Neuromuscular electrical stimulation to combat cognitive aging in people with spinal cord injury: protocol for a single case experimental design study.

INTRODUCTION: Individuals with spinal cord injury (SCI) can experience accelerated cognitive aging. Myokines (factors released from muscle cells during contractions), such as brain-derived neurotrophic factor (BDNF), are thought to have beneficial effects on cognition. Neuromuscular electrical stimulation (NMES) was shown to elicit a large release of myokines. However, the effects of NMES on cognitive function have not been studied. OBJECTIVE: To present the study protocol for a clinical trial evaluating the effects of NMES aimed at improving cognition and BDNF. METHODS: A replicated randomized three-phases single-case experimental design (SCED) with sequential multiple baseline time series and a single-armed prospective trial will be conducted with 15 adults with chronic SCI (> 12 months after injury) above L1 neurological level undergoing 30-min quadriceps NMES, 3 days per week for 12 weeks. MAIN STUDY ENDPOINTS: Primary endpoint is cognitive performance (assessed by a smartphone test) conducted three times per week during the baseline phase with random duration of 3 to 8 weeks, the intervention phase of 12 weeks, and the follow-up phase of 3 weeks after a no measurement rest period of 12 weeks. Secondary endpoints are changes in BDNF levels and cognitive performance measured before the baseline period, before and after intervention and after a 12 weeks follow-up. CONCLUSION: This will be the first study investigating the effects of 12 weeks NMES on both cognition and BDNF levels in individuals with SCI. The SCED results provide information on individual treatment effect courses which may direct future research. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05822297, 12/01/2023).

Resistance training's impact on blood biomarkers and cognitive function in older adults with low and high risk of mild cognitive impairment: a randomized controlled trial.

BACKGROUND: The aging brain exhibits a neuroinflammatory state, driven partly by peripheral pro-inflammatory stimuli, that accelerates cognitive deterioration. A growing body of evidence clearly indicates that physical exercise partly alleviates neuroinflammation and positively affects the aging process and cognition. In this randomized controlled trial, we aimed to observe the effect of 12 weeks of resistance training (RT) on peripheral biomarker levels, cognitive function changes and their interrelationship, and explore differences in those exercise-induced changes in older adults with high risk of mild cognitive impairment (MCI) compared to older adults with low risk of MCI. METHODS: Fifty-two participants (aged 60-85 years old, 28 female) were randomly allocated to a 12 week lower limb RT program consisting of two training sessions per week or waiting list control group. The Montreal Cognitive Assessment (MoCA) was used to stratify participants screened as high (< 26/30) or low risk (≥ 26/30) of MCI. We assessed serum Interleukin 6 (IL-6), Insulin-like Growth Factor-1 (IGF-1), and Kynurenine (KYN) levels. Cognitive measurement consisted of and four subtests of Automated Neuropsychological Assessment Metrics (ANAM), the two-choice reaction time, go/no-go, mathematical processing, and memory search test. RESULTS: Twelve weeks of RT improved Go/No-go test results in older adults with high MCI risk. RT did not significantly affect blood biomarkers. However, IGF-1 level increases were associated with improvements in response time on the mathematical processing test in the exercise group, and IL-6 level increases were associated with improvements in response time on the memory search test in the total group of participants. Finally, KYN levels significantly differed between older adults with low and high MCI risk but no significant associations with performance were found. CONCLUSION: Our study results suggest a different effect of RT on inhibitory control between older adults with low compared to high MCI risk. IGF-1 may play a role in the mechanism behind the cognitive benefit of RT and KYN may be a surrogate biomarker for neurodegeneration and cognitive decline.

Resistance exercise effects on hippocampus subfield volumes and biomarkers of neuroplasticity and neuroinflammation in older adults with low and high risk of mild cognitive impairment: a randomized controlled trial.

