Exercise-induced cortical disinhibition mediates the relationship between fitness and memory in older adults.

Regular exercise benefits learning and memory in older adults, but the neural mechanisms mediating these effects remain unclear. Evidence in young adults indicates that acute exercise creates a favourable environment for synaptic plasticity by enhancing cortical disinhibition. As such, we investigated whether plasticity-related disinhibition mediated the relationship between cardiorespiratory fitness and memory function in healthy older adults (n = 16, mean age = 66.06). Participants completed a graded maximal exercise test and assessments of visual and verbal memory, followed by two counterbalanced sessions involving 20 min of either high-intensity interval training exercise or rest. Disinhibition was measured following intermittent theta burst stimulation via paired-pulse transcranial magnetic stimulation. In line with our hypotheses, we observed a positive correlation between cardiorespiratory fitness and verbal memory, which was mediated by plasticity-related cortical disinhibition. Our novel finding implicates cortical disinhibition as a mechanism through which the effects of acute bouts of exercise may translate to improved memory in older adults. This finding extends current understanding of the physiological mechanisms underlying the positive influence of cardiorespiratory fitness for memory function in older adults, and further highlights the importance of promoting exercise engagement to maintain cognitive health in later life. KEY POINTS: There are well established benefits of regular exercise for memory function in older adults, but the mechanisms are unclear. Cortical disinhibition is important for laying down new memories, and is enhanced following acute exercise in young adults, suggesting it is a potential mechanism underlying these benefits in ageing. Older adults completed a fitness test and assessments of memory, followed by two sessions involving either 20 min of exercise or rest. Disinhibition was measured following intermittent theta burst stimulation via paired-pulse transcranial magnetic stimulation. Cardiorespiratory fitness was positively associated with memory performance. Higher fitness was associated with enhanced cortical disinhibition following acute exercise. Cortical disinhibition completely mediated the relationship between fitness and memory. This novel finding provides a mechanistic account for the positive influence of cardiorespiratory fitness on memory in later life, and emphasises the importance of regular exercise for cognitive health in older populations.

Dopamine D2 Receptor Modulates Exercise Related Effect on Cortical Excitation/Inhibition and Motor Skill Acquisition.

Exercise is known to benefit motor skill learning in health and neurological disease. Evidence from brain stimulation, genotyping, and Parkinson's disease studies converge to suggest that the dopamine D2 receptor, and shifts in the cortical excitation and inhibition (E:I) balance, are prime candidates for the drivers of exercise-enhanced motor learning. However, causal evidence using experimental pharmacological challenge is lacking. We hypothesized that the modulatory effect of the dopamine D2 receptor on exercise-induced changes in the E:I balance would determine the magnitude of motor skill acquisition. To test this, we measured exercise-induced changes in excitation and inhibition using paired-pulse transcranial magnetic stimulation (TMS) in 22 healthy female and male humans, and then had participants learn a novel motor skill-the sequential visual isometric pinch task (SVIPT). We examined the effect of D2 receptor blockade (800 mg sulpiride) on these measures within a randomized, double-blind, placebo-controlled design. Our key result was that motor skill acquisition was driven by an interaction between the D2 receptor and E:I balance. Specifically, poorer skill learning was related to an attenuated shift in the E:I balance in the sulpiride condition, whereas this interaction was not evident in placebo. Our results demonstrate that exercise-primed motor skill acquisition is causally influenced by D2 receptor activity on motor cortical circuits.

Micro-consolidation occurs when learning an implicit motor sequence, but is not influenced by HIIT exercise.

We investigated if micro-consolidation, a phenomenon recently discovered during the brief rest periods between practice when learning an explicit motor sequence, generalises to learning an implicit motor sequence task. We demonstrate micro-consolidation occurs in the absence of explicit sequence awareness. We also investigated the effect of a preceding bout of high-intensity exercise, as exercise is known to augment the consolidation of new motor skills. Micro-consolidation was not modified by exercise.

High-intensity acute exercise impacts motor learning in healthy older adults.

