Does intensity matter? A randomized crossover study of the role of acute exercise intensity on cognitive performance and motor speed and accuracy.

There is a well-recognized, yet nuanced, positive relationship between acute physical activity and cognitive function. However, the precise impact of exercise intensity remains ambiguous. We tested learning and memory, working memory and processing speed, and motor speed and accuracy across three distinct exercise intensities. A sample of 207 participants (100 female) between 18 and 44 years (mean age: 22.5±3.7years) completed all study procedures. Utilizing a within-subjects, cross-over design, participants completed moderate (35% VO2 Max), vigorous (70% VO2 Max), and sedentary (no exercise) conditions. Cognitive and motor assessments, including the Paced Auditory Serial Addition Test (PASAT), Rey Auditory Verbal Learning Test (RAVLT), Typing Speed Test, and Ten Key Data Entry Task, were conducted approximately 60min post-exercise. There were no significant differences in primary cognitive or motor outcome measures across the three exercise intensities, even with the study being strongly powered. There was, however, a small difference on the fastest trial of the PASAT, where vigorous-intensity exercise yielded slightly better performance compared to both sedentary and moderate-intensity exercise. This effect was no longer significant when including VO2 Max or maximum heart rate as indicators of fitness. There were no interactions on outcome variables by exercise intensity when including biological sex in the models. Thus, a single bout of acute exercise, regardless of its intensity, did not alter cognitive and motor performance when measured approximately 1h post-exercise. Findings highlight the importance of large samples and suggest that the temporal dynamics post-exercise might play a pivotal role in cognitive outcomes.

ENIGMA's simple seven: Recommendations to enhance the reproducibility of resting-state fMRI in traumatic brain injury.

Resting state functional magnetic resonance imaging (rsfMRI) provides researchers and clinicians with a powerful tool to examine functional connectivity across large-scale brain networks, with ever-increasing applications to the study of neurological disorders, such as traumatic brain injury (TBI). While rsfMRI holds unparalleled promise in systems neurosciences, its acquisition and analytical methodology across research groups is variable, resulting in a literature that is challenging to integrate and interpret. The focus of this narrative review is to address the primary methodological issues including investigator decision points in the application of rsfMRI to study the consequences of TBI. As part of the ENIGMA Brain Injury working group, we have collaborated to identify a minimum set of recommendations that are designed to produce results that are reliable, harmonizable, and reproducible for the TBI imaging research community. Part one of this review provides the results of a literature search of current rsfMRI studies of TBI, highlighting key design considerations and data processing pipelines. Part two outlines seven data acquisition, processing, and analysis recommendations with the goal of maximizing study reliability and between-site comparability, while preserving investigator autonomy. Part three summarizes new directions and opportunities for future rsfMRI studies in TBI patients. The goal is to galvanize the TBI community to gain consensus for a set of rigorous and reproducible methods, and to increase analytical transparency and data sharing to address the reproducibility crisis in the field.

Interhemispheric transfer time and concussion in adolescents: A longitudinal study using response time and event-related potential measures.

Introduction: Concussion in children and adolescents is a public health concern with higher concussion incidence than adults and increased susceptibility to axonal injury. The corpus callosum is a vulnerable location of concussion-related white matter damage that can be associated with short- and long-term effects of concussion. Interhemispheric transfer time (IHTT) of visual information across the corpus callosum can be used as a direct measure of corpus callosum functioning that may be impacted by adolescent concussion with slower IHTT relative to matched controls. Longitudinal studies and studies testing physiological measures of IHTT following concussion in adolescents are lacking. Methods: We used the N1 and P1 components of the scalp-recorded brain event-related potential (ERP) to measure IHTT in 20 adolescents (ages 12-19 years old) with confirmed concussion and 16 neurologically-healthy control participants within 3 weeks of concussion (subacute stage) and approximately 10 months after injury (longitudinal). Results: Separate two-group (concussion, control) by two-time (3 weeks, 10 months) repeated measures ANOVAs on difference response times and IHTT latencies of the P1 and N1 components showed no significant differences by group (ps ≥ 0.25) nor by time (ps ≥ 0.64), with no significant interactions (ps ≥ 0.15). Discussion: Results from the current sample suggest that measures of IHTT may not be strongly influenced at 3 weeks or longitudinally following adolescent concussion using the current IHTT paradigm.

Pevonedistat, a Nedd8-activating enzyme inhibitor, in combination with ibrutinib in patients with relapsed/refractory B-cell non-Hodgkin lymphoma.