Physical exercise is suggested to promote hippocampal neuroplasticity by increasing circulating neurotrophic and anti-inflammatory factors. Our aim was to explore the interplay between the effect of progressive resistance exercise on blood biomarker levels, hippocampal neurometabolite levels and hippocampal volume in older adults with a low compared to a high risk of mild cognitive impairment (MCI). Seventy apparently healthy male/female older adults (aged 60-85 years old) were randomly allocated to a 12 week lower limb progressive resistance or no intervention, stratified for low (< 26/30) or high (≥ 26/30) Montreal Cognitive Assessment (MoCA) score, indicating MCI risk. Outcome measures were blood levels of insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6) or kynurenine (KYN); hippocampal total and subfield volumes of the cornu ammonis 1 (CA1) and 4 (CA4), subiculum, presubiculum, and dentate gyrus measured with magnetic resonance imaging (MRI); and hippocampus neurometabolites including total N-acetylaspartate (NAA), myo-inositol (mIns), and total creatine (Cr) measured with proton magnetic resonance spectroscopy (1H-MRS). We evaluated the intervention effect, cognitive status effect, their interaction and the bivariate relationship between exercise-induced changes between the outcome measures. Higher kynurenine levels (p = 0.015) and lower subiculum volumes (p = 0.043) were found in older adults with high MCI risk compared to older adults with low MCI risk. Exercise-induced CA1 volume changes were negatively correlated with hippocampal tNAA/mIns level changes (r = -0.605, p = 0.006). This study provides valuable insight in the multifactorial processes related to resistance training in older adults with low or high MCI risk.

Hippocampal neurometabolic and structural changes from pre-to post-COVID-19: A case-series study.

BACKGROUND: Neurological complications of the COVID-19 infection may be caused in part by local neurochemical and structural abnormalities that could not be detected during routine medical examinations. We examined within subject neurometabolic and structural brain alterations from pre-to post-COVID-19 in the hippocampal region of three elderly individuals (aged 63-68 years) who had a COVID-19 infection with mild symptoms. Patients were participating in an interventional study in which they were closely monitored at the time they were diagnosed with COVID-19. Patients 1 and 2 just completed 18-20 resistance training sessions prior to their diagnosis. Patient 3 was assigned to a non-training condition in the same study. METHODS: Whole brain magnetic resonance imaging (MRI) images and proton magnetic resonance spectroscopy (1H-MRS) of the left hippocampus were collected before and after infection. Structural and spectroscopic imaging measures post-COVID-19 were contrasted to the pre-COVID-19 measures and were compared with values for Minimal Detectable Change at 95% (MDC95) and 90% (MDC90) confidence from a group of six elderly (aged 60-79 years) without COVID-19 that participated in the same study. RESULTS: After SARS-COV-2 infection, we observed a reduction of glutamate-glutamine (Glx) in Patients 1 and 2 (≥ 42.0%) and elevation of myo-inositol (mIns) and N-acetyl-aspartate (NAA) in Patient 3 (≥ 36.4%); all > MDC90. MRI findings showed increased (Patients 1 and 2) or unchanged (Patient 3) hippocampal volume. CONCLUSIONS: Overall, findings from this exploratory study suggest that mild COVID-19 infection could be associated with development of local neuroinflammation and reduced glutamate levels in the hippocampus. Our 1H-MRS findings may have clinical value for explaining chronic neurological and psychological complaints in COVID-19 long-haulers.

Selecting an appropriate control group for studying the effects of exercise on cognitive performance.

Differences in expectations between experimental and control groups can influence the outcomes of exercise interventions, emphasizing the need to match expectations across study groups. This online study examined whether the expectations to improve the performance of different cognitive tasks differ between various activities commonly used in research on the effects of exercise and cognitive function. Two hundred and five middle-aged adults performed two reaction-time tasks and one memory task. They were then asked to rate, on a 1-5 Likert scale, their expectations to improve performance in those tasks should they engage in six types of activities for three months: brisk walking, resistance exercise, stretching and balance exercises, watching videos with lectures on art, history, and science, a program of relaxation techniques, and yoga/tai chi/meditation. Results revealed that the highest expectations for improvement were associated with relaxation techniques and yoga/tai chi/meditation. Some activities, such as brisk walking and stretch and balance exercises, shared similar expectations. Previous knowledge of the possible beneficial effects of exercise on cognitive performance also led to higher expectations. To establish causal relationships, researchers should strive to use activities that share similar expectations to improve performance for the experimental and control groups. The findings of this study provide such activity pairs. Finally, researchers should also try to match participants with and without prior knowledge of the benefits of exercise to cognitive function between experimental and control groups.

Comparison of online and offline applications of dual-site transcranial alternating current stimulation (tACS) over the pre-supplementary motor area (preSMA) and right inferior frontal gyrus (rIFG) for improving response inhibition.