Healthy aging is associated with changes in motor sequence learning, with some studies indicating decline in motor skill learning in older age. Acute cardiorespiratory exercise has emerged as a potential intervention to improve motor learning, however research in healthy older adults is limited. The current study investigated the impact of high-intensity interval exercise (HIIT) on a subsequent sequential motor learning task. Twenty-four older adults (aged 55-75 years) completed either 20-minutes of cycling, or an equivalent period of active rest before practicing a sequential force grip task. Skill learning was assessed during acquisition and at a 6-hour retention test. In contrast to expectation, exercise was associated with reduced accuracy during skill acquisition compared to rest, particularly for the oldest participants. However, improvements in motor skill were retained in the exercise condition, while a reduction in skill was observed following rest. Our findings indicate that high-intensity exercise conducted immediately prior to learning a novel motor skill may have a negative impact on motor performance during learning in older adults. We also demonstrated that exercise may facilitate early offline consolidation of a motor skill within this population, which has implications for motor rehabilitation.

Ageing attenuates exercise-enhanced motor cortical plasticity.

Cardiorespiratory exercise is known to modulate motor cortical plasticity in young adults, but the influence of ageing on this relationship is unknown. Here, we compared the effects of a single session of cardiorespiratory exercise on motor cortical plasticity in young and older adults. We acquired measures of cortical excitatory and inhibitory activity of the primary motor cortex using transcranial magnetic stimulation (TMS) from 20 young (mean ± SD = 25.30 ± 4.00 years, 14 females) and 20 older (mean ± SD = 64.10 ± 6.50 years, 11 females) healthy adults. Single- and paired-pulse TMS measurements were collected before and after a 20 min bout of high-intensity interval cycling exercise or an equivalent period of rest, and again after intermittent theta burst stimulation (iTBS). In both young (P = 0.027, Cohen's d = 0.87) and older adults (P = 0.006, Cohen's d = 0.85), there was an increase in glutamatergic excitation and a reduction in GABAergic inhibition from pre- to postexercise. However, in contrast to younger adults, older adults showed an attenuated plasticity response to iTBS following exercise (P = 0.011, Cohen's d = 0.85). These results demonstrate an age-dependent decline in cortical plasticity and indicate that a preceding bout of high-intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults. Our findings align with the hypothesis that the capacity for cortical plasticity is altered in older age. KEY POINTS: Exercise enhances motor cortical plasticity in young adults, but how ageing influences this effect is unknown. Here, we compared primary motor cortical plasticity responses in young and older adults before and after a bout of high-intensity interval exercise and again after a plasticity-inducing protocol, intermittent theta burst stimulation. In both young and older adults, exercise led to an increase in glutamatergic excitation and a reduction in GABAergic inhibition. Our key result was that older adults showed an attenuated plasticity response to theta burst stimulation following exercise, relative to younger adults. Our findings demonstrate an age-dependent decline in exercise-enhanced cortical plasticity and indicate that a preceding bout of high-intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults.

Trans-ancestry meta-analysis of genome wide association studies of inhibitory control.

Deficits in effective executive function, including inhibitory control are associated with risk for a number of psychiatric disorders and significantly impact everyday functioning. These complex traits have been proposed to serve as endophenotypes, however, their genetic architecture is not yet well understood. To identify the common genetic variation associated with inhibitory control in the general population we performed the first trans-ancestry genome wide association study (GWAS) combining data across 8 sites and four ancestries (N = 14,877) using cognitive traits derived from the stop-signal task, namely - go reaction time (GoRT), go reaction time variability (GoRT SD) and stop signal reaction time (SSRT). Although we did not identify genome wide significant associations for any of the three traits, GoRT SD and SSRT demonstrated significant and similar SNP heritability of 8.2%, indicative of an influence of genetic factors. Power analyses demonstrated that the number of common causal variants contributing to the heritability of these phenotypes is relatively high and larger sample sizes are necessary to robustly identify associations. In Europeans, the polygenic risk for ADHD was significantly associated with GoRT SD and the polygenic risk for schizophrenia was associated with GoRT, while in East Asians polygenic risk for schizophrenia was associated with SSRT. These results support the potential of executive function measures as endophenotypes of neuropsychiatric disorders. Together these findings provide the first evidence indicating the influence of common genetic variation in the genetic architecture of inhibitory control quantified using objective behavioural traits derived from the stop-signal task.

