Beta Oscillatory Changes and Retention of Motor Skills during Practice in Healthy Subjects and in Patients with Parkinson's Disease.

Recently we found that modulation depth of beta power during movement increases with practice over sensory-motor areas in normal subjects but not in patients with Parkinson's disease (PD). As such changes might reflect use-dependent modifications, we concluded that reduction of beta enhancement in PD represents saturation of cortical plasticity. A few questions remained open: What is the relation between these EEG changes and retention of motor skills? Would a second task exposure restore beta modulation enhancement in PD? Do practice-induced increases of beta modulation occur within each block? We thus recorded EEG in patients with PD and age-matched controls in two consecutive days during a 40-min reaching task divided in fifteen blocks of 56 movements each. The results confirmed that, with practice, beta modulation depth over the contralateral sensory-motor area significantly increased across blocks in controls but not in PD, while performance improved in both groups without significant correlations between behavioral and EEG data. The same changes were seen the following day in both groups. Also, beta modulation increased within each block with similar values in both groups and such increases were partially transferred to the successive block in controls, but not in PD. Retention of performance improvement was present in the controls but not in the patients and correlated with the increase in day 1 modulation depth. Therefore, the lack of practice-related increase beta modulation in PD is likely due to deficient potentiation mechanisms that permit between-block saving of beta power enhancement and trigger mechanisms of memory formation.

Tracking neural correlates of successful learning over repeated sequence observations.

The neural correlates of memory formation in humans have long been investigated by exposing subjects to diverse material and comparing responses to items later remembered to those forgotten. Tasks requiring memorization of sensory sequences afford unique possibilities for linking neural memorization processes to behavior, because, rather than comparing across different items of varying content, each individual item can be examined across the successive learning states of being initially unknown, newly learned, and eventually, fully known. Sequence learning paradigms have not yet been exploited in this way, however. Here, we analyze the event-related potentials of subjects attempting to memorize sequences of visual locations over several blocks of repeated observation, with respect to pre- and post-block recall tests. Over centro-parietal regions, we observed a rapid P300 component superimposed on a broader positivity, which exhibited distinct modulations across learning states that were replicated in two separate experiments. Consistent with its well-known encoding of surprise, the P300 deflection monotonically decreased over blocks as locations became better learned and hence more expected. In contrast, the broader positivity was especially elevated at the point when a given item was newly learned, i.e., started being successfully recalled. These results implicate the Broad Positivity in endogenously-driven, intentional memory formation, whereas the P300, in processing the current stimulus to the degree that it was previously uncertain, indexes the cumulative knowledge thereby gained. The decreasing surprise/P300 effect significantly predicted learning success both across blocks and across subjects. This presents a new, neural-based means to evaluate learning capabilities independent of verbal reports, which could have considerable value in distinguishing genuine learning disabilities from difficulties to communicate the outcomes of learning, or perceptual impairments, in a range of clinical brain disorders.

Practice changes beta power at rest and its modulation during movement in healthy subjects but not in patients with Parkinson's disease.

BACKGROUND: PD (Parkinson's disease) is characterized by impairments in cortical plasticity, in beta frequency at rest and in beta power modulation during movement (i.e., event-related ERS [synchronization] and ERD [desynchronization]). Recent results with experimental protocols inducing long-term potentiation in healthy subjects suggest that cortical plasticity phenomena might be reflected by changes of beta power recorded with EEG during rest. Here, we determined whether motor practice produces changes in beta power at rest and during movements in both healthy subjects and patients with PD. We hypothesized that such changes would be reduced in PD. METHODS: We thus recorded EEG in patients with PD and age-matched controls before, during and after a 40-minute reaching task. We determined posttask changes of beta power at rest and assessed the progressive changes of beta ERD and ERS during the task over frontal and sensorimotor regions. RESULTS: We found that beta ERS and ERD changed significantly with practice in controls but not in PD. In PD compared to controls, beta power at rest was greater over frontal sensors but posttask changes, like those during movements, were far less evident. In both groups, kinematic characteristics improved with practice; however, there was no correlation between such improvements and the changes in beta power. CONCLUSIONS: We conclude that prolonged practice in a motor task produces use-dependent modifications that are reflected in changes of beta power at rest and during movement. In PD, such changes are significantly reduced; such a reduction might represent, at least partially, impairment of cortical plasticity.