Pevonedistat (TAK924) is a Nedd8-activating enzyme inhibitor with preclinical activity in non-Hodgkin lymphoma (NHL). This open-label, Phase I, multicenter, investigator-sponsored study enrolled patients with relapsed/refractory (R/R) NHL and chronic lymphocytic leukemia (CLL). The primary objective was safety. Pevonedistat was given intravenously on days 1, 3, 5 of a 21-day cycle for 8 cycles at five dose levels (15 to 50 mg/m2); ibrutinib was administered at 420 or 560 mg orally daily continuously. Eighteen patients with NHL were enrolled, including 8 patients with mantle cell lymphoma (MCL) and 4 patients with CLL. One dose-limiting toxicity (mediastinal hemorrhage) occurred at 50 mg/m2 of pevonedistat which is the estimated maximum tolerated dose. Bruising and diarrhea were the most common adverse events (56% and 44%). Atrial fibrillation occurred in 3 patients (17%). Grade ≥3 toxicities included arthralgia, atrial fibrillation, bone pain, diarrhea, hypertension, and mediastinal hemorrhage (one patient each). The overall response rate (ORR) was 65% (100% ORR in MCL). Pevonedistat disposition was not modified by ibrutinib. scRNA-Seq analysis showed that pevonedistat downregulated NFκB signaling in malignant B-cells in vivo. Thus, pevonedistat combined with ibrutinib demonstrated safety and promising early efficacy in NHL and CLL. NAE inhibition downregulated NFκB signaling in vivo.

Age and sex effects on advanced white matter microstructure measures in 15,628 older adults: A UK biobank study.

A comprehensive characterization of the brain's white matter is critical for improving our understanding of healthy and diseased aging. Here we used diffusion-weighted magnetic resonance imaging (dMRI) to estimate age and sex effects on white matter microstructure in a cross-sectional sample of 15,628 adults aged 45-80 years old (47.6% male, 52.4% female). Microstructure was assessed using the following four models: a conventional single-shell model, diffusion tensor imaging (DTI); a more advanced single-shell model, the tensor distribution function (TDF); an advanced multi-shell model, neurite orientation dispersion and density imaging (NODDI); and another advanced multi-shell model, mean apparent propagator MRI (MAPMRI). Age was modeled using a data-driven statistical approach, and normative centile curves were created to provide sex-stratified white matter reference charts. Participant age and sex substantially impacted many aspects of white matter microstructure across the brain, with the advanced dMRI models TDF and NODDI detecting such effects the most sensitively. These findings and the normative reference curves provide an important foundation for the study of healthy and diseased brain aging.

Experience of a smartphone ambulatory ECG clinic for emergency department patients with palpitation: a single-centre cohort study.

BACKGROUND AND IMPORTANCE: Palpitation is one of the commonest presenting complaints to the emergency department (ED). Diagnosis depends on capturing an ECG during the episode. Unlike syncope, patients retain consciousness and therefore their ability to activate an ECG event recorder. The Investigation of Palpitation in the ED study demonstrated Food and Drug Administration approved AliveCor/Kardia device that links to a smartphone app was safe and effective. A Smartphone Palpitation and Pre-syncope Ambulatory Care Clinic was therefore established. OBJECTIVES: To review the first year of patients attending the service to determine the number and cost-effectiveness of cardiac dysrhythmias diagnoses. DESIGN: Single-center cohort study. SETTINGS AND PARTICIPANTS: Royal Infirmary of Edinburgh, UK. All patients (over 16 years) presenting consecutively to ED with palpitation or pre-syncope, whose ECG was normal, had a compatible device and where an underlying cardiac dysrhythmia was possible were enrolled. INTERVENTION: Ambulatory Care Clinic utilizing the AliveCor/Kardia device. OUTCOME MEASURES AND ANALYSIS: Number diagnosed with cardiac dysrhythmia and mean cost per diagnosis. MAIN RESULTS: Between 24 July 2019 and 23 July 2020, 290 consecutive patients were referred of age 16-80 years (mean 43.3, SD 15.0). One hundred twenty (41.4%) were male. Two hundred thirty-seven (81.7%) were fitted with the device and 220 (75.9%) underwent full investigation. Seventeen of 237 (7.2%) patients had a cardiac diagnosis (12 atrial fibrillation/flutter, 5 supraventricular tachycardia and 1 atrial tachycardia). CONCLUSIONS: There were 17 cardiac diagnoses (7.2%). The cost per symptomatic rhythm diagnosis was 358 GBP (~415 Euro) and the cost per cardiac dysrhythmia diagnosis was 4570 GBP (~5298 Euro). A smartphone-based event recorder clinic should be considered for ED palpitation patients.

Dissociating the effect of reward uncertainty and timing uncertainty on neural indices of reward prediction errors: A reward positivity (RewP) event-related potential (ERP) study.

