Motor Sequence Learning Task Research Articles

Effect of positive social comparative feedback on the resting state connectivity of dopaminergic neural pathways: A preliminary investigation

Positive social comparative feedback is hypothesized to generate a dopamine response in the brain, similar to reward, by enhancing expectancies to support motor skill learning. However, no studies have utilized neuroimaging to examine this hypothesized dopaminergic mechanism. Therefore, the aim of this preliminary study was to investigate the effect of positive social comparative feedback on dopaminergic neural pathways measured by resting state connectivity. Thirty individuals practiced an implicit, motor sequence learning task and were assigned to groups that differed in feedback type. One group received feedback about their actual response time to complete the task (RT ONLY), while the other group received feedback about their response time with positive social comparison (RT + POS). Magnetic resonance imaging was acquired at the beginning and end of repetitive motor practice with feedback to measure practice-dependent changes in resting state brain connectivity. While both groups showed improvements in task performance and increases in performance expectancies, ventral tegmental area and the left nucleus accumbens (mesolimbic dopamine pathway) resting state connectivity increased in the RT + POS group but not in the RT ONLY group. Instead, the RT ONLY group showed increased connectivity between ventral tegmental area and primary motor cortex. Positive social comparative feedback during practice of a motor sequence task may induce a dopaminergic response in the brain along the mesolimbic pathway. However, given that absence of effects on expectancies and motor learning, more robust and individualized approaches may be needed to provide beneficial psychological and behavioral effects.

Motor Adaptation Deficits in Children with Developmental Coordination Disorder and/or Reading Disorder.

Procedural learning has been mainly tested through motor sequence learning tasks in children with neurodevelopmental disorders, especially with isolated Developmental Coordination Disorder (DCD) and Reading Disorder (RD). Studies on motor adaptation are scarcer and more controversial. This study aimed to compare the performance of children with isolated and associated DCD and RD in a graphomotor adaptation task. In total, 23 children with RD, 16 children with DCD, 19 children with DCD-RD, and 21 typically developing (TD) children wrote trigrams both in the conventional (from left to right) and opposite (from right to left) writing directions. The results show that movement speed and accuracy were more impacted by the adaptation condition (opposite writing direction) in children with neurodevelopmental disorders than TD children. Our results also reveal that children with RD have less difficulty adapting their movement than children with DCD. Children with DCD-RD had the most difficulty, and analysis of their performance suggests a cumulative effect of the two neurodevelopmental disorders in motor adaptation.

Motor learning and performance in schizophrenia and aging: two different patterns of decline

Psychomotor slowing has consistently been observed in schizophrenia, however research on motor learning in schizophrenia is limited. Additionally, motor learning in schizophrenia has never been compared with the waning of motor learning abilities in the elderly. Therefore, in an extensive study, 30 individuals with schizophrenia, 30 healthy age-matched controls and 30 elderly participants were compared on sensorimotor learning tasks including sequence learning and adaptation (both explicit and implicit), as well as tracking and aiming. This paper presents new findings on an explicit motor sequence learning task, an explicit verbal learning task and a simple aiming task and summarizes all previously published findings of this large investigation. Individuals with schizophrenia and elderly had slower Movement Time (MT)s compared with controls in all tasks, however both groups improved over time. Elderly participants learned slower on tracking and explicit sequence learning while individuals with schizophrenia adapted slower and to a lesser extent to movement perturbations in adaptation tasks and performed less well on cognitive tests including the verbal learning task. Results suggest that motor slowing is present in schizophrenia and the elderly, however both groups show significant but different motor skill learning. Cognitive deficits seem to interfere with motor learning and performance in schizophrenia while task complexity and decreased movement precision interferes with motor learning in the elderly, reflecting different underlying patterns of decline in these conditions. In addition, evidence for motor slowing together with impaired implicit adaptation supports the influence of cerebellum and the cerebello-thalamo-cortical-cerebellar (CTCC) circuits in schizophrenia, important for further understanding the pathophysiology of the disorder.

