Frailty Predicts Dementia and Death in Older Adults Living in Long-Term Care.

OBJECTIVES: To investigate how the accumulation of deficits traditionally related and not traditionally related to dementia predicts dementia and mortality. DESIGN: A retrospective cohort study with up to 9 years of follow-up. SETTING AND PARTICIPANTS: Long-term care residents aged ≥65 with or without dementia. METHODS: Frailty indices based on health deficit accumulation were constructed. The FI-t consisted of 27 deficits traditionally related to dementia; the FI-n consisted of 27 deficits not traditionally related to dementia; the FI-a consisted of all 54 deficits taken from the FI-t and the FI-n. RESULTS: In this long-term care sample (n = 29,758; mean age = 84.6 ± 8.0; 63.8% female), 91% of the residents had at least 1 impairment in activities of daily living, 61% had a diagnosis of dementia, and the vast majority were frail (53% had FI-a > 0.2). Residents with dementia had a higher FI-t compared with those without dementia (0.278 ± 0.110 vs. 0.272 ± 0.108), whereas residents without dementia had a higher FI-n (0.143 ± 0.082 vs. 0.136 ± 0.079). Within 9 years, 97% of the sample had died; a 0.01 increase of the FI-a was associated with a 4% increase of the mortality risk, adjusting for age, sex, admission year, stay length, and dementia type. Residents who developed dementia after admission to long-term care had higher baseline FI-t and FI-a (P's < .003) than those who remained without dementia. CONCLUSIONS AND IMPLICATIONS: Frailty is highly prevalent in older adults living in long-term care, irrespective of the presence or absence of dementia. Accumulation of deficits, either traditionally related or unrelated to dementia, is associated with risks of death and dementia, and more deficits increases the probability. Our findings have implications for improving the quality of care of older adults in long-term care, by monitoring the degree of frailty at admission, managing distinct needs in relation to dementia, and enhancing frailty level-informed care and services.

Combating Barriers to the Development of a Patient-Oriented Frailty Website.

Unlabelled: This viewpoint article, which represents the opinions of the authors, discusses the barriers to developing a patient-oriented frailty website and potential solutions. A patient-oriented frailty website is a health resource where community-dwelling older adults can navigate to and answer a series of health-related questions to receive a frailty score and health summary. This information could then be shared with health care professionals to help with the understanding of health status prior to acute illness, as well as to screen and identify older adult individuals for frailty. Our viewpoints were drawn from 2 discussion sessions that included caregivers and care providers, as well as community-dwelling older adults. We found that barriers to a patient-oriented frailty website include, but are not limited to, its inherent restrictiveness to frail persons, concerns over data privacy, time commitment worries, and the need for health and lifestyle resources in addition to an assessment summary. For each barrier, we discuss potential solutions and caveats to those solutions, including assistance from caregivers, hosting the website on a trusted source, reducing the number of health questions that need to be answered, and providing resources tailored to each users' responses, respectively. In addition to screening and identifying frail older adults, a patient-oriented frailty website will help promote healthy aging in nonfrail adults, encourage aging in place, support real-time monitoring, and enable personalized and preventative care.

Interhemispheric inhibition between dorsal premotor and primary motor cortices is released during preparation of unimanual but not bimanual movements.

Previous research applying transcranial magnetic stimulation during unimanual reaction time tasks indicates a transient change in the inhibitory influence of the dorsal premotor cortex over the contralateral primary motor cortex shortly after the presentation of an imperative stimulus. The degree of interhemispheric inhibition from the dorsal premotor cortex to the contralateral primary motor cortex shifts depending on whether the targeted effector representation in the primary motor cortex is selected for movement. Further, the timing of changes in inhibition covaries with the selection demands of the reaction time task. Less is known about modulation of dorsal premotor to primary motor cortex interhemispheric inhibition during the preparation of bimanual movements. In this study, we used a dual coil transcranial magnetic stimulation to measure dorsal premotor to primary motor cortex interhemispheric inhibition between both hemispheres during unimanual and bimanual simple reaction time trials. Interhemispheric inhibition was measured early and late in the 'pre-movement period' (defined as the period immediately after the onset of the imperative stimulus and before the beginning of voluntary muscle activity). We discovered that interhemispheric inhibition was more facilitatory early in the pre-movement period compared with late in the pre-movement period during unimanual reaction time trials. In contrast, interhemispheric inhibition was unchanged throughout the pre-movement period during symmetrical bimanual reaction time trials. These results suggest that there is greater interaction between the dorsal premotor cortex and contralateral primary motor cortex during the preparation of unimanual actions compared to bimanual actions.