Accurate reward predictions include forecasting both what a reward will be and when a reward will occur. We tested how variations in the certainty of reward outcome and certainty in timing of feedback presentation modulate neural indices of reward prediction errors using the reward positivity (RewP) component of the scalp-recorded brain event-related potential (ERP). In a within-subjects design, seventy-three healthy individuals completed two versions of a cued doors task; one cued the probability of a reward outcome while the other cued the probability of a delay before feedback. Replicating previous results, RewP amplitude was larger for uncertain feedback compared to certain feedback. Additionally, RewP amplitude was differentially associated with uncertainty of presence/absence of reward, but not uncertainty of feedback timing. Findings suggest a dissociation in that RewP amplitude is modulated by reward prediction certainty but is less affected by certainty surrounding timing of feedback.

The impact of exercise intensity on neurophysiological indices of food-related inhibitory control and cognitive control: A randomized crossover event-related potential (ERP) study.

Food-related inhibitory control, the ability to withhold a dominant response towards highly palatable foods, influences dietary decisions. Food-related inhibitory control abilities may increase following a bout of aerobic exercise; however, the impact of exercise intensity on both food-related inhibitory control and broader cognitive control processes is currently unclear. We used a high-powered, within-subjects, crossover design to test how relative intensity of aerobic exercise influenced behavioral (response time, accuracy) and neural (N2 and P3 components of the scalp-recorded event-related potential [ERP]) measures of food-related inhibitory and cognitive control. Two hundred and ten participants completed three separate conditions separated by approximately one week in randomized order: two exercise conditions (35% VO2max or 70% VO2max) and seated rest. Directly following exercise or rest, participants completed a food-based go/no-go task and a flanker task while electroencephalogram data were recorded. Linear mixed models showed generally faster response times (RT) and improved accuracy following 70% VO2max exercise compared to rest, but not 35% VO2max; RTs and accuracy did not differ between 35% VO2max exercise and rest conditions. N2 and P3 amplitudes were larger following 70% VO2max exercise for the food-based go/no-go task compared to rest and 35% VO2max exercise. There were no differences between exercise conditions for N2 amplitude during the flanker task; however, P3 amplitude was more positive following 70% VO2max compared to rest, but not 35% VO2max exercise. Biological sex did not moderate exercise outcomes. Results suggest improved and more efficient food-related recruitment of later inhibitory control and cognitive control processes following 70% VO2max exercise.

Establishing a Smartphone Ambulatory ECG Service for Patients Presenting to the Emergency Department with Pre-Syncope and Palpitations.

Background and Objectives: The Investigation of Palpitations in the ED (IPED) study showed that a smartphone-based event recorder increased the number of patients in whom an electrocardiogram (ECG) was captured during symptoms over five-fold to more than 55% at 90 days compared to standard care and concluded that this safe, non-invasive and easy-to-use device should be considered part of on-going care to all patients presenting acutely with unexplained palpitations or pre-syncope. This study reports the process of establishing a smartphone palpitation and pre-syncope ambulatory care Clinic (SPACC) service. Materials and Methods: A clinical standard operating procedure (SOP) was devised, and funding was secured through a business case for the purchase of 40 AliveCor devices in the first instance. The clinic was launched on 22 July 2019. Results: Between 22 July 2019 and 31 October 2019, 68 patients seen in the emergency departments (EDs) with palpitations or pre-syncope were referred to SPACC. Of those, 30 were male and 38 were female, and the mean age was 45.8 years old (SD 15.1) with a range from 18 years old to 80 years old. A total of 50 (74%) patients underwent full investigation. On the first assessment, seven (10%) patients were deemed to have non-cardiac palpitations and were not fitted with the device. All patients who underwent full investigation achieved symptomatic rhythm correlation most with sinus rhythm, ventricular ectopics, or bigeminy. A symptomatic cardiac dysrhythmia was detected in six (8.8%) patients. Three patients had supraventricular tachycardia (4%), two had atrial fibrillation (3%), and one had atrial flutter (2%). Qualitative feedback from the SPACC team suggested several areas where improvement to the clinic could be made. Conclusion: We believe a smartphone palpitation service based on ambulatory care is simple to implement and is effective at detecting cardiac dysrhythmia in ED palpitation patients.

Alzheimer's Disease Classification Accuracy is Improved by MRI Harmonization based on Attention-Guided Generative Adversarial Networks.

Alzheimer's disease (AD) accounts for 60% of dementia cases worldwide; patients with the disease typically suffer from irreversible memory loss and progressive decline in multiple cognitive domains. With brain imaging techniques such as magnetic resonance imaging (MRI), microscopic brain changes are detectable even before abnormal memory loss is detected clinically. Patterns of brain atrophy can be measured using MRI, which gives us an opportunity to facilitate AD detection using image classification techniques. Even so, MRI scanning protocols and scanners differ across studies. The resulting differences in image contrast and signal to noise make it important to train and test classification models on multiple datasets, and to handle shifts in image characteristics across protocols (also known as domain transfer or domain adaptation). Here, we examined whether adversarial domain adaptation can boost the performance of a Convolutional Neural Network (CNN) model designed to classify AD. To test this, we used an Attention-Guided Generative Adversarial Network (GAN) to harmonize images from three publicly available brain MRI datasets - ADNI, AIBL and OASIS - adjusting for scanner-dependent effects. Our AG-GAN optimized a joint objective function that included attention loss, pixel loss, cycle-consistency loss and adversarial loss; the model was trained bidirectionally in an end-to-end fashion. For AD classification, we adapted the popular 2D AlexNet CNN to handle 3D images. Classification based on harmonized MR images significantly outperformed classification based on the three datasets in non-harmonized form, motivating further work on image harmonization using adversarial techniques.

