The hippocampus represents information about movements in their temporal position in a learned motor sequence.

Our repertoire of motor skills is filled with sequential movements that need to be performed in a specific order. Here, we used functional Magnetic Resonance Imaging to investigate whether the human hippocampus, a region known to support temporal order in non-motor memory, represents information about the order of sequential motor actions in human participants (both sexes). We also examined such representations in other regions of the motor network (i.e., the premotor cortex, supplementary motor area, anterior superior parietal lobule and striatum) already known for their critical role in motor sequence learning. Results showed that the hippocampus represents information about movements in their learned temporal position in the sequence, but not about movements or temporal positions in random movement patterns. Other regions of the motor network coded for movements in their learned temporal position, as well as movements and positions in random movement patterns. Importantly, movement coding contributed to sequence learning patterns in primary, supplementary and premotor cortices but not in striatal and parietal regions. Our findings deepen our understanding of how striatal and cortical regions contribute to motor sequence learning and point to the capacity of the hippocampus to represent movements in their temporal context, an ability possibly explaining its contribution to motor learning.Significance statement Consistent evidence collected over the last two decades indicates that the hippocampus - a brain structure traditionally associated to declarative memory - is critically involved in motor memory. Yet, the functional role and representational contribution of the hippocampus to motor learning remains to be elucidated. Using a multivariate functional Magnetic Resonance Imaging approach, we show here that the hippocampus carries information about the temporal order of movements in a motor sequence. These results point towards the involvement of the hippocampus in preserving information about temporal order in motor memory - a process well described for declarative memories. We suggest that the ability of the hippocampus to encode temporal order during sequence learning is common across declarative and non-declarative memory systems.

Targeted memory reactivation during post-learning sleep does not enhance motor memory consolidation in older adults.

Targeted memory reactivation (TMR) during sleep enhances memory consolidation in young adults by modulating electrophysiological markers of neuroplasticity. Interestingly, older adults exhibit deficits in motor memory consolidation, an impairment that has been linked to age-related degradations in the same sleep features sensitive to TMR. We hypothesised that TMR would enhance consolidation in older adults via the modulation of these markers. A total of 17 older participants were trained on a motor task involving two auditory-cued sequences. During a post-learning nap, two auditory cues were played: one associated to a learned (i.e., reactivated) sequence and one control. Performance during two delayed re-tests did not differ between reactivated and non-reactivated sequences. Moreover, both associated and control sounds modulated brain responses, yet there were no consistent differences between the auditory cue types. Our results collectively demonstrate that older adults do not benefit from specific reactivation of a motor memory trace by an associated auditory cue during post-learning sleep. Based on previous research, it is possible that auditory stimulation during post-learning sleep could have boosted motor memory consolidation in a non-specific manner.

Somatosensory targeted memory reactivation enhances motor performance via hippocampal-mediated plasticity.

Increasing evidence suggests that reactivation of newly acquired memory traces during postlearning wakefulness plays an important role in memory consolidation. Here, we sought to boost the reactivation of a motor memory trace during postlearning wakefulness (quiet rest) immediately following learning using somatosensory targeted memory reactivation (TMR). Using functional magnetic resonance imaging, we examined the neural correlates of the reactivation process as well as the effect of the TMR intervention on brain responses elicited by task practice on 24 healthy young adults. Behavioral data of the post-TMR retest session showed a faster learning rate for the motor sequence that was reactivated as compared to the not-reactivated sequence. Brain imaging data revealed that motor, parietal, frontal, and cerebellar brain regions, which were recruited during initial motor learning, were specifically reactivated during the TMR episode and that hippocampo-frontal connectivity was modulated by the reactivation process. Importantly, the TMR-induced behavioral advantage was paralleled by dynamical changes in hippocampal activity and hippocampo-motor connectivity during task practice. Altogether, the present results suggest that somatosensory TMR during postlearning quiet rest can enhance motor performance via the modulation of hippocampo-cortical responses.

Hippocampal and striatal responses during motor learning are modulated by prefrontal cortex stimulation.

