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Memory consolidation in the declarative memory domain is known to be supported by the replay or reactivation of learning-related hippocampal activity during subsequent offline epochs (i.e., during post-encoding rest). Examinations into an analogous hippocampal reactivation process following motor learning have, until recently, been non-existent. This gap in the literature has been fueled by the traditional – yet outdated - view that the hippocampus is not involved in motor learning. Here, we discuss recent research in the motor memory domain that provides evidence in support of hippocampal reactivation following motor sequence learning. We conclude by highlighting several areas that warrant examination in future research, including experimentally manipulating post-learning hippocampal reactivation in an effort to enhance the motor memory consolidation process.

A plethora of daily motor tasks consist of sequences of movements or steps that need to be performed in a specific order. Yet, it remains unclear how the brain represents sequential motor actions in a way that preserves their temporal order. Here, we used multivoxel pattern similarity analysis of functional Magnetic Resonance Imaging (fMRI) data acquired during motor sequence practice to investigate whether the hippocampus, a brain region known to support temporal order in the non-motor memory domain, represents information about the temporal order of sequential motor actions. We also examined such representation in other regions of the motor network (i.e., the premotor cortex (PMC), supplementary motor area (SMA), anterior superior parietal lobule (aSPL) and striatum) known for their critical role in motor sequence learning. Our results show that hippocampal activation patterns carried information about movements in their learned temporal position in the sequence, but not about movements or positions in random movement patterns. A similar pattern of results was observed in the striatum. Our data also indicate that multivoxel patterns in M1, SMA and aSPL carried movement-based information while the PMC represented both movement- and position-based information. Altogether, our findings provide novel insight into the role of the hippocampus in the motor memory domain and point to its capacity to bind movements to their temporal position in a motor sequence. Our results also deepen our understanding of how striatal and cortical regions contribute to motor sequence learning via position and movement coding.

Functional brain responses in hippocampo- and striato-cortical networks during initial motor sequence learning (MSL) are critical for memory consolidation. We have recently shown that prefrontal stimulation applied prior to initial MSL can alter these learning-related responses. In the present study, we investigated whether such stimulation-induced modulations of brain responses can influence motor memory consolidation at different timescales. Specifically, we examined the effect of prefrontal stimulation on the behavioral and neural responses associated to (i) fast consolidation processes occurring during short rest episodes interspersed with practice during initial learning (i.e., micro timescale) and (ii) slow consolidation process taking place across practice sessions separated by 24h (i.e., macro timescale). To do so, we applied active (inhibitory or facilitatory) or control theta-burst stimulation to the prefrontal cortex of young healthy participants before they were trained on an MSL task while their brain activity was recorded using functional magnetic resonance imaging (fMRI). Motor performance was retested, in the MRI scanner, after a night of sleep. Both our behavioral and brain imaging results indicate that while stimulation did not modulate consolidation at the macro timescale, it disrupted the micro-offline consolidation process. Specifically, our behavioral data indicate that active - as compared to control - stimulation resulted in a decrease in micro-offline gains in performance over the short rest intervals. At the brain level, stimulation disrupted activity in the caudate nucleus and the hippocampus during the micro-offline intervals. Additionally, multivariate pattern persistence from task into inter-practice rest episodes - which is thought to reflect the reactivation of learning-related patterns - was hindered by active prefrontal stimulation in the hippocampus and caudate nucleus. Importantly, stimulation also altered the link between the brain and the behavioral markers of the micro-offline consolidation process. These results collectively suggest that active prefrontal stimulation prior to MSL disrupted both the behavioral and neural correlates of motor memory consolidation at the micro timescale.

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 hypothesized that TMR would enhance consolidation in older adults via the modulation of these markers. Seventeen 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 retests 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. It is possible, however, that auditory stimulation during post-learning sleep boosts motor memory consolidation in a non-specific manner.

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.

