Procedural Motor Memory Deficits in Patients With Long-COVID.

BACKGROUND AND OBJECTIVES: At least 15% of patients who recover from acute severe acute respiratory syndrome coronavirus 2 infection experience lasting symptoms ("Long-COVID") including "brain fog" and deficits in declarative memory. It is not known if Long-COVID affects patients' ability to form and retain procedural motor skill memories. The objective was to determine the ability of patients with Long-COVID to acquire and consolidate a new procedural motor skill over 2 training days. The primary outcome was to determine difference in early learning, measured as the increase in correct sequence typing speed over the initial 11 practice trials of a new skill. The secondary outcomes were initial and final typing speed on days 1 and 2, learning rate, overnight consolidation, and typing accuracy. METHODS: In this prospective, cross-sectional, online, case-control study, participants learned a sequential motor skill over 2 consecutive days (NCT05746624). Patients with Long-COVID (reporting persistent post-coronavirus disease 2019 [COVID-19] symptoms for more than 4 weeks) were recruited at the NIH. Patients were matched one-to-one by age and sex to controls recruited during the pandemic using a crowd-sourcing platform. Selection criteria included age 18-90 years, English speaking, right-handed, able to type with the left hand, denied active fever or respiratory infection, and no previous task exposure. Data were also compared with an age-matched and sex-matched control group who performed the task online before the COVID-19 pandemic (prepandemic controls). RESULTS: In total, 105 of 236 patients contacted agreed to participate and completed the experiment (mean ± SD age 46 ± 12.8 years, 82% female). Both healthy control groups had 105 participants (mean age 46 ± 13.1 and 46 ± 11.9 years, 82% female). Early learning was comparable across groups (Long-COVID: 0.36 ± 0.24 correct sequences/second, pandemic controls: 0.36 ± 0.53 prepandemic controls: 0.38 ± 0.57, patients vs pandemic controls [CI -0.068 to 0.067], vs prepandemic controls [CI -0.084 to 0.052], and between controls [CI -0.083 to 0.053], p = 0.82). Initial and final typing speeds on days 1 and 2 were slower in patients than controls. Patients with Long-COVID showed a significantly reduced overnight consolidation and a nonsignificant trend to reduced learning rates. DISCUSSION: Early learning was comparable in patients with Long-COVID and controls. Anomalous initial performance is consistent with executive dysfunction. Reduction in overnight consolidation may relate to deficits in procedural memory formation.

A translational roadmap for transcranial magnetic and direct current stimulation in stroke rehabilitation: Consensus-based core recommendations from the third stroke recovery and rehabilitation roundtable.

BACKGROUND AND AIMS: The purpose of this Third Stroke Recovery and Rehabilitation Roundtable (SRRR3) was to develop consensus recommendations to address outstanding barriers for the translation of preclinical and clinical research using the non-invasive brain stimulation (NIBS) techniques Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS) and provide a roadmap for the integration of these techniques into clinical practice. METHODS: International NIBS and stroke recovery experts (N = 18) contributed to the consensus process. Using a nominal group technique, recommendations were reached via a five-stage process, involving a thematic survey, two priority ranking surveys, a literature review and an in-person meeting. RESULTS AND CONCLUSIONS: Results of our consensus process yielded five key evidence-based and feasibility barriers for the translation of preclinical and clinical NIBS research, which were formulated into five core consensus recommendations. Recommendations highlight an urgent need for (1) increased understanding of NIBS mechanisms, (2) improved methodological rigor in both preclinical and clinical NIBS studies, (3) standardization of outcome measures, (4) increased clinical relevance in preclinical animal models, and (5) greater optimization and individualization of NIBS protocols. To facilitate the implementation of these recommendations, the expert panel developed a new SRRR3 Unified NIBS Research Checklist. These recommendations represent a translational pathway for the use of NIBS in stroke rehabilitation research and practice.

A translational roadmap for transcranial magnetic and direct current stimulation in stroke rehabilitation: Consensus-based core recommendations from the third stroke recovery and rehabilitation roundtable.