While it is widely accepted that motor sequence learning (MSL) is supported by a prefrontal-mediated interaction between hippocampal and striatal networks, it remains unknown whether the functional responses of these networks can be modulated in humans with targeted experimental interventions. The present proof-of-concept study employed a multimodal neuroimaging approach, including functional magnetic resonance (MR) imaging and MR spectroscopy, to investigate whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex can modulate responses in the hippocampus and the basal ganglia during motor learning. Our results indicate that while stimulation did not modulate motor performance nor task-related brain activity, it influenced connectivity patterns within hippocampo-frontal and striatal networks. Stimulation also altered the relationship between the levels of gamma-aminobutyric acid (GABA) in the stimulated prefrontal cortex and learning-related changes in both activity and connectivity in fronto-striato-hippocampal networks. This study provides the first experimental evidence, to the best of our knowledge, that brain stimulation can alter motor learning-related functional responses in the striatum and hippocampus.

Lateralized effects of post-learning transcranial direct current stimulation on motor memory consolidation in older adults: An fMRI investigation.

Previous research has consistently demonstrated that older adults have difficulties transforming recently learned movements into robust, long-lasting memories (i.e., motor memory consolidation). One potential avenue to enhance consolidation in older individuals is the administration of transcranial direct current stimulation (tDCS) to task-relevant brain regions after initial learning. Although this approach has shown promise, the underlying cerebral correlates have yet to be revealed. Moreover, it is unknown whether the effects of tDCS are lateralized, an open question with implications for rehabilitative approaches following predominantly unilateral neurological injuries. In this research, healthy older adults completed a sequential motor task before and 6 h after receiving anodal or sham stimulation to right or left primary motor cortex (M1) while functional magnetic resonance images were acquired. Unexpectedly, anodal stimulation to right M1 following left-hand sequence learning significantly hindered consolidation as compared to a sham control, whereas no differences were observed with left M1 stimulation following right-hand learning. Impaired performance following right M1 stimulation was paralleled by sustained engagement of regions known to be critical for early learning stages, including the caudate nucleus and the premotor and parietal cortices. Thus, post-learning tDCS in older adults not only exerts heterogenous effects across the two hemispheres but can also disrupt ongoing memory processing.

Baseline sensorimotor GABA levels shape neuroplastic processes induced by motor learning in older adults.

Previous research in young adults has demonstrated that both motor learning and transcranial direct current stimulation (tDCS) trigger decreases in the levels of gamma-aminobutyric acid (GABA) in the sensorimotor cortex, and these decreases are linked to greater learning. Less is known about the role of GABA in motor learning in healthy older adults, a knowledge gap that is surprising given the established aging-related reductions in sensorimotor GABA. Here, we examined the effects of motor learning and subsequent tDCS on sensorimotor GABA levels and resting-state functional connectivity in the brains of healthy older participants. Thirty-six older men and women completed a motor sequence learning task before receiving anodal or sham tDCS to the sensorimotor cortex. GABA-edited magnetic resonance spectroscopy of the sensorimotor cortex and resting-state (RS) functional magnetic resonance imaging data were acquired before and after learning/stimulation. At the group level, neither learning nor anodal tDCS significantly modulated GABA levels or RS connectivity among task-relevant regions. However, changes in GABA levels from the baseline to post-learning session were significantly related to motor learning magnitude, age, and baseline GABA. Moreover, the change in functional connectivity between task-relevant regions, including bilateral motor cortices, was correlated with baseline GABA levels. These data collectively indicate that motor learning-related decreases in sensorimotor GABA levels and increases in functional connectivity are limited to those older adults with higher baseline GABA levels and who learn the most. Post-learning tDCS exerted no influence on GABA levels, functional connectivity or the relationships among these variables in older adults.

Sensorimotor cortex neurometabolite levels as correlate of motor performance in normal aging: evidence from a 1H-MRS study.

