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The principles of motor learning have been applied in neurological rehabilitation for years. The underlying assumption is that these principles that have been identified in research on healthy individuals would also apply to those with neurological disorders, making them highly relevant for rehabilitation. However, there is currently no tool dedicated to evaluating motor learning abilities, that refers to procedural perceptual-motor learning (PPML) abilities, before rehabilitation. To address this gap, we created a new tool assessing PPML (EVALuation de l'APprentissage Procedural [EVAL_APP]), based on two experimental tasks known to assess motor sequence learning and visuomotor adaptation. The study aimed to determine whether this tool is suitable for clinical practice and meets care needs by conducting a cross-sectional online survey of psychomotor and occupational therapists in France. The results show that professionals are interested in measuring PPML, and over half of them indicated that they would use the tool. Participants who felt trained about PPML responded positively to the relevance of PPML assessment and to the future use of the EVAL_APP tool. While some parameters of the EVAL_APP tool are well adjusted, others may need improvement to be adapted for children with neurodevelopmental disorders, including Developmental Coordination Disorder. The results are encouraging for pursuing the conception of the new tool by considering the opinion of professionals specialized in pediatric rehabilitation. [ABSTRACT FROM AUTHOR]

The cholinergic system plays a key role in motor function, but whether pharmacological modulation of cholinergic activity affects motor sequence learning is unknown. The acetylcholine receptor antagonist biperiden, an established treatment in movement disorders, reduces attentional modulation, but whether it influences motor sequence learning is not clear. Using a randomized, double‐blind placebo‐controlled crossover design, we tested 30 healthy young participants and showed that biperiden impairs the ability to learn sequential finger movements, accompanied by widespread oscillatory broadband power changes (4–25 Hz) in the motor sequence learning network after receiving biperiden, with greater power in the theta, alpha and beta bands over ipsilateral motor and bilateral parietal–occipital areas. The reduced early theta power during a repeated compared with random sequence, likely reflecting disengagement of top‐down attention to sensory processes, was disrupted by biperiden. Alpha synchronization during repeated sequences reflects sensory gating and lower visuospatial attention requirements compared with visuomotor responses to random sequences. After biperiden, alpha synchronization was greater, potentially reflecting excessive visuospatial attention reduction, affecting visuomotor responding required to enable sequence learning. Beta oscillations facilitate sequence learning by integrating visual and somatosensory inputs, stabilizing repeated sequences and promoting prediction of the next stimulus. The beta synchronization after biperiden fits with a disruption of the selective visuospatial attention enhancement associated with initial sequence learning. These findings highlight the role of cholinergic processes in motor sequence learning. [ABSTRACT FROM AUTHOR]

The acquisition of skills, such as learning to play a musical instrument, involves various phases that make specific demands on the learner. Knowledge of the cognitive and motor contributions during learning phases can be helpful in developing effective and targeted interventions for healthy aging. Eighty-six healthy older participants underwent an extensive cognitive, motoric, and musical test battery. Within one session, one piano-related and one music-independent movement sequence were both learned. We tested the associations between skill performance and cognito-motor abilities with Bayesian mixed models accounting for individual learning rates. Results showed that performance was positively associated with all cognito-motor abilities. Learning a piano-related task was characterized by relatively strong initial associations between performance and abilities. These associations then weakened considerably before increasing exponentially from the second trial onwards, approaching a plateau. Similar performance–ability relationships were detected in the course of learning a music-unrelated motor task. Positive performance–ability associations emphasize the potential of learning new skills to produce positive cognitive and motor transfer effects. Consistent high-performance tasks that demand maximum effort from the participants could be very effective. However, interventions should be sufficiently long so that the transfer potential can be fully exploited. [ABSTRACT FROM AUTHOR]

Motor sequence learning gradually quickens reaction time, suggesting that sequence learning alters motor preparation processes. Interestingly, evidence has shown that preparing sequence movements decreases short intracortical inhibition (SICI) in the contralateral motor cortex (M1), but also that sequence learning alters motor preparation processes in both the contralateral and ipsilateral M1s. Therefore, one possibility is that sequence learning alters the SICI decreases occurring during motor preparation in bilateral M1s. To examine this, two novel hypotheses were tested: unilateral sequence preparation would decrease SICI in bilateral M1s, and sequence learning would alter such bilateral SICI responses. Paired-pulse transcranial magnetic stimulation was delivered over the contralateral and ipsilateral M1s to assess SICI in an index finger muscle during the preparation of sequences initiated by either the right index or little finger. In the absence of sequence learning, SICI decreased in both the contralateral and ipsilateral M1s during the preparation of sequences initiated by the right index finger, suggesting that SICI decreases in bilateral M1s during unilateral motor preparation. As sequence learning progressed, SICI decreased in the contralateral M1 whilst it increased in the ipsilateral M1. Moreover, these bilateral SICI responses were observed at the onset of motor preparation, suggesting that sequence learning altered baseline SICI levels rather than the SICI decreases occurring during motor preparation per se. Altogether, these results suggest that SICI responses in bilateral M1s reflect two motor processes: an acute decrease of inhibition during motor preparation, and a cooperative but bidirectional shift of baseline inhibition levels as sequence learning progresses.

Decreased long‐range temporal correlations (LRTC) in brain signals can be used to measure cognitive effort during task execution. Here, we examined how learning a motor sequence affects long‐range temporal memory within resting‐state functional magnetic resonance imaging signal. Using the Hurst exponent (HE), we estimated voxel‐wise LRTC and assessed changes over 5 consecutive days of training, followed by a retention scan 12 days later. The experimental group learned a complex visuomotor sequence while a complementary control group performed tightly matched movements. An interaction analysis revealed that HE decreases were specific to the complex sequence and occurred in well‐known motor sequence learning associated regions including left supplementary motor area, left premotor cortex, left M1, left pars opercularis, bilateral thalamus, and right striatum. Five regions exhibited moderate to strong negative correlations with overall behavioral performance improvements. Following learning, HE values returned to pretraining levels in some regions, whereas in others, they remained decreased even 2 weeks after training. Our study presents new evidence of HE's possible relevance for functional plasticity during the resting‐state and suggests that a cortical subset of sequence‐specific regions may continue to represent a functional signature of learning reflected in decreased long‐range temporal dependence after a period of inactivity. [ABSTRACT FROM AUTHOR]

When applied over the primary motor cortex (M1), anodal transcranial direct current stimulation (a-tDCS) could enhance the effects of a single motor imagery training (MIt) session on the learning of a sequential finger-tapping task (SFTT). This study aimed to investigate the effect of a-tDCS on the learning of an SFTT during multiple MIt sessions. Two groups of 16 healthy young adults participated in three consecutive MIt sessions over 3 days, followed by a retention test 1 week later. They received active or sham a-tDCS during a MIt session in which they mentally rehearsed an eight-item complex finger sequence with their left hand. Before and after each session, and during the retention test, they physically repeated the sequence as quickly and accurately as possible. Both groups (i) improved their performance during the first two sessions, showing online learning; (ii) stabilised the level they reached during all training sessions, reflecting offline consolidation; and (iii) maintained their performance level one week later, showing retention. However, no significant difference was found between the groups, regardless of the MSL stage. These results emphasise the importance of performing several MIt sessions to maximise performance gains, but they do not support the additional effects of a-tDCS. [ABSTRACT FROM AUTHOR]