The flexible adjustment of ongoing behavior challenges the nervous system's dynamic control mechanisms and has shown to be specifically susceptible to age-related decline. Previous work links endogenous gamma-aminobutyric acid (GABA) with behavioral efficiency across perceptual and cognitive domains, with potentially the strongest impact on those behaviors that require a high level of dynamic control. Our analysis integrated behavior and modulation of interhemispheric phase-based connectivity during dynamic motor-state transitions with endogenous GABA concentration in adult human volunteers. We provide converging evidence for age-related differences in the preferred state of endogenous GABA concentration for more flexible behavior. We suggest that the increased interhemispheric connectivity observed in the older participants represents a compensatory neural mechanism caused by phase-entrainment in homotopic motor cortices. This mechanism appears to be most relevant in the presence of a less optimal tuning of the inhibitory tone as observed during healthy aging to uphold the required flexibility of behavioral action. Future work needs to validate the relevance of this interplay between neural connectivity and GABAergic inhibition for other domains of flexible human behavior. ispartof: COMMUNICATIONS BIOLOGY vol:5 issue:1 ispartof: location:England status: published

The functional interaction between hippocampo- and striato-cortical regions during motor sequence learning is essential to trigger optimal memory consolidation. Based on previous evidence from other memory domains that stress alters the balance between these systems, we investigated whether exposure to stress prior to motor learning modulates motor memory processes. Seventy-two healthy young individuals were exposed to a stressful or nonstressful control intervention prior to training on a motor sequence learning task in a magnetic resonance imaging (MRI) scanner. Consolidation was assessed with an MRI retest after a sleep episode. Behavioral results indicate that stress prior to learning did not influence motor performance. At the neural level, stress induced both a larger recruitment of sensorimotor regions and a greater disengagement of hippocampo-cortical networks during training. Brain-behavior regression analyses showed that while this stress-induced shift from (hippocampo-)fronto-parietal to motor networks was beneficial for initial performance, it was detrimental for consolidation. Our results provide the first experimental evidence that stress modulates the neural networks recruited during motor memory processing and therefore effectively unify concepts and mechanisms from diverse memory fields. Critically, our findings suggest that intersubject variability in brain responses to stress determines the impact of stress on motor learning and subsequent consolidation.

Administering anodal 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 minutes of 2 mA of tDCS and motor training of an eight-element SRTT. The anode was placed at right M1 with the cathode at left M1, and the left hand was used to execute the SRTT. Test blocks were administered 1 and 24 hours 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 exogenous stimulation as an adjunct to motor training for fostering skill learning.HighlightsTime-dependent consolidation of a novel motor skill occurred within 1 hour after the first practice blockFurther consolidation of this memory still occurred 24 hours after practicetDCS at M1 before, during, or after the initial bout of practice did not modify online or offline performance gains

© The Author(s) 2021. Motor sequence learning (MSL) is supported by dynamical interactions between hippocampal and striatal networks that are thought to be orchestrated by the prefrontal cortex. In the present study, we tested whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex (DLPFC) prior to MSL can modulate multivoxel response patterns in the stimulated cortical area, the hippocampus and the striatum. Response patterns were assessed with multivoxel correlation structure analyses of functional magnetic resonance imaging data acquired during task practice and during resting-state scans before and after learning/stimulation. Results revealed that, across stimulation conditions, MSL induced greater modulation of task-related DLPFC multivoxel patterns than random practice. A similar learning-related modulatory effect was observed on sensorimotor putamen patterns under inhibitory stimulation. Furthermore, MSL as well as inhibitory stimulation affected (posterior) hippocampal multivoxel patterns at post-intervention rest. Exploratory analyses showed that MSL-related brain patterns in the posterior hippocampus persisted into post-learning rest preferentially after inhibitory stimulation. These results collectively show that prefrontal stimulation can alter multivoxel brain patterns in deep brain regions that are critical for the MSL process. They also suggest that stimulation influenced early offline consolidation processes as evidenced by a stimulation-induced modulation of the reinstatement of task pattern into post-learning wakeful rest. Belgian Research Foundation Flanders (FWO; G099516N); KU Leuven; FWO (G0D7918N, G0B1419N, 1524218N); Excellence of Science (EOS, 30446199, MEMODYN); European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (703490); FWO (132635) postdoctoral fellowship; Air Force Office of Scientific Research (AFOSR, Virginia, USA; FA9550-16-1-0191).

Previous research has demonstrated that stress modulates the competitive interaction between the hippocampus and striatum, two structures known to be critically involved in motor sequence learning. These earlier investigations, however, have largely focused on blood oxygen-level dependent (BOLD) responses. No study to date has examined the link between stress, motor learning and levels of striatal and hippocampal gamma-aminobutyric acid (GABA). This knowledge gap is surprising given the known role of GABA in neuroplasticity subserving learning and memory. The current study thus examined: a) the effects of motor learning and stress on striatal and hippocampal GABA levels; and b) how learning- and stress-induced changes in GABA relate to the neural correlates of learning. To do so, fifty-three healthy young adults were exposed to a stressful or non-stressful control intervention before motor sequence learning. Striatal and hippocampal GABA levels were assessed at baseline and post-intervention/learning using magnetic resonance spectroscopy. Regression analyses indicated that stress modulated the link between striatal GABA levels and functional plasticity in both the hippocampus and striatum during learning as measured with fMRI. This study provides evidence for a role of GABA in the stress-induced modulation of striatal and hippocampal systems., Using fMRI and MRS measurements from healthy, young adults, Dolfen et al examined the effects of motor learning and stress on striatal and hippocampal GABA levels, as well as effects on neural correlates of learning. They demonstrated that stress modulated the link between striatal GABA levels and functional plasticity in the hippocampus and striatum, which reveals a role for GABA in the stress-induced modulation of these systems.