Aging is associated with gradual alterations in the neurochemical characteristics of the brain, which can be assessed in-vivo with proton-magnetic resonance spectroscopy (1H-MRS). However, the impact of these age-related neurochemical changes on functional motor behavior is still poorly understood. Here, we address this knowledge gap and specifically focus on the neurochemical integrity of the left sensorimotor cortex (SM1) and the occipital lobe (OCC), as both regions are main nodes of the visuomotor network underlying bimanual control. 1H-MRS data and performance on a set of bimanual tasks were collected from a lifespan (20-75 years) sample of 86 healthy adults. Results indicated that aging was accompanied by decreased levels of N-acetylaspartate (NAA), glutamate-glutamine (Glx), creatine â€‹+ â€‹phosphocreatine (Cr) and myo-inositol (mI) in both regions, and decreased Choline (Cho) in the OCC region. Lower NAA and Glx levels in the SM1 and lower NAA levels in the OCC were related to poorer performance on a visuomotor bimanual coordination task, suggesting that NAA could serve as a potential biomarker for the integrity of the motor system supporting bimanual control. In addition, lower NAA, Glx, and mI levels in the SM1 were found to be correlates of poorer dexterous performance on a bimanual dexterity task. These findings highlight the role for 1H-MRS to study neurochemical correlates of motor performance across the adult lifespan.

Glucocorticoid response to stress induction prior to learning is negatively related to subsequent motor memory consolidation.

Hippocampal activity during early motor sequence learning is critical to trigger subsequent sleep-related consolidation processes. Based on previous evidence that stress-induced cortisol release modulates hippocampal activity, the current study investigates whether exposure to stress prior to motor sequence learning influences the ensuing learning and overnight consolidation process. Seventy-four healthy young adults were exposed to a stressor (i.e., the socially evaluated cold pressor test, SECPT) or a control procedure before initial training on a bimanual motor sequence learning task. Participants were retested on the motor task 24 h (including a night of sleep) after training to assess memory consolidation. Our results indicate that the SECPT, as compared to the control condition, induced significant physiological stress responses as evidenced by increased heart rate and blood pressure as well as elevated salivary cortisol concentrations. Cortisol concentration in the stress group reached peak levels immediately before and stayed significantly elevated for the full duration of initial motor learning before returning to baseline during the consolidation period. Stress induction prior to learning did not, on average, influence initial performance nor subsequent motor memory consolidation as indicated by similar overnight gains in performance in both groups. However, higher levels of stress-induced cortisol prior to training were correlated to smaller overnight gains in performance speed. These results indicate that the glucocorticoid response to a stressful encounter experienced prior to hippocampal-mediated motor learning is negatively related to subsequent memory consolidation processes.

Schema and Motor-Memory Consolidation.

Recent research has demonstrated that memory-consolidation processes can be accelerated if newly learned information is consistent with preexisting knowledge. Until now, investigations of this fast integration of new information into memory have focused on the declarative and perceptual systems. We employed a unique manipulation of a motor-sequence-learning paradigm to examine the effect of experimentally acquired memory on the learning of new motor information. Results demonstrate that new information is rapidly integrated into memory when practice occurs in a framework that is compatible with the previously acquired memory. This framework consists of the ordinal representation of the motor sequence. This enhanced integration cannot be explained by differences in the explicit awareness of the sequence and is observed only if the previously acquired motor memory was consolidated overnight. Results are consistent with the schema model of memory consolidation and offer insights into how previous motor experience can accelerate learning and consolidation processes.

Cerebral Activation During Initial Motor Learning Forecasts Subsequent Sleep-Facilitated Memory Consolidation in Older Adults.