Motor sequence learning gradually quickens reaction time, suggesting that sequence learning alters motor preparation processes. Interestingly, evidence has shown that preparing sequence movements decreases short intracortical inhibition (SICI) in the contralateral motor cortex (M1), but also that sequence learning alters motor preparation processes in both the contralateral and ipsilateral M1s. Therefore, one possibility is that sequence learning alters the SICI decreases occurring during motor preparation in bilateral M1s. To examine this, two novel hypotheses were tested: unilateral sequence preparation would decrease SICI in bilateral M1s, and sequence learning would alter such bilateral SICI responses. Paired-pulse transcranial magnetic stimulation was delivered over the contralateral and ipsilateral M1s to assess SICI in an index finger muscle during the preparation of sequences initiated by either the right index or little finger. In the absence of sequence learning, SICI decreased in both the contralateral and ipsilateral M1s during the preparation of sequences initiated by the right index finger, suggesting that SICI decreases in bilateral M1s during unilateral motor preparation. As sequence learning progressed, SICI decreased in the contralateral M1 whilst it increased in the ipsilateral M1. Moreover, these bilateral SICI responses were observed at the onset of motor preparation, suggesting that sequence learning altered baseline SICI levels rather than the SICI decreases occurring during motor preparation per se. Altogether, these results suggest that SICI responses in bilateral M1s reflect two motor processes: an acute decrease of inhibition during motor preparation, and a cooperative but bidirectional shift of baseline inhibition levels as sequence learning progresses. • Here, ppTMS was used to assess bilateral SICI in the FDI muscle as participants prepared unilateral sequence movements. • In the absence of sequence learning, SICI decreased in bilateral M1s during motor preparation, which was replicated. • As sequence learning progressed, SICI decreased in the contralateral M1 whilst it increased in the ipsilateral M1. • These bidirectional SICI responses in bilateral M1s were only observed at the onset of motor preparation. • The results suggest that SICI in bilateral M1s is altered during motor preparation and as sequence learning progresses. [ABSTRACT FROM AUTHOR]

Both the hippocampal and striatal systems participate in motor sequence learning (MSL) in healthy subjects, and the prominent role of the hippocampal system in sleep-related consolidation has been demonstrated. However, some pathological states may change the functional dominance between these two systems in MSL consolidation. To better understand the functional performance within these two systems under the pathological condition of hippocampal impairment, we compared the functional differences after consolidation between patients with left medial temporal lobe epilepsy (LmTLE) and healthy control subjects (HCs). We assessed participants' performance on the finger-tapping task (FTT) during acquisition (on day 1) and after consolidation during sleep (on day 2). All participants underwent an MRI scan (T1 and resting state) before each FTT. We found that the LmTLE group showed performance deficits in offline consolidation compared to the HC group. The LmTLE group exhibited structural changes, such as decreased gray matter volume (GMV) in the left hippocampus and increased GMV in the right putamen (striatum). Our results also revealed that whereas the main effect of consolidation was observed in the hippocampus-related functional connection in the HC group, it was only evident in the striatum-related functional loop in the LmTLE group. Our findings indicated that LmTLE patients may rely more on the striatal system for offline consolidation because of structural impairments in the hippocampus. Additionally, this compensatory mechanism may not fully substitute for the role of the impaired hippocampus itself. [ABSTRACT FROM AUTHOR]

Sleep benefits motor memory consolidation, which is mediated by sleep spindle activity and associated memory reactivations during non-rapid eye movement (NREM) sleep. However, the particular role of NREM2 and NREM3 sleep spindles and the mechanisms triggering this memory consolidation process remain unclear. Here, simultaneous electroencephalographic and functional magnetic resonance imaging (EEG-fMRI) recordings were collected during night-time sleep following the learning of a motor sequence task. Adopting a time-based clustering approach, we provide evidence that spindles iteratively occur within clustered and temporally organized patterns during both NREM2 and NREM3 sleep. However, the clustering of spindles in trains is related to motor memory consolidation during NREM2 sleep only. Altogether, our findings suggest that spindles' clustering and rhythmic occurrence during NREM2 sleep may serve as an intrinsic rhythmic sleep mechanism for the timed reactivation and subsequent consolidation of motor memories, through synchronized oscillatory activity within a subcortical–cortical network involved during learning. [ABSTRACT FROM AUTHOR]

This study investigates the goal/habit imbalance theory of compulsion in obsessive-compulsive disorder (OCD), which postulates enhanced habit formation, increased automaticity, and impaired goal/habit arbitration. It directly tests these hypotheses using newly developed behavioral tasks. First, OCD patients and healthy participants were trained daily for a month using a smartphone app to perform chunked action sequences. Despite similar procedural learning and attainment of habitual performance (measured by an objective automaticity criterion) by both groups, OCD patients self-reported higher subjective habitual tendencies via a recently developed questionnaire. Subsequently, in a re-evaluation task assessing choices between established automatic and novel goal-directed actions, both groups were sensitive to re-evaluation based on monetary feedback. However, OCD patients, especially those with higher compulsive symptoms and habitual tendencies, showed a clear preference for trained/habitual sequences when choices were based on physical effort, possibly due to their higher attributed intrinsic value. These patients also used the habit-training app more extensively and reported symptom relief post-study. The tendency to attribute higher intrinsic value to familiar actions may be a potential mechanism leading to compulsions and an important addition to the goal/habit imbalance hypothesis in OCD. We also highlight the potential of smartphone app training as a habit reversal therapeutic tool.

Background: Recent evidence suggests that hippocampal replay in humans support rapid motor memory consolidation during epochs of wakefulness interleaved with task practice. Objectives/Hypotheses: The goal of this study was to test whether such reactivation patterns can be modulated with experimental interventions and in turn influence fast consolidation. We hypothesized that non-invasive brain stimulation targeting hippocampal and striatal networks via the prefrontal cortex would influence brain reactivation and the rapid form of motor memory consolidation. Methods: Theta-burst stimulation was applied to a prefrontal cluster functionally connected to both the hippocampus and striatum of young healthy participants before they learned a motor sequence task in a functional magnetic resonance imaging (fMRI) scanner. Neuroimaging data acquired during task practice and the interleaved rest epochs were analyzed to comprehensively characterize the effect of stimulation on the neural processes supporting fast motor memory consolidation. Results: Our results collectively show that active, as compared to control, theta-burst stimulation of the prefrontal cortex hindered fast motor memory consolidation. Converging evidence from both univariate and multivariate analyses of fMRI data indicate that active stimulation disrupted hippocampal and caudate responses during inter-practice rest, presumably altering the reactivation of learning-related patterns during the micro-offline consolidation episodes. Last, stimulation altered the link between the brain and the behavioral markers of the fast consolidation process. Conclusion: These results suggest that stimulation targeting deep brain regions via the prefrontal cortex can be used to modulate hippocampal and striatal reactivations in the human brain and influence motor memory consolidation.