Motor skills are acquired and refined across alternating phases of practice (online) and subsequent consolidation in the absence of further skill execution (offline). Both stages of learning are sustained by dynamic interactions within a widespread motor learning network including the premotor and primary motor cortices. Here, we aimed to investigate the role of the dorsal premotor cortex (dPMC) and its interaction with the primary motor cortex (M1) during motor memory consolidation. Forty-eight healthy human participants (age 22.1 ± 3.1 years) were assigned to three different groups corresponding to different offline repetitive transcranial magnetic stimulation (rTMS) interventions. 1Hz rTMS of either left dPMC, left M1, or sham rTMS was applied immediately after explicit motor sequence training with the right hand. Motor evoked potentials were recorded before training and after rTMS to assess changes of corticospinal excitability (CSE). Participants were retested on the motor sequence after eight hours to assess consolidation. While CSE was not modulated in the sham rTMS group, post-training rTMS increased and decreased CSE when targeting dPMC and M1, respectively. However, all groups demonstrated similar significant offline learning over the day indicating that offline consolidation was not modulated by the post-training rTMS interventions despite evidence of an interaction of dPMC and M1 at the level of CSE. Motor memory consolidation ensuing explicit motor sequence training seems to be a rather robust process that is not affected by rTMS-induced perturbations of dPMC or M1. Findings further indicate that consolidation of explicitly acquired motor skills is neither mediated nor reflected by post-training CSE.

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. This work was supported by the Belgian Research Foundation Flanders (FWO; G099516N) and internal funds from KU Leuven. GA also received support from FWO (G0D7918N, G0B1419N, 1524218N) and Excellence of Science (EOS, 30446199, MEMODYN, with SPS and DM). MAG, ND and MPV received salary support from these grants. MAG is funded by a predoctoral fellowship from FWO (1141320N). Financial support for author BRK was provided by the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (703490) and a postdoctoral fellowship from FWO (132635). This study applies tools developed under National Institutes of Health (NIH) Grants R01- EB-016089, R01-023963, and P41-EB015909; RAEE also receives salary support from these grants. NAJP receives salary support from NIH Grant R00-MH-107719. EMR received salary support from the Air Force Office of Scientific Research (AFOSR, Virginia, USA; FA9550-16-1-0191).

Neuropsychologia : an international journal in behavioural and cognitive neuroscience 159, 107921 (2021). doi:10.1016/j.neuropsychologia.2021.107921, Published by Elsevier Science, Amsterdam [u.a.]

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. ispartof: NEUROIMAGE vol:223 ispartof: location:United States status: published

Previous research has shown that targeted memory reactivation (TMR) protocols using acoustic or olfactory stimuli can boost motor memory consolidation. While somatosensory information is crucial for motor control and learning, the effects of somatosensory TMR on motor memory consolidation remain elusive. Here, healthy young adults (n = 28) were trained on a sequential serial reaction time task and received, during the offline consolidation period that followed, sequential electrical stimulation of the fingers involved in the task. This somatosensory TMR procedure was applied during either a 90-minute diurnal sleep (NAP) or wake (NONAP) interval that was monitored with electroencephalography. Consolidation was assessed with a retest following the NAP/NONAP episode. Behavioral results revealed no effect of TMR on motor performance in either of the groups. At the brain level, somatosensory stimulation elicited changes in oscillatory activity in both groups. Specifically, TMR induced an increase in power in the mu band in the NONAP group and in the beta band in both the NAP and NONAP groups. Additionally, TMR elicited an increase in sigma power and a decrease in delta oscillations in the NAP group. None of these TMR-induced modulations of oscillatory activity, however, were correlated with measures of motor memory consolidation. The present results collectively suggest that while somatosensory TMR modulates oscillatory brain activity during post-learning sleep and wakefulness, it does not influence motor performance in an immediate retest.

