Biomedical subjects

Julien Doyon

Publications and source records attributed to Julien Doyon.

27 records · Page 2Linked to original sources

PubMed2003

Distinct contribution of the cortico-striatal and cortico-cerebellar systems to motor skill learning.

This review paper focuses on studies in healthy human subjects that examined the functional neuroanatomy and cerebral plasticity associated with the learning, consolidation and retention phases of motor skilled behaviors using modern brain imaging techniques. Evidence in support of a recent model proposed by Doyon and Ungerleider [Functional Anatomy of Motor Skill Learning. In: Squire LR, Schacter DL, editors. Neuropsychology of Memory. New York: Guilford Press, 2002.] is also discussed. The latter suggests that experience-dependent changes in the brain depend not only on the stage of learning, but also on whether subjects are required to learn a new sequence of movements (motor sequence learning) or learn to adapt to environmental perturbations (motor adaptation). This model proposes that the cortico-striatal and cortico-cerebellar systems contribute differentially to motor sequence learning and motor adaptation, respectively, and that this is most apparent during the slow learning phase (i.e. automatization) when subjects achieve asymptotic performance, as well as during reactivation of the new skilled behavior in the retention phase.

Animals↗

PubMed2003

Functional cerebral reorganization following motor sequence learning through mental practice with motor imagery.

The goal of the present study was to examine, via positron emission tomography, the functional changes associated with the learning of a sequence of foot movements through mental practice with motor imagery (MI). Following intensive MI training over several days, which led to a modest but significant improvement in performance, healthy subjects showed an increase in activity restricted to the medial aspect of the orbitofrontal cortex (OFC), and a decrease in the cerebellum. These main results are largely consistent with those found in a previous study of sequence learning performed in our laboratory after physical practice of the same task [NeuroImage 16 (2002) 142]. Further analyses showed a positive correlation between the blood flow increase in the OFC and the percentage of improvement on the foot sequence task. Moreover, the increased involvement of the medial OFC revealed a modality specific anatomo-functional organization, as imagination of the sequential task after MI practice activated a more posterior region than its execution. These results demonstrate that learning a sequential motor task through motor imagery practice produces cerebral functional changes similar to those observed after physical practice of the same task. Moreover, the findings are in accord with the hypothesis that mental practice with MI, at least initially, improves performance by acting on the preparation and anticipation of movements rather than on execution per se.

Adult↗

PubMed2003

[New perspectives of locomotor rehabilitation after stroke].

The task-oriented approach incorporating treadmill walking for retraining gait early after stroke has contributed to promote locomotor recovery. To augment practice, training strategies such as mental practice and training in virtual environments are proposed. While the former offers more practice with less physical exertion, the latter allows safe practice in a variety of challenging environments. Work is under way to assess whether these new strategies can further enhance locomotor recovery.

Gait↗

PubMed2002

Dynamic cortical and subcortical networks in learning and delayed recall of timed motor sequences.

We used positron emission tomography to examine learning and retention of timed motor sequences. Subjects were scanned during learning (LRN) and baseline (ISO) on 3 d: day 1, after 5 d of practice (day 5) and after a 4 week delay (recall). Blood flow was compared across days of learning and between the LRN and ISO conditions. Overall, significant changes in activity were seen across days for the LRN condition, but not the ISO baseline. Day 1 results revealed extensive activation in the cerebellar cortex, particularly lobules III/IV and VI. Day 5 results showed increased activity in the basal ganglia (BG) and frontal lobe, with no significant cerebellar activity. At recall, significantly greater activity was seen in M1, premotor, and parietal cortex. Blood flow in the cerebellum decreased significantly between day 1 and recall. These results reveal a dynamic network of motor structures that are differentially active during different phases of learning and delayed recall. For the first time our findings show that recall of motor sequences in humans is mediated by a predominantly cortical network. Based on these results, we suggest that during early learning cerebellar mechanisms are involved in adjusting movement kinematics according to sensory input to produce accurate motor output. Thereafter, the cerebellar mechanisms required for early learning are no longer called into play. During late learning, the BG may be involved in automatization. At delayed recall, movement parameters appear to be encoded in a distributed representation mediated by M1, premotor, and parietal cortex.

Adult↗

PubMed2002

Experience-dependent changes in cerebellar contributions to motor sequence learning.

Studies in experimental animals and humans have stressed the role of the cerebellum in motor skill learning. Yet, the relative importance of the cerebellar cortex and deep nuclei, as well as the nature of the dynamic functional changes occurring between these and other motor-related structures during learning, remains in dispute. Using functional magnetic resonance imaging and a motor sequence learning paradigm in humans, we found evidence of an experience-dependent shift of activation from the cerebellar cortex to the dentate nucleus during early learning, and from a cerebellar-cortical to a striatal-cortical network with extended practice. The results indicate that intrinsic modulation within the cerebellum, in concert with activation of motor-related cortical regions, serves to set up a procedurally acquired sequence of movements that is then maintained elsewhere in the brain.

