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.

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.

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.

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.

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.

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.NEW & NOTEWORTHY Motor sequence learning (MSL) relies on both the hippocampal and striatal systems, but whether functional performance is altered after MSL consolidation when the hippocampus is impaired remains unknown. Our results indicated that whereas the main effect of consolidation was observed in the hippocampus-related functional connection in the healthy control (HC) group, it was only evident in the striatum-related functional loop in the left medial temporal lobe epilepsy (LmTLE) group.

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.

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.

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.

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.