Frontoparietal function and underlying structure reflect capacity for motor skill acquisition during healthy aging.

While capacity for motor skill acquisition changes with healthy aging, there has been little consideration of how age-related changes in brain function or baseline brain structure support motor skill acquisition. We examined: (1) age-dependent changes in functional reorganization related to frontoparietal regions during motor skill acquisition, and (2) whether capacity for motor skill acquisition relates to baseline white matter microstructure in frontoparietal tracts. Healthy older and younger adults engaged in 4 weeks of skilled motor practice. Resting-state functional connectivity (rsFC) assessed functional reorganization before and after practice. Diffusion tensor imaging indexed microstructure of a frontoparietal tract at baseline, generated by rsFC seeds. Motor skill acquisition was associated with decreases in rsFC in healthy older adults and increases in rsFC in healthy younger adults. Frontoparietal tract microstructure was lower in healthy older versus younger adults, yet it was negatively associated with rate of skill acquisition regardless of group. Findings indicate that age-dependent alterations in frontoparietal function and baseline structure of a frontoparietal tract reflect capacity for motor skill acquisition.

Improved processing speed and decreased functional connectivity in individuals with chronic stroke after paired exercise and motor training.

After stroke, impaired motor performance is linked to an increased demand for cognitive resources. Aerobic exercise improves cognitive function in neurologically intact populations and may be effective in altering cognitive function post-stroke. We sought to determine if high-intensity aerobic exercise paired with motor training in individuals with chronic stroke alters cognitive-motor function and functional connectivity between the dorsolateral prefrontal cortex (DLPFC), a key region for cognitive-motor processes, and the sensorimotor network. Twenty-five participants with chronic stroke were randomly assigned to exercise (n = 14; 66 ± 11 years; 4 females), or control (n = 11; 68 ± 8 years; 2 females) groups. Both groups performed 5-days of paretic upper limb motor training after either high-intensity aerobic exercise (3 intervals of 3 min each, total exercise duration of 23-min) or watching a documentary (control). Resting-state fMRI, and trail making test part A (TMT-A) and B were recorded pre- and post-intervention. Both groups showed implicit motor sequence learning (p < 0.001); there was no added benefit of exercise for implicit motor sequence learning (p = 0.738). The exercise group experienced greater overall cognitive-motor improvements measured with the TMT-A. Regardless of group, the changes in task score, and dwell time during TMT-A were correlated with a decrease in DLPFC-sensorimotor network functional connectivity (task score: p = 0.025; dwell time: p = 0.043), which is thought to reflect a reduction in the cognitive demand and increased automaticity. Aerobic exercise may improve cognitive-motor processing speed post-stroke.

Preserving the discreteness of deficits during coding leads to a lower frailty index in individuals living in long-term care.

This study assesses two coding approaches on the frailty index (FI). Two FI were calculated using 43 variables from 29,758 older adults (84.6 ± 8 years old; 64 % female) in long-term care. Scores were coded as 0, 0.5, or 1 regardless of the number of levels (grouped), or preserved (e.g., a 4 level variable was coded as 0, 0.33, 0.67, or 1; discrete). Grouped and discrete FI were compared with each ordinal variable removed but all other ordinal variables included. This was repeated until 28 unique (14 grouped, 14 discrete) FI had been constructed each with one ordinal variable removed per FI. FI was correlated to age and mortality separated by sex. The median grouped (0.302 (0.221-0.372)) was higher relative to the discrete (0.237 (0.170-0.307)) FI. The discrete (r = 0.91, r = 0.87) and grouped (r = 0.93, r = 0.87) FI showed similar relationships to age and mortality. Removal of any ordinal variable reduced grouped FI by 0.004 or 0.016, whereas removal led to both increases (range: 0.003-0.001) and reductions (range: 0.002-0.008) for discrete FI. A grouped approach inflates FI. A discrete approach provides a more accurate measure of frailty.

Exploring biomarkers of processing speed and executive function: The role of the anterior thalamic radiations.