The efficacy of transcranial alternating current stimulation (tACS) is thought to be brain state-dependent, such that tACS during task performance would be hypothesised to offer greater potential for improving performance compared to tACS at rest. However, to date, no empirical study has tested this postulation. The current study compared the effects of dual-site beta tACS applied during a stop signal task (online) to the effects of the same tACS protocol applied prior to the task (offline) and a sham control stimulation in 53 young, healthy adults (32 female; 18-35 yrs). The right inferior frontal gyrus (rIFG) and centre (midline) of the pre-supplementary motor area (preSMA), which are thought to play critical roles in action cancellation, were simultaneously stimulated, sending phase-synchronised stimulation for 15 min with the aim of increasing functional connectivity. The offline group showed significant within-group improvement in response inhibition without showing overt task-related changes in functional connectivity measured with EEG connectivity analysis, suggesting offline tACS is efficacious in inducing behavioural changes potentially via a post-stimulation early plasticity mechanism. In contrast, neither the online nor sham group showed significant improvements in response inhibition. However, EEG connectivity analysis revealed significantly increased task-related functional connectivity following online stimulation and a medium effect size observed in correlation analyses suggested that an increase in functional connectivity in the beta band at rest was potentially associated with an improvement in response inhibition. Overall, the results indicate that both online and offline dual-site beta tACS can be beneficial in improving inhibitory control via distinct underlying mechanisms.

The effect of acute exercise on cognitive and motor inhibition - Does fitness moderate this effect?

BACKGROUND: Given the extensive evidence on improvements in cognitive inhibition immediately following exercise, and the literature indicating that cognitive and motor inhibitory functions are mediated by overlapping brain networks, the aim of this study was to assess, for the first time, the effect of moderate intensity acute aerobic exercise on multi-limb motor inhibition, as compared to cognitive inhibition. METHOD: Participants were 36 healthy adults aged 40-60 years old (mean age 46.8 ± 5.7), who were randomly assigned to experimental or control groups. One-to-two weeks following baseline assessment, participants were asked to perform a three-limb (3-Limb) inhibition task and a vocal version of the Stroop before and after either acute moderate-intense aerobic exercise (experimental group) or rest (control). RESULTS: Similar rates of improvement were observed among both groups from baseline to the pre-test. Conversely, a meaningful, yet non-significant trend was seen among the experimental group in their pretest to posttest improvement in both cognitive and motor tasks. In addition, exploratory analysis revealed significant group differences in favor of the experimental group among highly fit participants on the 3-Limb task. A significant correlation was indicated between the inhibition conditions, i.e., choice in the motor inhibition and color/word (incongruent) in the cognitive inhibition, especially in the improvement observed following the exercise. DISCUSSION: Moderate-intensity acute aerobic exercise is a potential stimulator of both multi-limb motor inhibition and cognitive inhibition. It appears that high-fit participants benefit from exercise more than low-fit people. Additionally, performance on behavioral tasks that represent motor and cognitive inhibition is related. This observation suggests that fitness levels and acute exercise contribute to the coupling between cognitive and motor inhibition. Neuroimaging methods would allow examining brain-behavior associations of exercise-induced changes in the brain.

Myokines as mediators of exercise-induced cognitive changes in older adults: protocol for a comprehensive living systematic review and meta-analysis.

Background: The world's population is aging, but life expectancy has risen more than healthy life expectancy (HALE). With respect to brain and cognition, the prevalence of neurodegenerative disorders increases with age, affecting health and quality of life, and imposing significant healthcare costs. Although the effects of physical exercise on cognition in advanced age have been widely explored, in-depth fundamental knowledge of the underlying mechanisms of the exercise-induced cognitive improvements is lacking. Recent research suggests that myokines, factors released into the blood circulation by contracting skeletal muscle, may play a role in mediating the beneficial effect of exercise on cognition. Our goal in this ongoing (living) review is to continuously map the rapidly accumulating knowledge on pathways between acute or chronic exercise-induced myokines and cognitive domains enhanced by exercise. Method: Randomized controlled studies will be systematically collected at baseline and every 6 months for at least 5 years. Literature search will be performed online in PubMed, EMBASE, PsycINFO, Web of Science, SportDiscus, LILACS, IBECS, CINAHL, SCOPUS, ICTRP, and ClinicalTrials.gov. Risk of bias will be assessed using the Revised Cochrane Risk of Bias tool (ROB 2). A random effects meta-analysis with mediation analysis using meta-analytic structural equation modeling (MASEM) will be performed. The primary research question is to what extent exercise-induced myokines serve as mediators of cognitive function. Secondarily, the pooled effect size of specific exercise characteristics (e.g., mode of exercise) or specific older adults' populations (e.g., cognitively impaired) on the relationship between exercise, myokines, and cognition will be assessed. The review protocol was registered in PROSPERO (CRD42023416996). Discussion: Understanding the triad relationship between exercise, myokines and cognition will expand the knowledge on multiple integrated network systems communicating between skeletal muscles and other organs such as the brain, thus mediating the beneficial effects of exercise on health and performance. It may also have practical implications, e.g., if a certain myokine is found to be a mediator between exercise and cognition, the optimal exercise characteristics for inducing this myokine can be prescribed. The living review is expected to improve our state of knowledge and refine exercise regimes for enhancing cognitive functioning in diverse older adults' populations. Registration: Systematic review and meta-analysis protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on the 24th of April 2023 (registration number CRD42023416996).