BACKGROUND AND AIMS: The purpose of this Third Stroke Recovery and Rehabilitation Roundtable (SRRR3) was to develop consensus recommendations to address outstanding barriers for the translation of preclinical and clinical research using the non-invasive brain stimulation (NIBS) techniques Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS) and provide a roadmap for the integration of these techniques into clinical practice. METHODS: International NIBS and stroke recovery experts (N = 18) contributed to the consensus process. Using a nominal group technique, recommendations were reached via a five-stage process, involving a thematic survey, two priority ranking surveys, a literature review and an in-person meeting. RESULTS AND CONCLUSIONS: Results of our consensus process yielded five key evidence-based and feasibility barriers for the translation of preclinical and clinical NIBS research, which were formulated into five core consensus recommendations. Recommendations highlight an urgent need for (1) increased understanding of NIBS mechanisms, (2) improved methodological rigor in both preclinical and clinical NIBS studies, (3) standardization of outcome measures, (4) increased clinical relevance in preclinical animal models, and (5) greater optimization and individualization of NIBS protocols. To facilitate the implementation of these recommendations, the expert panel developed a new SRRR3 Unified NIBS Research Checklist. These recommendations represent a translational pathway for the use of NIBS in stroke rehabilitation research and practice.

Health, Wellbeing, and Social Interaction: An International and Demographic Analysis of Perceived Life Changes and the Positives and Negatives of the COVID-19 Lockdown.

Research suggests that people's experiences of COVID-19 lockdowns have been detrimental to their lives and wellbeing. The current research compared the experiences and perceptions on health, wellbeing and social interaction of 300 UK adults and 450 adults in California. Individuals reported whether aspects of their life had changed for the better, worse, or not at all during lockdown in April 2020, and what the "best" and "worst" things about lockdown were. There were more similarities than differences in the regional comparison of perceptions of changes in specific aspects of 'health and wellbeing' and 'social interaction'. Both regions reported the same number and nature of best and worst things about lockdown. Overarching themes of 'health, self and wellbeing', 'being with others', and 'concerns with daily living' were identified. Although reports of life changes and the positives and negatives of lockdown were similar across different demographic groups, some differences were present by age, sex, relationship, and family-status. Incorporating knowledge of unified and positive experiences of lockdown can be useful in informing future lockdown restrictions and supporting the population when restrictions are lifted.

Applied strategies of neuroplasticity.

Various levels of somatotopic organization are present throughout the human nervous system. However, this organization can change when needed based on environmental demands, a phenomenon known as neuroplasticity. Neuroplasticity can occur when learning a new motor skill, adjusting to life after blindness, or following a stroke. Following an injury, these neuroplastic changes can be adaptive or maladaptive, and often occur regardless of whether rehabilitation occurs or not. But not all movements produce neuroplasticity, nor do all rehabilitation interventions. Here, we focus on research regarding how to maximize adaptive neuroplasticity while also minimizing maladaptive plasticity, known as applied neuroplasticity. Emphasis is placed on research exploring how best to apply neuroplastic principles to training environments and rehabilitation protocols. By studying and applying these principles in research and clinical practice, it is hoped that learning of skills and regaining of function and independence can be optimized.

Combined low-frequency brain oscillatory activity and behavior predict future errors in human motor skill.

Human skills are composed of sequences of individual actions performed with utmost precision. When occasional errors occur, they may have serious consequences, for example, when pilots are manually landing a plane. In such cases, the ability to predict an error before it occurs would clearly be advantageous. Here, we asked whether it is possible to predict future errors in a keyboard procedural human motor skill. We report that prolonged keypress transition times (KTTs), reflecting slower speed, and anomalous delta-band oscillatory activity in cingulate-entorhinal-precuneus brain regions precede upcoming errors in skill. Combined anomalous low-frequency activity and prolonged KTTs predicted up to 70% of future errors. Decoding strength (posterior probability of error) increased progressively approaching the errors. We conclude that it is possible to predict future individual errors in skill sequential performance.

Reactivation-induced motor skill modulation does not operate at a rapid micro-timescale level.

