispheric specialization in a real-world context.

Quantification approaches for magnetic resonance imaging following intravenous gadolinium injection: A window into brain-wide glymphatic function.

The glymphatic system is a brain-wide network of perivascular pathways along which cerebrospinal fluid and interstitial fluid rapidly exchange, facilitating solute and waste clearance from the brain parenchyma. The characterization of this exchange process in humans has relied primarily upon serial magnetic resonance imaging following intrathecal gadolinium-based contrast agent injection. However, less invasive approaches are needed. Here, we administered a gadolinium-based contrast agent intravenously in eight healthy participants and acquired magnetic resonance imaging scans prior to and 30, 90, 180, and 360 min post contrast injection. Using a region-of-interest approach, we observed that peripheral tissues and blood vessels exhibited high enhancement at 30 min after contrast administration, likely reflecting vascular and peripheral interstitial distribution of the gadolinium-based contrast agent. Ventricular, grey matter and white matter enhancement peaked at 90 min, declining thereafter. Using k-means clustering, we identify distinct distribution volumes reflecting the leptomeningeal perivascular network, superficial grey matter and deep grey/white matter that exhibit a sequential enhancement pattern consistent with parenchymal contrast enhancement via the subarachnoid cerebrospinal fluid compartment. We also outline the importance of correcting for (otherwise automatic) autoscaling of signal intensities, which could potentially lead to misinterpretation of gadolinium-based contrast agent distribution kinetics. In summary, we visualize and quantify delayed tissue enhancement following intravenous administration of gadolinium-based contrast agent in healthy human participants.

Developmental and age differences in visuomotor adaptation across the lifespan.

In the present cross-sectional study, we examined age and sex differences in sensorimotor adaptation. We tested 253 individuals at a local science museum (NEMO Science Museum, Amsterdam). Participants spanned a wide age range (8-70 years old; 54% male), allowing us to examine effects of both development and healthy aging within a single study. Participants performed a visuomotor adaptation task in which they had to adapt manual joystick movements to rotated visual feedback. We assessed the rate of adaptation following the introduction of the visual perturbation (both for early and later stages of adaptation), and the rate of de-adaptation following its removal. Results showed reliable adaptation patterns which did not differ by sex. We observed a quadratic relationship between age and both early adaptation and de-adaptation rates, with younger and older adults exhibiting the fasted adaptation rates. Our findings suggest that both younger and older age are associated with poorer strategic, cognitive processes involved in adaptation. We propose that developmental and age differences in cognitive functions and brain properties may underlie these effects on sensorimotor functioning.

Effects of Prefrontal Transcranial Direct Current Stimulation on Retention of Performance Gains on an Obstacle Negotiation Task in Older Adults.

OBJECTIVES: Complex walking in older adults can be improved with task practice and might be further enhanced by pairing transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex. We tested the hypothesis that a single session of practice of a complex obstacle negotiation task paired with active tDCS in older adults would produce greater within-session improvements in walking performance and retention of gains, compared to sham tDCS and no tDCS conditions. MATERIALS AND METHODS: A total of 50 older adults (mean age = 74.46 years ± 6.49) with self-reported walking difficulty were randomized to receive either active tDCS (active-tDCS group) or sham tDCS (sham-tDCS group) bilaterally to the dorsolateral prefrontal cortex or no tDCS (no-tDCS group). Each group performed ten practice trials of an obstacle negotiation task at their fastest safe speed. Retention of gains in walking performance was assessed with three trials conducted one week later. Within-session effects of practice and between-session retention effects on obstacle negotiation speed were examined. RESULTS: At the practice session, all three groups exhibited significant within-session gains in walking speed (p ≤ 0.005). However, the gains were significantly greater in the sham-tDCS group than in the active-tDCS and no-tDCS groups (p ≤ 0.03) and were comparable between the active-tDCS and no-tDCS groups (p = 0.89). At one-week follow-up, the active-tDCS group exhibited significant between-session retention of gains and continued "offline" improvement in walking speed (p = 0.005). The active-tDCS group showed significantly greater retention of gains than the no-tDCS (p = 0.02) but not the sham-tDCS group (p = 0.24). CONCLUSIONS: Pairing prefrontal active tDCS with a single session of obstacle negotiation practice may enhance one-week retention of gains in walking performance compared to no tDCS. However, the evidence is insufficient to suggest a benefit of active tDCS over sham tDCS for enhancing the gains in walking performance. Additional studies with a multisession intervention design and larger sample size are needed to further investigate these findings. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03122236.