Connecting the dots: Motor and default mode network crossroads in post-stroke motor learning deficits

BackgroundStrokes frequently result in long-term motor deficits, imposing significant personal and economic burdens. However, our understanding of the underlying neural mechanisms governing motor learning in stroke survivors remains limited - a fact that poses significant challenges to the development and optimisation of therapeutic strategies. ObjectiveThis study investigates the diversity in motor learning aptitude and its associated neurological mechanisms. We hypothesised that stroke patients exhibit compromised overall motor learning capacity, which is associated with altered activity and connectivity patterns in the motor- and default-mode-network in the brain. MethodsWe assessed a cohort of 40 chronic-stage, mildly impaired stroke survivors and 39 age-matched healthy controls using functional Magnetic Resonance Imaging (fMRI) and connectivity analyses. We focused on neural activity and connectivity patterns during an unilateral motor sequence learning task performed with the unimpaired or non-dominant hand. Primary outcome measures included task-induced changes in neural activity and network connectivity. ResultsCompared to controls, stroke patients showed significantly reduced motor learning capacity, associated with diminished cerebral lateralization. Task induced activity modulation was reduced in the motor network but increased in the default mode network. The modulated activation strength was associated with an opposing trend in task-induced functional connectivity, with increased connectivity in the motor network and decreased connectivity in the DMN. ConclusionsStroke patients demonstrate altered neural activity and connectivity patterns during motor learning with their unaffected hand, potentially contributing to globally impaired motor learning skills. The reduced ability to lateralize cerebral activation, along with the enhanced connectivity between the right and left motor cortices in these patients, may signify maladaptive neural processes that impede motor adaptation, possibly affecting long-term rehabilitation post-stroke. The contrasting pattern of activity modulation and connectivity alteration in the default mode network suggests a nuanced role of this network in post-stroke motor learning. These insights could have significant implications for the development of customised rehabilitation strategies for stroke patients.

Investigating mechanisms of sport-related cognitive improvement using measures of motor learning.

An increasing number of studies have linked engagement in sport or increased physical fitness with improved cognitive performance. Additionally, studies have employed physical activity as an intervention to help with cognition in aging individuals. Despite this, the underlying mechanism (or mechanisms) by which benefits occur remain unclear. We investigated whether improved trainability for individuals engaged in sport or fitness training might underlie such benefits. Specifically, we assessed motor skill performance and learning rates in young adult runners, baseball players, and "control" individuals who did not regularly engage in sport or exercise using an implicit motor sequence learning task. Better initial performance on the task was seen for both the runner group and the baseball group but no benefits were seen for the baseball/runner groups for rates of improvement on the task. This was the case for both non-specific learning (or general motor skill learning-learning not associated with specific sequences of responses) and for sequence-specific learning (or improvement on repeated sequences of responses that participants were not aware of). This pattern may mean that either engagement in sport/physical activity results in improvements that are transferable beyond the context of the sport/training activity or that engagement in sport/exercise may relate to initial differences in the motor competence of an individual. Further work could beneficially investigate learning in more directly cognitive-related tasks and consolidation/improvement of performance over more prolonged time periods. Importantly, assessment of a fitness/sport intervention on performance and learning rates may provide a better context for some of the benefits reported in cross-sectional investigations of the effects of sport/fitness on cognition and aid in determining which differences are due to engaging in exercise and which differences affect the tendency for such engagement.

Increased cortical inhibition following brief motor memory reactivation supports reconsolidation and overnight offline learning gains.

