Faculty Bibliography

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)

When reaching movements are performed in an unusual area of work, normal subjects produce a rightward directional error. This has been considered to be caused by an impaired representation of limb configuration, which hampers the actual movement vector. Motor programming has been found to be impaired in dystonia. To understand how patients affected by idiopathic cervical dystonia (CD) perform reaching movements in an unusual area of work, we investigated 10 CD patients and 10 age-matched controls. Reaching movements on a digitized tablet were recorded both with the right arm aligned to the midline (central position) and shifted to the right (lateral position), but hidden from view. While differences in the main kinematic parameters were not affected by the position both in patients and controls, the directional error was significantly increased in dystonic patients for the lateral position. We hypothesise that an impaired integration of proprioceptive information with the motor output and egocentric spatial perception could be responsible for a greater error in spatial representation of hand location and consequently to an increased directional error in dystonic patients

In a recent series of experiments, we demonstrated that a visuomotor adaptation task, 12 hours of left arm immobilization, and rapid transcranial magnetic stimulation (rTMS) during waking can each induce local changes in the topography of electroencephalographic (EEG) slow wave activity (SWA) during subsequent non-rapid eye movement (NREM) sleep. However, the poor spatial resolution of EEG and the difficulty of relating scalp potentials to the activity of the underlying cortex limited the interpretation of these results. In order to better understand local cortical regulation of sleep, we used source modeling to show that plastic changes in specific cortical areas during waking produce correlated changes in SWA during sleep in those same areas. We found that implicit learning of a visuomotor adaptation task induced an increase in SWA in right premotor and sensorimotor cortices when compared to a motor control. These same areas have previously been shown to be selectively involved in the performance of this task. We also found that arm immobilization resulted in a decrease in SWA in sensorimotor cortex. Inducing cortical potentiation with repetitive transcranial magnetic stimulation (rTMS) caused an increase in SWA in the targeted area and a decrease in SWA in the contralateral cortex. Finally, we report the first evidence that these modulations in SWA may be related to the dynamics of individual slow waves. We conclude that there is a local, plasticity dependent component to sleep regulation and confirm previous inferences made from the scalp data

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

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

Repetitive transcranial magnetic stimulation (rTMS) induces neuronal long-term potentiation or depression. Although brain-derived neurotrophic factor (BDNF) and its cognate tyrosine receptor kinase B (TrkB) contribute to the effects of rTMS, their precise role and underlying mechanism remain poorly understood. Here we show that daily 5 Hz rTMS for 5 d improves BDNF-TrkB signaling in rats by increasing the affinity of BDNF for TrkB, which results in higher tyrosine-phosphorylated TrkB, increased recruitment of PLC-gamma1 and shc/N-shc to TrkB, and heightened downstream ERK2 and PI-3K activities in prefrontal cortex and in lymphocytes. The elevated BDNF-TrkB signaling is accompanied by an increased association between the activated TrkB and NMDA receptor (NMDAR). In normal human subjects, 5 d rTMS to motor cortex decreased resting motor threshold, which correlates with heightened BDNF-TrkB signaling and intensified TrkB-NMDAR association in lymphocytes. These findings suggest that rTMS to cortex facilitates BDNF-TrkB-NMDAR functioning in both cortex and lymphocytes

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 (<8Hz) NREM sleep activity only in the control session. CONCLUSIONS: Visuomotor learning leaves a trace in the wake EEG alpha power that appears to be renormalized by sleep slow waves. SIGNIFICANCE: These findings link visuomotor learning to regional changes in wake EEG and sleep homeostasis

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 degrees in four incremental steps of 15 degrees . 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

We have previously shown that, in early stages of Parkinson's disease (PD), patients with higher reaction times are also more impaired in visual sequence learning, suggesting that movement preparation shares resources with the learning of visuospatial sequences. Here, we ascertained whether, in patients with PD, the pattern of the neural correlates of attentional processes of movement planning predict sequence learning and working memory abilities. High density Electroencephalography (EEG, 256 electrodes) was recorded in 19 patients with PD performing reaching movements in a choice reaction time paradigm. Patients were also tested with Digit Span and performed a visuomotor sequence learning task that has an important declarative learning component. We found that attenuation of alpha/beta oscillatory activity before the stimulus presentation in frontoparietal regions significantly correlated with reaction time in the choice reaction time task, similarly to what we had previously found in normal subjects. In addition, such activity significantly predicted the declarative indices of sequence learning and the scores in the Digit Span task. These findings suggest that some motor and non motor PD signs might have common neural bases, and thus, might have a similar response to the same behavioral therapy. In addition, these results might help in designing and testing the efficacy of novel rehabilitative approaches to improve specific aspects of motor performance in PD and other neurological disorders

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