Movement preparation and bilateral modulation of beta activity in aging and Parkinson's disease.

In previous studies of young subjects performing a reaction-time reaching task, we found that faster reaction times are associated with increased suppression of beta power over primary sensorimotor areas just before target presentation. Here we ascertain whether such beta decrease similarly occurs in normally aging subjects and also in patients with Parkinson's disease (PD), where deficits in movement execution and abnormalities of beta power are usually present. We found that in both groups, beta power decreased during the motor task in the electrodes over the two primary sensorimotor areas. However, before target presentation, beta decreases in PD were significantly smaller over the right than over the left areas, while they were symmetrical in controls. In both groups, functional connectivity between the two regions, measured with imaginary coherence, increased before the target appearance; however, in PD, it decreased immediately after, while in controls, it remained elevated throughout motor planning. As in previous studies with young subjects, the degree of beta power before target appearance correlated with reaction time. The values of coherence during motor planning, instead, correlated with movement time, peak velocity and acceleration. We conclude that planning of prompt and fast movements partially depends on coordinated beta activity of both sensorimotor areas, already at the time of target presentation. The delayed onset of beta decreases over the right region observed in PD is possibly related to a decreased functional connectivity between the two areas, and this might account for deficits in force programming, movement duration and velocity modulation.

TMS enhances retention of a motor skill in Parkinson's disease.

BACKGROUND: In Parkinson's disease (PD), skill retention is poor, even when acquisition rate is generally preserved. Recent work in normal subjects suggests that 5 Hz-repetitive transcranial magnetic stimulation (5Hz-rTMS) may induce phenomena of long-term potentiation at the cortical level. OBJECTIVE/HYPOTHESIS: We thus verified whether, in PD, 5Hz-rTMS enhances retention of a visuo-motor skill that involves the activity of the right posterior parietal cortex. METHODS: A group of patients with PD was tested in two two-day sessions, separated by one week (treatment and placebo sessions). The first day of each session, they learned to adapt their movements to a step-wise 60° visual rotation. Immediately after the task, either real 5Hz-rTMS (treatment) or sham (placebo) stimulation was applied over the right posterior parietal cortex (P6). Retention of this motor skill was tested the following day. RESULTS: In patients with PD, adaptation achieved at the end of training was comparable in the treatment and placebo sessions and was similar to that of a group of age-matched controls. However, retention indices tested on the following day were significantly lower in the placebo compared to the treatment session in which retention indices were restored to the level of the controls. Importantly, reaction and movement time as well as other kinematic measures were the same in the treatment and placebo sessions. CONCLUSION: These results suggest that rTMS applied after the acquisition of a motor skill over specific areas involved in this process might enhance skill retention in PD.

Neural activations during visual sequence learning leave a trace in post-training spontaneous EEG.

Recent EEG studies have shown that implicit learning involving specific cortical circuits results in an enduring local trace manifested as local changes in spectral power. Here we used a well characterized visual sequence learning task and high density-(hd-)EEG recording to determine whether also declarative learning leaves a post-task, local change in the resting state oscillatory activity in the areas involved in the learning process. Thus, we recorded hd-EEG in normal subjects before, during and after the acquisition of the order of a fixed spatial target sequence (VSEQ) and during the presentation of targets in random order (VRAN). We first determined the temporal evolution of spectral changes during VSEQ and compared it to VRAN. We found significant differences in the alpha and theta bands in three main scalp regions, a right occipito-parietal (ROP), an anterior-frontal (AFr), and a right frontal (RFr) area. The changes in frontal theta power during VSEQ were positively correlated with the learning rate. Further, post-learning EEG recordings during resting state revealed a significant increase in alpha power in ROP relative to a pre-learning baseline. We conclude that declarative learning is associated with alpha and theta changes in frontal and posterior regions that occur during the task, and with an increase of alpha power in the occipito-parietal region after the task. These post-task changes may represent a trace of learning and a hallmark of use-dependent plasticity.

Protracted exercise without overt neuromuscular fatigue influences cortical excitability.