INTRODUCTION: Processing speed and executive function are often impaired after stroke and in typical aging. However, there are no reliable neurological markers of these cognitive impairments. The trail making test (TMT) is a common index of processing speed and executive function. Here, we tested candidate MRI markers of TMT performance in a cohort of older adults and individuals with chronic stroke. METHODS: In 61 older adults and 32 individuals with chronic stroke, we indexed white matter structure with region-specific lesion load (of white matter hyperintensities (WMHs) and stroke lesions) and diffusion tensor imaging (DTI) from four regions related to TMT performance: the anterior thalamic radiations (ATR), superior longitudinal fasciculus (SLF), forceps minor, and cholinergic pathways. Regression modelling was used to identify the marker(s) that explained the most variance in TMT performance. RESULTS: DTI metrics of the ATR related to processing speed in both the older adult (TMT A: ß = -3.431, p < 0.001) and chronic stroke (TMT A: ß = 11.282, p < 0.001) groups. In the chronic stroke group executive function was best predicted by a combination of ATR and forceps minor DTI metrics (TMT B: adjustedR2 = 0.438, p < 0.001); no significant predictors of executive function (TMT B) emerged in the older adult group. No imaging metrics related to set shifting (TMT B-A). Regional DTI metrics predicted TMT performance above and beyond whole-brain stroke and WMH volumes and removing whole-brain lesion volumes improved model fits. CONCLUSIONS: In this comprehensive assessment of candidate imaging markers, we demonstrate an association between ATR microstructure and processing speed and executive function performance. Regional DTI metrics provided better predictors of cognitive performance than whole-brain lesion volumes or regional lesion load, emphasizing the importance of lesion location in understanding cognition. We propose ATR DTI metrics as novel candidate imaging biomarker of post-stroke cognitive impairment.

In vivo myelin imaging and tissue microstructure in white matter hyperintensities and perilesional white matter.

White matter hyperintensities negatively impact white matter structure and relate to cognitive decline in aging. Diffusion tensor imaging detects changes to white matter microstructure, both within the white matter hyperintensity and extending into surrounding (perilesional) normal-appearing white matter. However, diffusion tensor imaging markers are not specific to tissue components, complicating the interpretation of previous microstructural findings. Myelin water imaging is a novel imaging technique that provides specific markers of myelin content (myelin water fraction) and interstitial fluid (geometric mean T2). Here we combined diffusion tensor imaging and myelin water imaging to examine tissue characteristics in white matter hyperintensities and perilesional white matter in 80 individuals (47 older adults and 33 individuals with chronic stroke). To measure perilesional normal-appearing white matter, white matter hyperintensity masks were dilated in 2 mm segments up to 10 mm in distance from the white matter hyperintensity. Fractional anisotropy, mean diffusivity, myelin water fraction, and geometric mean T2 were extracted from white matter hyperintensities and perilesional white matter. We observed a spatial gradient of higher mean diffusivity and geometric mean T2, and lower fractional anisotropy, in the white matter hyperintensity and perilesional white matter. In the chronic stroke group, myelin water fraction was reduced in the white matter hyperintensity but did not show a spatial gradient in perilesional white matter. Across the entire sample, white matter metrics within the white matter hyperintensity related to whole-brain white matter hyperintensity volume; with increasing white matter hyperintensity volume there was increased mean diffusivity and geometric mean T2, and decreased myelin water fraction in the white matter hyperintensity. Normal-appearing white matter adjacent to white matter hyperintensities exhibits characteristics of a transitional stage between healthy white matter and white matter hyperintensities. This effect was observed in markers sensitive to interstitial fluid, but not in myelin water fraction, the specific marker of myelin concentration. Within the white matter hyperintensity, interstitial fluid was higher and myelin concentration was lower in individuals with more severe cerebrovascular disease. Our data suggests white matter hyperintensities have penumbra-like effects in perilesional white matter that specifically reflect increased interstitial fluid, with no changes to myelin concentration. In contrast, within the white matter hyperintensity there are varying levels of demyelination, which vary based on the severity of cerebrovascular disease. Diffusion tensor imaging and myelin imaging may be useful clinical markers to predict white matter hyperintensity formation, and to stage neuronal damage within white matter hyperintensities.

Individuals with Higher Levels of Physical Activity after Stroke Show Comparable Patterns of Myelin to Healthy Older Adults.