Acute exercise as a modifier of neocortical plasticity and aperiodic activity in the visual cortex.

Long-term potentiation (LTP) is a form of neuroplasticity commonly implicated in mechanistic models of learning and memory. Acute exercise can boost LTP in the motor cortex, and is associated with a shift in excitation/inhibition (E:I) balance, but whether this extends to other regions such as the visual cortex is unknown. We investigated the effect of a preceding bout of exercise on LTP induction and the E:I balance in the visual cortex using electroencephalography (EEG). Young adults (N = 20, mean age = 24.20) engaged in 20 min of high-intensity interval training (HIIT) exercise and rest across two counterbalanced sessions. LTP was induced using a high frequency presentation of a visual stimulus; a "visual tetanus". Established EEG markers of visual LTP, the N1b and P2 component of the visual evoked potential, and an EEG-derived measure of the E:I balance, the aperiodic exponent, were measured before and after the visual tetanus. As expected, there was a potentiation of the N1b following the visual tetanus, with specificity to the tetanised stimulus, and a non-specific potentiation of the P2. These effects were not sensitive to a preceding bout of exercise. However, the E:I balance showed a late shift towards inhibition following the visual tetanus. A preceding bout of exercise resulted in specificity of this E:I balance shift to the tetanised stimulus, that was not seen following rest. This novel finding suggests a possible exercise-induced tuning of the visual cortex to stimulus details following LTP induction.

D2 receptor blockade eliminates exercise-induced changes in cortical inhibition and excitation.

BACKGROUND: Although cardiorespiratory exercise is known to affect cortical excitatory and inhibitory activity, the neurochemical mechanisms driving this effect are poorly understood. Animal models of Parkinson's disease identify dopamine D2 receptor expression as a candidate mechanism, but the link between the D2 receptor and exercise-induced changes in cortical activity in humans is unknown. OBJECTIVE: Here, we examined the effect of a selective dopamine D2 receptor antagonist, sulpiride, on exercise-induced changes in cortical activity. METHODS: We acquired measures of excitatory and inhibitory activity of the primary motor cortex using transcranial magnetic stimulation (TMS) from 23 healthy adults, both before and after a 20-min bout of high-intensity interval cycling exercise. We examined the effect of D2 receptor blockade (800 mg sulpiride) on these measures within a randomised, double-blind, placebo-controlled crossover design. RESULTS: Sulpiride abolished exercise-induced modulation of the cortical excitation:inhibition balance relative to placebo (P < 0.001, Cohen's d = 1.76). Sulpiride blocked both the increase in glutamatergic excitation and reduction in gamma-aminobutyric acid (GABA) inhibition that was observed following exercise in the placebo condition. CONCLUSION: Our results provide causal evidence that D2 receptor blockade eliminates exercise-induced changes in excitatory and inhibitory cortical networks, and have implications for how exercise should be prescribed in diseases of dopaminergic dysfunction.

A single bout of moderate-intensity aerobic exercise improves motor learning in premanifest and early Huntington's disease.

Introduction: Cardiorespiratory exercise has emerged as a promising candidate to modify disease progression in Huntington's disease (HD). In animal models, exercise has been found to alter biomarkers of neuroplasticity and delay evidence of disease, and some interventions-including exercise-have shown benefits in human HD patients. In healthy human populations, increasing evidence suggests that even a single bout of exercise can improve motor learning. In this pilot study, we investigated the effect of a single bout of moderate intensity aerobic exercise on motor skill learning in presymptomatic and early manifest HD patients. Methods: Participants were allocated to either an exercise (n = 10) or control (n = 10) group. They performed either 20 min of moderate intensity cycling or rest before practicing a novel motor task, the sequential visual isometric pinch force task (SVIPT). After 1 week, the retention of the SVIPT was measured in both groups. Results: We found that the exercise group performed significantly better during initial task acquisition. There were no significant differences in offline memory consolidation between groups, but total skill gain across both acquisition and retention sessions was greater in the group who exercised. The better performance of the exercise group was driven by improvements in accuracy, rather than speed. Discussion: We have shown that a single bout of moderate intensity aerobic exercise can facilitate motor skill learning in people with HD gene-expansion. More research is needed to investigate the underlying neural mechanisms and to further explore the potential for neurocognitive and functional benefits of exercise for people with HD.