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., Gamma‐aminobutyric acid (GABA)‐edited magnetic resonance spectroscopy of the sensorimotor cortex and resting‐state (RS) functional magnetic resonance imaging data were acquired before and after a motor learning task and either anodal or sham transcranial direct current stimulation (tDCS). Results demonstrated that neither motor sequence learning nor subsequent tDCS significantly modulated GABA+ levels or RS functional connectivity at the group level in older adults. However, individual differences in the learning‐related modulations in GABA+ levels were associated with the participants' age, baseline GABA+ levels, and the magnitude of learning. Higher baseline GABA was also linked to a learning‐related increase in RS functional connectivity between motor task‐relevant regions, including bilateral motor cortices.

Consolidation, by which performance increments after a training intervention are secured and sometimes generated, is reduced in elderly humans. The present study addressed the question whether transcranial direct current stimulation (tDCS) applied after motor training improves consolidation of explicit motor sequence learning in healthy older humans. In the first experiment, anodal or cathodal tDCS to the left primary motor cortex, anodal tDCS to premotor cortex, or sham tDCS was applied immediately after completion of a finger sequence learning task. Performance was retested at 8 and 22 hours after the initial training session. Whereas all groups achieved similar performance at the end of training, off-line improvements differed between groups at later retesting, depending on the type of intervention. Relative to the other 3 interventions, anodal tDCS to primary motor cortex (M1) led to performance improvements already at retesting 8 hours after initial learning and were maintained on the next day. In the second experiment, effects of the timing of post-training anodal tDCS to M1 with respect to the end of training were studied. Participants received anodal tDCS of M1 immediately or 60 or 120 minutes after training and were retested on sequence performance 8 hours post training. Only application of tDCS immediately after the end of training, but not after 1 or 2 hours, enhanced off-line consolidation. These findings suggest that anodal tDCS applied off-line immediately post training to M1 interacts specifically with early processes promoting consolidation of motor sequence learning in healthy older individuals.

Aging is associated with gradual alterations in the neurochemical characteristics of the brain, which can be assessed in-vivo with proton-magnetic resonance spectroscopy (

Reconsolidation theory posits that upon retrieval, consolidated memories are destabilized and need to be restabilized in order to persist. It has been suggested that experience with a competitive task immediately after memory retrieval may interrupt these restabilization processes leading to memory loss. Indeed, using a motor sequence learning paradigm, we have recently shown that, in humans, interference training immediately after active task-based retrieval of the consolidated motor sequence knowledge may negatively affect its performance levels. Assessing changes in tapping pattern before and after interference training, we also demonstrated that this performance deficit more likely indicates a genuine memory loss rather than an initial failure of memory retrieval. Here, applying a similar approach, we tested the necessity of the hypothetical retrieval-induced destabilization of motor memory to allow its impairment. The impact of memory retrieval on performance of a new motor sequence knowledge acquired during the interference training was also evaluated. Similar to the immediate post-retrieval interference, interference training alone without the preceding active task-based memory retrieval was also associated with impairment of the pre-established motor sequence memory. Performance levels of the sequence trained during the interference training, on the other hand, were impaired only if this training was given immediately after memory retrieval. Noteworthy, an 8-hour interval between memory retrieval and interference allowed to express intact performance levels for both sequences. The current results suggest that susceptibility of the consolidated motor memory to behavioral interference is independent of its active task-based retrieval. Differential effects of memory retrieval on performance levels of the new motor sequence encoded during the interference training further suggests that memory retrieval may influence the way new information is stored by facilitating its integration within the retrieved memory trace. Thus, impairment of the pre-established motor memory may reflect interference from a competing memory trace rather than involve interruption of reconsolidation. ispartof: PLoS One vol:14 issue:1 pages:e0210876-e0210876 ispartof: location:United States status: published

Aging is typically associated with substantial declines in motor functioning as well as robust changes in the functional organization of brain networks. Previous research has investigated the link between these 2 age-varying factors but examinations were predominantly limited to the functional organization within motor-related brain networks. Little is known about the relationship between age-related behavioral impairments and changes in functional organization at the whole brain (i.e., multiple network) level. This knowledge gap is surprising given that the decreased segregation of brain networks (i.e., increased internetwork connectivity) can be considered a hallmark of the aging process. Accordingly, we investigated the association between declines in motor performance across the adult lifespan (20-75 years) and age-related modulations of functional connectivity within and between resting state networks. Results indicated that stronger internetwork resting state connectivity observed as a function of age was significantly related to worse motor performance. Moreover, performance had a significantly stronger association with the strength of internetwork as compared with intranetwork connectivity, including connectivity within motor networks. These findings suggest that age-related declines in motor performance may be attributed to a breakdown in the functional organization of large-scale brain networks rather than simply age-related connectivity changes within motor-related networks.