White matter and neurochemical mechanisms underlying age-related differences in motor processing speed.

Aging is associated with changes in the central nervous system and leads to reduced life quality. Here, we investigated the age-related differences in the CNS underlying motor performance deficits using magnetic resonance spectroscopy and diffusion MRI. MRS measured N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) concentrations in the sensorimotor and occipital cortex, whereas dMRI quantified apparent fiber density (FD) in the same voxels to evaluate white matter microstructural organization. We found that aging was associated with increased reaction time and reduced FD and NAA concentration in the sensorimotor voxel. Both FD and NAA mediated the association between age and reaction time. The NAA concentration was found to mediate the association between age and FD in the sensorimotor voxel. We propose that the age-related decrease in NAA concentration may result in reduced axonal fiber density in the sensorimotor cortex which may ultimately account for the response slowness of older participants.

Body fat and components of sarcopenia relate to inflammation, brain volume, and neurometabolism in older adults.

Obesity and sarcopenia are associated with cognitive impairments at older age. Current research suggests that blood biomarkers may mediate this body-brain crosstalk, altering neurometabolism and brain structure eventually resulting in cognitive performance changes. Seventy-four older adults (60-85 years old) underwent bio-impedance body composition analysis, handgrip strength measurements, 8-Foot Up-and-Go (8UG) test, Montreal Cognitive Assessment (MoCA), blood analysis of interleukin-6 (IL-6), kynurenine, and insulin-like growth factor-1 (IGF-1), as well as brain magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS), estimating neurodegeneration and neuroinflammation. Normal fat% or overweight was associated with larger total gray matter volume compared to underweight or obesity in older adults and obesity was associated with higher N-acetylaspartate/Creatine levels in the sensorimotor and dorsolateral prefrontal cortex. Muscle strength, not muscle mass/physical performance, corresponded to lower kynurenine and higher N-acetylaspartate/Creatine levels in the dorsal posterior cingulate and dorsolateral prefrontal cortex. The inflammatory and neurotrophic blood biomarkers did not significantly mediate these body-brain associations. This study used a multimodal approach to comprehensively assess the proposed mechanism of body-brain crosstalk.

Asymmetric effects of different training-testing mismatch types on myoelectric regression via deep learning.

This paper investigates how predictions of a convolutional neural network (CNN) suited for myoelectric simultaneous and proportional control (SPC) are affected when training and testing conditions differ. We used a dataset composed of electromyogram (EMG) signals and joint angular accelerations measured from volunteers drawing a star. This task was repeated multiple times using different combinations of motion amplitude and frequency. CNNs were trained with data from a given combination and tested under different combinations. Predictions were compared between situations in which training and testing conditions matched versus when there was a training-testing mismatch. Changes in predictions were assessed through three metrics: normalized root mean squared error (NRMSE), correlation, and slope of the linear regression between targets and predictions. We found that predictive performance declined differently depending on whether the confounding factors (amplitude and frequency) increased or decreased between training and testing. Correlations dropped as the factors decreased, whereas slopes deteriorated when factors increased. NRMSEs worsened when factors increased or decreased, with more accentuated deterioration for increasing factors. We argue that worse correlations could be related to differences in EMG signal-to-ratio (SNR) between training and testing, which affected the noise robustness of the CNNs' learned internal features. Slope deterioration could be a result of the networks' inability to predict accelerations outside the range seen during training. These two mechanisms may also asymmetrically increase NRMSE. Finally, our findings open further possibilities to develop strategies to mitigate the negative impact of confounding factor variability on myoelectric SPC devices.