Neural correlates of risky decision making in Parkinson's disease patients with impulse control disorders.

Some patients with Parkinson's disease (PD) experience impulse control disorders (ICDs), characterized by deficient voluntary control over impulses, drives, or temptations regarding excessive hedonic behavior. The present study aimed to better understand the neural basis of impulsive, risky decision making in PD patients with ICDs by disentangling potential dysfunctions in decision and outcome mechanisms. We collected fMRI data from 20 patients with ICDs and 28 without ICDs performing an information gathering task. Patients viewed sequences of bead colors drawn from hidden urns and were instructed to infer the majority bead color in each urn. With each new bead, they could choose to either seek more evidence by drawing another bead (draw choice) or make an urn-inference (urn choice followed by feedback). We manipulated risk via the probability of bead color splits (80/20 vs. 60/40) and potential loss following an incorrect inference ($10 vs. $0). Patients also completed the Barratt Impulsiveness Scale (BIS) to assess impulsivity. Patients with ICDs showed greater urn choice-specific activation in the right middle frontal gyrus, overlapping the dorsal premotor cortex. Across all patients, fewer draw choices (i.e., more impulsivity) were associated with greater activation during both decision making and outcome processing in a variety of frontal and parietal areas, cerebellum, and bilateral striatum. Our findings demonstrate that ICDs in PD are associated with differences in neural processing of risk-related information and outcomes, implicating both reward and sensorimotor dopaminergic pathways.

Retention Effects of Long-Term Balance Training with Vibrotactile Sensory Augmentation in Healthy Older Adults.

Vibrotactile sensory augmentation (SA) decreases postural sway during real-time use; however, limited studies have investigated the long-term effects of training with SA. This study assessed the retention effects of long-term balance training with and without vibrotactile SA among community-dwelling healthy older adults, and explored brain-related changes due to training with SA. Sixteen participants were randomly assigned to the experimental group (EG) or control group (CG), and trained in their homes for eight weeks using smart-phone balance trainers. The EG received vibrotactile SA. Balance performance was assessed before, and one week, one month, and six months after training. Functional MRI (fMRI) was recorded before and one week after training for four participants who received vestibular stimulation. Both groups demonstrated significant improvement of SOT composite and MiniBESTest scores, and increased vestibular reliance. Only the EG maintained a minimal detectable change of 8 points in SOT scores six months post-training and greater improvements than the CG in MiniBESTest scores one month post-training. The fMRI results revealed a shift from activation in the vestibular cortex pre-training to increased activity in the brainstem and cerebellum post-training. These findings showed that additional balance improvements were maintained for up to six months post-training with vibrotactile SA for community-dwelling healthy older adults.

Brain connectivity and behavioral changes in a spaceflight 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 6o 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 that 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.

The effects of a spaceflight analog with elevated CO2 on sensorimotor adaptation.

Aboard the International Space Station (ISS), astronauts must adapt to altered vestibular and somatosensory inputs due to microgravity. Sensorimotor adaptation on Earth is often studied with a task that introduces visuomotor conflict. Retention of the adaptation process, known as savings, can be measured when subjects are exposed to the same adaptive task multiple times. It is unclear how adaptation demands found on the ISS might interfere with the ability to adapt to other sensory conflict at the same time. In the present study, we investigated the impact of 30 days' head-down tilt bed rest combined with elevated carbon dioxide (HDBR + CO2) as a spaceflight analog on sensorimotor adaptation. Eleven subjects used a joystick to move a cursor to targets presented on a computer screen under veridical cursor feedback and 45° rotated feedback. During this NASA campaign, five individuals presented with optic disk edema, a sign of spaceflight-associated neuro-ocular syndrome (SANS). Thus, we also performed post hoc exploratory analyses between subgroups who did and did not show signs of SANS. HDBR + CO2 had some impact on sensorimotor adaptation, with a lack of savings across the whole group. SANS individuals showed larger, more persistent after-effects, suggesting a shift from relying on cognitive to more implicit processing of adaptive behaviors. Overall, these findings suggest that HDBR + CO2 alters the way in which individuals engage in sensorimotor processing. These findings have important implications for missions and mission training, which require individuals to adapt to altered sensory inputs over long periods in space.NEW & NOTEWORTHY This is the first bed rest campaign examining sensorimotor adaptation and savings in response to the combined effect of HDBR + CO2 and to observe signs of spaceflight-associated neuro-ocular syndrome (SANS) in HDBR participants. Our findings suggest that HDBR + CO2 alters the way that individuals engage in sensorimotor processing. Individuals who developed signs of SANS seem to rely more on implicit rather than cognitive processing of adaptive behaviors than subjects who did not present signs of SANS.