Adult↗

PubMed2002

Motor learning produces parallel dynamic functional changes during the execution and imagination of sequential foot movements.

The aim of the present positron emission tomography study was to measure the dynamic changes in cerebral activity before and after practice of an explicitly known sequence of foot movements when executed physically and to compare them to those elicited during motor imagery of the same movements. Nine healthy volunteers were scanned while performing both types of movement at an early phase of learning and after a 1-h training period of a sequence of dorsiflexions and plantarflexions with the left foot. These experimental conditions were compared directly, as well as to a perceptual control condition. Changes in regional cerebral blood flow associated with physical execution of the sequence early in the learning process were observed bilaterally in the dorsal premotor cortex and cerebellum, as well as in the left inferior parietal lobule. After training, however, most of these brain regions were no longer significantly activated, suggesting that they are critical for establishing the cognitive strategies and motor routines involved in executing sequential foot movements. By contrast, after practice, an increased level of activity was seen bilaterally in the medial orbitofrontal cortex and striatum, as well as in the left rostral portion of the anterior cingulate and a different region of the inferior parietal lobule, suggesting that these structures play an important role in the development of a long lasting representation of the sequence. Finally, as predicted, a similar pattern of dynamic changes was observed in both phases of learning during the motor imagery conditions. This last finding suggests that the cerebral plasticity occurring during the incremental acquisition of a motor sequence executed physically is reflected by the covert production of this skilled behavior using motor imagery.

Adult↗

PubMed2002

Imaging brain plasticity during motor skill learning.

The search for the neural substrates mediating the incremental acquisition of skilled motor behaviors has been the focus of a large body of animal and human studies in the past decade. Much less is known, however, with regard to the dynamic neural changes that occur in the motor system during the different phases of learning. In this paper, we review recent findings, mainly from our own work using fMRI, which suggest that: (i) the learning of sequential finger movements produces a slowly evolving reorganization within primary motor cortex (M1) over the course of weeks and (ii) this change in M1 follows more dynamic, rapid changes in the cerebellum, striatum, and other motor-related cortical areas over the course of days. We also briefly review neurophysiological and psychophysical evidence for the consolidation of motor skills, and we propose a working hypothesis of its underlying neural substrate in motor sequence learning.

Brain↗

PubMed2002

Differential role for the striatum and cerebellum in response to novel movements using a motor learning paradigm.

The aim of this pilot study was to examine the role of the striatum and cerebellum in the adaptation to a novel movement within a sequence of practiced movements using a motor learning paradigm. The performance of patients in the early or advanced stages of Parkinson's disease (PD) and of patients with damage to the cerebellum (CE) was compared, respectively to a group of aged and young matched controls on an adapted version of the Mirror-Tracing Test. In this task, subjects were required to trace a series of complex figures in two conditions: (1) a Practiced condition, in which the figures were composed of the juxtaposition of three simple designs that were extensively practiced before; and (2) a Mixed condition in which triads were created by replacing the last simple figure of the triads in the Practiced condition by a new simple figure that had never been traced individually before. Results showed that all clinical groups were slower than controls at tracing the Practiced triads. Most interestingly, however, only patients in the advanced stages of PD showed increased completion time to trace the triads in the Mixed condition. This suggests that a bilateral striatal dysfunction affects the ability to adapt to a novel motion within a sequence of practiced movements. Although exploratory, these results support a functional dissociation between the striatum and cerebellum in acquiring visuomotor skilled behaviors.

Adult↗

PubMed1999

Stereocontrolled Synthesis of Key Advanced Intermediates toward Simplified Acetogenin Analogues.

The stereo- and enantiocontrolled synthesis of substituted beta-hydroxy ethers based on glycol and catechol bearing an alkyne group and a series of substituents is reported. These substrates were designed to mimic the bis-THF array of annonaceous acetogenins and to provide an access to simplified and modified analogues. The key steps of the synthesis involve the condensation of the nonracemic mesylate of solketal with ethylene glycol and catechol, followed by an alkylation with a glycidyl derivative. Under appropriate conditions, the reaction is completely stereoselective and allows the synthesis of all the diastereomers. After the epoxide was opened with triethylsilylacetylene, the second epoxide was unmasked and reacted with a series of alkyl, aryl, amine, and alcohol reagents. A series of 28 analogues was prepared having a glycol or a catechol core, a stereodefined configuration of the flanking hydroxyl groups, and an acetylenic appendage suitable for a coupling to a lactone-bearing fragment.

Journal Article↗