The authors' aim was to determine the cortical mechanisms that underlie the transition from effective performance to its disruption. They thus used transcranial magnetic stimulation (TMS) to study changes of corticospinal excitability after a motor exercise that did not produce overt or perceived neuromuscular fatigue. Forty-four subjects performed either 5 or 10 min of repetitive finger movements paced by tones at 2 Hz, a frequency below the spontaneous movement rate. Changes of corticospinal excitability were assessed with TMS at rest and during motor response preparation (premovement facilitation paradigm). Over time, variability of movement rate increased, while the average movement rate shifted toward self-paced rhythms, without significant changes in other kinematic parameters. Amplitudes of motor evoked potentials at rest decreased depending on task duration and TMS intensity. Moreover, 5-min exercise induced fully compensatory increases in premovement facilitation, while 10-min exercise produced partially compensatory increases with loss of temporal modulation. Our findings suggest that protracted exercise induces significant decrements in corticospinal excitability with initial impairment of the phasic motor neurons that are recruited at higher stimulus intensities. Changes in premovement facilitation likely represent compensation of premotor areas for decreased efficiency of the primary motor cortex induced by exercise.

Acquisition and retention of motor sequences: the effects of time of the day and sleep.

STUDY OBJECTIVES: We used a sequence-learning task to assess whether: 1. The time interval between awakening and training equally affects the rate of acquisition of sequence order, a declarative component, and the kinematic optimization process, an implicit component; 2. Sleep enhances the retention of both these aspects of sequence learning. DESIGN: For aim 1, we compare the acquisition rate of a new motor sequence in a group trained in the morning and another in the evening. For aim 2., we tested retention of the same motor sequence twelve hours later, either without sleep (normal day activity or a night of sleep deprivation) or with interposed sleep (afternoon napping or regular full night sleep). SETTING: Training and Testing were performed in a controlled laboratory setting. PARTICIPANTS: Thirty-six right-handed normal subjects (age range 18-24 years; 16 women). RESULTS: During the training, acquisition rate of the sequence order was significantly higher in the AM-trained than in the PM-trained group, without differences in the kinematic optimization processes. Both declarative and implicit learning indices were significantly higher in the subjects tested after sleep compared to those tested without interposed sleep. CONCLUSION: The best time for fast and efficient acquisition of new declarative material is the morning, while the kinematic aspects of skill acquisition are not sensitive to the time of day. However, better retention of both declarative material and motor skills requires two conditions: a period of post-training sleep and the achievement of performance saturation during training.

Dopaminergic striatal innervation predicts interlimb transfer of a visuomotor skill.

We investigated whether dopamine influences the rate of adaptation to a visuomotor distortion and the transfer of this learning from the right to the left limb in human subjects. We thus studied patients with Parkinson disease as a putative in vivo model of dopaminergic denervation. Despite normal adaptation rates, patients showed a reduced transfer compared with age-matched healthy controls. The magnitude of the transfer, but not of the adaptation rate, was positively predicted by the values of dopamine-transporter binding of the right caudate and putamen. We conclude that striatal dopaminergic activity plays an important role in the transfer of visuomotor skills.

Modulation of gamma and theta spectral amplitude and phase synchronization is associated with the development of visuo-motor learning.

The formation of new motor memories, which is fundamental for efficient performance during adaptation to a visuo-motor rotation, occurs when accurate planning is achieved mostly with feedforward mechanisms. The dynamics of brain activity underlying the switch from feedback to feedforward control is still matter of debate. Based on the results of studies in declarative learning, it is likely that phase synchronization of low and high frequencies as well as their temporal modulation in power amplitude underlie the formation of new motor memories during visuo-motor adaptation. High-density EEG (256 electrodes) was recorded in 17 normal human subjects during adaptation to a visuo-motor rotation of 60° in four incremental steps of 15°. We found that initial learning is associated with enhancement of gamma power in a right parietal region during movement execution as well as gamma/theta phase coherence during movement planning. Late stages of learning are instead accompanied by an increase of theta power over that same right parietal region during movement planning, which is correlated with the degree of learning and retention. Altogether, these results suggest that the formation of new motor memories and, thus, the switch from feedback to feedforward control is associated with the modulation of gamma and theta spectral activities, with respect to their amplitude and phase, during movement planning and execution. Specifically, we propose that gamma/theta phase coupling plays a pivotal role in the integration of a new representation into motor memories.

Basal ganglia and kinematics modulation: insights from Parkinson's and Huntington's diseases.