Sleep Restriction Reduces Cognitive but Not Physical Motivation.

Purpose: Motivation is an important driver of behaviour, and several frameworks distinguish the willingness of individuals to invest cognitive versus physical effort to achieve a goal. One outstanding question is whether sleep loss lowers motivation within specific domains of effort, or has a global effect on motivation across multiple domains. Here, we investigated the effects of sleep restriction on the motivation to invest cognitive or physical effort in return for reward. Materials and Methods: 24 healthy young adults (11 females) completed an effort-based decision-making task over two laboratory sessions - once while sleep restricted (three consecutive nights with a three-hour sleep opportunity), and the other while fully rested (nine-hour sleep opportunity on each night). In an initial reinforcement phase, participants were trained to ceiling performance across six levels of effort on separate cognitively and physically demanding tasks. Then, in the critical decision-making phase, participants revealed their preference for how much cognitive or physical effort they would be willing to invest for reward. Results: Sleep restriction reduced the willingness to exert cognitive effort, but spared motivation in the physical domain. Furthermore, the reduction in cognitive motivation appeared to be a primary motivational deficit, which could not be attributed to differences in reward-likelihood of different levels of effort or the temporal structure of the task. Conclusion: The results suggest that sleep restriction has a selective effect on cognitive over physical motivation, which has significant implications for real-world settings in which individuals must maintain high levels of cognitive motivation in the face of chronic sleep loss.

Personalized brain stimulation of memory networks.

BACKGROUND: The finding that transcranial magnetic stimulation (TMS) can enhance memory performance via stimulation of parietal sites within the Cortical-Hippocampal Network counts as one of the most exciting findings in this field in the past decade. However, the first independent effort aiming to fully replicate this finding found no discernible influence of TMS on memory performance. OBJECTIVE: We examined whether this might relate to interindividual spatial variation in brain connectivity architecture, and the capacity of personalisation methodologies to overcome the noise inherent across independent scanners and cohorts. METHODS: We implemented recently detailed personalisation methodology to retrospectively compute individual-specific parietal targets and then examined relation to TMS outcomes. RESULTS: Closer proximity between actual and novel fMRI-personalized targets associated with greater improvement in memory performance. CONCLUSION: These findings demonstrate the potential importance of aligning brain stimulation targets according to individual-specific differences in brain connectivity, and extend upon recent findings in prefrontal cortex.

Effort Reinforces Learning.

Humans routinely learn the value of actions by updating their expectations based on past outcomes - a process driven by reward prediction errors (RPEs). Importantly, however, implementing a course of action also requires the investment of effort. Recent work has revealed a close link between the neural signals involved in effort exertion and those underpinning reward-based learning, but the behavioral relationship between these two functions remains unclear. Across two experiments, we tested healthy male and female human participants (N = 140) on a reinforcement learning task in which they registered their responses by applying physical force to a pair of hand-held dynamometers. We examined the effect of effort on learning by systematically manipulating the amount of force required to register a response during the task. Our key finding, replicated across both experiments, was that greater effort increased learning rates following positive outcomes and decreased them following negative outcomes, which corresponded to a differential effect of effort in boosting positive RPEs and blunting negative RPEs. Interestingly, this effect was most pronounced in individuals who were more averse to effort in the first place, raising the possibility that the investment of effort may have an adaptive effect on learning in those less motivated to exert it. By integrating principles of reinforcement learning with neuroeconomic approaches to value-based decision-making, we show that the very act of investing effort modulates one's capacity to learn, and demonstrate how these functions may operate within a common computational framework.SIGNIFICANCE STATEMENT Recent work suggests that learning and effort may share common neurophysiological substrates. This raises the possibility that the very act of investing effort influences learning. Here, we tested whether effort modulates teaching signals in a reinforcement learning paradigm. Our results showed that effort resulted in more efficient learning from positive outcomes and less efficient learning from negative outcomes. Interestingly, this effect varied across individuals, and was more pronounced in those who were more averse to investing effort in the first place. These data highlight the importance of motivational factors in a common framework of reward-based learning, which integrates the computational principles of reinforcement learning with those of value-based decision-making.