Cerebellum (CB) and primary motor cortex (M1) have been associated with motor learning, with different putative roles. Modulation of task performance through application of transcranial direct current stimulation (TDCS) to brain structures provides causal evidence for their engagement in the task. Studies evaluating and comparing TDCS to these structures have provided conflicting results, however, likely due to varying paradigms and stimulation parameters. Here we applied TDCS to CB and M1 within the same experimental design, to enable direct comparison of their roles in motor sequence learning. We examined the effects of anodal TDCS during motor sequence learning in 60 healthy participants, randomly allocated to CB-TDCS, M1-TDCS, or Sham stimulation groups during a serial reaction time task. Key to the design was an equal number of repeated and random sequences. Reaction times (RTs) to implicitly learned and random sequences were compared between groups using ANOVAs and post hoc t-tests. A speed–accuracy trade-off was excluded by analogous analysis of accuracy scores. An interaction was observed between whether responses were to learned or random sequences and the stimulation group. Post hoc analyses revealed a preferential slowing of RTs to implicitly learned sequences in the group receiving CB-TDCS. Our findings provide evidence that CB function can be modulated through transcranial application of a weak electrical current, that the CB and M1 cortex perform separable functions in the task, and that the CB plays a specific role in motor sequence learning during implicit motor sequence learning. [ABSTRACT FROM AUTHOR]

Generalization in motor control is the extent to which motor learning affects movements in situations different than those in which it originally occurred. Recent data on orofacial speech movements indicates that motor sequence learning generalizes to novel syllable sequences containing phonotactically illegal, but previously practiced, consonant clusters. Practicing an entire syllable, however, results in even larger performance gains compared to practicing just its clusters. These patterns of generalization could reflect language-general changes in phonological memory storage and/or inter-articulator coordination during motor sequence learning. To disentangle these factors, we conducted two experiments in which talkers intensively practiced producing novel syllables containing illegal onset and coda clusters over two consecutive days. During the practice phases of both experiments, we observed that, through repetition, talkers gradually produced the syllables with fewer errors, indicative of learning. After learning, talkers were tested for generalization to single syllables (Experiment 1) or syllable pairs (Experiment 2) that overlapped to varying degrees with the practiced syllables. Across both experiments, we found that performance improvements from practicing syllables with illegal clusters partially generalized to novel syllables that contained those clusters, but performance was more error prone if the clusters occurred in a different syllable position (onset versus coda) as in practice, demonstrating that inter-articulator coordination is contextually sensitive. Furthermore, changing the position of a cluster was found to be more deleterious to motor performance during the production of the second syllables in syllable pairs, which required talkers to store more phonological material in memory prior to articulation, compared to single syllables. This interaction effect reveals a complex interplay between memory storage and inter-articulator coordination on generalization in speech motor sequence learning. [ABSTRACT FROM AUTHOR]

The acquisition of skills, such as learning to play a musical instrument, involves various phases that make specific demands on the learner. Knowledge of the cognitive and motor contributions during learning phases can be helpful in developing effective and targeted interventions for healthy aging. Eighty-six healthy older participants underwent an extensive cognitive, motoric, and musical test battery. Within one session, one piano-related and one music-independent movement sequence were both learned. We tested the associations between skill performance and cognito-motor abilities with Bayesian mixed models accounting for individual learning rates. Results showed that performance was positively associated with all cognito-motor abilities. Learning a piano-related task was characterized by relatively strong initial associations between performance and abilities. These associations then weakened considerably before increasing exponentially from the second trial onwards, approaching a plateau. Similar performance–ability relationships were detected in the course of learning a music-unrelated motor task. Positive performance–ability associations emphasize the potential of learning new skills to produce positive cognitive and motor transfer effects. Consistent high-performance tasks that demand maximum effort from the participants could be very effective. However, interventions should be sufficiently long so that the transfer potential can be fully exploited.

Recent evidence suggests that hippocampal replay in humans support rapid motor memory consolidation during epochs of wakefulness interleaved with task practice. The goal of this study was to test whether such reactivation patterns can be modulated with experimental interventions and in turn influence fast consolidation. We hypothesized that non-invasive brain stimulation targeting hippocampal and striatal networks via the prefrontal cortex would influence brain reactivation and the rapid form of motor memory consolidation. Theta-burst stimulation was applied to a prefrontal cluster functionally connected to both the hippocampus and striatum of young healthy participants before they learned a motor sequence task in a functional magnetic resonance imaging (fMRI) scanner. Neuroimaging data acquired during task practice and the interleaved rest epochs were analyzed to comprehensively characterize the effect of stimulation on the neural processes supporting fast motor memory consolidation. Our results collectively show that active, as compared to control, theta-burst stimulation of the prefrontal cortex hindered fast motor memory consolidation. Converging evidence from both univariate and multivariate analyses of fMRI data indicate that active stimulation disrupted hippocampal and caudate responses during inter-practice rest, presumably altering the reactivation of learning-related patterns during the micro-offline consolidation episodes. Last, stimulation altered the link between the brain and the behavioral markers of the fast consolidation process. These results suggest that stimulation targeting deep brain regions via the prefrontal cortex can be used to modulate hippocampal and striatal reactivations in the human brain and influence motor memory consolidation. • Hippocampal and striatal networks were targeted via prefrontal stimulation. • Stimulation hindered fast motor memory consolidation. • Stimulation disrupted micro-offline hippocampal and striatal reactivations. • Stimulation altered the brain-behavior link of fast consolidation markers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Little is known about the effects of physical exercise on sleep-dependent consolidation of procedural memory in individuals with schizophrenia. We conducted a randomized controlled trial (RCT) to assess the effectiveness of physical exercise in improving this cognitive function in schizophrenia. Methods: A three-arm parallel open-labeled RCT took place in a university hospital. Participants were randomized and allocated into either the high-intensity-interval-training group (HIIT), aerobic-endurance exercise group (AE), or psychoeducation group for 12 weeks, with three sessions per week. Seventy-nine individuals with schizophrenia spectrum disorder were contacted and screened for their eligibility. A total of 51 were successfully recruited in the study. The primary outcome was sleep-dependent procedural memory consolidation performance as measured by the finger-tapping motor sequence task (MST). Assessments were conducted during baseline and follow-up on week 12. Results: The MST performance scored significantly higher in the HIIT (n = 17) compared to the psychoeducation group (n = 18) after the week 12 intervention (p < 0.001). The performance differences between the AE (n = 16) and the psychoeducation (p = 0.057), and between the AE and the HIIT (p = 0.999) were not significant. Yet, both HIIT (p < 0.0001) and AE (p < 0.05) showed significant within-group post-intervention improvement. Conclusions: Our results show that HIIT and AE were effective at reverting the defective sleep-dependent procedural memory consolidation in individuals with schizophrenia. Moreover, HIIT had a more distinctive effect compared to the control group. These findings suggest that HIIT may be a more effective treatment to improve sleep-dependent memory functions in individuals with schizophrenia than AE alone. [ABSTRACT FROM AUTHOR]

