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Biomedical subjects

J Doyon

Publications and source records attributed to J Doyon.

At least 19 recordsLinked to original sources
PubMed2005

Cerebellum and M1 interaction during early learning of timed motor sequences.

We used positron emission tomography (PET) to examine within-day learning of timed motor sequences. The results of this experiment are novel in showing an interaction between cerebellum and primary motor cortex (M1) during learning that appears to be mediated by the dentate nucleus (DN) and in demonstrating that activity in these regions is directly related to performance. Subjects were scanned during learning (LRN) across three blocks of practice and during isochronous (ISO) and perceptual (PER) baseline conditions. CBF was compared across blocks of learning and between the LRN and baseline conditions. Results demonstrated an interaction between the cerebellum and M1 such that earlier, poorer performance was associated with greater activity in the cerebellar hemispheres and later, better performance was associated with greater activity in M1. Inter-regional correlation analyses confirmed that as CBF in the cerebellum decreases, blood flow in M1 increases. Importantly, these analyses also revealed that activity in cerebellar cortex was positively correlated with activity in right DN and that DN activity was negatively correlated with blood flow in M1. Activity in the cerebellar hemispheres early in learning is likely related to error correction mechanisms which optimize movement kinematics resulting in improved performance. Concurrent DN activity may be related to encoding of this information and DN output to M1 may play a role in consolidation processes that lay down motor memories. Increased activity in M1 later in learning may reflect strengthening of synaptic connections associated with changes in motor maps that are characteristic of learning in both animals and humans.

Adult↗
PubMed2005

Effect of amantadine on motor memory consolidation in humans.

Motor skills, once learned, need to be consolidated over time in order to become resistant to disruption or interference. In some instances, the consolidation phase can also include spontaneous gains in performance even in the absence of further rehearsal on a motor task. Clinical and behavioral evidence suggest that N-methyl-D-aspartate (NMDA)-receptor activity is required for motor learning acquisition and behavioral synaptic plasticity. However, the involvement of NMDA receptors in motor consolidation, leading to stabilization of the recently formed motor memory, has not yet been assessed in humans. To address this issue, we used post-training administration of amantadine, a low-affinity NMDA-receptor channel blocker. In a double-blind design, 200 mg of amantadine or a matching placebo was given orally to two different groups of 11 healthy young volunteers each. The subjects were tested twice 24 h apart, using a motor adaptation paradigm consisting of an eight-target-pointing task. Comparison of the mean performance levels on this task revealed that subjects in both groups improved their performance levels significantly on Day 2 compared to Day 1, regardless of the treatment administered. Our data indicate that amantadine failed to block motor learning consolidation in subjects that had already learned the motor adaptation task. Thus, although required in some stages (e.g. acquisition) of motor memory processes, the present results suggest that NMDA-receptor activation may not be essential for consolidation of motor adaptation in humans.

Adaptation, Physiological↗
PubMed2003

Dynamic functional changes associated with cognitive skill learning of an adapted version of the Tower of London task.

In this study, we used a modified version of the Tower of London (TOL) planning task, in conjunction with positron emission tomography, to examine the neural substrates mediating cognitive skill learning. Twelve healthy, right-handed participants solved a total of 90 different TOL problems. They were scanned on four occasions during the fast learning stage as well as in a condition designed to control for internally guided movements. Practice of the TOL task resulted in a significant decrease in planning, execution, and total time taken to solve the problems. Consistent with the results of previous studies, early performance of the TOL task was associated with increased blood flow activity in the dorsolateral prefrontal, orbitofrontal, and parietal cortices on the left, as well as in the caudate nucleus, cerebellum, and premotor cortex, bilaterally. Interestingly, however, activity in the left caudate nucleus was maintained from the beginning to the end of the learning process, suggesting that this structure plays a role in this type of cognitive skill learning. In addition, correlational analyses revealed that improved performance on the TOL task was associated with a significant decrease of activity in the medial orbitofrontal and frontopolar cortices over the course of learning, areas thought to be involved in decision making, guessing, and monitoring of feedback information. In sum, the results lend further support to the idea that the learning of cognitive skills requiring planning and working memory capacities is mediated through a fronto-striatal network.

Aged↗
PubMed2001

Identification of the transmembrane dimer interface of the bovine papillomavirus E5 protein.