Does inhibitory control training reduce weight and caloric intake in adults with overweight and obesity? A pre-registered, randomized controlled event-related potential (ERP) study.

A cognitive intervention that may reduce weight and caloric intake is inhibitory control training (ICT; having individuals repeatedly withhold dominant responses to unhealthy food images). We conducted a randomized controlled trial where 100 individuals with overweight or obesity were assigned to complete a generic (n = 48) or food-specific ICT (n = 52) training four times per week for four weeks. Weight and caloric intake were obtained at baseline, four-weeks, and 12-weeks. Participants also completed high-calorie and neutral go/no-go tasks while N2 event-related potential (ERP) data, a neural indicator of inhibitory control, was measured at all visits. Results from mixed model analyses indicate that neither weight, caloric intake, nor N2 ERP component amplitude towards high-calorie foods changed at post-testing or at the 12-week follow up. Regression analyses suggest that individuals with smaller N2 difference amplitudes to food may show greater weight loss and reductions in caloric intake after a generic ICT, while individuals with larger N2 difference amplitudes to food may show greater weight loss and reductions in caloric intake after a food-specific ICT. Overall, multiple food-specific or generic ICT sessions over the course of a four-week period do not affect overall weight loss, caloric intake, or N2 ERP amplitude.

Dimensions of anxiety and depression and neurophysiological indicators of error-monitoring: Relationship with delta and theta oscillatory power and error-related negativity amplitude.

Error-monitoring processes may be affected by transdiagnostic dimensions of psychopathology symptoms including trait anxiety, worry, and severity of depressive symptoms. We tested the relationship between continuous measures of anxiety and depressive symptomology and neural correlates of error-monitoring as measured by time-frequency domain delta and theta oscillatory power and time-domain error-related negativity (ERN) amplitude extracted from the electroencephalogram (EEG). Secondary analyses tested for diagnostic group differences in error-related neural responses in individuals with generalized anxiety disorder (GAD), major depressive disorder (MDD), and comorbid psychiatric disorders. About 178 participants (104 female, M[SD]age  = 21.7[4.6]) with a wide range of psychopathology symptoms completed a modified version of the Eriksen flanker task and symptom questionnaires. Residualized difference values between correct and error trials for delta/theta power and error/correct ERN amplitude were used as dependent variables. Linear regression analyses adjusted for age, sex, and task accuracy showed nonsignificant associations of symptom dimension measures with error-related residualized delta/theta power or residualized ERN amplitude. Subset analyses on those with confirmed psychopathology diagnoses also did not predict residualized error-related delta/theta power nor residualized ERN amplitude (nGAD  = 14, nMDD  = 28, nComorbid  = 19, nControl  = 85). Taken in the context of the previous literature, results suggest a heterogeneous relationship between depressive and anxiety symptom dimensions and neurophysiological indices of error-monitoring.

Differentiating electrophysiological indices of internal and external performance monitoring: Relationship with perfectionism and locus of control.

The impact of individual differences on performance monitoring and psychopathology is a question of active debate. Personality traits associated with psychopathology may be related to poor internal performance monitoring (as measured by the error-related negativity [ERN]) but intact external performance monitoring (as measured by the reward positivity [RewP]), suggesting that there are underlying neural differences between internal and external performance monitoring processes. We tested the relationships between individual difference measures of perfectionism, locus of control, and ERN, error-positivity (Pe), and RewP component difference amplitude in a healthy undergraduate sample. A total of 128 participants (69 female, M(SD)age = 20.6(2.0) years) completed two tasks: a modified version of the Eriksen Flanker and a doors gambling task along with the Frost Multidimensional Perfectionism scale, the Rotter Locus of Control scale, and the Levenson Multidimensional Locus of Control scale to quantify perfectionism and locus of control traits, respectively. Linear regressions adjusting for age and gender showed that neither ΔERN nor ΔRewP amplitude were significantly moderated by perfectionism or locus of control scores. Findings suggest that, in psychiatrically-healthy individuals, there is not a strong link between perfectionism, locus of control, and ERN or RewP amplitude. Future research on individual difference measures in people with psychopathology may provide further insight into how these personality traits affect performance monitoring.