Training inhibitory control in adolescents with elevated attention deficit hyperactivity disorder traits: a randomised controlled trial of the Alfi Virtual Reality programme.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is characterised by significant deficits in attention and inhibition. These deficits are associated with negative sequelae that emerge in childhood and often continue throughout adolescence. Despite these difficulties adolescents with ADHD often demonstrate poor treatment compliance with traditional interventions (eg, psychostimulant medication). Virtual reality (VR) presents an innovative means of delivering engaging cognitive interventions for adolescents with ADHD and offers the potential to improve compliance with such interventions. The current parallel, randomised controlled trial aims to evaluate the effects of a VR intervention (Alfi) designed to improve inhibition in adolescents with ADHD. METHODS AND ANALYSIS: A sample of 100 adolescents (aged 13-17) with elevated ADHD symptoms will be recruited from secondary schools and ADHD organisations located in the state of Victoria, Australia. Participants will be randomly assigned to either an 8-week VR intervention or a usual care control. The VR intervention involves the completion of 14 sessions, each 20 min in duration. Participants will complete computerised assessments of inhibition and risk-taking preintervention and immediately postintervention. Parents/guardians will complete online questionnaires about their child's ADHD symptoms and social functioning at each of these timepoints. The primary outcome is change in inhibition performance in adolescents who received the intervention from preintervention to postintervention compared with adolescents in the control condition. Secondary outcomes include change in risk-taking, ADHD symptoms and social functioning in adolescents who received the intervention from preintervention to postintervention compared with adolescents in the control condition. If the intervention is shown to be effective, it may offer a supplementary approach to traditional interventions for adolescents with ADHD experiencing inhibitory control difficulties. ETHICS AND DISSEMINATION: This trial has ethics approval from the Monash University Human Research Ethics Committee (HREC) (21530) and the Victorian Department of Education and Training HREC (2020_004271). Results will be disseminated through peer-reviewed journals, conference proceedings and community activities. Individual summaries of the results will be provided to participants on request. TRIAL REGISTRATION NUMBER: ACTRN12620000647932.

Associations of cardiorespiratory fitness and exercise with brain white matter in healthy adults: A systematic review and meta-analysis.

Magnetic resonance imaging (MRI) studies have revealed positive associations between brain structure and physical activity, cardiorespiratory fitness, and exercise (referred to here as PACE). While a considerable body of research has investigated the effects of PACE on grey matter, much less is known about effects on white matter (WM). Hence, we conducted a systematic review of peer-reviewed literature published prior to 5th July 2021 using online databases (PubMed and Scopus) and PRISMA guidelines to synthesise what is currently known about the relationship between PACE and WM in healthy adults. A total of 60 studies met inclusion criteria and were included in the review. Heterogeneity across studies was calculated using Qochran's q test, and publication bias was assessed for each meta-analysis using Begg and Mazumdar rank correlation test. A meta-regression was also conducted to explore factors contributing to any observed heterogeneity. Overall, we observed evidence of positive associations between PACE and global WM volume (effect size (Hedges's g) = 0.137, p < 0.001), global WM anomalies (effect size = 0.182, p < 0.001), and local microstructure integrity (i.e., corpus callosum: effect size = 0.345, p < 0.001, and anterior limb of internal capsule: effect size = 0.198, p < 0.001). These findings suggest that higher levels of PACE are associated with improved global WM volume and local integrity. We appraise the quality of evidence, and discuss the implications of these findings for the preservation of WM across the lifespan. We conclude by providing recommendations for future research in order to advance our understanding of the specific PACE parameters and neurobiological mechanisms underlying these effects.