Movement kinematic variables related to force production can be modulated to respond appropriately to different contexts. We previously showed that in a choice-reaction time and a predictable timed-response task, normal subjects perform reaching movements to the same targets with two different kinematic patterns, a marker of flexibility. Here, we used the two tasks to determine whether basal ganglia are involved in the selection and modulation of movement kinematics and therefore in flexible force production. We tested seventeen patients in the early stages of Parkinson's disease, eleven pre-symptomatic Huntington's disease carriers and sixteen age-matched normal controls with the above-mentioned motor tasks. In both patient groups, the difference in kinematics (movement duration, peak velocity and acceleration) between the two tasks was significantly reduced compared to controls, indicating a limited range of choices or flexibility. However, this reduction was skewed in opposite directions in the two disorders, with force production being generally higher in Huntington's carriers and lower in Parkinson's patients compared to controls. We conclude that basal ganglia are involved in adapting movement to different contexts and selecting the appropriate movement force. The opposite trends in Parkinson's and Huntington's disease suggest that such regulation might depend on the balance between the outputs of direct and indirect pathways.

Motor sequence learning: acquisition of explicit knowledge is concomitant to changes in motor strategy of finger opposition movements.

Motor sequence learning is not a unitary phenomenon, but involves optimizing different components that include declarative and procedural aspects. In this work we designed an experimental approach that allows monitoring all the aspects of sequence learning using a finger opposition task and a movement-by-movement analysis. Subjects performed a visuomotor sequence learning paradigm with (Explicit) or without (Implicit) instructions and we measured response time (RT) and touch duration (TD) for each finger opposition movement of the sequence. Our results indicated that sequence learning induced a double-faced effect on motor performance: a decrease of RT and an increase of TD. However, the above changes manifested differently among subjects: all subjects that, by the end of session, had complete recall of the sequence order, reached an equal level of performance by the last sequence block while in those who had on average only a poor recall of the sequence order, learning was evident only as a slight decrease of RT across sequence blocks, while no kinematic changes (i.e., changes in TD) occurred. Our results indicate that, in the absence of specific instructions, learning evolves from an early stage in which only small decreases of RT are observed to a phase in which progressive knowledge of the sequential structure allows for dramatic changes of RT, together with a progressive change of motor performance (i.e., changes in TD).

Temporal evolution of oscillatory activity predicts performance in a choice-reaction time reaching task.

In this study, we characterized the patterns and timing of cortical activation of visually guided movements in a task with critical temporal demands. In particular, we investigated the neural correlates of motor planning and on-line adjustments of reaching movements in a choice-reaction time task. High-density electroencephalography (EEG, 256 electrodes) was recorded in 13 subjects performing reaching movements. The topography of the movement-related spectral perturbation was established across five 250-ms temporal windows (from prestimulus to postmovement) and five frequency bands (from theta to beta). Nine regions of interest were then identified on the scalp, and their activity was correlated with specific behavioral outcomes reflecting motor planning and on-line adjustments. Phase coherence analysis was performed between selected sites. We found that motor planning and on-line adjustments share similar topography in a fronto-parietal network, involving mostly low frequency bands. In addition, activities in the high and low frequency ranges have differential function in the modulation of attention with the former reflecting the prestimulus, top-down processes needed to promote timely responses, and the latter the planning and control of sensory-motor processes.

Increased reaction time predicts visual learning deficits in Parkinson's disease.

To determine whether the process involved in movement preparation of patients in the early stages of Parkinson's disease (PD) shares attentional resources with visual learning, we tested 23 patients with PD and 13 healthy controls with two different tasks. The first was a motor task where subjects were required to move as soon as possible to randomly presented targets by minimizing reaction time. The second was a visual learning task where targets were presented in a preset order and subjects were asked to learn the sequence order by attending to the display without moving. Patients with PD showed higher reaction and movement times, while visual learning was reduced compared with controls. For patients with PD, reaction times, but not movement times, displayed an inverse significant correlation with the scores of visual learning. We conclude that visual declarative learning and movement preparation might share similar attentional and working memory resources. (c) 2010 Movement Disorder Society.

Spontaneous movement tempo is influenced by observation of rhythmical actions.