BACKGROUND: Myelin asymmetry ratios (MARs) relate and contribute to motor impairment and function after stroke. Physical activity (PA) may induce myelin plasticity, potentially mitigating hemispheric myelin asymmetries that can occur after a stroke. OBJECTIVE: The aim of this study was to determine whether individuals with higher levels of PA showed lower MAR compared to individuals with lower levels of PA. METHODS: Myelin water fraction was obtained from 5 bilateral motor regions in 22 individuals with chronic stroke and 26 healthy older adults. Activity levels were quantified with wrist accelerometers worn for a period of 72 hours (3 days). Higher and lower PA levels were defined by a cluster analysis within each group. RESULTS: MAR was similar regardless of PA level within the older adult group. Compared to the higher PA stroke group, lower PA stroke participants displayed greater MAR. There was no difference in MAR between the stroke and older adult higher PA groups. Within the lower PA groups, individuals with stroke showed greater MAR compared to the older adults. Arm impairment, lesion volume, age, time since stroke, and preferential arm use were not different between the PA stroke groups, suggesting that motor impairment severity and extent of brain damage did not drive differences in PA. CONCLUSION: Individuals who have had a stroke and are also physically active display lower MAR (i.e., similar myelin in both hemispheres) in motor regions. High levels of PA may be neuroprotective and mitigate myelin asymmetries once a neurological insult, such as a stroke, occurs. Alternately, it is possible that promoting high levels of PA after a stroke may reduce myelin asymmetries.

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.

Acute High-Intensity Interval Exercise Modulates Corticospinal Excitability in Older Adults.

INTRODUCTION: Acute exercise can modulate the excitability of the nonexercised upper limb representation in the primary motor cortex (M1). Measures of M1 excitability using transcranial magnetic stimulation (TMS) are modulated after various forms of acute exercise in young adults, including high-intensity interval training (HIIT). However, the impact of HIIT on M1 excitability in older adults is currently unknown. Therefore, the purpose of the current study was to investigate the effects of lower limb cycling HIIT on bilateral upper limb M1 excitability in older adults. METHODS: We assessed the impact of acute lower limb HIIT or rest on bilateral corticospinal excitability, intracortical inhibition and facilitation, and interhemispheric inhibition of the nonexercised upper limb muscle in healthy older adults (mean age 66 ± 8 yr). We used single and paired-pulse TMS to assess motor evoked potentials, short-interval intracortical inhibition, intracortical facilitation, and the ipsilateral silent period. Two groups of healthy older adults completed either HIIT exercise or seated rest for 23 min, with TMS measures performed before (T0), immediately after (T1), and 30 min after (T2) HIIT/rest. RESULTS: Motor evoked potentials were significantly increased after HIIT exercise at T2 compared with T0 in the dominant upper limb. Contrary to our hypothesis, we did not find any significant change in short-interval intracortical inhibition, intracortical facilitation, or ipsilateral silent period after HIIT. CONCLUSIONS: Our findings demonstrate that corticospinal excitability of the nonexercised upper limb is increased after HIIT in healthy older adults. Our results indicate that acute HIIT exercise impacts corticospinal excitability in older adults, without affecting intracortical or interhemispheric circuitry. These findings have implications for the development of exercise strategies to potentiate neuroplasticity in healthy older and clinical populations.

Multiple bouts of high-intensity interval exercise reverse age-related functional connectivity disruptions without affecting motor learning in older adults.

Exercise has emerged as an intervention that may mitigate age-related resting state functional connectivity and sensorimotor decline. Here, 42 healthy older adults rested or completed 3 sets of high-intensity interval exercise for a total of 23 min, then immediately practiced an implicit motor task with their non-dominant hand across five separate sessions. Participants completed resting state functional MRI before the first and after the fifth day of practice; they also returned 24-h and 35-days later to assess short- and long-term retention. Independent component analysis of resting state functional MRI revealed increased connectivity in the frontoparietal, the dorsal attentional, and cerebellar networks in the exercise group relative to the rest group. Seed-based analysis showed strengthened connectivity between the limbic system and right cerebellum, and between the right cerebellum and bilateral middle temporal gyri in the exercise group. There was no motor learning advantage for the exercise group. Our data suggest that exercise paired with an implicit motor learning task in older adults can augment resting state functional connectivity without enhancing behaviour beyond that stimulated by skilled motor practice.