Posttraining meditation has been shown to promote wakeful memory stabilization of explicit motor sequence information in learners who are experienced meditators. We investigated the effect of single-session mindfulness meditation on wakeful and sleep-dependent forms of implicit motor memory consolidation in meditation naïve adults. Immediately after training with a target implicit motor sequence, participants (N = 20, eight females, 23.9 ± 3.3 years) completed either a 10-min mindfulness meditation (N = 10) or a control listening task before exposure to task interference induced by training with a novel implicit sequence. Target sequence performance was tested following 5-hr wakeful and 15-hr postsleep periods. Bayesian inference was applied to group comparisons of mean reaction time (RT) changes across training, interference, wakeful, and postsleep timepoints. Relative to control conditions, posttraining meditation reduced RT slowing between target sequence training and interference sequence introduction (BF10 [Bayes factors] = 6.61) and supported RT performance gains over the wakeful period (BF10 = 8.34). No group differences in postsleep RT performance were evident (BF10 = 0.38). These findings illustrate that posttraining mindfulness meditation expedites wakeful, but not sleep-dependent, offline learning with implicit motor sequences. Previous meditation experience is not required to obtain wakeful consolidation gains from posttraining mindfulness meditation. [ABSTRACT FROM AUTHOR]

The current study used functional near-infrared spectroscopy (fNIRS) to examine cerebral oxygenation changes in the prefrontal cortex (PFC) associated with dual-task processing before and after motor sequence learning. Participants performed self-initiated sequential finger movements that were 4 and 12 units in length with a visual letter-counting task. After practice, dual-task sequence-4 performance revealed decreased activity in the right dorsolateral PFC, medial PFC, and orbitofrontal cortex. However, dual-task sequence-12 performance revealed increased activity in the right ventrolateral PFC when compared to the left hemisphere. The findings suggest that dual-task interference was reduced following practice for dual-task sequence-4. The results also suggest that increased right hemisphere activation is needed to maintain performance when the primary sequential task (e.g., dual-task sequence-12) has a high level of difficulty. [ABSTRACT FROM AUTHOR]

Abstract Background Wearable devices have been found effective in training ankle control in patients with neurological diseases. However, the neural mechanisms associated with using wearable devices for ankle training remain largely unexplored. This study aimed to investigate the ankle tracking performance and brain white matter changes associated with ankle tracking learning using a wearable-device system and the behavior–brain structure relationships in middle-aged and older adults. Methods Twenty-six middle-aged and older adults (48–75 years) participated in this study. Participants underwent 5-day ankle tracking learning with their non-dominant foot using a custom-built ankle tracking system equipped with a wearable sensor and a sensor-computer interface for real-time visual feedback and data acquisition. Repeated and random sequences of target tracking trajectories were both used for learning and testing. Ankle tracking performance, calculated as the root-mean-squared-error (RMSE) between the target and actual ankle trajectories, and brain diffusion spectrum MR images were acquired at baseline and retention tests. The general fractional anisotropy (GFA) values of eight brain white matter tracts of interest were calculated to indicate their integrity. Two-way (Sex × Time) mixed repeated measures ANOVA procedures were used to investigate Sex and Time effects on RMSE and GFA. Correlations between changes in RMSE and those in GFA were analyzed, controlling for age and sex. Results After learning, both male and female participants reduced the RMSE of tracking repeated and random sequences (both p

Background: Motor imagery practice (MIP) and anodal transcranial direct current stimulation (a-tDCS) are innovative methods with independent positive influence on motor sequence learning (MSL) in older adults. Objective: The present study investigated the effect of MIP combined with a-tDCS over the primary motor cortex (M1) on the learning of a finger tapping sequence of the non-dominant hand in healthy older adults. Methods: Thirty participants participated in this double-blind sham-controlled study. They performed three MIP sessions, one session per day over three consecutive days and a retention test 1 week after the last training session. During training / MIP, participants had to mentally rehearse an 8-element finger tapping sequence with their left hand, concomitantly to either real (a-tDCS group) or sham stimulation (sham-tDCS group). Before and after MIP, as well as during the retention test, participants had to physically perform the same sequence as fast and accurately as possible. Results: Our main results showed that both groups (i) improved their performance during the first two training sessions, reflecting acquisition/online performance gains, (ii) stabilized their performance from one training day to another, reflecting off-line consolidation; as well as after 7 days without practice, reflecting retention, (iii) for all stages of MSL, there was no significant difference between the sham-tDCS and a-tDCS groups. Conclusion: This study highlights the usefulness of MIP in motor sequence learning for older adults. However, 1.5 mA a-tDCS did not enhance the beneficial effects of MIP, which adds to the inconsistency of results found in tDCS studies. Future work is needed to further explore the best conditions of use of tDCS to improve motor sequence learning with MIP. [ABSTRACT FROM AUTHOR]

Purpose: Interictal epileptic discharges (IEDs) are known to affect cognitive function in patients with epilepsy, but the mechanism has not been elucidated. Sleep spindles appearing in synchronization with IEDs were recently demonstrated to impair memory consolidation in rat, but this has not been investigated in humans. On the other hand, the increase of sleep spindles at night after learning is positively correlated with amplified learning effects during sleep for motor sequence learning. In this study, we examined the effects of IEDs and IED-coupled spindles on motor sequence learning in patients with epilepsy, and clarified their pathological significance. Materials and methods: Patients undergoing long-term video-electroencephalography (LT-VEEG) at our hospital from June 2019 to November 2021 and age-matched healthy subjects were recruited. Motor sequence learning consisting of a finger-tapping task was performed before bedtime and the next morning, and the improvement rate of performance was defined as the sleep-dependent learning effect. We searched for factors associated with the changes in learning effect observed between the periods of when antiseizure medications (ASMs) were withdrawn for LT-VEEG and when they were returned to usual doses after LT-VEEG. Results: Excluding six patients who had epileptic seizures at night after learning, nine patients and 11 healthy subjects were included in the study. In the patient group, there was no significant learning effect when ASMs were withdrawn. The changes in learning effect of the patient group during ASM withdrawal were not correlated with changes in sleep duration or IED density; however, they were significantly negatively correlated with changes in IED-coupled spindle density. Conclusion: We found that the increase of IED-coupled spindles correlated with the decrease of sleep-dependent learning effects of procedural memory. Pathological IED-coupled sleep spindles could hinder memory consolidation, that is dependent on physiological sleep spindles, resulting in cognitive dysfunction in patients with epilepsy. [ABSTRACT FROM AUTHOR]