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, 11 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.

Altered cerebral perfusion in response to chronic mild hypercapnia and head-down tilt Bed rest as an analog for Spaceflight.

PURPOSE: Following prolonged stays on the International Space Station (ISS), some astronauts exhibit visual acuity changes, ophthalmological findings, and mildly elevated intracranial pressures as part of a novel process called spaceflight-associated neuro-ocular syndrome (SANS). To determine the pathophysiology of SANS, NASA conducted a multi-investigator study in which 11 healthy participants underwent head-down tilt bed rest, mimicking microgravity-induced cephalad fluid shifts, combined with elevated ambient CO2 levels similar to those on the ISS (HDT+CO2). As part of that study, we examined the effects of HDT+CO2 on cerebral perfusion. METHODS: Using arterial spin labeling, we compared cerebral perfusion before, during, and after HDT+CO2 in participants who developed SANS (n = 5) with those who did not (n = 6). RESULTS: All participants demonstrated a decrease in perfusion during HDT+CO2 (mean decrease of 25.1% at HDT7 and 16.2% at HDT29); however, the timing and degree of change varied between the groups. At day 7 of HDT+CO2, the SANS group experienced a greater reduction in perfusion than the non-SANS group (p =.05, 95% CI:-0.19 to 16.11, d=.94, large effect). Conversely, by day 29 of HDT+CO2, the SANS group had significantly higher perfusion (approaching their baseline) than the non-SANS group (p = .04, 95% CI:0.33 to 13.07, d=1.01, large effect). CONCLUSION: Compared with baseline and recovery, HDT+CO2 resulted in reduced cerebral perfusion which varied based on SANS status. Further studies are needed to unravel the relative role of HDT vs hypercapnia, to determine if these perfusion changes are clinically relevant, and whether perfusion changes contribute to the development of SANS during spaceflight.

Neural Dedifferentiation across the Lifespan in the Motor and Somatosensory Systems.

Age-related declines in sensorimotor performance have been linked to dedifferentiation of neural representations (i.e., more widespread activity during task performance in older versus younger adults). However, it remains unclear whether changes in neural representations across the adult lifespan are related between the motor and somatosensory systems, and whether alterations in these representations are associated with age declines in motor and somatosensory performance. To investigate these issues, we collected functional magnetic resonance imaging and behavioral data while participants aged 19-76 years performed a visuomotor tapping task or received vibrotactile stimulation. Despite one finding indicative of compensatory mechanisms with older age, we generally observed that 1) older age was associated with greater activity and stronger positive connectivity within sensorimotor and LOC regions during both visuomotor and vibrotactile tasks; 2) increased activation and stronger positive connectivity were associated with worse performance; and 3) age differences in connectivity in the motor system correlated with those in the somatosensory system. Notwithstanding the difficulty of disentangling the relationships between age, brain, and behavioral measures, these results provide novel evidence for neural dedifferentiation across the adult lifespan in both motor and somatosensory systems and suggest that dedifferentiation in these two systems is related.

Network segregation varies with neural distinctiveness in sensorimotor cortex.

Normal aging is associated with declines in sensorimotor function. Previous studies have linked age-related behavioral declines to decreases in neural differentiation (i.e., dedifferentiation), including decreases in the distinctiveness of neural activation patterns and in the segregation of large-scale neural networks at rest. However, no studies to date have explored the relationship between these two neural measures and whether they explain the same aspects of behavior. To investigate these issues, we collected a battery of sensorimotor behavioral measures in older and younger adults and estimated (a) the distinctiveness of neural representations in sensorimotor cortex and (b) sensorimotor network segregation in the same participants. Consistent with prior findings, sensorimotor representations were less distinct and sensorimotor resting state networks were less segregated in older compared to younger adults. We also found that participants with the most distinct sensorimotor representations exhibited the most segregated sensorimotor networks. However, only sensorimotor network segregation was associated with individual differences in sensorimotor performance, particularly in older adults. These novel findings link network segregation to neural distinctiveness, but also suggest that network segregation may play a larger role in maintaining sensorimotor performance with age.