Cortical N-acetylaspartate concentrations are impacted in chronic stroke but do not relate to motor impairment: A magnetic resonance spectroscopy study.

Magnetic resonance spectroscopy (MRS) measures cerebral metabolite concentrations, which can inform our understanding of the neurobiological processes associated with stroke recovery. Here, we investigated whether metabolite concentrations in primary motor and somatosensory cortices (sensorimotor cortex) are impacted by stroke and relate to upper-extremity motor impairment in 45 individuals with chronic stroke. Cerebral metabolite estimates were adjusted for cerebrospinal fluid and brain tissue composition in the MRS voxel. Upper-extremity motor impairment was indexed with the Fugl-Meyer (FM) scale. N-acetylaspartate (NAA) concentration was reduced bilaterally in stroke participants with right hemisphere lesions (n = 23), relative to right-handed healthy older adults (n = 15; p = .006). Within the entire stroke sample (n = 45) NAA and glutamate/glutamine (GLX) were lower in the ipsilesional sensorimotor cortex, relative to the contralesional cortex (NAA: p < .001; GLX: p = .003). Lower ipsilesional NAA was related to greater extent of corticospinal tract (CST) injury, quantified by a weighted CST lesion load (p = .006). Cortical NAA and GLX concentrations did not relate to the severity of chronic upper-extremity impairment (p > .05), including after a sensitivity analysis imputing missing metabolite data for individuals with large cortical lesions (n = 5). Our results suggest that NAA, a marker of neuronal integrity, is sensitive to stroke-related cortical damage and may provide mechanistic insights into cellular processes of cortical adaptation to stroke. However, cortical MRS metabolites may have limited clinical utility as prospective biomarkers of upper-extremity outcomes in chronic stroke.

Aberrant Cerebellar Resting-State Functional Connectivity Related to Reading Performance in Struggling Readers.

Reading is a critical neurodevelopmental skill for school-aged children, which requires a distributed network of brain regions including the cerebellum. However, we do not know how functional connectivity between the cerebellum and other brain regions contributes to reading. Here we used resting-state functional connectivity to understand the cerebellum's role in decoding, reading speed, and comprehension in a group of struggling readers (RD) and a group of adolescents and children with typical reading abilities (TD). We observed an increase in functional connectivity between the sensorimotor network and the left angular gyrus, left lateral occipital cortex, and right inferior frontal gyrus in the RD group relative to the TD group. Additionally, functional connectivity between the cerebellum network and the precentral gyrus was decreased and was related to reading fluency in the RD group. Seed-based analysis revealed increased functional connectivity between crus 1, lobule 6, and lobule 8 of the cerebellum and brain regions related to the default mode network and the motor system for the RD group. We also found associations between reading performance and the functional connectivity between lobule 8 of the cerebellum and the left angular gyrus for both groups, with stronger relationships in the TD group. Specifically, the RD group displayed a positive relationship between functional connectivity, whereas the TD group displayed the opposite relationship. These results suggest that the cerebellum is involved in multiple components of reading performance and that functional connectivity differences observed in the RD group may contribute to poor reading performance.

Learning-Challenged Youth Show an Abnormal Relationship Between Fronto-Parietal Myelination and Mathematical Ability.

BACKGROUND AND PURPOSE: Differences in the microstructure of fronto-parietal white matter tracts have been associated with mathematical achievement. However, much of the supporting evidence relies on nonspecific diffusion-weighted magnetic resonance imaging, making it difficult to isolate the role of myelin in math ability. METHODS: We used myelin water imaging to measure brain myelin. We related myelin water fraction (MWF) to Woodcock-Johnson III (WJ-III) basic math scores using region of interest (ROI) and tract-based spatial statistics (TBSS) analyses, in 14 typically developing and 36 learning challenged youth aged 9-17 years. RESULTS: The ROI analysis found a positive relationship between fronto-parietal MWF and math in typically developing youth, but not in learning challenged youth. The relationship between fronto-parietal MWF and math observed in typically developing youth was fully mediated by age. No group differences in fronto-parietal MWF were found between typically developing and learning challenged youth. TBSS also found no group differences in MWF values. TBSS indicated math-MWF relationships extend beyond fronto-parietal tracts to descending and ascending projection tracts in typically developing youth. TBSS identified math-MWF relationships in the cerebral peduncles of learning challenged youth. CONCLUSIONS: Our results suggest that in typically developing youth, brain myelination contributes to individual differences in basic math achievement. In contrast, youth with learning challenges appear to have less capacity to leverage myelin to improve math achievement.