The network of brain structures engaged in motor sequence learning comprises the same structures as those involved in tremor, including basal ganglia, cerebellum, thalamus, and motor cortex. Deep brain stimulation (DBS) of the ventrointermediate nucleus of the thalamus (VIM) reduces tremor, but the effects on motor sequence learning are unknown. We investigated whether VIM stimulation has an impact on motor sequence learning and hypothesized that stimulation effects depend on the laterality of electrode location. Twenty patients (age: 38–81 years; 12 female) with VIM electrodes implanted to treat essential tremor (ET) successfully performed a serial reaction time task, varying whether the stimuli followed a repeating pattern or were selected at random, during which VIM‐DBS was either on or off. Analyses of variance were applied to evaluate motor sequence learning performance according to reaction times (RTs) and accuracy. An interaction was observed between whether the sequence was repeated or random and whether VIM‐DBS was on or off (F[1,18] = 7.89, p =.012). Motor sequence learning, reflected by reduced RTs for repeated sequences, was greater with DBS on than off (T[19] = 2.34, p =.031). Stimulation location correlated with the degree of motor learning, with greater motor learning when stimulation targeted the lateral VIM (n = 23, ρ = 0.46; p =.027). These results demonstrate the beneficial effects of VIM‐DBS on motor sequence learning in ET patients, particularly with lateral VIM electrode location, and provide evidence for a role for the VIM in motor sequence learning. [ABSTRACT FROM AUTHOR]

Acquisition of learned motor sequences involves saccades directed toward the goal to gather visual information prior to reaching. While goal-directed actions involve both eye and hand movements, the role of brain areas controlling saccades during motor sequence learning is still unclear. This study aimed to determine whether resting-state functional connectivity of oculomotor regions is associated with behavioral changes resulting from motor sequence learning. We investigated connectivity between oculomotor control regions and candidate regions involved in oculomotor control and motor sequence learning. Twenty adults had brain scans before 3 days of motor task practice and after a 24-hour retention test, which was used to assess sequence-specific learning. During testing, both saccades and reaches were tracked. Stronger connectivity in multiple oculomotor regions prior to motor task practice correlated with greater sequence-specific learning for both saccades and reaches. A more negative connectivity change involving oculomotor regions from pre- to post-training correlated with greater sequence-specific learning for both saccades and reaches. Overall, oculomotor functional connectivity was associated with the magnitude of behavioral change resulting from motor sequence learning, providing insight into the function of the oculomotor system during motor sequence learning., (© The Author(s) 2024. Published by Oxford University Press.)

Learning new motor skills through training, also termed motor learning, is central for everyday life. Current training strategies recommend intensive task-repetitions aimed at inducing local activation of motor areas, associated with changes in oscillation amplitudes ("event-related power") during training. More recently, another neural mechanism was suggested to influence motor learning: modulation of functional connectivity (FC), that is, how much spatially separated brain regions communicate with each other before and during training. The goal of the present study was to compare the impact of these two neural processing types on motor learning. We measured EEG before, during, and after a finger-tapping task (FTT) in 20 healthy subjects. The results showed that training gain, long-term expertise (i.e., average motor performance), and consolidation were all predicted by whole-brain alpha- and beta-band FC at motor areas, striatum, and mediotemporal lobe (MTL). Local power changes during training did not predict any dependent variable. Thus, network dynamics seem more crucial than local activity for motor sequence learning, and training techniques should attempt to facilitate network interactions rather than local cortical activation., Competing Interests: Competing Interests: The authors have declared that no competing interests exist., (© 2024 Massachusetts Institute of Technology.)

BackgroundMotor imagery practice (MIP) and anodal transcranial direct current stimulation (a-tDCS) are innovative methods with independent positive influence on motor sequence learning (MSL) in older adults.ObjectiveThe present study investigated the effect of MIP combined with a-tDCS over the primary motor cortex (M1) on the learning of a finger tapping sequence of the non-dominant hand in healthy older adults.MethodsThirty participants participated in this double-blind sham-controlled study. They performed three MIP sessions, one session per day over three consecutive days and a retention test 1 week after the last training session. During training / MIP, participants had to mentally rehearse an 8-element finger tapping sequence with their left hand, concomitantly to either real (a-tDCS group) or sham stimulation (sham-tDCS group). Before and after MIP, as well as during the retention test, participants had to physically perform the same sequence as fast and accurately as possible.ResultsOur main results showed that both groups (i) improved their performance during the first two training sessions, reflecting acquisition/on-line performance gains, (ii) stabilized their performance from one training day to another, reflecting off-line consolidation; as well as after 7 days without practice, reflecting retention, (iii) for all stages of MSL, there was no significant difference between the sham-tDCS and a-tDCS groups.ConclusionThis study highlights the usefulness of MIP in motor sequence learning for older adults. However, 1.5 mA a-tDCS did not enhance the beneficial effects of MIP, which adds to the inconsistency of results found in tDCS studies. Future work is needed to further explore the best conditions of use of tDCS to improve motor sequence learning with MIP.

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.

Background: Wearable devices have been found effective in training ankle control in patients with neurological diseases. However, the neural mechanisms associated with using wearable devices for ankle training remain largely unexplored. This study aimed to investigate the ankle tracking performance and brain white matter changes associated with ankle tracking learning using a wearable-device system and the behavior-brain structure relationships in middle-aged and older adults.Methods: Twenty-six middle-aged and older adults (48-75 years) participated in this study. Participants underwent 5-day ankle tracking learning with their non-dominant foot using a custom-built ankle tracking system equipped with a wearable sensor and a sensor-computer interface for real-time visual feedback and data acquisition. Repeated and random sequences of target tracking trajectories were both used for learning and testing. Ankle tracking performance, calculated as the root-mean-squared-error (RMSE) between the target and actual ankle trajectories, and brain diffusion spectrum MR images were acquired at baseline and retention tests. The general fractional anisotropy (GFA) values of eight brain white matter tracts of interest were calculated to indicate their integrity. Two-way (Sex × Time) mixed repeated measures ANOVA procedures were used to investigate Sex and Time effects on RMSE and GFA. Correlations between changes in RMSE and those in GFA were analyzed, controlling for age and sex.Results: After learning, both male and female participants reduced the RMSE of tracking repeated and random sequences (both p < 0.001). Among the eight fiber tracts, the right superior longitudinal fasciculus II (R SLF II) was the only one which showed both increased GFA (p = 0.039) after learning and predictive power of reductions in RMSE for random sequence tracking with its changes in GFA [β = 0.514, R2 change = 0.259, p = 0.008].Conclusions: Our findings implied that interactive tracking movement learning using wearable sensors may place high demands on the attention, sensory feedback integration, and sensorimotor transformation functions of the brain. Therefore, the SLF II, which is known to perform these brain functions, showed corresponding neural plasticity after such learning, and its plasticity also predicted the behavioral gains. The SLF II appears to be a very important anatomical neural correlate involved in such learning paradigms. [ABSTRACT FROM AUTHOR]