We have developed a genetic method to determine the active orientation of dimeric transmembrane protein helices. The bovine papillomavirus E5 protein, a 44-amino acid homodimeric protein that appears to traverse membranes as a left-handed coiled-coil, transforms fibroblasts by binding and activating the platelet-derived growth factor (PDGF) beta receptor. A heterologous dimerization domain was used to force E5 monomers to adopt all seven possible symmetric coiled-coil registries relative to one another within the dimer. Focus formation assays demonstrated that dimerization of the E5 protein is required for transformation and identified a single preferred orientation of the monomers. The essential glutamine residue at position 17 resided in the dimer interface in this active orientation. The active chimera formed complexes with the PDGF beta receptor and induced receptor tyrosine phosphorylation. We also identified E5-like structures that underwent non-productive interactions with the receptor.

Animals↗
PubMed2001

Distinct contribution of the striatum and cerebellum to motor learning.

The striatum and cerebellum have been shown to be key structures of a distributed system for the control of skilled movements. However, the mechanisms under which they operate remain unclear. This study compared the performance of patients with Parkinson's disease (PD) or with cerebellar damage (CE) to that of age-matched controls. Each group performed two visuomotor paradigms: a random variant of the serial reaction time (SRT) task that tested the subject's ability to make efficient stimulus-response associations and an adapted version of the mirror-tracing task that measured their capacity to combine simple movements into complex ones. PD patients with bilateral striatal damage showed an impaired learning profile on the SRT task and a normal facilitation effect in the tracing task, while CE patients showed the reverse pattern. Although further research is needed, the present findings suggest that the striatum and cerebellum are involved in distinct learning mechanisms.

Cerebellum↗
PubMed2001

Potential role of mental practice using motor imagery in neurologic rehabilitation.

For many patients with damage to the central nervous system (CNS), execution of motor tasks is very difficult, sometimes impossible, even after early participation in an active rehabilitation program. Several investigators have recently proposed that mental practice could be used by these patients as a therapeutic tool to improve their performance of motor functions, yet very little empirical work addresses this issue directly. This article discusses the rationale for investigating mental practice as a means of promoting motor recovery in patients with a neurologic disorder. We first present evidence supporting the existence of a similarity between executed and imagined actions using data from psychophysical, neurophysiologic, and brain imaging studies. This parallel is then extended to the repetition of movements during physical and mental practice of a motor skill. Finally, a new model is proposed to emphasize the key role of motor imagery as an essential process of mental practice, and also to stimulate additional research on this type of training in the rehabilitation of patients with motor impairments of cerebral origin.

Brain↗
PubMed2000

Synthesis and cytotoxic activity of acetogenin analogues.

A set of 16 new simplified analogues of acetogenins has been designed based on: (i) the replacement of the bis THF moiety of these natural products by an ethylene glycol bis ether unit; (ii) the introduction of different lipophilic side chains (alkyl, aryl, dialkylamino, O-cholesteryl); (iii) the presence of the same terminal isolactone. In vitro cytotoxic activity against L1210 leukemia is reported.

Animals↗
PubMed2000

Defective representation of knowledge in Parkinson's disease: evidence from a script-production task.

The deficits seen in frontal-lobe patients and in the elderly show clearly that spontaneous script generation depends on good frontal-lobe function. Shallice, however, has proposed that one aspect of script generation (contention scheduling, CS) which is involved in the activation and maintenance of overlearned or routine scripts may depend more on the basal ganglia. Patients with Parkinson's disease would thus be expected to manifest deficits somewhat different from those observed in frontal-lobe patients when generating scripts. The performances of 16 nondemented and nondepressed patients with idiopathic Parkinson's disease were compared to those of 16 age-matched normal control subjects under two experimental conditions; routine, forward script generation and nonroutine, backward script generation. Parkinsonian patients generated scripts significantly deprived of contextual elements in the forward condition and made significantly more sequencing and perseverative errors in both forward and backward conditions than did normal subjects. They also produced a significantly higher number of irrelevant intrusions, in both conditions, than did controls. These results support, in a general sense, Shallice's notion that the basal ganglia are important in script generation; however, other specific predictions of Shallice's model were not supported by our findings.

Cognition Disorders↗
PubMed1999

Three-dimensional MRI atlas of the human cerebellum in proportional stereotaxic space.