Older adults exhibit deficits in motor memory consolidation; however, little is known about the cerebral correlates of this impairment. We thus employed fMRI to investigate the neural substrates underlying motor sequence memory consolidation, and the modulatory influence of post-learning sleep, in healthy older adults. Participants were trained on a motor sequence and retested following an 8-h interval including wake or diurnal sleep as well as a 22-h interval including a night of sleep. Results demonstrated that a post-learning nap improved offline consolidation across same- and next-day retests. This enhanced consolidation was reflected by increased activity in the putamen and the medial temporal lobe, including the hippocampus, regions that have previously been implicated in sleep-dependent neural plasticity in young adults. Moreover, for the first time in older adults, the neural substrates subserving initial motor learning, including the putamen, cerebellum, and parietal cortex, were shown to forecast subsequent consolidation depending on whether a post-learning nap was afforded. Specifically, sufficient activation in a motor-related network appears to be necessary to trigger sleep-facilitated consolidation in older adults. Our findings not only demonstrate that post-learning sleep can enhance motor memory consolidation in older adults, but also provide the system-level neural correlates of this beneficial effect.

Maintaining vs. enhancing motor sequence memories: respective roles of striatal and hippocampal systems.

It is now accepted that hippocampal- and striatal-dependent memory systems do not act independently, but rather interact during both memory acquisition and consolidation. However, the respective functional roles of the hippocampus and the striatum in these processes remain unknown. Here, functional magnetic resonance imaging (fMRI) was used in a daytime sleep/wake protocol to investigate this knowledge gap. Using a protocol developed earlier in our lab (Albouy et al., 2013a), the manipulation of an explicit sequential finger-tapping task, allowed us to isolate allocentric (spatial) and egocentric (motor) representations of the sequence, which were supported by distinct hippocampo- and striato-cortical networks, respectively. Importantly, a sleep-dependent performance enhancement emerged for the hippocampal-dependent memory trace, whereas performance was maintained for the striatal-dependent memory trace, irrespective of the sleep condition. Regression analyses indicated that the interaction between these two systems influenced subsequent performance improvements. While striatal activity was negatively correlated with performance enhancement after both sleep and wakefulness in the allocentric representation, hippocampal activity was positively related to performance improvement for the egocentric representation, but only if sleep was allowed after training. Our results provide the first direct evidence of a functional dissociation in consolidation processes whereby memory stabilization seems supported by the striatum in a time-dependent manner whereas memory enhancement seems linked to hippocampal activity and sleep-dependent processes.

fMRI and sleep correlates of the age-related impairment in motor memory consolidation.

Behavioral studies indicate that older adults exhibit normal motor sequence learning (MSL), but paradoxically, show impaired consolidation of the new memory trace. However, the neural and physiological mechanisms underlying this impairment are entirely unknown. Here, we sought to identify, through functional magnetic resonance imaging during MSL and electroencephalographic (EEG) recordings during daytime sleep, the functional correlates and physiological characteristics of this age-related motor memory deficit. As predicted, older subjects did not exhibit sleep-dependent gains in performance (i.e., behavioral changes that reflect consolidation) and had reduced sleep spindles compared with young subjects. Brain imaging analyses also revealed that changes in activity across the retention interval in the putamen and related brain regions were associated with sleep spindles. This change in striatal activity was increased in young subjects, but reduced by comparison in older subjects. These findings suggest that the deficit in sleep-dependent motor memory consolidation in elderly individuals is related to a reduction in sleep spindle oscillations and to an associated decrease of activity in the cortico-striatal network.

Associations between age-related differences in occipital alpha power and the broadband parameters of the EEG power spectrum: A cross-sectional cohort study.

In adulthood, neurological structure and function are often affected by aging, with negative implications for daily life as well as laboratory-based tasks. Some of these changes include decreased efficiency modulating cortical activity and lower signal-to-noise ratios in neural processing (as inferred from surface electroencephalography). To better understand mechanisms influencing age-related changes in cortical activity, we explored the effects of aging on narrow-band alpha power (7.5-12.5 Hz) and broadband/aperiodic components that span a wider range (1.5-30.5 Hz) over the occipital region during eyes-open and eyes-closed wakeful rest in 19 healthy young adults (18-35 years) and 21 community-dwelling older adults (59+ years). Older adults exhibited a smaller change in alpha power across conditions compared to younger adults. Older adults also showed flatter aperiodic slopes in both conditions. These changes in narrow-band alpha are consistent with previous work and suggest that older adults may have a reduced ability to modulate state-specific activity. Differences in the aperiodic slope suggest age-related changes in the signal-noise-ratio in cortical oscillations. However, the relationship between narrow-band alpha modulation and the aperiodic slope was unclear, warranting further investigation into how these variables relate to each other in the aging process. In summary, aging is associated with a broadband flattening of the EEG power spectrum and reduced state-specific modulation of narrow-band alpha power, but these changes appear to be (at least partially) independent of each other. The present findings suggest that separate mechanisms may underlie age-related differences in aperiodic power and narrow-band oscillations.

