Biomedical subjects

François Chollet

Publications and source records attributed to François Chollet.

11 recordsLinked to original sources

PubMed2006

Methylphenidate modulates cerebral post-stroke reorganization.

OBJECTIVE: We hypothesized that a single dose of methylphenidate (MP) would modulate cerebral motor activation and behavior in patients having suffered a subcortical stroke. METHODS: Eight men with a single stroke on the corticospinal tract resulting in a pure motor hemiparesia were included in a randomized, cross-over, double-blind, placebo-controlled study. Patients were first evaluated 17 days after stroke onset by validated neurological scales, motor tests and fMRI (flexion/extension of the digits) after 20 mg MP or placebo. Seven days later, the patients underwent the same protocol and received the drug they had not taken at the first evaluation. Each patient was his own control. RESULTS: Placebo intake did not change performance. MP compared to placebo elicited a significant improvement in motor performance of the affected hand at the finger tapping test. MP induced: (1) a hyperactivation of the ipsilesional primary sensorimotor cortex including the motor hand and face areas and of the contralesional premotor cortex; (2) a hypoactivation of the ipsilesional anterior cingulum. Hyperactivation in the face motor area correlated positively with the improvement in performance. CONCLUSION: We demonstrated that the reorganized network may efficiently be targeted by the drug and that the effect of MP might partly rely on an improvement in attention/effort through cingulum modulation.

Aged↗

PubMed2005

Modulation of behavior and cortical motor activity in healthy subjects by a chronic administration of a serotonin enhancer.

UNLABELLED: SSRIs are postulated to modulate motor behavior. A single dose of selective serotoninergic reuptake inhibitors (SSRIs) like fluoxetine, paroxetine, or fluvoxamine, has been shown to improve motor performance and efficiency of information processing for simple sensorimotor tasks in healthy subjects. At a cortical level, a single dose of SSRI was shown to induce a hyperactivation of the primary sensorimotor cortex (S1M1) involved in the movement (Loubinoux, I., Boulanouar, K., Ranjeva, J. P., Carel, C., Berry, I., Rascol, O., Celsis, P., and Chollet, F., 1999. Cerebral functional magnetic resonance imaging activation modulated by a single dose of the monoamine neurotransmission enhancers fluoxetine and fenozolone during hand sensorimotor tasks. J. Cereb. Blood Flow Metab. 19 1365--1375, Loubinoux, I., Pariente, J., Boulanouar, K., Carel, C., Manelfe, C., Rascol, O., Celsis, P., and Chollet, F., 2002. A Single Dose of Serotonin Neurotransmission Agonist Paroxetine Enhances Motor Output. A double-blind, placebo-controlled, fMRI study in healthy subjects. NeuroImage 15 26--36). Since SSRIs are usually given for several weeks, we assessed the behavioral and cerebral effects of a one-month chronic administration of paroxetine on a larger group. In a double-blind, placebo controlled and crossover study, 19 subjects received daily 20 mg paroxetine or placebo, respectively, over a period of 30 days separated by a wash-out period of 3 months. After each period, the subjects underwent an fMRI (active or passive movement, dexterity task, sensory discrimination task) and a behavioral evaluation. Concurrently, a TMS (transcranial magnetic stimulation) study was conducted (Gerdelat-Mas, A., Loubinoux, I., Tombari, D., Rascol, O., Chollet, F., Simonetta-Moreau, M., 2005. Chronic administration of selective serotonin re-uptake inhibitor (SSRI) paroxetine modulates human motor cortex excitability in healthy subjects. NeuroImage 27,314--322). RESULTS: On the one hand, paroxetine improved motor performances at the finger tapping test (P=0.02) without affecting choice reaction time, strength and dexterity significantly. Subjects were also faster in processing the spatial incongruency between a stimulus and the motor response (P=0.04). In order to differentiate behavioral components, a principal component analysis was performed on all motor tests, and several characteristics were differentiated: strength, speed, skill, attention, and motor response coding. Paroxetine would improve the efficiency of motor response coding (MANOVA on the factors; factor 3, P=0.01). On the other hand, the chronic administration induced a significant hypoactivation of S1M1 whatever the task: motor or sensory, simple or complex (random effect analysis, P<0.05). The hypoactivation correlated with the improvement of performances at the finger tapping test (P<0.05) suggesting more efficiency in cerebral motor processing. CONCLUSIONS: Our results showed a clear modulation of sensory and motor cerebral activation after a chronic paroxetine administration. An improvement in both behavior and cerebral efficiency was suggested. It could be hypothesized that monoamines, by an unspecific effect, may tune the response of pyramidal neurons to optimize performances.