We have prepared an atlas of the human cerebellum using high-resolution magnetic resonance-derived images warped into the proportional stereotaxic space of Talairach and Tournoux. Software that permits simultaneous visualization of the three cardinal planes facilitated the identification of the cerebellar fissures and lobules. A revised version of the Larsell nomenclature facilitated a simple description of the cerebellum. This atlas derived from a single individual was instrumental in addressing longstanding debates about the gross morphologic organization of the cerebellum. It may serve as the template for more precise identification of cerebellar topography in functional imaging studies in normals, for investigating clinical-pathologic correlations in patients, and for the development of future probabilistic maps of the human cerebellum.

Cerebellum↗
PubMed1998

Role of the striatum, cerebellum and frontal lobes in the automatization of a repeated visuomotor sequence of movements.

Recently, Doyon et al. [20] demonstrated that lesions to both the striatum and to the cerebellum in humans produce a similar deficit in the learning of a repeated visuomotor sequence, which occurs late in the acquisition process. We now report the results of two experiments that were designed to examine whether this impairment was due to a lack of automatization of the repeating sequence of finger movements by using a dual-task paradigm and by testing for long-term retention of this skill. In Experiment 1, the performance of groups of patients with Parkinson's disease, or with damage to the cerebellum or to the frontal lobes, was compared to that of matched control subjects on the Repeated Sequence Test (primary task) and the Brooks' Matrices Test (secondary task). These two tests were administered concomitantly in both early and late learning phases of the visuomotor sequence. Overall, the groups did not differ in their ability to execute the primary task. By contrast, in accordance with the predictions, patients in Stages 2-3 of Parkinson's disease or with a cerebellar lesion failed to reveal the expected increase in performance on the secondary task seen with learning, suggesting that the latter groups of patients did not have access to the same level of residual cognitive resources to complete the matrices compared to controls. In Experiment 2, the same groups of patients and control subjects were retested again 10-18 months later. They were given four blocks of 100 trials each of the repeating sequence task, followed by a questionnaire and a self-generation task that measured their declarative knowledge of that sequence. The results revealed a long-term retention impairment only in patients who changed from Stage I to Stage II of the disease (suggesting further striatal degeneration) during the one-year interval, or who had a cerebellar lesion. By contrast, performance of the three clinical groups did not differ from controls on declarative memory tests. These findings suggest that both the striatum and the cerebellum participate to the automatization process during the late (slow) learning stage of a sequence of finger movements and that these structures also play a role in the neuronal mechanism subserving long-term retention of such a motor sequence behavior.

Adult↗
PubMed1998

Abnormal basal ganglia outflow in Parkinson's disease identified with PET. Implications for higher cortical functions.

In this study we examined the effects of striatal dopamine depletion on cortical and subcortical blood flow changes during two tasks known to involve frontostriatal circuitry. Regional cerebral blood flow was measured in six patients with moderate Parkinson's disease and in six age-matched control subjects while they performed easy and difficult versions of a modified Tower of London planning task and a mnemonic variant of this task that required short-term retention and reproduction of problem solutions, as well as a control condition that involved identical visual stimuli and motor responses. Relative to control conditions, the planning task was associated with an increase in cerebral blood flow centred on the internal segment of the right globus pallidus in the age-matched control subjects, and a decrease in the same region in the patients with Parkinson's disease. A similar inverse relationship between the task-specific blood flow change observed in the control group and that observed in the Parkinson's disease patients was not found in any other subcortical or cortical area examined, including regions of the dorsolateral frontal cortex known to be involved in this task. When blood flow in the spatial working memory task was examined, a similarly specific dissociation between the two groups of subjects was observed at similar coordinates in the right pallidum. We conclude that striatal dopamine depletion disrupts the normal pattern of basal ganglia outflow in Parkinson's disease and consequently, affects the expression of frontal-lobe functions by interrupting normal transmission of information through frontostriatal circuitry.

Basal Ganglia↗
PubMed1997

Role of the striatum, cerebellum, and frontal lobes in the learning of a visuomotor sequence.