Evidence-based yet still challenging! Research on physical activity in old age.

Preserving functional health and quality-of-life in old age is a major goal and global challenge in public health. The high rate of sedentary behavior that is characteristic of the older adult population exacerbates impairments of physiological and structural systems that are typically seen in the aging process. Achieving an understanding of the profound influence of physical activity on all aspects of health in old age is the driving force behind the emergence of "physical activity in old age" as a growing area of research. Accumulated evidence implies that being physically active and exercising is far superior to other optimal aging facilitators. Yet this area of research faces numerous constraints and obstacles. This commentary addresses some of these challenges, primarily the heterogeneity of the aging process, which induces both inter- and intra-individual differences among aged individuals, heterogeneity in assessment tools, unjustified inclusion/exclusion criteria and insufficient recruitment strategies, difficulties in implementing research results in real-world conditions, and rudimentary exploitation of innovative technology. We explain the importance of establishing a network of multidisciplinary scientists and stakeholders to propose consensus-based goals and scientifically evidenced wide-ranging plans for dealing with these challenges. In addition, we suggest work directions for this network.

N-acetyl-aspartate and Myo-inositol as Markers of White Matter Microstructural Organization in Mild Cognitive Impairment: Evidence from a DTI-1H-MRS Pilot Study.

We implemented a multimodal approach to examine associations between structural and neurochemical changes that could signify neurodegenerative processes related to mild cognitive impairment (MCI). Fifty-nine older adults (60-85 years; 22 MCI) underwent whole-brain structural 3T MRI (T1W, T2W, DTI) and proton magnetic resonance spectroscopy (1H-MRS). The regions of interest (ROIs) for 1H-MRS measurements were the dorsal posterior cingulate cortex, left hippocampal cortex, left medial temporal cortex, left primary sensorimotor cortex, and right dorsolateral prefrontal cortex. The findings revealed that subjects in the MCI group showed moderate to strong positive associations between the total N-acetylaspartate to total creatine and the total N-acetylaspartate to myo-inositol ratios in the hippocampus and dorsal posterior cingulate cortex and fractional anisotropy (FA) of WM tracts crossing these regions-specifically, the left temporal tapetum, right corona radiata, and right posterior cingulate gyri. In addition, negative associations between the myo-inositol to total creatine ratio and FA of the left temporal tapetum and right posterior cingulate gyri were observed. These observations suggest that the biochemical integrity of the hippocampus and cingulate cortex is associated with a microstructural organization of ipsilateral WM tracts originating in the hippocampus. Specifically, elevated myo-inositol might be an underlying mechanism for decreased connectivity between the hippocampus and the prefrontal/cingulate cortex in MCI.

Myokines may target accelerated cognitive aging in people with spinal cord injury: A systematic and topical review.

Persons with spinal cord injury (SCI) can suffer accelerated cognitive aging, even when correcting for mood and concomitant traumatic brain injury. Studies in healthy older adults have shown that myokines (i.e. factors released from muscle tissue during exercise) may improve brain health and cognitive function. Myokines may target chronic neuroinflammation, which is considered part of the mechanism of cognitive decline both in healthy older adults and SCI. An empty systematic review, registered in PROSPERO (CRD42022335873), was conducted as proof of the lack of current research on this topic in people with SCI. Pubmed, Embase, Cochrane and Web of Science were searched, resulting in 387 articles. None were considered eligible for full text screening. Hence, the effect of myokines on cognitive function following SCI warrants further investigation. An in-depth narrative review on the mechanism of SCI-related cognitive aging and the myokine-cognition link was added to substantiate our hypothetical framework. Readers are fully updated on the potential role of exercise as a treatment strategy against cognitive aging in persons with SCI.

Strength gains after 12 weeks of resistance training correlate with neurochemical markers of brain health in older adults: a randomized control 1H-MRS study.