Practicing motor skills stabilizes and strengthens motor memories by repeatedly reactivating and reconsolidating them. The conventional view, by which a repetitive practice is required for substantially improving skill performance, has been recently challenged by behavioral experiments, in which even brief reactivations of the motor memory have led to significant improvements in skill performance. However, the mechanisms which facilitate brief reactivation-induced skill improvements remain elusive. While initial memory consolidation has been repeatedly associated with increased neural excitation and disinhibition, reconsolidation has been shown to involve a poorly understood mixture of both excitatory and inhibitory alterations. Here, we followed a 3-d reactivation-reconsolidation framework to examine whether the excitatory/inhibitory mechanisms which underlie brief reactivation and repetitive practice differ. Healthy volunteers practiced a motor sequence learning task using either brief reactivation or repetitive practice and were assessed using ultrahigh field (7T) magnetic resonance spectroscopy at the primary motor cortex (M1). We found that increased inhibition (GABA concentrations) and decreased excitation/inhibition (glutamate/GABA ratios) immediately following the brief reactivation were associated with overnight offline performance gains. These gains were on par with those exhibited following repetitive practice, where no correlations with inhibitory or excitatory changes were observed. Our findings suggest that brief reactivation and repetitive practice depend on fundamentally different neural mechanisms and that early inhibition-and not excitation-is particularly important in supporting the learning gains exhibited by brief reactivation.

Neuronavigated Cerebellar 50 Hz tACS: Attenuation of Stimulation Effects by Motor Sequence Learning.

Cerebellar transcranial alternating current stimulation (tACS) is an emerging non-invasive technique that induces electric fields to modulate cerebellar function. Although the effect of cortical tACS seems to be state-dependent, the impact of concurrent motor activation and the duration of stimulation on the effects of cerebellar tACS has not yet been examined. In our study, 20 healthy subjects received neuronavigated 50 Hz cerebellar tACS for 40 s or 20 min, each during performance using a motor sequence learning task (MSL) and at rest. We measured the motor evoked potential (MEP) before and at two time points after tACS application to assess corticospinal excitability. Additionally, we investigated the online effect of tACS on MSL. Individual electric field simulations were computed to evaluate the distribution of electric fields, showing a focal electric field in the right cerebellar hemisphere with the highest intensities in lobe VIIb, VIII and IX. Corticospinal excitability was only increased after tACS was applied for 40 s or 20 min at rest, and motor activation during tACS (MSL) cancelled this effect. In addition, performance was better (shorter reaction times) for the learned sequences after 20 min of tACS, indicating more pronounced learning under 20 min of tACS compared to tACS applied only in the first 40 s.

Impact of a pediatric posterior fossa tumor and its treatments on motor procedural learning.

Posterior fossa tumor (PFT) survivors have difficulty learning new skills. Procedural memory is a skill learning system that allows, through training, the automatization of procedures and progressive improvement of performance. It underlies most of the motor procedures in everyday life that we perform automatically, such as riding a bike or writing. Motor procedural memory is divided into two components: motor sequence learning involving mainly cortico-striatal networks, and motor adaptation involving mainly cortico-cerebellar networks. The aim of this work was to explore the impact of a tumor and its treatment during childhood on procedural learning hypothesizing that sequence learning would be impaired in PFT survivors who have been treated with radiotherapy, whereas motor adaptation would be impaired in all PFT survivors. 22 irradiated survivors of PFT, 17 non-irradiated survivors and 21 healthy controls from the IMPALA study (NCT04324450) performed a motor sequence learning task and a motor adaptation task. Doses received by striatal and cerebellar structures were reported from the initial dosimetry plans. Sequence learning was preserved in both tumor groups, but at the individual level 7/22 irradiated, and 4/17 non-irradiated participants failed to learn the motor sequence. Motor adaptation was impaired in both tumor groups, predominantly in the irradiated group. This study sheds new light on the long-term impact of PFT treatments in childhood on a rarely-studied part of memory, which is perceptual-motor procedural learning. Our results suggest that the cerebellum and striatum could be considered as organs at risk with regard to procedural learning.