In motor learning, sequence specificity, i.e. the learning of specific sequential associations, has predominantly been studied using task-based fMRI paradigms. However, offline changes in resting state functional connectivity after sequence-specific motor learning are less well understood. Previous research has established that plastic changes following motor learning can be divided into stages including fast learning, slow learning and retention. A description of how resting state functional connectivity after sequence-specific motor sequence learning (MSL) develops across these stages is missing. This study aimed to identify plastic alterations in whole-brain functional connectivity after learning a complex motor sequence by contrasting an active group who learned a complex sequence with a control group who performed a control task matched for motor execution. Resting state fMRI and behavioural performance were collected in both groups over the course of 5 consecutive training days and at follow-up after 12 days to encompass fast learning, slow learning, overall learning and retention. Between-group interaction analyses showed sequence-specific decreases in functional connectivity during overall learning in the right supplementary motor area (SMA). We found that connectivity changes in a key region of the motor network, the superior parietal cortex (SPC) were not a result of sequence-specific learning but were instead linked to motor execution. Our study confirms the sequence-specific role of SMA that has previously been identified in online task-based learning studies, and extends it to resting state network changes after sequence-specific MSL. [ABSTRACT FROM AUTHOR]

Aging is associated with declines in sensorimotor function. Several studies have demonstrated that transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, can be combined with training to mitigate age-related cognitive and motor declines. However, in some cases, the application of tDCS disrupts performance and learning. Here, we applied anodal tDCS either over the left prefrontal cortex (PFC), right PFC, supplementary motor complex (SMC), the left M1, or in a sham condition while older adults (n = 63) practiced a Discrete Sequence Production (DSP), an explicit motor sequence, task across 3 days. We hypothesized that stimulation to either the right or left PFC would enhance motor learning for older adults, based on the extensive literature showing increased prefrontal cortical activity during motor task performance in older adults. Contrary to our predictions, stimulation to the right and left PFC resulted in slowed motor learning, as evidenced by a slower reduction rate of reduction of reaction time and the number of sequence chunks across trials relative to sham in session one and session two, respectively. These findings suggest an integral role of the right PFC early in sequence learning and a role of the left PFC in chunking in older adults, and contribute to mounting evidence of the difficultly of using tDCS in an aging population. [ABSTRACT FROM AUTHOR]

The human brain undergoes structural and functional changes across the lifespan. The study of motor sequence learning in elderly subjects is of particularly interest since previous findings in young adults might not replicate during later stages of adulthood. The present functional magnetic resonance imaging (fMRI) study assessed the performance, brain activity and functional connectivity patterns associated with motor sequence learning in late middle adulthood. For this purpose, a total of 25 subjects were evaluated during early stages of learning [i.e., fast learning (FL)]. A subset of these subjects (n = 11) was evaluated after extensive practice of a motor sequence [i.e., slow learning (SL) phase]. As expected, late middle adults improved motor performance from FL to SL. Learning-related brain activity patterns replicated most of the findings reported previously in young subjects except for the lack of hippocampal activity during FL and the involvement of cerebellum during SL. Regarding functional connectivity, precuneus and sensorimotor lobule VI of the cerebellum showed a central role during improvement of novel motor performance. In the sample of subjects evaluated, connectivity between the posterior putamen and parietal and frontal regions was significantly decreased with aging during SL. This age-related connectivity pattern may reflect losses in network efficiency when approaching late adulthood. Altogether, these results may have important applications, for instance, in motor rehabilitation programs. [ABSTRACT FROM AUTHOR]

Oscillatory neural activity during sleep, such as that in the delta and sigma bands, is important for motor learning consolidation. This activity is reduced with typical aging, and this reduction may contribute to aging-related declines in motor learning consolidation. Evidence suggests that brain regions involved in motor learning contribute to oscillatory neural activity during subsequent sleep. However, aging-related differences in regional contributions to sleep oscillatory activity following motor learning are unclear. To characterize these differences, we estimated the cortical sources of consolidation-related oscillatory activity using individual anatomical information in young and older adults during non-rapid eye movement sleep after motor learning and analyzed them in light of cortical thickness and pre-sleep functional brain activation. High-density electroencephalogram was recorded from young and older adults during a midday nap, following completion of a functional magnetic resonance imaged serial reaction time task as part of a larger experimental protocol. Sleep delta activity was reduced with age in a left-weighted motor cortical network, including premotor cortex, primary motor cortex, supplementary motor area, and pre-supplementary motor area, as well as non-motor regions in parietal, temporal, occipital, and cingulate cortices. Sleep theta activity was reduced with age in a similar left-weighted motor network, and in non-motor prefrontal and middle cingulate regions. Sleep sigma activity was reduced with age in left primary motor cortex, in a non-motor right-weighted prefrontal-temporal network, and in cingulate regions. Cortical thinning mediated aging-related sigma reductions in lateral orbitofrontal cortex and frontal pole, and partially mediated delta reductions in parahippocampal, fusiform, and lingual gyri. Putamen, caudate, and inferior parietal cortex activation prior to sleep predicted frontal and motor cortical contributions to sleep delta and theta activity in an age-moderated fashion, reflecting negative relationships in young adults and positive or absent relationships in older adults. Overall, these results support the local sleep hypothesis that brain regions active during learning contribute to consolidation-related neural activity during subsequent sleep and demonstrate that sleep oscillatory activity in these regions is reduced with aging. [ABSTRACT FROM AUTHOR]

Aging is associated with declines in sensorimotor function. Several studies have demonstrated that transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, can be combined with training to mitigate age-related cognitive and motor declines. However, in some cases, the application of tDCS disrupts performance and learning. Here, we applied anodal tDCS either over the left prefrontal cortex (PFC), right PFC, supplementary motor complex (SMC), the left M1, or in a sham condition while older adults (n = 63) practiced a Discrete Sequence Production (DSP), an explicit motor sequence, task across 3 days. We hypothesized that stimulation to either the right or left PFC would enhance motor learning for older adults, based on the extensive literature showing increased prefrontal cortical activity during motor task performance in older adults. Contrary to our predictions, stimulation to the right and left PFC resulted in slowed motor learning, as evidenced by a slower reduction rate of reduction of reaction time and the number of sequence chunks across trials relative to sham in session one and session two, respectively. These findings suggest an integral role of the right PFC early in sequence learning and a role of the left PFC in chunking in older adults, and contribute to mounting evidence of the difficultly of using tDCS in an aging population.

The human brain undergoes structural and functional changes across the lifespan. The study of motor sequence learning in elderly subjects is of particularly interest since previous findings in young adults might not replicate during later stages of adulthood. The present functional magnetic resonance imaging (fMRI) study assessed the performance, brain activity and functional connectivity patterns associated with motor sequence learning in late middle adulthood. For this purpose, a total of 25 subjects were evaluated during early stages of learning [i.e., fast learning (FL)]. A subset of these subjects (n = 11) was evaluated after extensive practice of a motor sequence [i.e., slow learning (SL) phase]. As expected, late middle adults improved motor performance from FL to SL. Learning-related brain activity patterns replicated most of the findings reported previously in young subjects except for the lack of hippocampal activity during FL and the involvement of cerebellum during SL. Regarding functional connectivity, precuneus and sensorimotor lobule VI of the cerebellum showed a central role during improvement of novel motor performance. In the sample of subjects evaluated, connectivity between the posterior putamen and parietal and frontal regions was significantly decreased with aging during SL. This age-related connectivity pattern may reflect losses in network efficiency when approaching late adulthood. Altogether, these results may have important applications, for instance, in motor rehabilitation programs.