Brain networks undergo widespread changes in older age. A large body of knowledge gathered about those changes evidenced an increase of functional connectivity between brain networks. Previous work focused mainly on cortical networks during the resting state. Subcortical structures, however, are of critical importance during the performance of motor tasks. In this study, we investigated age-related changes in cortical, striatal and cerebellar functional connectivity at rest and its modulation by motor task execution. To that end, functional MRI from twenty-five young (mean age 21.5 years) and eighteen older adults (mean age 68.6 years) were analysed during rest and while performing a bimanual tracking task practiced over a two-week period. We found that inter-network connectivity among cortical structures was more positive in older adults both during rest and task performance. Functional connectivity within striatal structures decreased with age during rest and task execution. Network flexibility, the changes in network composition from rest to task, was also reduced in older adults, but only in networks with an age-related increase in connectivity. Finally, flexibility of areas in the prefrontal cortex were associated with lower error scores during task execution, especially in older adults. In conclusion, our findings indicate an age-related reduction in the ability to suppress irrelevant network communication, leading to less segregated and less flexible cortical networks. At the same time, striatal connectivity is impaired in older adults, while cerebellar connectivity shows heterogeneous age-related effects during rest and task execution. Future research is needed to clarify how cortical and subcortical connectivity changes relate to one another.

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.

Animal models suggest that consolidated memories return to their labile state when reactivated and need to be restabilized through reconsolidation processes to persist. Consistent with this notion, post-reactivation pharmacological protein synthesis blockage results in mnemonic failure in hippocampus-dependent memories. It has been proposed that, in humans, post-reactivation experience with a competitive task can also interfere with memory restabilization. However, several studies failed to induce performance deficit implementing this approach. Moreover, even upon effective post-reactivation interference, hindered performance may rapidly recover, raising the possibility of a retrieval rather than a storage deficit. Here, to address these issues in procedural memory domain, we used new learning to interfere with restabilization of motor memory acquired through training on a sequence of finger movements. Only immediate post-reactivation interference was associated with the loss of post-training delayed gains in performance, a hallmark of motor sequence memory consolidation. We also demonstrate that such performance deficit more likely indicates a genuine memory impairment rather than a retrieval failure. However, the reconsolidation view on a reactivation-induced plasticity is not supported. Instead, our results are in line with the integration model according to which new knowledge acquired during the interfering experience, is integrated through its consolidation creating memory competition. ispartof: Scientific Reports vol:7 issue:1 pages:9406-9406 ispartof: location:England status: published

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.

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 ​+ ​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. This work was supported by the KU Leuven Special Research Fund (grant C16/15/070), the Research Foundation – Flanders (FWO; G.089818N), the Excellence of Science grant (EOS, 30446199, MEMODYN), and the Francqui Foundation awarded to SPS and coworkers. AW and UH acknowledge financial support by the EC-FP7 MC ITN ’TRANSACT’ 2012 (No. 316679) and the KU Leuven program financing ‘IMIR’ (PF10/017). BRK acknowledges financial support by European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement (No. 703490) and a postdoctoral fellowship from the Research Foundation-Flanders (FWO; No 132635). The authors wish to thank Joren Bosman and Jeroen Buvé for assistance with data processing.

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.

Motor memory consolidation is characterized, in part, by a sleep-facilitated decrease in susceptibility to subsequent interfering experiences. Surprisingly, the cerebral substrates supporting this phenomenon have never been examined. We used fMRI to investigate the neural correlates of the influence of sleep on interference to motor memory consolidation. Healthy young adults were trained on a sequential motor task, and subsequently practiced a second competing sequence after an interval including diurnal sleep or wakefulness. Participants were then retested on the initial sequence 8 h and 24 h (including nocturnal sleep) after training. Results demonstrated that a post-training nap significantly protected memory against interference at 8 h and modulated the link between cerebral activity and behavior, such that a smaller post-interference decrease in cortico-striatal activity was associated with better performance. Interestingly, the protective effect of a nap was only transitory, as both groups performed similarly at 24 h. Activity in cortico-striatal areas that was disrupted during the day, presumably due to interference and accentuated in the absence of a nap, was restored overnight. Altogether, our findings offer the first evidence that cortico-striatal areas play a critical role in the transient sleep-facilitated reduction in motor memory vulnerability and in the overnight restoration of previously degraded memories., SCOPUS: ar.j, info:eu-repo/semantics/published