Targeting the frontoparietal network using bifocal transcranial alternating current stimulation during a motor sequence learning task in healthy older adults

BackgroundHealthy older adults show a decrease in motor performance and motor learning capacity as well as in working memory (WM) performance. WM has been suggested to be involved in motor learning processes, such as sequence learning. Correlational evidence has shown the involvement of the frontoparietal network (FPN), a network underlying WM processes, in motor sequence learning. However, causal evidence is currently lacking. Non-invasive brain stimulation (NIBS) studies have focused so far predominantly on motor-related areas to enhance motor sequence learning while areas associated with more cognitive aspects of motor learning have not yet been addressed. HypothesisIn this study, we aim to provide causal evidence for the involvement of WM processes and the underlying FPN in the successful performance of a motor sequence learning task by using theta transcranial alternating current stimulation (tACS) targeting the FPN during a motor sequence learning task. MethodsIn a cohort of 20 healthy older adults, we applied bifocal tACS in the theta range to the FPN during a sequence learning task. With the use of a double-blind, cross-over design, we tested the efficacy of active compared to sham stimulation. Two versions of the motor task were used: one with high and one with low WM load, to explore the efficacy of stimulation on tasks differing in WM demand. Additionally, the effects of stimulation on WM performance were addressed using an N-back task. The tACS frequency was personalized by means of EEG measuring the individual theta peak frequency during the N-back task. ResultsThe application of personalized theta tACS to the FPN improved performance during the motor sequence learning task with high WM load (p < .001), but not with low WM load. Active stimulation significantly improved both speed (p < .001), and accuracy (p = .03) during the task with high WM load. In addition, the stimulation paradigm improved performance on the N-back task for the 2-back task (p = .013), but not for 1-back and 3-back. ConclusionThe performance during a motor sequence learning task can be enhanced by means of personalized bifocal theta tACS to the FPN when WM load is high, indicating that the efficacy of this stimulation paradigm is dependent on the cognitive demand during the learning task. These data provide further causal evidence for the critical involvement of WM processes and the FPN during the execution of a motor sequence learning task in healthy older. These findings open new exciting possibilities to counteract the age-related decline in motor performance, learning capacity and WM performance.

Connectivity in Large-Scale Resting-State Brain Networks Is Related to Motor Learning: A High-Density EEG Study.

Previous research has shown that resting-state functional connectivity (rsFC) between different brain regions (seeds) is related to motor learning and motor memory consolidation. Using high-density electroencephalography (hdEEG), we addressed this question from a brain network perspective. Specifically, we examined frequency-dependent functional connectivity in resting-state networks from twenty-nine young healthy participants before and after they were trained on a motor sequence learning task. Consolidation was assessed with an overnight retest on the motor task. Our results showed training-related decreases in gamma-band connectivity within the motor network, and between the motor and functionally distinct resting-state networks including the attentional network. Brain-behavior correlation analyses revealed that baseline beta, delta, and theta rsFC were related to subsequent motor learning and memory consolidation such that lower connectivity within the motor network and between the motor and several distinct resting-state networks was correlated with better learning and overnight consolidation. Lastly, training-related increases in beta-band connectivity between the motor and the visual networks were related to greater consolidation. Altogether, our results indicate that connectivity in large-scale resting-state brain networks is related to—and modulated by—motor learning and memory consolidation processes. These finding corroborate previous seed-based connectivity research and provide evidence that frequency-dependent functional connectivity in resting-state networks is critically linked to motor learning and memory consolidation.

Effects of Sleep on Language and Motor Consolidation: Evidence of Domain General and Specific Mechanisms.