Neural distinctiveness declines with age in auditory cortex and is associated with auditory GABA levels.

Neural activation patterns in the ventral visual cortex in response to different categories of visual stimuli (e.g., faces vs. houses) are less selective, or distinctive, in older adults than in younger adults, a phenomenon known as age-related neural dedifferentiation. In this study, we investigated whether neural dedifferentiation extends to the auditory cortex. Inspired by previous animal work, we also investigated whether individual differences in GABA are associated with individual differences in neural distinctiveness in humans. 20 healthy young adults (ages 18-29) and 23 healthy older adults (over 65) completed a functional magnetic resonance imaging (fMRI) scan, during which neural activity was estimated while they listened to music and foreign speech. GABA levels in the auditory, ventrovisual and sensorimotor cortex were estimated in the same individuals in a separate magnetic resonance spectroscopy (MRS) scan. Relative to the younger adults, the older adults exhibited both (1) less distinct activation patterns for music vs. speech stimuli and (2) lower GABA levels in the auditory cortex. Also, individual differences in auditory GABA levels (but not ventrovisual or sensorimotor GABA levels) were associated with individual differences in neural distinctiveness in the auditory cortex in the older adults. These results demonstrate that age-related neural dedifferentiation extends to the auditory cortex and suggest that declining GABA levels may play a role in neural dedifferentiation in older adults.

Sensorimotor network segregation declines with age and is linked to GABA and to sensorimotor performance.

Aging is typically associated with declines in sensorimotor performance. Previous studies have linked some age-related behavioral declines to reductions in network segregation. For example, compared to young adults, older adults typically exhibit weaker functional connectivity within the same functional network but stronger functional connectivity between different networks. Based on previous animal studies, we hypothesized that such reductions of network segregation are linked to age-related reductions in the brain's major inhibitory transmitter, gamma aminobutyric acid (GABA). To investigate this hypothesis, we conducted graph theoretical analyses of resting state functional MRI data to measure sensorimotor network segregation in both young and old adults. We also used magnetic resonance spectroscopy to measure GABA levels in the sensorimotor cortex and collected a battery of sensorimotor behavioral measures. We report four main findings. First, relative to young adults, old adults exhibit both less segregated sensorimotor brain networks and reduced sensorimotor GABA levels. Second, less segregated networks are associated with lower GABA levels. Third, less segregated networks and lower GABA levels are associated with worse sensorimotor performance. Fourth, network segregation mediates the relationship between GABA and performance. These findings link age-related differences in network segregation to age-related differences in GABA levels and sensorimotor performance. More broadly, they suggest a neurochemical substrate of age-related dedifferentiation at the level of large-scale brain networks.

Differential effects of left and right prefrontal cortex anodal transcranial direct current stimulation during probabilistic sequence learning.

Left and right prefrontal cortex and the primary motor cortex (M1) are activated during learning of motor sequences. Previous literature is mixed on whether prefrontal cortex aids or interferes with sequence learning. The present study investigated the roles of prefrontal cortices and M1 in sequence learning. Participants received anodal transcranial direct current stimulation (tDCS) to right or left prefrontal cortex or left M1 during a probabilistic sequence learning task. Relative to sham, the left prefrontal cortex and M1 tDCS groups exhibited enhanced learning evidenced by shorter response times for pattern trials, but only for individuals who did not gain explicit awareness of the sequence (implicit). Right prefrontal cortex stimulation in participants who did not gain explicit sequence awareness resulted in learning disadvantages evidenced by slower overall response times for pattern trials. These findings indicate that stimulation to left prefrontal cortex or M1 can lead to sequence learning benefits under implicit conditions. In contrast, right prefrontal cortex tDCS had negative effects on sequence learning, with overall impaired reaction time for implicit learners. There was no effect of tDCS on accuracy, and thus our reaction time findings cannot be explained by a speed-accuracy tradeoff. Overall, our findings suggest complex and hemisphere-specific roles of left and right prefrontal cortices in sequence learning. NEW & NOTEWORTHY Prefrontal cortices are engaged in motor sequence learning, but the literature is mixed on whether the prefrontal cortices aid or interfere with learning. In the current study, we used anodal transcranial direct current stimulation to target left or right prefrontal cortex or left primary motor cortex while participants performed a probabilistic sequence learning task. We found that left prefrontal and motor cortex stimulation enhanced implicit learning whereas right prefrontal stimulation negatively impacted performance.

