Search

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.

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 forty-minute 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.

Adapting movements to a visual rotation involves the activation of right posterior parietal areas. Further performance improvement requires an increase of slow wave activity in subsequent sleep in the same areas. Here we ascertained whether a post-learning trace is present in wake EEG and whether such a trace is influenced by sleep slow waves.In two separate sessions, we recorded high-density EEG in 17 healthy subjects before and after a visuomotor rotation task, which was performed both before and after sleep. High-density EEG was recorded also during sleep. One session aimed to suppress sleep slow waves, while the other session served as a control.After learning, we found a trace in the eyes-open wake EEG as a local, parietal decrease in alpha power. After the control night, this trace returned to baseline levels, but it failed to do so after slow wave deprivation. The overnight change of the trace correlated with the dissipation of low frequency (8 Hz) NREM sleep activity only in the control session.Visuomotor learning leaves a trace in the wake EEG alpha power that appears to be renormalized by sleep slow waves.These findings link visuomotor learning to regional changes in wake EEG and sleep homeostasis.

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 putativein vivomodel 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.

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 normal 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. PD patients showed higher reaction and movement times, while visual learning was reduced compared to controls. For PD patients, 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.

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.

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.

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.

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.

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.

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 electroencephalograohy (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.

Learning deficits may be part of the early symptoms of Huntington's disease (HD). Here we characterized implicit and explicit aspects of sequence learning in eleven pre-symptomatic HD gene carriers (pHD) and eleven normal controls. Subjects moved a cursor on a digitizing tablet and performed the following tasks: SEQ: learning to anticipate the appearance of a target sequence in two blocks; VSEQ: learning a sequence by attending to the display without moving for one block, and by moving to the sequence in a successive block (VSEQtest). Explicit learning was measured with declarative scores and number of anticipatory movements. Implicit learning was measured as a strategy change reflected in movement time. By the end of SEQ, pHD had a significantly lower number of correct anticipatory movements and lower declarative scores than controls, while in VSEQ and VSEQtest these indices improved. During all three tasks, movement time changed in controls, but not in pHD. These results suggest that both explicit and implicit aspects of sequence learning may be impaired before the onset of motor symptoms. However, when attentional demands decrease, explicit, but not implicit, learning may improve.