Effects of beta-band and gamma-band rhythmic stimulation on motor inhibition.

To investigate whether beta oscillations are causally related to motor inhibition, thirty-six participants underwent two concurrent transcranial alternating current stimulation (tACS) and electroencephalography (EEG) sessions during which either beta (20 Hz) or gamma (70 Hz) stimulation was applied while participants performed a stop-signal task. In addition, we acquired magnetic resonance images to simulate the electric field during tACS. 20 Hz stimulation targeted at the pre-supplementary motor area enhanced inhibition and increased beta oscillatory power around the time of the stop-signal in trials directly following stimulation. The increase in inhibition on stop trials followed a dose-response relationship with the strength of the individually simulated electric field. Computational modeling revealed that 20 and 70 Hz stimulation had opposite effects on the braking process. These results highlight that the effects of tACS are state-dependent and demonstrate that fronto-central beta activity is causally related to successful motor inhibition, supporting its use as a functional biomarker.

Motor cortex plasticity response to acute cardiorespiratory exercise and intermittent theta-burst stimulation is attenuated in premanifest and early Huntington's disease.

Huntington's disease (HD) mouse models suggest that cardiovascular exercise may enhance neuroplasticity and delay disease signs, however, the effects of exercise on neuroplasticity in people with HD are unknown. Using a repeated-measures experimental design, we compared the effects of a single bout of high-intensity exercise, moderate-intensity exercise, or rest, on motor cortex synaptic plasticity in 14 HD CAG-expanded participants (9 premanifest and 5 early manifest) and 20 CAG-healthy control participants, using transcranial magnetic stimulation. Measures of cortico-motor excitability, short-interval intracortical inhibition and intracortical facilitation were obtained before and after a 20-min bout of either high-intensity interval exercise, moderate-intensity continuous exercise, or rest, and again after intermittent theta burst stimulation (iTBS). HD participants showed less inhibition at baseline compared to controls. Whereas the control group showed increased excitability and facilitation following high-intensity exercise and iTBS, the HD group showed no differences in neuroplasticity responses following either exercise intensity or rest, with follow-up Bayesian analyses providing consistent evidence that these effects were absent in the HD group. These findings indicate that exercise-induced synaptic plasticity mechanisms in response to acute exercise may be attenuated in HD, and demonstrate the need for future research to further investigate exercise and plasticity mechanisms in people with HD.

Regular aerobic exercise is positively associated with hippocampal structure and function in young and middle-aged adults.

Regular exercise has numerous benefits for brain health, including the structure and function of the hippocampus. The hippocampus plays a critical role in memory function, and is altered in a number of psychiatric disorders associated with memory impairments (e.g., depression and schizophrenia), as well as healthy aging. While many studies have focused on how regular exercise may improve hippocampal integrity in older individuals, less is known about these effects in young to middle-aged adults. Therefore, we assessed the associations of regular exercise and cardiorespiratory fitness with hippocampal structure and function in these age groups. We recruited 40 healthy young to middle-aged adults, comprised of two groups (n = 20) who self-reported either high or low levels of exercise, according to World Health Organization guidelines. We assessed cardiorespiratory fitness using a graded exercise test (VO2 max) and hippocampal structure via manual tracing of T1-weighted magnetic resonance images. We also assessed hippocampal function using magnetic resonance spectroscopy to derive estimates of N-acetyl-aspartate concentration and hippocampal-dependent associative memory and pattern separation tasks. We observed evidence of increased N-acetyl-aspartate concentration and associative memory performance in individuals engaging in high levels of exercise. However, no differences in hippocampal volume or pattern separation capacity were observed between groups. Cardiorespiratory fitness was positively associated with left and right hippocampal volume and N-acetyl-aspartate concentration. However, no associations were observed between cardiorespiratory fitness and associative memory or pattern separation. Therefore, we provide evidence that higher levels of exercise and cardiorespiratory fitness are associated with improved hippocampal structure and function. Exercise may provide a low-risk, effective method of improving hippocampal integrity in an early-to-mid-life stage.