Michigan Neural Distinctiveness (MiND) study protocol: investigating the scope, causes, and consequences of age-related neural dedifferentiation.

BACKGROUND: Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway). METHODS: The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity. DISCUSSION: By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines. TRIAL REGISTRATION: This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136 .

Change of cortical foot activation following 70 days of head-down bed rest.

Head-down tilt bed rest (HDBR) has been used as a spaceflight analog to study some of the effects of microgravity on human physiology, cognition, and sensorimotor functions. Previous studies have reported declines in balance control and functional mobility after spaceflight and HDBR. In this study we investigated how the brain activation for foot movement changed with HDBR. Eighteen healthy men participated in the current HDBR study. They were in a 6° head-down tilt position continuously for 70 days. Functional MRI scans were acquired to estimate brain activation for foot movement before, during, and after HDBR. Another 11 healthy men who did not undergo HDBR participated as control subjects and were scanned at four time points. In the HDBR subjects, the cerebellum, fusiform gyrus, hippocampus, and middle occipital gyrus exhibited HDBR-related increases in activation for foot tapping, whereas no HDBR-associated activation decreases were found. For the control subjects, activation for foot tapping decreased across sessions in a couple of cerebellar regions, whereas no activation increase with session was found. Furthermore, we observed that less HDBR-related decline in functional mobility and balance control was associated with greater pre-to-post HDBR increases in brain activation for foot movement in several cerebral and cerebellar regions. Our results suggest that more neural control is needed for foot movement as a result of HDBR. NEW & NOTEWORTHY Long-duration head-down bed rest serves as a spaceflight analog research environment. We show that brain activity in the cerebellum and visual areas during foot movement increases from pre- to post-bed rest and then shows subsequent recovery. Greater increases were seen for individuals who exhibited less decline in functional mobility and balance control, suggestive of adaptive changes in neural control with long-duration bed rest.

Effects of long-term balance training with vibrotactile sensory augmentation among community-dwelling healthy older adults: a randomized preliminary study.

BACKGROUND: Sensory augmentation has been shown to improve postural stability during real-time balance applications. Limited long-term controlled studies have examined retention of balance improvements in healthy older adults after training with sensory augmentation has ceased. This pilot study aimed to assess the efficacy of long-term balance training with and without sensory augmentation among community-dwelling healthy older adults. METHODS: Twelve participants (four males, eight females; 75.6 ± 4.9 yrs) were randomly assigned to the experimental group (n = 6) or control group (n = 6). Participants trained in their homes for eight weeks, completing three 45-min exercise sessions per week using smart phone balance trainers that provided written, graphic, and video guidance, and monitored trunk sway. During each session, participants performed six repetitions of six exercises selected from five categories (static standing, compliant surface standing, weight shifting, modified center of gravity, and gait). The experimental group received vibrotactile sensory augmentation for four of the six repetitions per exercise via the smart phone balance trainers, while the control group performed exercises without sensory augmentation. The smart phone balance trainers sent exercise performance data to a physical therapist, who recommended exercises on a weekly basis. Balance performance was assessed using a battery of clinical balance tests (Activity Balance Confidence Scale, Sensory Organization Test, Mini Balance Evaluation Systems Test, Five Times Sit to Stand Test, Four Square Step Test, Functional Reach Test, Gait Speed Test, Timed Up and Go, and Timed Up and Go with Cognitive Task) before training, after four weeks of training, and after eight weeks of training. RESULTS: Participants in the experimental group were able to use vibrotactile sensory augmentation independently in their homes. After training, the experimental group had significantly greater improvements in Sensory Organization Test and Mini Balance Evaluation Systems Test scores than the control group. Significant improvement was also observed for Five Times Sit to Stand Test duration within the experimental group, but not in the control group. No significant improvements between the two groups were observed in the remaining clinical outcome measures. CONCLUSION: The findings of this study support the use of sensory augmentation devices by community-dwelling healthy older adults as balance rehabilitation tools, and indicate feasibility of telerehabilitation therapy with reduced input from clinicians.