Physical exercise is considered a potent countermeasure against various age-associated physiological deterioration processes. We therefore assessed the effect of 12 weeks of resistance training on brain metabolism in older adults (age range: 60-80 years). Participants either underwent two times weekly resistance training program which consisted of four lower body exercises performed for 3 sets of 6-10 repetitions at 70-85% of 1 repetition maximum (n = 20) or served as the passive control group (n = 21). The study used proton magnetic resonance spectroscopy to quantify the ratio of total N-acetyl aspartate, total choline, glutamate-glutamine complex, and myo-inositol relative to total creatine (tNAA/tCr, tCho/tCr, Glx/tCr, and mIns/tCr respectively) in the hippocampus (HPC), sensorimotor (SM1), and prefrontal (dlPFC) cortices. The peak torque (PT at 60°/s) of knee extension and flexion was assessed using an isokinetic dynamometer. We used repeated measures time × group ANOVA to assess time and group differences and correlation coefficient analyses to examine the pre-to-post change (∆) associations between PT and neurometabolite variables. The control group showed significant declines in tNAA/tCr and Glx/tCr of SM1, and tNAA/tCr of dlPFC after 12 weeks, which were not seen in the experimental group. A significant positive correlation was found between ∆PT knee extension and ∆SM1 Glx/tCr, ∆dlPFC Glx/tCr and between ∆PT knee flexion and ∆dlPFC mIns/tCr in the experimental group. Overall, findings suggest that resistance training seems to elicit alterations in various neurometabolites that correspond to exercise-induced "preservation" of brain health, while simultaneously having its beneficial effect on augmenting muscle functional characteristics in older adults.

Organization of neurochemical interactions in young and older brains as revealed with a network approach: Evidence from proton magnetic resonance spectroscopy (1H-MRS).

Aging is associated with alterations in the brain including structural and metabolic changes. Previous research has focused on neurometabolite level differences associated to age in a variety of brain regions, but the relationship among metabolites across the brain has been much less studied. Investigating these relationships can reveal underlying neurometabolic processes, their interdependency, and their progress throughout the lifespan. Using 1H-MRS, we investigated the relationship among metabolite concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myo-Inositol (mIns) and glutamate-glutamine complex (Glx) in seven voxel locations, i.e., bilateral sensorimotor cortex, bilateral striatum, pre-supplementary motor area, right inferior frontal gyrus and occipital cortex. These measurements were performed on 59 human participants divided in two age groups: young adults (YA: 23.2 ± 4.3; 18-34 years) and older adults (OA: 67.5 ± 3.9; 61-74 years). Our results showed age-related differences in NAA, Cho, and mIns across brain regions, suggesting the presence of neurodegeneration and altered gliosis. Moreover, associative patterns among NAA, Cho and Cr were observed across the selected brain regions, which differed between young and older adults. Whereas most of metabolite concentrations were inhomogeneous across different brain regions, Cho levels were shown to be strongly related across brain regions in both age groups. Finally, we found metabolic associations between homologous brain regions (SM1 and striatum) in the OA group, with NAA showing a significant correlation between bilateral sensorimotor cortices (SM1) and mIns levels being correlated between the bilateral striata. We posit that a network perspective provides important insights regarding the potential interactions among neurochemicals underlying metabolic processes at a local and global level and their relationship with aging.

Neurometabolic correlates of posturography in normal aging and older adults with mild cognitive impairment: Evidence from a 1H-MRS study.

Proton magnetic resonance spectroscopy (1H-MRS) holds promise for revealing and understanding neurodegenerative processes associated with cognitive and functional impairments in aging. In the present study, we examined the neurometabolic correlates of balance performance in 42 cognitively intact older adults (healthy controls - HC) and 26 older individuals that were diagnosed with mild cognitive impairment (MCI). Neurometabolite ratios of total N-acetyl aspartate (tNAA), glutamate-glutamine complex (Glx), total choline (tCho) and myo-inositol (mIns) relative to total creatine (tCr) were assessed using single voxel 1H-MRS in four different brain regions. Regions of interest were the left hippocampus (HPC), dorsal posterior cingulate cortex (dPCC), left sensorimotor cortex (SM1), and right dorsolateral prefrontal cortex (dlPFC). Center-of-pressure velocity (Vcop) and dual task effect (DTE) were used as measures of balance performance. Results indicated no significant group differences in neurometabolite ratios and balance performance measures. However, our observations revealed that higher tCho/tCr and mIns/tCr in hippocampus and dPCC were generic predictors of worse balance performance, suggesting that neuroinflammatory processes in these regions might be a driving factor for impaired balance performance in aging. Further, we found that higher tNAA/tCr and mIns/tCr and lower Glx/tCr in left SM1 were predictors of better balance performance in MCI but not in HC. The latter observation hints at the possibility that individuals with MCI may upregulate balance control through recruitment of sensorimotor pathways.