Observation of people performing movements facilitates motor planning, execution and memory formation. Tempo, a crucial aspect involved in the execution of rhythmic movements, is normally perceived and learned through auditory channels. In this work, we ascertained whether: first, the frequency of self-paced finger movements (SPMs), which in normal subjects is around 2 Hz, is modified by prior observation of movements performed at either 1 or 3 Hz; second, such changes are lasting; third, there is an effect of time interval between observation and performance. We finally determined the effect of providing explicit information about the upcoming motor task. Seventy-two normal subjects (12 groups) performed a simple finger sequence at different intervals after observation of videos of either landscapes or finger opposition movements. Both with and without information about the upcoming task, observation influenced the tempo of SPMs and led to memory formation. With knowledge of the upcoming task, such changes occurred at all observation-execution intervals, while without instructions, changes took place only when SPMs were performed immediately after observation. Compared to explicit instructions, the absence of instructions produced tempo's changes that more closely resembled the observed rhythms. We conclude that learning requires a prompt comparison between visual and sensorimotor representations of movements; moreover, learning with explicit instructions is more efficient, as activity in both the dorsal and ventral streams might be potentiated by the chatecholaminergic attentional systems that promote long-term potentiation. These results provide the bases for novel neurorehabilitation strategies in terms of temporal re-organization of movement.

The serial reaction time task revisited: a study on motor sequence learning with an arm-reaching task.

With a series of novel arm-reaching tasks, we have shown that visuomotor sequence learning encompasses the acquisition of the order of sequence elements, and the ability to combine them in a single, skilled behavior. The first component, which is mostly declarative, is reflected by changes in movement onset time (OT); the second, which occurs without subject's awareness, is measured by changes in kinematic variables, including movement time (MT). Key-press-based serial reaction time tasks (SRTT) have been used to investigate sequence learning and results interpreted as indicative of the implicit acquisition of the sequence order. One limitation to SRT studies, however, is that only one measure is used, the response time, the sum of OT and MT: this makes interpretation of which component is learnt difficult and disambiguation of implicit and explicit processes problematic. Here, we used an arm-reaching version of SRTT to propose a novel interpretation of such results. The pattern of response time changes we obtained was similar to the key-press-based tasks. However, there were significant differences between OT and MT, suggesting that both partial learning of the sequence order and skill improvement took place. Further analyses indicated that the learning of the sequence order might not occur without subjects' awareness.

Learning of a sequential motor skill comprises explicit and implicit components that consolidate differently.

The ability to perform accurate sequential movements is essential to normal motor function. Learning a sequential motor behavior is comprised of two basic components: explicit identification of the order in which the sequence elements should be performed and implicit acquisition of spatial accuracy for each element. Here we investigated the time course of learning of these components for a first sequence (SEQA) and their susceptibility to interference from learning a second sequence (SEQB). We assessed explicit learning with a discrete index, the number of correct anticipatory movements, and implicit learning with a continuous variable, spatial error, which decreased during learning without subject awareness. Spatial accuracy to individual sequence elements reached asymptotic levels only when the whole sequence order was known. Interference with recall of the order of SEQA persisted even when SEQB was learned 24 h after SEQA. However, there was resistance to interference by SEQB with increased initial training with SEQA. For implicit learning of spatial accuracy, SEQB interfered at 5 min but not 24 h after SEQA. As in the case of sequence order, prolonged initial training with SEQA induced resistance to interference by SEQB. We conclude that explicit sequence learning is more susceptible to anterograde interference and implicit sequence learning is more susceptible to retrograde interference. However, both become resistant to interference with saturation training. We propose that an essential feature of motor skill learning is the process by which discrete explicit task elements are combined with continuous implicit features of movement to form flawless sequential actions.

Short-term limb immobilization affects motor performance.

C. Ghez, J. Gordon, and M. R Ghilardi (1995; J. Gordon, M. R Ghilardi, & C. Ghez, 1995; R. L. Sainburg, M. R Ghilardi, H. Poizner, & C. Ghez, 1995) have found that proprio-ceptive deafferentation impairs feedforward and feedback mechanisms that control reaching movements. In the present study, the authors found immobilization-induced changes in limb kinematics, including joint motion, in 32 healthy participants who performed out-and-back movements before and after 0, 6, or 12 hr of immobilization of the left arm. Control participants did not undergo the arm immobilization procedure. Immobilization for 12 hr, but not 6 hr, caused trajectories with increased hand-path areas and altered interjoint coordination. The abnormalities were smaller in amplitude but similar in quality to those reported in deafferented patients (R. L. Sainburg et al.). In addition, movement onset point significantly drifted after immobilization. Thus, short-term limb disuse can affect interjoint coordination by acting on feedforward mechanisms. These behavioral alterations are potentially related to cortical plastic changes.