The current study explores the effects of time and sleep on the consolidation of a novel language learning task containing both item-specific knowledge and the extraction of grammatical regularities. We also compare consolidation effects in language and motor sequence learning tasks, to ask whether consolidation mechanisms are domain general. Young adults learned to apply plural inflections to novel words based on morphophonological rules embedded in the input, and learned to type a motor sequence using a keyboard. Participants were randomly assigned into one of two groups, practicing each task during either the morning or evening hours. Both groups were retested 12 and 24 hours post-training. Performance on frequent trained items in the language task stabilized only following sleep, consistent with a hippocampal mechanism for item-specific learning. However, regularity extraction, indicated by generalization to untrained items in the linguistic task, as well as performance on motor sequence learning, improved 24 hours post-training, irrespective of the timing of sleep. This consolidation process is consistent with a frontostriatal skill-learning mechanism, common across the language and motor domains. This conclusion is further reinforced by cross-domain correlations at the individual level between improvement across 24 hours in the motor task and in the low-frequency trained items in the linguistic task, which involve regularity extraction. Taken together, our results at the group and individual levels suggest that some aspects of consolidation are shared across the motor and language domains, and more specifically, between motor sequence learning and grammar learning.

Habitual or hyper-controlled behavior: OCD symptoms and explicit sequence learning

Background and objectivesThis study examined whether ritualistic behaviors characteristic of obsessive-compulsive disorder (OCD) are a product of dysfunctional goal-directed behavior leading to habitual behavior (Gillan & Robbins, 2014). We used an explicit motor sequence learning task to investigate the repetition of chunked action sequences across the OC spectrum. As sequential motor behavior is practiced, action movements appear to get bundled together, and the initial movement of the sequence activates the entire sequence, leaving it relatively insensitive to change. Therefore, compulsive behavior in OCD may be a result of failing to inhibit the full activation of an extensively learned action sequence. Methods: Fifty-seven participants across the range of OCD symptoms practiced one sequence and then tested on a novel sequence in which one of the middle movements was omitted. Optimal performance for the new sequence required goal-directed inhibition of the original sequence and goal-directed execution of the new sequence instead. To manipulate activation of goal-directed behavior, we added a dual-task condition with a competing auditory tonal N-Back task. Data were analyzed using mixed-effects models. Results: Although we did observe expected learning patterns during learning of the original sequence, slower reaction times for the new sequences, and higher errors in the dual-task condition, performance was not significantly related to either obsessive-compulsive symptoms or distress symptoms. Limitations: The current study used an analog sample; replication in a treatment seeking sample is warranted. Conclusions: These findings challenge the goal-directed dysfunction model of OCD.

Differential Effects of a Nap on Motor Sequence Learning-Related Functional Connectivity Between Young and Older Adults.

In older adults, motor sequence learning (MSL) is largely intact. However, consolidation of newly learned motor sequences is impaired compared to younger adults, and there is evidence that brain areas supporting enhanced consolidation via sleep degrade with age. It is known that brain activity in hippocampal–cortical–striatal areas is important for sleep-dependent, off-line consolidation of motor-sequences. Yet, the intricacies of how both age and sleep alter communication within this network of brain areas, which facilitate consolidation, are not known. In this study, 37 young (age 20–35) and 49 older individuals (age 55–75) underwent resting state functional magnetic resonance imaging (fMRI) before and after training on a MSL task as well as after either a nap or a period of awake rest. Young participants who napped showed strengthening of functional connectivity (FC) between motor, striatal, and hippocampal areas, compared to older subjects regardless of sleep condition. Follow-up analyses revealed this effect was driven by younger participants who showed an increase in FC between striatum and motor cortices, as well as older participants who showed decreased FC between the hippocampus, striatum, and precuneus. Therefore, different effects of sleep were observed in younger vs. older participants, where young participants primarily showed increased communication in the striatal-motor areas, while older participants showed decreases in key nodes of the default mode network and striatum. Performance gains correlated with FC changes in young adults, and this association was much greater in participants who napped compared to those who stayed awake. Performance gains also correlated with FC changes in older adults, but only in those who napped. This study reveals that, while there is no evidence of time-dependent forgetting/deterioration of performance, older adults exhibit a completely different pattern of FC changes during consolidation compared to younger adults, and lose the benefit that sleep affords to memory consolidation.