Timing of transcranial direct current stimulation at M1 does not affect motor sequence learning.

Administering anodal transcranial direct current stimulation (tDCS) at the primary motor cortex (M1) at various temporal loci relative to motor training is reported to affect subsequent performance gains. Stimulation administered in conjunction with motor training appears to offer the most robust benefit that emerges during offline epochs. This conclusion is made, however, based on between-experiment comparisons that involved varied methodologies. The present experiment addressed this shortcoming by administering the same 15-minute dose of anodal tDCS at M1 before, during, or after practice of a serial reaction time task (SRTT). It was anticipated that exogenous stimulation during practice with a novel SRTT would facilitate offline gains. Ninety participants were randomly assigned to one of four groups: tDCS before practice, tDCS during practice, tDCS after practice, or no tDCS. Each participant was exposed to 15 min of 2 mA of tDCS and motor training of an eight-element SRTT. The anode was placed at the right M1 with the cathode at the left M1, and the left hand was used to execute the SRTT. Test blocks were administered 1 and 24 h after practice concluded. The results revealed significant offline gain for all conditions at the 1-hour and 24-hour test blocks. Importantly, exposure to anodal tDCS at M1 at any point before, during, or after motor training failed to change the trajectory of skill development as compared to the no-stimulation control condition. These data add to the growing body of evidence questioning the efficacy of a single bout of exogenous stimulation as an adjunct to motor training for fostering skill learning.

Hippocampus and striatum: dynamics and interaction during acquisition and sleep-related motor sequence memory consolidation.

While several models of memory consolidation have previously associated hippocampal activity with declarative memory, there is now increasing evidence that the hippocampus also plays a crucial role in procedural memory. Here, we review recent human functional neuroimaging studies demonstrating that the hippocampus is involved in the acquisition and sleep-related consolidation of procedural memories, and motor sequence-based skills in particular. More specifically, we present evidence that hippocampal activity and its functional interactions with other brain structures, particularly competition with the striatum, contribute to initial learning of sequential motor behavior. Interestingly, these early cerebral representations in the hippocampus and striatum, which may interact through the prefrontal cortex, can even predict subsequent sleep-related memory consolidation processes. We propose that sleep can reorganize the activity within, as well as the functional interactions between, these structures, ultimately favoring overnight performance enhancement. Finally, we conclude by offering insights into the respective roles of these structures in procedural memory consolidation processes. We argue that, in the context of motor sequence memory consolidation, the hippocampal system triggers subsequent sleep-dependent performance enhancement whereas the striatal system is involved in the maintenance of the motor behavior over time.

Sleep does not influence schema-facilitated motor memory consolidation.

STUDY OBJECTIVES: Novel information is rapidly learned when it is compatible with previous knowledge. This "schema" effect, initially described for declarative memories, was recently extended to the motor memory domain. Importantly, this beneficial effect was only observed 24 hours-but not immediately-following motor schema acquisition. Given the established role of sleep in memory consolidation, we hypothesized that sleep following the initial learning of a schema is necessary for the subsequent rapid integration of novel motor information. METHODS: Two experiments were conducted to investigate the effect of diurnal and nocturnal sleep on schema-mediated motor sequence memory consolidation. In Experiment 1, participants first learned an 8-element motor sequence through repeated practice (Session 1). They were then afforded a 90-minute nap opportunity (N = 25) or remained awake (N = 25) before learning a second motor sequence (Session 2) which was highly compatible with that learned prior to the sleep/wake interval. Experiment 2 was similar; however, Sessions 1 and 2 were separated by a 12-hour interval that included nocturnal sleep (N = 28) or only wakefulness (N = 29). RESULTS: For both experiments, we found no group differences in motor sequence performance (reaction time and accuracy) following the sleep/wake interval. Furthermore, in Experiment 1, we found no correlation between sleep features (non-REM sleep duration, spindle and slow wave activity) and post-sleep behavioral performance. CONCLUSIONS: The results of this research suggest that integration of novel motor information into a cognitive-motor schema does not specifically benefit from post-learning sleep.