OSARI, an Open-Source Anticipated Response Inhibition Task.

The stop-signal paradigm has become ubiquitous in investigations of inhibitory control. Tasks inspired by the paradigm, referred to as stop-signal tasks, require participants to make responses on go trials and to inhibit those responses when presented with a stop-signal on stop trials. Currently, the most popular version of the stop-signal task is the 'choice-reaction' variant, where participants make choice responses, but must inhibit those responses when presented with a stop-signal. An alternative to the choice-reaction variant of the stop-signal task is the 'anticipated response inhibition' task. In anticipated response inhibition tasks, participants are required to make a planned response that coincides with a predictably timed event (such as lifting a finger from a computer key to stop a filling bar at a predefined target). Anticipated response inhibition tasks have some advantages over the more traditional choice-reaction stop-signal tasks and are becoming increasingly popular. However, currently, there are no openly available versions of the anticipated response inhibition task, limiting potential uptake. Here, we present an open-source, free, and ready-to-use version of the anticipated response inhibition task, which we refer to as the OSARI (the Open-Source Anticipated Response Inhibition) task.

Heightened effort discounting is a common feature of both apathy and fatigue.

Apathy and fatigue have distinct aetiologies, yet can manifest in phenotypically similar ways. In particular, each can give rise to diminished goal-directed behaviour, which is often cited as a key characteristic of both traits. An important issue therefore is whether currently available approaches are capable of distinguishing between them. Here, we examined the relationship between commonly administered inventories of apathy and fatigue, and a measure of goal-directed activity that assesses the motivation to engage in effortful behaviour. 103 healthy adults completed self-report inventories on apathy (the Dimensional Apathy Scale), and fatigue (the Multidimensional Fatigue Inventory, and/or Modified Fatigue Impact Scale). In addition, all participants performed an effort discounting task, in which they made choices about their willingness to engage in physically effortful activity. Importantly, self-report ratings of apathy and fatigue were strongly correlated, suggesting that these inventories were insensitive to the fundamental differences between the two traits. Furthermore, greater effort discounting was strongly associated with higher ratings across all inventories, suggesting that a common feature of both traits is a lower motivation to engage in effortful behaviour. These results have significant implications for the assessment of both apathy and fatigue, particularly in clinical groups in which they commonly co-exist.

A Short-Term Intervention of High-Intensity Exercise and Anodal-tDCS on Motor Learning in Middle-Aged Adults: An RCT.

High-intensity exercise has enhanced motor learning in healthy young adults. Anodal-transcranial direct current stimulation (a-tDCS) may optimize these effects. This study aimed to determine the effects of a short-term high-intensity interval exercise intervention either with or without a-tDCS on the learning and retention of a novel motor task in middle-aged adults. Forty-two healthy middle-aged adults (age = 44.6 ± 6.3, female = 76%) were randomized into three groups: exercise and active a-tDCS, exercise and sham a-tDCS, and a non-exercise and sham a-tDCS control. Participants completed a baseline testing session, followed by three intervention sessions 48-h apart. The exercise groups completed 20-min of high-intensity exercise followed by a novel sequential visual isometric pinch task (SVIPT) while receiving 20-min of 1.5 mA a-tDCS, or sham tDCS. The control group completed 20-min of reading before receiving sham a-tDCS during the SVIPT. Learning was assessed by skill change within and between intervention sessions. Participants returned 5-7 days after the final intervention session and performed the SVIPT task to assess retention. All three groups showed evidence of learning on the SVIPT task. Neither group displayed enhanced overall learning or retention when compared to the control group. High-intensity exercise with or without a-tDCS did not improve learning or retention of a novel motor task in middle-aged adults. The methodological framework provides direction for future research to investigate the potential of differing exercise intensity effects on learning and retention.