Abundant evidence shows that consolidated memories are susceptible to modifications following their reactivation. Processes of memory consolidation and reactivation-induced skill modulation have been commonly documented after hours or days. Motivated by studies showing rapid consolidation in early stages of motor skill acquisition, here we asked whether motor skill memories are susceptible to modifications following brief reactivations, even at initial stages of learning. In a set of experiments, we collected crowdsourced online motor sequence data to test whether post-encoding interference and performance enhancement occur following brief reactivations in early stages of learning. Results indicate that memories forming during early learning are not susceptible to interference nor to enhancement within a rapid reactivation-induced time window, relative to control conditions. This set of evidence suggests that reactivation-induced motor skill memory modulation might be dependent on consolidation at the macro-timescale level, requiring hours or days to occur.

Robust enhancement of motor sequence learning with 4 mA transcranial electric stimulation.

BACKGROUND AND OBJECTIVES: Motor learning experiments with transcranial direct current stimulation (tDCS) at 2 mA have produced mixed results. We hypothesize that tDCS boosts motor learning provided sufficiently high field intensity on the motor cortex. METHODS: In a single-blinded design, 108 healthy participants received either anodal (N = 36) or cathodal (N = 36) tDCS at 4 mA total, or no stimulation (N = 36) while they practiced a 12-min sequence learning task. Anodal stimulation was delivered across four electrode pairs (1 mA each), with anodes above the right parietal lobe and cathodes above the right frontal lobe. Cathodal stimulation, with reversed polarities, served as an active control for sensation, while the no-stimulation condition established baseline performance. fMRI-localized targets on the primary motor cortex in 10 subjects were used in current flow models to optimize electrode placement for maximal field intensity. A single electrode montage was then selected for all participants. RESULTS: We found a significant difference in performance with anodal vs. cathodal stimulation (Cohen's d = 0.71) and vs. no stimulation (d = 0.56). This effect persisted for at least 1 h, and subsequent learning for a new sequence and the opposite hand also improved. Sensation ratings were comparable in the active groups and did not exceed moderate levels. Current flow models suggest the new electrode montage can achieve stronger motor cortex polarization than alternative montages. CONCLUSION: The present paradigm shows a medium to large effect size and is well-tolerated. It may serve as a go-to experiment for future studies on motor learning and tDCS.

Barriers to Enrollment in Post-Stroke Brain Stimulation in a Racially and Ethnically Diverse Population.

BACKGROUND AND PURPOSE: Brain stimulation is an adjuvant strategy to promote rehabilitation after stroke. Here, we evaluated the influence of inclusion/exclusion criteria on enrollment in a transcranial direct current stimulation (tDCS) trial in the context of a racially/ethnically diverse acute stroke service at University of Texas Southwestern (UTSW). METHODS: 3124 (59.7 ± 14.5 years) racially/ethnically diverse (38.4% non-Hispanic white, (W), Hispanic (H) 22%, African American (AA) 33.5%, Asian (A) 2.3%) patients were screened in the acute stroke service at UTSW. Demographics, stroke characteristics, and reasons for exclusion were recorded prospectively. RESULTS: 2327 (74.5%) patients had a verified stroke. Only 44 of them (1.9%) were eligible. Causes for exclusion included in order of importance: (1) magnitude of upper extremity (UE) motor impairment, (2) prior strokes (s), (3) hemorrhagic stroke, (4) psychiatric condition or inability to follow instructions, and (5) old age, of these (2) and (4) were more common in AA patients but not in other minorities. 31 of the 44 eligible individuals were enrolled (W 1.68%, H 1.37%, AA .77%, A 3.774%). 90.5% of verified stroke patients did not exhibit contraindications for stimulation. CONCLUSIONS: 3 main conclusions emerged: (a) The main limitations for inclusion in brain stimulation trials of motor recovery were magnitude of UE motor impairments and stroke lesion characteristics, (b) most stroke patients could be stimulated with tDCS without safety concerns and (c) carefully tailored inclusion criteria could increase diversity in enrollment.Clinical Trial Registration-URL: http://clinicaltrials.gov. Unique identifier: NCT01007136.

Identifying transcranial magnetic stimulation induced EEG signatures of different neuronal elements in primary motor cortex.