Prefrontal stimulation as a tool to disrupt hippocampal and striatal reactivations underlying fast motor memory consolidation.

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.

Development of state estimation explains improvements in sensorimotor performance across childhood.

Previous developmental research examining sensorimotor control of the arm in school-age children has demonstrated age-related improvements in movement kinematics. However, the mechanisms that underlie these age-related improvements are still unclear. This study hypothesized that changes in sensorimotor performance across childhood can be attributed, in part, to the development of state estimation, defined as estimates computed by the central nervous system, which specify both current and future hand positions and velocities (i.e., hand "state"). Two behavioral experiments were conducted, in which 6- to 12-year-old children and young adults executed goal-directed arm movements. Results from Experiment 1 revealed that young children (i.e., ∼6-8 years) have less precise proprioceptive feedback for static (i.e., stationary) hand state estimation compared with older children (i.e., ∼10-12 years), resulting in increased variability of target-directed reaching movements. Experiment 2 demonstrated that young children rely on delayed and unreliable state estimates during the execution of goal-directed hand movements (i.e., dynamic state estimation), resulting in both increased movement errors and directional variability. Collectively, these results suggest that improvements in sensorimotor behavior across childhood can be attributed, at least partially, to the development of both static and dynamic state estimation.

Developmental delay of finger torque control in children with developmental coordination disorder.

AIM: We examined whether the behavioral impairments in finger torque control evident in children with developmental coordination disorder (DCD) follow a delayed or different developmental trajectory compared with their typically developing peers. METHOD: Children with DCD (n=36; 18 males, 18 females; mean age 9y 7mo, SD 1y 8mo) and 36 typically developing children (15 males, 21 females; mean age 9y 7mo, SD 2y), between 6 years 10 months and 12 years 7 months of age were recruited from schools in Porto Alegre, Brazil. Particpants completed finger torque control and maximum finger torque production tasks. The inclusion criterion for children with DCD was a Movement Assessment Battery for Children score below the fifth centile. Group means and cross-sectional age-related landscapes of the two groups were compared. RESULTS: Children with DCD were more variable (p<0.001), less accurate (p=0.007), and less irregular (p<0.001), on average, in their finger torque control than their typically developing peers, despite producing nearly equivalent levels of maximum torque (p=0.49). Despite these mean differences, the cross-sectional age-related changes in torque control were similar in the two groups (all p>0.05). INTERPRETATION: The developmental trajectory of finger torque control in children with DCD, compared with typically developing children, is delayed. This suggests the behavioral deficits in finger torque control in children with DCD persist as a function of age, rather than progressing or resolving.

Persistence of hippocampal and striatal multivoxel patterns during awake rest after motor sequence learning.

Memory consolidation, the process by which newly encoded and fragile memories become more robust, is thought to be supported by the reactivation of brain regions - including the hippocampus - during post-learning rest. While hippocampal reactivations have been demonstrated in humans in the declarative memory domain, it remains unknown whether such a process takes place after motor learning. Using multivariate analyses of task-related and resting state fMRI data, here we show that patterns of brain activity within both the hippocampus and striatum elicited during motor learning persist into post-learning rest, indicative of the reactivation of learning-related neural activity patterns. Moreover, results indicate that hippocampal reactivation reflects the spatial representation of the learned motor sequence. These results thus provide insights into the functional significance of neural reactivation after motor sequence learning.