P163 Slow wave transcranial electrical stimulation during wake to investigate the consolidation of new learning

Abstract Introduction Slow, oscillatory, transcranial electrical stimulation (so-tES) applies a current over the scalp that oscillates in intensity at a frequency associated with slow wave sleep (SWS; 0.75Hz). When applied during SWS, so-tES can enhance SWS EEG power compared to sham stimulation, as well as overnight declarative memory consolidation. When applied during wake, so-tES can enhance local EEG power in the slow wave frequency range (0.5–4.5Hz) compared to sham. Therefore, this study will investigate whether so-tES can enhance the early consolidation of new learning compared to sham, when applied during wake. A preliminary analysis of data will be presented. Methods Healthy, young, right-handed adults (18–35 years) practiced a motor sequence learning task for 30 minutes, before receiving 15 minutes of active or sham so-tES (0.75Hz) during quiet wakefulness. Task performance was assessed by recording the total number of correct sequences performed in 30 seconds before practice, after practice, and after stimulation. Performance improvements will be compared between stimulation conditions. Non-invasive, electrophysiological corticospinal excitability measurements (i.e., motor-evoked potentials) were also recorded at six timepoints throughout each session, to investigate whether active so-tES can modulate corticospinal excitability differently to sham. Progress to date Data collection is ongoing, and completion is expected by late 2021. Intended outcome and impact We expect so-tES to enhance early skill consolidation during wake, and that enhanced consolidation will be associated with less variable measurements of corticospinal excitability, when compared with sham stimulation.

P 36. rTMS-induced offline-modulation of premotor-motor interaction after motor sequence learning does not affect consolidation

Introduction. The acquisition of novel motor skills depends on active training and further offline processing of the motor engram (i.e., consolidation). Previous studies suggest an essential role of post-training corticospinal excitability (CSE) for the induction of offline motor memory consolidation. Furthermore, it was shown that the interaction of the primary motor cortex (M1) and the premotor cortex (PMC) after training affects the consolidation process. In this study, we modulated the post-training interaction of M1 and PMC by applying inhibitory repetitive transcranial magnetic stimulation (rTMS) and investigated the effects on CSE and consolidation. Methods. 48 healthy, right-handed subjects (age 22.13 ± 3.2 a) were assigned to 3 groups. All participants practiced an explicit motor sequence learning task with their right hand. Immediately after training, participants received 1 Hz rTMS to either left M1, left PMC, or sham stimulation. Motor evoked potentials (MEP) were recorded before training and after rTMS. Task performance was retested eight hours after the end of stimulation to assess offline performance changes. Task performance was assessed using a performance index (PI) that integrated speed and accuracy of sequence execution. Consolidation was quantified as the difference of task performance at the end of the training session compared to the beginning of the retest (mean PI of 4 blocks each). Results. In terms of changes of MEP amplitudes, rmANOVA revealed an interaction of factors group*time ( p = 0.001). When applied to M1, rTMS induced a decrease of CSE compared to the pre-training assessments ( p = 0.007), whereas stimulation of the PMC led to an increase of MEP amplitudes ( p = 0.009). No relevant change of corticospinal excitability was seen after sham stimulation ( p = 0.862). Training performance did not differ between groups (group*block, p = 0.781) and all groups demonstrated significant offline-improvements at delayed retesting. However, there were no significant differences of consolidation between groups ( p = 0.456). Furthermore, correlation analysis revealed no significant association of CSE modulation and offline performance changes ( r = 0.101, p = 0.493). Discussion. The increase of CSE induced by post-training PMC demonstrated here differs from results of previous studies that applied inhibitory PMC stimulation at rest or before a training intervention, which resulted in decreased CSE. We, therefore, interpret our findings as further evidence of a state-dependent function of the PMC. Despite significant modulation of CSE by post-training rTMS of M1 and PMC, there was no behavioral effect on consolidation. This challenges the relevance of immediate post-training CSE changes as a key mechanism in terms of the induction of consolidation. Although proximal intracortical physiological mechanisms are still not excluded, they are not detected by changes in post-training corticospinal excitability.