OBJECTIVE: To investigate the neuronal elements involved in the activation of corticospinal neurons in the primary motor cortex (M1). METHODS: We studied 10 healthy subjects. Cortical evoked potentials with different components induced by monophasic transcranial magnetic stimulation (TMS) in anterior-posterior and posterior-anterior currents recorded with electroencephalography (EEG) were analyzed. RESULTS: EEG signatures with P25 and N45 components recorded at the C3 electrode with posterior-anterior current were larger than those with anterior-posterior current, while the signatures with P180 and N280 components recorded at the FC1 electrode with anterior-posterior current were larger than those with posterior-anterior current. The source localization analysis revealed that the cortical evoked potential with anterior-posterior current distributed both in the M1 and premotor cortex while that with posterior-anterior current only located in the M1. CONCLUSIONS: We conclude that the activation of corticospinal pyramidal neurons in the M1 is affected by various neuronal elements including the local intracortical circuits in the M1 and inputs from premotor cortex with different sensitivities to TMS in opposite current directions. SIGNIFICANCE: Our finding helped answer a longstanding question about how the corticospinal pathway from the M1 is functionally organized and activated.

Breaking the boundaries of interacting with the human brain using adaptive closed-loop stimulation.

The human brain is arguably one of the most complex systems in nature. To understand how it operates, it is essential to understand the link between neural activity and behavior. Experimental investigation of that link requires tools to interact with neural activity during behavior. Human neuroscience, however, has been severely bottlenecked by the limitations of these tools. While invasive methods can support highly specific interaction with brain activity during behavior, their applicability in human neuroscience is limited. Despite extensive development in the last decades, noninvasive alternatives have lacked spatial specificity and yielded results that are commonly fraught with variability and replicability issues, along with relatively limited understanding of the neural mechanisms involved. Here we provide a comprehensive review of the state-of-the-art in interacting with human brain activity and highlight current limitations and recent efforts to overcome these limitations. Beyond crucial technical and scientific advancements in electromagnetic brain stimulation, new frontiers in interacting with human brain activity such as task-irrelevant sensory stimulation and focal ultrasound stimulation are introduced. Finally, we argue that, along with technological improvements and breakthroughs in noninvasive methods, a paradigm shift towards adaptive closed-loop stimulation will be a critical step for advancing human neuroscience.

The Gamblification of Investing: How a New Generation of Investors Is Being Born to Lose.

Investing and gambling share key features, in that both involve risk, the coming together of two or more people, and both are voluntary activities. However, investing is generally a much better way than gambling for the average person to make long-run profits. This paper reviews evidence on two types of "gamblified" investment products where this advantage does not hold for investing: high-frequency stock trading and high-risk derivatives. This review defines a gamblified investment product as one that leads most investors to lose, that attracts people at risk of experiencing gambling-related harm, and that utilizes product design principles from gambling (either by encouraging a high frequency of use or by providing the allure of big lottery-like wins). The gamblification of investing produces novel challenges for the regulation of both financial markets and gambling.

Impact of the "when the fun stops, stop" gambling message on online gambling behaviour: a randomised, online experimental study.

BACKGROUND: Safer gambling messages are a common freedom-preserving method of protecting individuals from gambling-related harm. Yet, there is little independent and rigorous evidence assessing the effectiveness of safer gambling messages. In our study, we aimed to test the effect of the historically most commonly-used UK safer gambling message on concurrent gambling behaviour of people who gamble in the UK. METHODS: In this study, three preregistered, incentivised, and randomised online experiments, testing the UK's "when the fun stops, stop" message, were carried out via the crowdsourcing platform Prolific. Adults based in the UK who had previously participated in the gambling activities relevant to each experiment were eligible to participate. Experiments 1 and 3 involved bets on real soccer events, and experiment 2 used a commercially available online roulette game. Safer gambling message presence was varied between participants in each experiment. In experiment 2, exposed participants could be shown either a yellow or a black-and-white version of the safer gambling message. Participants were provided with a monetary endowment with which they were allowed to bet. Any of this money not bet was afterwards paid to participants as a bonus, in addition to the payouts from any winning bets. In experiment 2 participants had the opportunity to re-wager any winnings from the roulette game. The primary outcome in experiment 1 was participants' decisions to accept (or reject) a series of football bets, which varied in their specificity (and payoffs), and the primary outcomes of experiments 2 and 3 were the proportion of available funds bet, which were defined as the total amount of money bet by a participant out of the total that could have been bet. FINDINGS: Participants for all three experiments were recruited between May 17, 2019, and Oct 17, 2020. Of the 506 participants in experiment 1, 41·3% of available bets were made by the 254 participants in the gambling message condition, which was not significantly different (p=0·15, odds ratio 1·22 [95% CI 0·93 to 1·61]) to the 37·8% of available bets made by the 252 participants in the control condition. In experiment 2, the only credible difference between conditions was that the 501 participants in the condition with the yellow version of the gambling message bet 3·64% (95% Bayesian credibility interval 0·00% to 7·27%) more of available funds left over than the 499 participants in the control condition. There were no credible differences between the bets made by the 500 participants in the black-and-white gambling message condition and the other conditions. In experiment 3, there were no credible differences between the 502 participants in the gambling message condition and the 501 participants in the control condition, with the largest effect being a 5·87% (95% Bayesian credibility interval -1·44% to 13·20%) increase in the probability of betting everything in the gambling message condition. INTERPRETATION: In our study, no evidence was found for a protective effect of the most common UK safer gambling message. Alternative interventions should be considered as part of an evidence-based public health approach to reducing gambling-related harm. FUNDING: University of Warwick, British Academy and Leverhume, Swiss National Science Foundation.