Adult↗

PubMed2005

Subcortical aphasia: a longitudinal PET study.

BACKGROUND AND PURPOSE: Very few neuroimaging studies have focused on follow-up of subcortical aphasia. Here, overt language production tasks were used to correlate regional cerebral blood flow (rCBF) changes and language performance in patients with vascular subcortical lesions. METHODS: Seven aphasic patients were scanned twice with positron emission tomography (PET) at 1-year interval during a word-generation task. Using SPM2, Language-Rest contrast at PET1 was correlated to language performance and to time-lag from stroke. The same contrast was performed at PET2 and session effect (PET2-PET1) was correlated with performance improvement. RESULTS: At PET1, correlation between rCBF and delay from stroke involved mainly ventral regions of the left temporal cortex and mesial frontal cortex. Correlations between rCBF and performance showed predominantly left dorsal regions in the frontal, temporal, and parietal lobes, but also the left ventral temporal cortex. One year apart, language performance improved and rCBF increased in perisylvian regions bilaterally. Best performers at PET2 showed an increase of activity in left ventral temporal cortex as well as in right middle temporal gyrus. CONCLUSIONS: On follow-up, expected language improvement and increase of activation in the classical language areas and their counterparts were observed. Moreover, all correlational analyses both at PET1 and on follow-up implicated the anterior part of the left inferior temporal gyrus, suggesting a disconnection between the superior and inferior parts of the left temporal cortex and a specific role for this region in lexical semantic processing.

Adult↗

PubMed2005

Effect of levodopa on pain threshold in Parkinson's disease: a clinical and positron emission tomography study.

Patients suffering from Parkinson's disease (PD) frequently experienced painful sensations that could be in part due to central modification of nociception. We compared pain threshold before and after administration of levodopa in PD patients and in controls, and investigated cerebral activity with positron emission tomography (PET) during experimental nociceptive stimulation. Pain threshold was determined using thermal stimulation during two randomized conditions: off and on. We performed H(2) (15)O PET analysis of regional cerebral blood flow on subjects while they received alternate randomized noxious and innocuous stimuli during off and on conditions. In off condition, pain threshold in nine PD patients was significantly lower than in nine controls. Administration of levodopa significantly raised pain threshold in PD patients but not in controls. During off condition, there was a significant increase in pain-induced activation in right insula and prefrontal and left anterior cingulate cortices in PD compared to control group. Levodopa significantly reduced pain-induced activation in these areas in PD. This study shows that pain threshold is lower in PD patients but returns to normal ranges after levodopa administration. Moreover, PD patients have higher pain-induced activation in nociceptive pathways, which can be reduced by levodopa.

Aged↗

PubMed2004

Cortical motor activation in akinetic schizophrenic patients: a pilot functional MRI study.

Akinesia is associated with supplementary motor area (SMA) dysfunction in Parkinson's disease. We looked for a similar association in patients with schizophrenia. Using functional magnetic resonance imaging (fMRI), we compared motor activation in 6 akinetic neuroleptic-treated schizophrenic patients and 6 normal subjects. Schizophrenic patients had a defective activation in the SMA, left primary sensorimotor cortex, bilateral lateral premotor and inferior parietal cortices, whereas the right primary sensorimotor cortex and a mesial frontal area were hyperactive. SMA was hypoactive in akinetic schizophrenic patients, emphasizing the role of this area in motor slowness. Other abnormal signals likely reflect schizophrenia-related abnormal intracortical connections.

Adult↗

PubMed2004

A longitudinal fMRI study: in recovering and then in clinically stable sub-cortical stroke patients.