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. [ABSTRACT FROM AUTHOR]

Alpha oscillations (8-13 Hz) have been suggested to play an important role in dynamic neural processes underlying learning and memory. The goal of this study was to scrutinize the role of alpha oscillations in communication within a cortico-cerebellar network implicated in motor sequence learning. To this end, we conducted two EEG experiments using a serial reaction time task. In the first experiment, we explored changes in alpha power and cross-channel alpha coherence as subjects learned a motor sequence. We found a gradual decrease in spectral alpha power over left premotor cortex (PMC) and sensorimotor cortex (SM1) during learning blocks. In addition, alpha coherence between left PMC/SM1 and left cerebellar crus I was specifically decreased during sequence learning, possibly reflecting a functional decoupling in the broader motor learning network. In the second experiment in a different cohort, we applied 10Hz transcranial alternating current stimulation (tACS), a method shown to entrain local oscillatory activity, to left M1 (lM1) and right cerebellum (rCB) during sequence learning. We observed a tendency for diminished learning following rCB tACS compared to sham, but not following lM1 tACS. Learning-related alpha power following rCB tACS was increased in left PMC, possibly reflecting increase in local inhibitory neural activity. Importantly, learning-specific alpha coherence between left PMC and right cerebellar lobule VIIb was enhanced following rCB tACS. These findings provide strong evidence for a causal role of alpha oscillations in controlling information transfer in a premotor-cerebellar loop during motor sequence learning. Our findings are consistent with a model in which sequence learning may be impaired by enhancing premotor cortical alpha oscillation via external modulation of cerebellar oscillations.

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.

Efficient neural transmission is crucial for optimal brain function, yet the plastic potential of white matter (WM) has long been overlooked. Growing evidence now shows that modifications to axons and myelin occur not only as a result of long-term learning, but also after short training periods. Motor sequence learning (MSL), a common paradigm used to study neuroplasticity, occurs in overlapping learning stages and different neural circuits are involved in each stage. However, most studies investigating short-term WM plasticity have used a pre-post design, in which the temporal dynamics of changes across learning stages cannot be assessed. In this study, we used multiple magnetic resonance imaging (MRI) scans at 7 T to investigate changes in WM in a group learning a complex visuomotor sequence (LRN) and in a control group (SMP) performing a simple sequence, for five consecutive days. Consistent with behavioral results, where most improvements occurred between the two first days, structural changes in WM were observed only in the early phase of learning (d1–d2), and in overall learning (d1–d5). In LRNs, WM microstructure was altered in the tracts underlying the primary motor and sensorimotor cortices. Moreover, our structural findings in WM were related to changes in functional connectivity, assessed with resting-state functional MRI data in the same cohort, through analyses in regions of interest (ROIs). Significant changes in WM microstructure were found in a ROI underlying the right supplementary motor area. Together, our findings provide evidence for highly dynamic WM plasticity in the sensorimotor network during short-term MSL. [ABSTRACT FROM AUTHOR]

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.

Training under high interference conditions through interleaved practice (IP) results in performance suppression during training but enhances long-term performance relative to repetitive practice (RP) involving low interference. Previous neuroimaging work addressing this contextual interference effect of motor learning has relied heavily on the blood-oxygen-level-dependent (BOLD) response using functional magnetic resonance imaging (fMRI) methodology resulting in mixed reports of prefrontal cortex (PFC) recruitment under IP and RP conditions. We sought to clarify these equivocal findings by imaging bilateral PFC recruitment using functional near-infrared spectroscopy (fNIRS) while discrete key pressing sequences were trained under IP and RP schedules and subsequently tested following a 24-h delay. An advantage of fNIRS over the fMRI BOLD response is that the former measures oxygenated and deoxygenated hemoglobin changes independently allowing for assessment of cortical hemodynamics even when there is neurovascular decoupling. Despite slower sequence performance durations under IP, bilateral PFC oxygenated and deoxygenated hemoglobin values did not differ between practice conditions. During test, however, slower performance from those previously trained under RP coincided with hemispheric asymmetry in PFC recruitment. Specifically, following RP, test deoxygenated hemoglobin values were significantly lower in the right PFC. The present findings contrast with previous behavioral demonstrations of increased cognitive demand under IP to illustrate a more complex involvement of the PFC in the contextual interference effect. IP and RP incur similar levels of bilateral PFC recruitment, but the processes underlying the recruitment are dissimilar. PFC recruitment during IP supports action reconstruction and memory elaboration while RP relies on PFC recruitment to maintain task variation information in working memory from trial to trial. While PFC recruitment under RP serves to enhance immediate performance, it does not support long-term performance.

Several canonical experimental paradigms (e.g., serial reaction time task, discrete sequence production task, m × n task) have been proposed to study the typical behavioral phenomenon and the nature of learning in sequential keypress tasks. A characteristic feature of most paradigms is that they are representative of externally-specified sequencing—motor tasks where the environment or task paradigm extrinsically provides the sequence of stimuli, i.e., the responses are stimulus-driven. Previous studies utilizing such canonical paradigms have largely overlooked the learning behaviors in a more realistic class of motor tasks that involve internally-guided sequencing—where the sequence of motor actions is self-generated or internally-specified. In this work, we use the grid-navigation task as an instance of internally-guided sequencing to investigate the nature of learning in such paradigms. The participants performed Grid-Sailing Task (GST), which required navigating (by executing sequential keypresses) a 5 × 5 grid from start to goal (SG) position while using a particular key-mapping (KM) among the three cursor-movement directions and the three keyboard buttons. The participants performed two behavioral experiments—Single-SG and Mixed-SG condition. The Single-SG condition required performing GST on a single SG position repeatedly, whereas the Mixed-SG condition involved performing GST using the same KM on two novel SG positions presented in a random, inter-mixed manner. In the Single-SG condition, we show that motor learning contributes to the sequence-specific learning in GST with the repeated execution of the same trajectories. In the Mixed-SG condition, since the participants utilize the previously learned KM, we anticipate a transfer of learning from the Single-SG condition. The acquisition and transfer of a KM-specific internal model facilitates efficient trajectory planning on novel SG conditions. The acquisition of such a KM-specific internal model amounts to trajectory-independent cognitive learning in GST. We show that cognitive learning contributes to the learning in GST by showing transfer-related performance improvements in the Mixed-SG condition. In sum, we show the role of cognitive and motor learning processes in internally-guided sequencing and further make a case for using GST-like grid-navigation paradigms in investigating internally guided skill learning.