Reward and plasticity: Implications for neurorehabilitation.

Neuroplasticity follows nervous system injury in the presence or absence of rehabilitative treatments. Rehabilitative interventions can be used to modulate adaptive neuroplasticity, reducing motor impairment and improving activities of daily living in patients with brain lesions. Learning principles guide some rehabilitative interventions. While basic science research has shown that reward combined with training enhances learning, this principle has been only recently explored in the context of neurorehabilitation. Commonly used reinforcers may be more or less rewarding depending on the individual or the context in which the task is performed. Studies in healthy humans showed that both reward and punishment can enhance within-session motor performance; but reward, and not punishment, improves consolidation and retention of motor skills. On the other hand, neurorehabilitative training after brain lesions involves complex tasks (e.g., walking and activities of daily living). The contribution of reward to neurorehabilitation is incompletely understood. Here, we discuss recent research on the role of reward in neurorehabilitation and the needed directions of future research.

A speed-of-play limit reduces gambling expenditure in an online roulette game: Results of an online experiment.

UK online casino games are presently not subject to any limitations on speed-of-play or stakes. One recent policy proposal is to ensure that no online casino game can be played faster than its in-person equivalent. Another policy proposal is to limit the maximum stakes on online casino games to £2, to match the current stake limit on electronic gambling machines. This research experimentally investigated the speed-of-play proposal subject to a £2 stake limit, in an online experiment using incentivized payouts based on £4 endowments and a commercial online roulette game, which was slowed-down in one condition to enforce a speed-of-play limit of one spin every 60 seconds. UK residents, aged 18 years and over and with experience in playing online roulette (N = 1,002), were recruited from an online crowdsourcing panel. In the slowed-down condition there was a credible reduction in the amount gambled. This effect occurred via a credible reduction in the mean number of spins which outweighed any potential increases in bet sizes. Speed-of-play limits may be effective in reducing gambling expenditure for online roulette.

Persistence is futile: Chasing of past performance in repeated investment choices.

When deciding where to invest, individuals choose mutual funds based on recent past performance, despite standard mandated disclaimers that "past performance does not guarantee future results." Investors would receive better long-term returns by choosing funds with lower fees. We explored the impact of fees and past performance on realistic mutual fund selections across three preregistered repeated-choice experiments (N = 1,600), while manipulating the presence of disclaimers between participants. Participants persistently chased past performance despite the opportunity to learn about the futility of this strategy during 60 repeated decisions with feedback. The standard regulatory-mandated disclaimer did not help most participants, compared to giving no advice at all, and was even counter-productive for participants with low levels of financial literacy. An alternative disclaimer that explicitly highlighted the advantages of fee minimization reliably helped participants. We show how individuals who lack both financial literacy and prior investment experience are the most susceptible to making poor mutual fund choices and can benefit the most from behavioral interventions such as the new disclaimer tested here. We discuss how these results generalize into real-world investment decisions, and how to design more efficient disclaimers that can be used beyond investment choices. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Crowdsourcing in Cognitive and Systems Neuroscience.