This study was designed to examine the role of the striatum, cerebellum, and frontal lobes in the implicit learning of a visuomotor sequence. The performance of patients with idiopathic Parkinson's disease (PD), with damage to the cerebellum, or with a circumscribed lesion to the frontal lobes was thus compared to that of separate groups of matched normal control subjects on an adapted version of the Repeated Sequence Test. This paradigm consists of a visual reaction-time task with a fixed embedded sequence of finger movements to be performed based on presentation of visual stimuli. Subjects received four blocks of trials (i.e., 40 presentations of a 10-item sequence) per day over 6 training days. Following the last experimental session, subjects were also given two tests measuring their declarative knowledge of the sequence. Only PD patients with a bilateral striatal-dysfunction or patients with lesions to the cerebellum failed to improve their performance in the last three training sessions, hence suggesting an impairment late in the acquisition process. Further analyses revealed that such impairment was mainly implicit in nature, and that it could not be ascribed to a general decline in cognitive functioning, to mood disturbances, or to the severity of the motor symptoms. By contrast, the level of declarative knowledge of the sequence did not differ between the three clinical groups and their respective groups of normal subjects. These findings suggest that, unlike declarative memory, the incremental acquisition of a new visuomotor skill depends upon the integrity of both the striatum and the cerebellum, but not of the frontal lobes.

Adult↗
PubMed1997

Skill learning.

This chapter reviews recent experiments that have examined the functional neuroanatomy of motor and visuomotor skill learning using brain imaging techniques such as single photon emission computed tomography, positron emission tomography, and functional magnetic resonance imaging. Special attention has been given to the cerebral blood flow changes in the cerebellum that are associated with the acquisition of these skills, although localizations of other activated regions (cortical and subcortical) are also included. The cognitive processes involved in different skill acquisition paradigms are discussed with particular reference to the learning stages at which subjects were scanned. This approach examines the conditions that are likely to produce cerebellar activation and helps us understand the role of the cerebellum in acquiring skilled behaviors.

Animals↗
PubMed1997

[The consensual approach in geriatrics].

Caregivers are often ill-equipped to cope with repeated verbal and physical aggression by geriatric residents with cognitive deficits. Cooperation from other members of the health care team is rarely automatic and there is little adherence to established interventions. This article offers valuable insights on patient care to caregivers who work with aggressive individuals in geriatric settings. With the consensual approach, nursing assistants and attendants who are assigned to these patients daily are able to participate in the problem-solving process. They help design the approach and willingly become stakeholders in the actions presented by the patient care plans. By the end of the process they are able to view the aggressive person as someone worthy of attention and love, rather than a disruptive element to be endured.

Aged↗
PubMed1996

The clinicopathologic spectrum of myxoid and round cell liposarcoma. A study of 95 cases.

BACKGROUND: The prognosis of patients with myxoid liposarcoma (ML) or round cell liposarcoma (RCL) has never been adequately defined. METHODS: We evaluated the clinical and pathologic features of 95 patients with biopsy proven ML or RCL examined at the Mayo Clinic between 1971 and 1992. Routine hematoxylin and eosin stained slides of all cases were reviewed. Morphologic variable evaluated included percent of round cell differentiation, percent of lipoblastic differentiation, and presence of tumor necrosis. Clinical follow-up was available for 86 patients (range: 6 months-23.4 years; mean: 7.2 years; median: 5.9 years). Flow cytometry for determination of DNA ploidy was performed on paraffin embedded tissue available from 46 cases. Survival analyses for the 86 patients with adequate clinical follow-up were performed by the Kaplan-Meier test using the approximate chi-square statistic for the log rank test. RESULTS: Age at diagnosis ranged from 16 to 81 years (median: 44 years). The extremities were involved in 91 cases, the retroperitoneum in 3 cases, and the perineum in 1 case. The single most common location was the thigh (61 cases). Histologically, round cell differentiation was present in 41 cases (43%) ranging from 5% to 100% of the tumor volume. Only one case of "pure" RCL was used in the study. Spontaneous tumor necrosis was noted in 4 cases. By flow cytometry, 38 tumors were diploid, 6 were aneuploid, and 1 was tetraploid. The data from 1 case was uninterpretable. Thirty patients (35%) developed metastasis; 27 (31%) died from the disease. CONCLUSIONS: With multivariate analysis, age ( > 45 years), percent of round cell differentiation ( > or = 25%), and the presence of spontaneous tumor necrosis are significantly associated with a poor prognosis. No correlation was observed between DNA ploidy (i.e., diploid vs. aneuploid) and percent of round cell differentiation or clinical outcome.

Adipocytes↗