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. [ABSTRACT FROM AUTHOR]

Training under high interference conditions through interleaved practice (IP) results in performance suppression during training but enhances long-term performance relative to repetitive practice (RP) involving low interference. Previous neuroimaging work addressing this contextual interference effect of motor learning has relied heavily on the blood-oxygen-level-dependent (BOLD) response using functional magnetic resonance imaging (fMRI) methodology resulting in mixed reports of prefrontal cortex (PFC) recruitment under IP and RP conditions. We sought to clarify these equivocal findings by imaging bilateral PFC recruitment using functional near-infrared spectroscopy (fNIRS) while discrete key pressing sequences were trained under IP and RP schedules and subsequently tested following a 24-h delay. An advantage of fNIRS over the fMRI BOLD response is that the former measures oxygenated and deoxygenated hemoglobin changes independently allowing for assessment of cortical hemodynamics even when there is neurovascular decoupling. Despite slower sequence performance durations under IP, bilateral PFC oxygenated and deoxygenated hemoglobin values did not differ between practice conditions. During test, however, slower performance from those previously trained under RP coincided with hemispheric asymmetry in PFC recruitment. Specifically, following RP, test deoxygenated hemoglobin values were significantly lower in the right PFC. The present findings contrast with previous behavioral demonstrations of increased cognitive demand under IP to illustrate a more complex involvement of the PFC in the contextual interference effect. IP and RP incur similar levels of bilateral PFC recruitment, but the processes underlying the recruitment are dissimilar. PFC recruitment during IP supports action reconstruction and memory elaboration while RP relies on PFC recruitment to maintain task variation information in working memory from trial to trial. While PFC recruitment under RP serves to enhance immediate performance, it does not support long-term performance. [ABSTRACT FROM AUTHOR]

Several canonical experimental paradigms (e.g., serial reaction time task, discrete sequence production task, m × n task) have been proposed to study the typical behavioral phenomenon and the nature of learning in sequential keypress tasks. A characteristic feature of most paradigms is that they are representative of externally-specified sequencing—motor tasks where the environment or task paradigm extrinsically provides the sequence of stimuli, i.e., the responses are stimulus-driven. Previous studies utilizing such canonical paradigms have largely overlooked the learning behaviors in a more realistic class of motor tasks that involve internally-guided sequencing—where the sequence of motor actions is self-generated or internally-specified. In this work, we use the grid-navigation task as an instance of internally-guided sequencing to investigate the nature of learning in such paradigms. The participants performed Grid-Sailing Task (GST), which required navigating (by executing sequential keypresses) a 5 × 5 grid from start to goal (SG) position while using a particular key-mapping (KM) among the three cursor-movement directions and the three keyboard buttons. The participants performed two behavioral experiments—Single-SG and Mixed-SG condition. The Single-SG condition required performing GST on a single SG position repeatedly, whereas the Mixed-SG condition involved performing GST using the same KM on two novel SG positions presented in a random, inter-mixed manner. In the Single-SG condition, we show that motor learning contributes to the sequence-specific learning in GST with the repeated execution of the same trajectories. In the Mixed-SG condition, since the participants utilize the previously learned KM, we anticipate a transfer of learning from the Single-SG condition. The acquisition and transfer of a KM-specific internal model facilitates efficient trajectory planning on novel SG conditions. The acquisition of such a KM-specific internal model amounts to trajectory-independent cognitive learning in GST. We show that cognitive learning contributes to the learning in GST by showing transfer-related performance improvements in the Mixed-SG condition. In sum, we show the role of cognitive and motor learning processes in internally-guided sequencing and further make a case for using GST-like grid-navigation paradigms in investigating internally guided skill learning. [ABSTRACT FROM AUTHOR]

This study investigates the goal/habit imbalance theory of compulsion in obsessive-compulsive disorder (OCD), which postulates enhanced habit formation, increased automaticity, and impaired goal/habit arbitration. It directly tests these hypotheses using newly developed behavioral tasks. First, OCD patients and healthy participants were trained daily for a month using a smartphone app to perform chunked action sequences. Despite similar procedural learning and attainment of habitual performance (measured by an objective automaticity criterion) by both groups, OCD patients self-reported higher subjective habitual tendencies via a recently developed questionnaire. Subsequently, in a re-evaluation task assessing choices between established automatic and novel goal-directed actions, both groups were sensitive to re-evaluation based on monetary feedback. However, OCD patients, especially those with higher compulsive symptoms and habitual tendencies, showed a clear preference for trained/habitual sequences when choices were based on physical effort, possibly due to their higher attributed intrinsic value. These patients also used the habit-training app more extensively and reported symptom relief post-study. The tendency to attribute higher intrinsic value to familiar actions may be a potential mechanism leading to compulsions and an important addition to the goal/habit imbalance hypothesis in OCD. We also highlight the potential of smartphone app training as a habit reversal therapeutic tool., Competing Interests: PB, MH, MG, MB, AM, TP, AS No competing interests declared, NF NAF in the past three years has received research funding paid to her institution from the NIHR, COST Action and Orchard. She has received payment for lectures from the Global Mental Health Academy and for expert advisory work on psychopharmacology from the Medicines and Healthcare Products Regulatory Agency and an honorarium from Elsevier for editorial work. She has additionally received financial support to attend meetings from the British Association for Psychopharmacology, European College for Neuropsychopharmacology, Royal College of Psychiatrists, International College for Neuropsychopharmacology, World Psychiatric Association, International Forum for Mood and Anxiety Disorders, American College for Neuropsychopharmacology. In the past she has received funding from various pharmaceutical companies for research into the role of SSRIs and other forms of medication as treatments for OCD and for giving lectures and attending scientific meetings, TR TWR discloses consultancy with Cambridge Cognition and receives research grants from Shionogi & Co. He also has editorial honoraria from Springer Verlag and Elsevier, (© 2023, Banca et al.)

Non-invasive transcranial stimulation of cerebellum and primary motor cortex (M1) has been shown to enhance motor learning. However, the mechanisms by which stimulation improves learning remain largely unknown. Here, we sought to shed light on the neural correlates of transcranial direct current stimulation (tDCS) during motor learning by simultaneously recording functional magnetic resonance imaging (fMRI). We found that right cerebellar tDCS, but not left M1 tDCS, led to enhanced sequence learning in the serial reaction time task. Performance was also improved following cerebellar tDCS compared to sham in a sequence production task, reflecting superior training effects persisting into the post-training period. These behavioral effects were accompanied by increased learning-specific activity in right M1, left cerebellum lobule VI, left inferior frontal gyrus and right inferior parietal lobule during cerebellar tDCS compared to sham. Despite the lack of group-level changes comparing left M1 tDCS to sham, activity increase in right M1, supplementary motor area, and bilateral middle frontal cortex, under M1 tDCS, was associated with better sequence performance. This suggests that lack of group effects in M1 tDCS relate to inter-individual variability in learning-related activation patterns. We further investigated how tDCS modulates effective connectivity in the cortico-striato-cerebellar learning network. Using dynamic causal modelling, we found altered connectivity patterns during both M1 and cerebellar tDCS when compared to sham. Specifically, during cerebellar tDCS, negative modulation of a connection from putamen to cerebellum was decreased for sequence learning only, effectively leading to decreased inhibition of the cerebellum. These results show specific effects of cerebellar tDCS on functional activity and connectivity in the motor learning network and may facilitate the optimization of motor rehabilitation involving cerebellar non-invasive stimulation.