Behavioral research in cognitive and human systems neuroscience has been largely carried out in-person in laboratory settings. Underpowering and lack of reproducibility due to small sample sizes have weakened conclusions of these investigations. In other disciplines, such as neuroeconomics and social sciences, crowdsourcing has been extensively utilized as a data collection tool, and a means to increase sample sizes. Recent methodological advances allow scientists, for the first time, to test online more complex cognitive, perceptual, and motor tasks. Here we review the nascent literature on the use of online crowdsourcing in cognitive and human systems neuroscience. These investigations take advantage of the ability to reliably track the activity of a participant's computer keyboard, mouse, and eye gaze in the context of large-scale studies online that involve diverse research participant pools. Crowdsourcing allows for testing the generalizability of behavioral hypotheses in real-life environments that are less accessible to lab-designed investigations. Crowdsourcing is further useful when in-laboratory studies are limited, for example during the current COVID-19 pandemic. We also discuss current limitations of crowdsourcing research, and suggest pathways to address them. We conclude that online crowdsourcing is likely to widen the scope and strengthen conclusions of cognitive and human systems neuroscience investigations.

The seductive allure of technical language and its effect on covid-19 vaccine beliefs and intentions.

Previous research has demonstrated a 'seductive allure' of technical or reductive language such that bad (e.g., circular) explanations are judged better when irrelevant technical terms are included. We aimed to explore if such an effect was observable in relation to a covid-19 vaccinations and if this subsequently affected behavioural intentions to take up a covid-19 vaccine. Using a between subjects design we presented participants (N = 996) with one of four possible types of vignette that explained how covid-19 vaccination and herd immunity works. The explanations varied along two factors: (1) Quality, explanations were either good or bad (i.e., tautological); (2) Language, explanations either contained unnecessary technical language or did not. We measured participants' evaluation of the explanations and intentions to vaccinate. We demonstrate a 'seductive allure' effect of technical language on bad vaccine explanations. However, an opposite 'repellent disdain' effect occurred for good explanations which were rated worse when they contained technical language. Moreover, we show that evaluations of explanations influence intentions to vaccinate. We suggest that misinformation that includes technical language could be more detrimental to vaccination rates. Importantly, however, clear explanatory public health information that omits technical language will be more effective in increasing intentions to vaccinate.

Repetitive Peripheral Sensory Stimulation as an Add-On Intervention for Upper Limb Rehabilitation in Stroke: A Randomized Trial.

INTRODUCTION: Repetitive peripheral sensory stimulation (RPSS) followed by 4-hour task-specific training (TST) improves upper limb motor function in subjects with stroke who experience moderate to severe motor upper limb impairments. Here, we compared effects of RPSS vs sham followed by a shorter duration of training in subjects with moderate to severe motor impairments in the chronic phase after stroke. METHODS: This single-center, randomized, placebo-controlled, parallel-group clinical trial compared effects of 18 sessions of either 1.5 h of active RPSS or sham followed by a supervised session that included 45 min of TST of the paretic upper limb. In both groups, subjects were instructed to perform functional tasks at home, without supervision. The primary outcome measure was the Wolf Motor Function Test (WMFT) after 6 weeks of treatment. Grasp and pinch strength were secondary outcomes. RESULTS: In intention-to-treat analysis, WMFT improved significantly in both active and sham groups at 3 and 6 weeks of treatment. Grasp strength improved significantly in the active, but not in the sham group, at 3 and 6 weeks. Pinch strength improved significantly in both groups at 3 weeks, and only in the active group at 6 weeks. CONCLUSIONS: The between-group difference in changes in WMFT was not statistically significant. Despite the short duration of supervised treatment, WMFT improved significantly in subjects treated with RPSS or sham. These findings are relevant to settings that impose constraints in duration of direct contact between therapists and patients. In addition, RPSS led to significant gains in hand strength.Trial Registry Name: Peripheral Nerve Stimulation and Motor Training in Stroke Clinical Trials.gov identifier: NCT0265878 https://clinicaltrials.gov/ct2/show/NCT02658578.