The aim of this 1-year longitudinal fMRI study was to compare hand motor activation patterns between cerebrovascular paretic patients with a subcortical infarction and healthy elderly subjects and to evaluate the changes between the subacute phase and the chronic phase of recovery. We studied eight right-handed patients with pure motor hemiparesis due to a single ischemic infarct of the corticospinal tract. Each patient underwent a first fMRI (E1) 20 +/- 9 days after stroke, a second (E2) after 4 months and a third (E3) 12 months after stroke. During each fMRI session, the patients performed an active motor task consisting of audio-paced (1 Hz) finger flexion-extension of the paretic hand and underwent a passive motor task consisting of flexion-extension of the paretic hand performed by an examiner. Data were analyzed with SPM99 (random effect analyses). Patients had recovered at E2, were stable between E2 and E3, but still experienced a hand weakness. Displacement of activation maxima coordinates in patients compared to healthy subjects suggested an early reorganization within the SMA and a secondary reorganization within the ipsilesional S1M1 at E2. The main differences between patients and healthy subjects were (1) recruitment of the posterior part of the cingulate cortex and SMA, (2) a general hyperactivation (except in the deefferented primary motor cortex) and (3) an evolution in the S1M1 activation from an early (20 days after stroke) contralesional hyperactivation to a later (4 months after stroke) ipsilesional hyperactivation concomitant to recovery. Changes in activation were confirmed by the passive task that involved no effort and little attention. Despite clinical stability, changes in brain processing seemed to occur between E2 and E3 corresponding to a normalization of ipsilesional S1M1 activation, a decrease of bilateral cerebellar activation, and a progressive increase in SII-BA 40 activity suggesting evolving compensatory networks to sustain recovery.

Adult↗

PubMed2003

Correlation between cerebral reorganization and motor recovery after subcortical infarcts.

Our objective was to investigate correlations between clinical motor scores and cerebral sensorimotor activation to demonstrate that this reorganization is the neural substratum of motor recovery. Correlation analyses identified reorganization processes shared by all patients. Nine patients with first-time corticospinal tract lacuna were clinically evaluated using the NIH stroke scale, the motricity index, and the Barthel index. Patients were strictly selected for pure motor deficits. They underwent a first fMRI session (E1) 11 days after stroke, and then a second (E2) 4 weeks later. The task used was a calibrated repetitive passive flexion/extension of the paretic wrist. The control task was rest. Six healthy subjects followed the same protocol. Patients were also clinically evaluated 4 and 12 months after stroke. All patients improved significantly between E1 and E2. For E1 and E2, the ipsilesional primary sensorimotor and premotor cortex, supplementary motor area (SMA), and bilateral Broadmann area (BA) 40 were activated. Activation intensity was greater at the second examination except in the ipsilesional superior BA 40. Magnitude of activation was lower than that of controls except for well-recovered patients. E1 clinical hand motor score and E1 cerebral activation correlated in the SMA proper and inferior ipsilesional BA 40. Thus, we demonstrated early functionality of the sensorimotor system. The whole sensorimotor network activation correlated with motor status at E2, indicating a recovery of its function when activated. Moreover, the activation pattern in the acute phase (E1) had a predictive value: early recruitment and high activation of the SMA and inferior BA 40 were correlated with a faster or better motor recovery. On the contrary, activation of the contralesional hemisphere (prefrontal cortex and BA 39-40) and of the posterior cingulate/precuneus (BA 7-31) predicted a slower recovery.

Adult↗

PubMed2003

Writing, calculating, and finger recognition in the region of the angular gyrus: a cortical stimulation study of Gerstmann syndrome.

OBJECT: In an attempt to gain a better understanding of the cerebral functions represented in the angular gyrus and to spare them during surgery, the authors studied patients with brain tumors located close to the angular gyrus and mapped cortical sites by using electrostimulation. METHODS: Before undergoing tumor removal, six right-handed patients (five with left and one with right hemisphere tumors) were studied using cortical mapping with the aid of calculating, writing, finger-recognition, and color-naming tasks in addition to standard reading and object-naming tasks (for a total of 36 brain mapping studies). Strict conditions of functional site validation were applied to include only those cortical sites that produced repetitive interferences in the function tested. Preoperatively, four of the patients exhibited discrete symptoms related to Gerstmann syndrome while performing very specific tasks, whereas the other two patients presented with no symptoms of the syndrome. No patient had significant language or apraxic deficits. Distinct or shared cortical sites producing interferences in calculating, finger recognition, and writing were repeatedly found in the angular gyrus. Object- or color-naming sites and reading-interference sites were also found in or close to the angular gyrus; although frequently demonstrated, these latter results were variable and unpredictable in the group of patients studied. Finger agnosia and acalculia sites were also found elsewhere, such as in the supramarginal gyrus or close to the intraparietal sulcus. Mechanisms involved in acalculia, agraphia, or finger agnosia (either complete interferences or hesitations) during stimulation were various, from an aphasia-like form (for instance, the patient did not understand the numbers or words given for calculating or writing tasks) to an apparently pure interference in the function tested (patients understood the numbers, but were unable to perform a simple addition). CONCLUSIONS: Symptoms of Gerstmann syndrome can be found during direct brain mapping in the angular gyrus region. In this series of patients, sites producing interferences in writing, calculating, and finger recognition were demonstrated in the angular gyrus, which may or may not have been associated with object-naming, color-naming, or reading sites.