Motor sequence learning in patients with ideomotor apraxia: Effects of long-term training

Recent studies show that limb apraxia is a quite frequent, yet often underdiagnosed, higher motor impairment following stroke. Because it adversely affects every-day life and personal independence, successful rehabilitation of apraxia is essential for personal well-being. Nevertheless, evidence of long-term efficacy of training schemes and generalization to untrained actions is still scarce. One possible reason for the tendency of this neurological disorder to persist may be a deficit in planning, conceptualisation and storage of complex motor acts.This pilot study aims at investigating explicit motor learning in apractic stroke patients. In particular, we addressed the ability of apractic patients to learn and to retain new explicit sequential finger movements across 10 training sessions over a 3-week interval.Nine stroke patients with ideomotor apraxia in its chronic stage participated in a multi-session training regimen and were included in data analyses. Patients performed an explicit finger sequence learning task (MSLT – motor sequence learning task), which is a well-established paradigm to investigate motor learning and memory processes.Patients improved task performance in terms of speed and accuracy across sessions. Specifically, they showed a noticeable reduction in the mean time needed to perform a correct sequence and the number of erroneous sequences. We found also a trend for improved performance at the Goldenberg apraxia test protocol: “imitation of meaningless hand and finger gestures” relative to when assessed before the MSLT training.Patients with ideomotor apraxia demonstrated the ability to acquire and maintain a novel sequence of movements; and, this training was associated with hints towards improvement of apraxia symptoms.

Motor Sequence Learning Deficits in Idiopathic Parkinson’s Disease Are Associated With Increased Substantia Nigra Activity

Previous studies have shown that persons with Parkinson’s disease (pwPD) share specific deficits in learning new sequential movements, but the neural substrates of this impairment remain unclear. In addition, the degree to which striatal dopaminergic denervation in PD affects the cortico-striato-thalamo-cerebellar motor learning network remains unknown. We aimed to answer these questions using fMRI in 16 pwPD and 16 healthy age-matched control subjects while they performed an implicit motor sequence learning task. While learning was absent in both pwPD and controls assessed with reaction time differences between sequential and random trials, larger error-rates during the latter suggest that at least some of the complex sequence was encoded. Moreover, we found that while healthy controls could improve general task performance indexed by decreased reaction times across both sequence and random blocks, pwPD could not, suggesting disease-specific deficits in learning of stimulus-response associations. Using fMRI, we found that this effect in pwPD was correlated with decreased activity in the hippocampus over time. Importantly, activity in the substantia nigra (SN) and adjacent bilateral midbrain was specifically increased during sequence learning in pwPD compared to healthy controls, and significantly correlated with sequence-specific learning deficits. As increased SN activity was also associated (on trend) with higher doses of dopaminergic medication as well as disease duration, the results suggest that learning deficits in PD are associated with disease progression, indexing an increased drive to recruit dopaminergic neurons in the SN, however, unsuccessfully. Finally, there were no differences between pwPD and controls in task modulation of the cortico-striato-thalamo-cerebellar network. However, a restricted nigral-striatal model showed that negative modulation of SN to putamen connection was larger in pwPD compared to controls during random trials, while no differences between the groups were found during sequence learning. We speculate that learning-specific SN recruitment leads to a relative increase in SN- > putamen connectivity, which returns to a pathological reduced state when no learning takes place.