Providing choice of feedback affects perceived choice but does not affect performance.

Background: Autonomy or choice can lead to improved learning in various educational domains. The purpose of this online study was to examine whether giving participants a choice regarding the frequency of their received feedback (either after each individual trial or after a block of trials) in a computerized alternate task-switching task, will affect their performance. Methods: Participants (n = 148) were randomly assigned to three groups: choice group (n = 49), online feedback group (n = 51), and summary feedback group (n = 48). From those three groups we created two groups: a choice group and a no-choice group (n = 49 in each group). All participants performed eight familiarization trials, a pre-test of 24 trials, five blocks of 24 trials for practice, and a post-test of 24 trials. After completing the task, the participants were asked about their perceived feeling of choice and completed the short form of the International Positive and Negative Affect Schedule. Results: The participants in the choice group had higher perceived choice compared with the participants in the no-choice group (8.41 vs 5.47 out of 10, respectively). However, this higher perceived choice did not materialize into better performance during practice or in the post-test.

Reaction time and working memory in middle-aged gamers and non-gamers.

The purpose of this study was to explore whether asking middle-aged gamers and non-gamers about their video games habits will affect their performance of cognitive-motor tasks. One-hundred and twenty-one participants were randomly assigned to four groups: (a) gamers who were asked about their playing habits prior to the study, (b) gamers who were asked about their playing habits following the study, (c) non-gamers who were asked about their playing habits prior to the study, and (d) non-gamers who were asked about their playing habits following the study. The participants performed three reaction time (RT) tasks and a digit-span memory task. In a task-switching task, gamers had more correct responses when they answered the questionnaire before performing the task compared with after the task. For the non-gamers, the opposite occurred. We conclude that some performance measures of cognitive-motor tasks could have been affected by the timing of the completion of the questionnaire. This finding should be known to researchers as it may lead to biases gaming research.

Inflammatory Blood Biomarker Kynurenine Is Linked With Elevated Neuroinflammation and Neurodegeneration in Older Adults: Evidence From Two 1H-MRS Post-Processing Analysis Methods.

Rationale and Objectives: Pro-inflammatory processes have been argued to play a role in conditions associated with cognitive decline and neurodegeneration, like aging and obesity. Only a limited number of studies have tried to measure both peripheral and central biomarkers of inflammation and examined their interrelationship. The primary aim of this study was to examine the hypothesis that chronic peripheral inflammation would be associated with neurometabolic changes that indicate neuroinflammation (the combined elevation of myoinositol and choline), brain gray matter volume decrease, and lower cognitive functioning in older adults. Materials and Methods: Seventy-four older adults underwent bio-impedance body composition analysis, cognitive testing with the Montreal Cognitive Assessment (MoCA), blood serum analysis of inflammatory markers interleukin-6 (IL-6) and kynurenine, magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopy (1H-MRS) of the brain. Neurometabolic findings from both Tarquin and LCModel 1H-MRS post-processing software packages were compared. The regions of interest for MRI and 1H-MRS measurements were dorsal posterior cingulate cortex (DPCC), left hippocampal cortex (HPC), left medial temporal cortex (MTC), left primary sensorimotor cortex (SM1), and right dorsolateral prefrontal cortex (DLPFC). Results: Elevated serum kynurenine levels were associated with signs of neuroinflammation, specifically in the DPCC, left SM1 and right DLPFC, and signs of neurodegeneration, specifically in the left HPC, left MTC and left SM1, after adjusting for age, sex and fat percentage (fat%). Elevated serum IL-6 levels were associated with increased Glx levels in left HPC, left MTC, and right DLPFC, after processing the 1H-MRS data with Tarquin. Overall, the agreement between Tarquin and LCModel results was moderate-to-strong for tNAA, tCho, mIns, and tCr, but weak to very weak for Glx. Peripheral inflammatory markers (IL-6 and kynurenine) were not associated with older age, higher fat%, decreased brain gray matter volume loss or decreased cognitive functioning within a cohort of older adults. Conclusion: Our results suggest that serum kynurenine may be used as a peripheral inflammatory marker that is associated with neuroinflammation and neurodegeneration, although not linked to cognition. Future studies should consider longitudinal analysis to assess the causal inferences between chronic peripheral and neuroinflammation, brain structural and neurometabolic changes, and cognitive decline in aging.