While the influence of sleep on motor memory consolidation has been extensively investigated, its relation to initial skill acquisition is less well understood. The purpose of the present study was to investigate the influence of sleep quality and quantity on subsequent motor skill acquisition in young adults without sleep disorders. Fifty-five healthy adults (mean age = 23.8 years; 34 women) wore actigraph wristbands for four nights, which provided data on sleep patterns prior to the experiment, and then returned to the laboratory to engage in a motor sequence learning task (explicit 5-item finger sequence tapping task). Indicators of sleep quality and quantity were then regressed on a measure of motor skill acquisition (Gains Within Training, GWT). Wake After Sleep Onset (WASO; i.e., the total amount of time the participants spent awake after falling asleep) was significantly and negatively related to GWT. This effect was not due to general arousal level, which was measured immediately before the motor task. Conversely, there was no relationship between GWT and sleep duration or self-reported sleep quality. These results indicate that sleep quality, as assessed by WASO and objectively measured with actigraphy prior to the motor task, significantly impacts motor skill acquisition in young healthy adults without sleep disorders. ispartof: Behavioral Neuroscience vol:130 issue:3 pages:290-297 ispartof: location:NV, Las Vegas status: published

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 0.05). 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.

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.

Recent research has demonstrated that adaptation to a visuomotor distortion systematically influenced movements to auditory targets in adults and typically developing (TD) children, suggesting that the adaptation of spatial-to-motor transformations for reaching movements is multisensory (i.e., generalizable across sensory modalities). The multisensory characteristics of these transformations in children with developmental coordination disorder (DCD) have not been examined. Given that previous research has demonstrated that children with DCD have deficits in sensorimotor integration, these children may also have impairments in the formation of multisensory spatial-to-motor transformations for target-directed arm movements. To investigate this hypothesis, children with and without DCD executed discrete arm movements to visual and acoustic targets prior to and following exposure to an abrupt visual feedback rotation. Results demonstrated that the magnitudes of the visual aftereffects were equivalent in the TD children and the children with DCD, indicating that both groups of children adapted similarly to the visuomotor perturbation. Moreover, the influence of visuomotor adaptation on auditory-motor performance was similar in the two groups of children. This suggests that the multisensory processes underlying adaptation of spatial-to-motor transformations are similar in children with DCD and TD children.

To determine the influence of arousal on cerebral cortical dynamics and motor behavior, 58 channels of EEG were recorded in 13 college-age men (n=6) and women during an aiming task performed alone and in a social evaluation condition. Moderate arousal, as measured by heart rate, skin conductance, and self-reported mood, was induced during the social evaluation. In accord with the Yerkes-Dodson Hypothesis, which posits optimal performance during moderate arousal, improved performance (i.e., quality of the aiming trajectories) was observed. During social evaluation, changes in electroencephalogram dynamics included decreased coherence between the motor planning (Fz) and right temporal region (T4), increased coherence in the sensorimotor networks subserving the task, and increased local processing (gamma, 30-44 Hz) in the temporal regions. The results imply that moderate arousal promotes specific alterations in cortical dynamics that facilitate motor performance.

The extant developmental literature investigating age-related differences in the execution of aiming movements has predominantly focused on visuomotor coordination, despite the fact that additional sensory modalities, such as audition and somatosensation, may contribute to motor planning, execution, and learning. The current study investigated the execution of aiming movements toward both visual and acoustic stimuli. In addition, we examined the interaction between visuomotor and auditory-motor coordination as 5- to 10-yr-old participants executed aiming movements to visual and acoustic stimuli before and after exposure to a visuomotor rotation. Children in all age groups demonstrated significant improvement in performance under the visuomotor perturbation, as indicated by decreased initial directional and root mean squared errors. Moreover, children in all age groups demonstrated significant visual aftereffects during the postexposure phase, suggesting a successful update of their spatial-to-motor transformations. Interestingly, these updated spatial-to-motor transformations also influenced auditory-motor performance, as indicated by distorted movement trajectories during the auditory postexposure phase. The distorted trajectories were present during auditory postexposure even though the auditory-motor relationship was not manipulated. Results suggest that by the age of 5 yr, children have developed a multisensory spatial-to-motor transformation for the execution of aiming movements toward both visual and acoustic targets.