Agnosia↗

PubMed2002

A single dose of the serotonin neurotransmission agonist paroxetine enhances motor output: double-blind, placebo-controlled, fMRI study in healthy subjects.

Since serotonin (5-HT) stimulates motor function, pharmacological potentiation of 5-HT neurotransmission may improve motor function in healthy subjects and, possibly, recovery in post-stroke patients. Indeed, fluoxetine, a selective serotonin reuptake inhibitor (SSRI), increased activation in executive motor areas of healthy subjects as fenozolone, a releaser of monoamines (including noradrenaline, dopamine, and serotonin) from intracellular stores. This study is intended to test the hypothesis that paroxetine can likewise modulate brain motor activity in a dose-dependent manner in healthy subjects. In a double-blind counterbalanced study, six subjects underwent functional MRI examinations on three sessions 1 week apart (E1, E2, and E3) at the time of peak plasma concentrations (5 h after drug intake, i.e., either 20 or 60 mg of paroxetine or placebo) with a complex sequential opposition task. Rest and activation alternated in a block design. During activation, subjects performed, with the right hand, a 1-Hz-paced task that alternated two fist closings with a sequential opposition task. Paroxetine elicited effects similar to those reported for fluoxetine; notable changes were hyperactivation in the contralateral S1/M1, and posterior SMA and widespread hypoactivation of basal ganglia and cerebellum. There was an inverse correlation between dose and effect: significantly greater effects were observed with the 20-mg dose compared with 60 mg. Paroxetine dose-dependently modulates activation of the entire motor pathway in a way that favors motor output. Thus, a single dose of the SSRI paroxetine reorganized motor processing.

Adult↗

PubMed2002

Selective serotonin reuptake inhibitor paroxetine modulates motor behavior through practice. A double-blind, placebo-controlled, multi-dose study in healthy subjects.

We hypothesized that selective serotonin reuptake inhibitors (SSRIs) could modulate motor activity in healthy subjects in a dose-dependent manner. The effects of a single dose of paroxetine were tested in a double-blind, placebo-controlled study. Six randomized and counterbalanced subjects performed behavioral tests in three sessions 1 week apart (E1, E2 and E3) at peak plasma concentration (5 h after drug intake). Each subject was given 20 mg or 60 mg of the drug, or a placebo. Tasks were the Nine Peg Hole test (three trials), Moede dexteritymeter (two trials), and compatible and incompatible reaction time tasks. The results show that at the first trials, performance did not differ after placebo or paroxetine intake. However, 20 and 60 mg of paroxetine improved performance significantly at the third trial of the Nine Peg Hole test and subjects receiving the drug performed 7% faster than those under placebo. An amount of 20 mg, but not 60 mg, of paroxetine improved dexterity significantly at the second trial of the Moede test and subjects performed 30% faster. Conversely, the drug did not affect reaction time for the compatible task and subjects were 11% slower under 20 mg with the incompatible task. Thus, paroxetine decreased the ability to inhibit automatism. Thus, it was concluded that a single dose of paroxetine improved motor performance through practice. But negative effects occurred on tasks including the inhibition of an automatism. Paroxetine enhanced brain motor output (motor activity in S1M1) [NeuroImage, 15 (2002) 26]. This S1M1 hyperactivation is likely to be responsible for the better performance. The brain effect and motor improvement were dose dependent. For both, 20 mg was the optimal dose.

Aged↗

PubMed2002

[Post-ischemia neurologic recovery].

Stroke is one of the most common affliction of patients with neurological symptoms. Rehabilitation of stroke patients is a difficult task. Our knowledge on rehabilitation has recently improved with the emergence of data from new neuroimaging techniques. A prospective, double blind, cross over, placebo, controlled study on 8 patients with pure motor hemiparesia, is conducted to determine the influence of a single dose of fluoxetine on motor performance and cerebral activation of patients recovering from stroke. Each patient undergoes two functional magnetic resonance imaging (fMRI) examinations, one under fluoxetine and one under placebo. A single dose of fluoxetine is enough to modulate cerebral sensori-motor activation and significantly improves motor skills of the affected side. Further studies are required to investigate the effect of chronic administration of fluoxetine on motor function.

Cross-Over Studies↗