Multi-session Transcranial Direct Current Stimulation Over Primary Motor Cortex Facilitates Sequence Learning, Chunking, and One Year Retention.

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) can facilitate motor learning, but it has not been established how stimulation to other brain regions impacts online and offline motor sequence learning, as well as long-term retention. Here, we completed three experiments comparing the effects of tDCS and sham stimulation to the prefrontal cortex (PFC), M1, and the supplementary motor area complex to understand the contributions of these brain regions to motor sequence learning. In Experiment 1, we found that both left and right PFC tDCS groups displayed a slowing in learning in both reaction time and number of chunks, whereas stimulation over M1 improved both metrics over the course of three sessions. To better understand the sequence learning impairment of left PFC anodal stimulation, we tested a left PFC cathodal tDCS group in Experiment 2. The cathodal group demonstrated learning impairments similar to the left PFC anodal stimulation group. In Experiment 3, a subset of participants from the left PFC, M1, and sham tDCS groups of Experiment 1 returned to complete a single session without tDCS on the same sequences assigned to them 1 year previously. We found that the M1 tDCS group reduced reaction time at a faster rate relative to the sham and left PFC groups, demonstrating faster relearning after a one-year delay. Thus, our findings suggest that, regardless of the polarity of stimulation, tDCS to PFC impairs sequence learning, whereas stimulation to M1 facilitates learning and relearning, especially in terms of chunk formation.

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.

Mood induction effects on motor sequence learning and stop signal reaction time.

The neurobiological theory of positive affect proposes that positive mood states may benefit cognitive performance due to an increase of dopamine throughout the brain. However, the results of many positive affect studies are inconsistent; this may be due to individual differences. The relationship between dopamine and performance is not linear, but instead follows an inverted "U" shape. Given this, we hypothesized that individuals with high working memory capacity, a proxy measure for dopaminergic transmission, would not benefit from positive mood induction and in fact performance in dopamine-mediated tasks would decline. In contrast, we predicted that individuals with low working memory capacities would receive the most benefit after positive mood induction. Here, we explored the effect of positive affect on two dopamine-mediated tasks, an explicit serial reaction time sequence learning task and the stop signal task, predicting that an individual's performance is modulated not only by working memory capacity, but also on the type of mood. Improvements in explicit sequence learning from pre- to post-positive mood induction were associated with working memory capacity; performance declined in individuals with higher working memory capacities following positive mood induction, but improved in individuals with lower working memory capacities. This was not the case for negative or neutral mood induction. Moreover, there was no relationship between the change in stop signal reaction time with any of the mood inductions and individual differences in working memory capacity. These results provide partial support for the neurobiological theory of positive affect and highlight the importance of taking into account individual differences in working memory when examining the effects of positive mood induction.

Right prefrontal cortex transcranial direct current stimulation enhances multi-day savings in sensorimotor adaptation.

We have previously reported that visuospatial working memory performance and magnitude of activation in the right dorsolateral prefrontal cortex predict the rate of visuomotor adaptation. Recent behavioral studies suggest that sensorimotor savings, or faster relearning on second exposure to a task, are due to recall of these early, strategic components of adaptation. In the present study we applied anodal transcranial direct current stimulation to right or left prefrontal cortex or left motor cortex. We found that all groups adapted dart throwing movements while wearing prism lenses at the same rate as subjects receiving sham stimulation on day 1 On test day 2, which was conducted a few days later, the right prefrontal and left motor cortex groups adapted faster than the sham group. Moreover, only the right prefrontal group exhibited greater savings, expressed as a greater difference between day 1 and day 2 errors, compared with sham stimulation. These findings support the hypothesis that the right prefrontal cortex contributes to sensorimotor adaptation and savings. NEW & NOTEWORTHY: We have previously reported that visuospatial working memory performance and magnitude of activation in the right dorsolateral prefrontal cortex predict the rate of manual visuomotor adaptation. Sensorimotor savings, or faster adaptation to a previously experienced perturbation, has been recently linked to cognitive processes. We show that facilitating the right prefrontal cortex with anodal transcranial direct current stimulation enhances sensorimotor savings compared with sham stimulation.