Phase-dependent offline enhancement of human motor memory

BackgroundSkill learning engages offline activity in the primary motor cortex (M1). Sensorimotor cortical activity oscillates between excitatory trough and inhibitory peak phases of the mu (8–12 Hz) rhythm. We recently showed that these mu phases influence the magnitude and direction of neuroplasticity induction within M1. However, the contribution of M1 activity during mu peak and trough phases to human skill learning has not been investigated. ObjectiveTo evaluate the effects of phase-dependent TMS during mu peak and trough phases on offline learning of a newly-acquired motor skill. MethodsOn Day 1, three groups of healthy adults practiced an explicit motor sequence learning task with their non-dominant left hand. After practice, phase-dependent TMS was applied to the right M1 during either mu peak or mu trough phases. The third group received sham TMS during random mu phases. On Day 2, all subjects were re-tested on the same task to evaluate offline learning. ResultsSubjects who received phase-dependent TMS during mu trough phases showed increased offline skill learning compared to those who received phase-dependent TMS during mu peak phases or sham TMS during random mu phases. Additionally, phase-dependent TMS during mu trough phases elicited stronger whole-brain broadband oscillatory power responses than phase-dependent TMS during mu peak phases. ConclusionsWe conclude that sensorimotor mu trough phases reflect brief windows of opportunity during which TMS can strengthen newly-acquired skill memories.

Daytime Exposure to Short Wavelength-Enriched Light Improves Cognitive Performance in Sleep-Restricted College-Aged Adults.

We tested the effect of daytime indoor light exposure with varying melanopic strength on cognitive performance in college-aged students who maintained an enforced nightly sleep opportunity of 7 h (i.e., nightly sleep duration no longer than 7 h) for 1 week immediately preceding the day of light exposure. Participants (n = 39; mean age ± SD = 24.5 ± 3.2 years; 21 F) were randomized to an 8 h daytime exposure to one of four white light conditions of equal photopic illuminance (~50 lux at eye level in the vertical plane) but different melanopic illuminance [24–45 melanopic-EDI lux (melEDI)] generated by varying correlated color temperatures [3000K (low-melEDI) or 5000K (high-melEDI)] and spectra [conventional or daylight-like]. Accuracy on a 2-min addition task was 5% better in the daylight-like high-melEDI condition (highest melEDI) compared to the conventional low-melEDI condition (lowest melEDI; p < 0.01). Performance speed on the motor sequence learning task was 3.2 times faster (p < 0.05) during the daylight-like high-melEDI condition compared to the conventional low-melEDI. Subjective sleepiness was 1.5 times lower in the conventional high-melEDI condition compared to the conventional low-melEDI condition, but levels were similar between conventional low- and daylight-like high-melEDI conditions. These results demonstrate that exposure to high-melanopic (short wavelength-enriched) white light improves processing speed, working memory, and procedural learning on a motor sequence task in modestly sleep restricted young adults, and have important implications for optimizing lighting conditions in schools, colleges, and other built environments.

Investigating the Effects of Seizures on Procedural Memory Performance in Patients with Epilepsy.

Memory complaints are frequently reported by patients with epilepsy and are associated with seizure occurrence. Yet, the direct effects of seizures on memory retention are difficult to assess given their unpredictability. Furthermore, previous investigations have predominantly assessed declarative memory. This study evaluated within-subject effects of seizure occurrence on retention and consolidation of a procedural motor sequence learning task in patients with epilepsy undergoing continuous monitoring for five consecutive days. Of the total sample of patients considered for analyses (N = 53, Mage = 32.92 ± 13.80 y, range = 18–66 y; 43% male), 15 patients experienced seizures and were used for within-patient analyses. Within-patient contrasts showed general improvements over seizure-free (day + night) and seizure-affected retention periods. Yet, exploratory within-subject contrasts for patients diagnosed with temporal lobe epilepsy (n = 10) showed that only seizure-free retention periods resulted in significant improvements, as no performance changes were observed following seizure-affected retention. These results indicate general performance improvements and offline consolidation of procedural memory during the day and night. Furthermore, these results suggest the relevance of healthy temporal lobe functioning for successful consolidation of procedural information, as well as the importance of seizure control for effective retention and consolidation of procedural memory.