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Gaël Nicolas,
Cyril Pottier,
David Maltête,
Sophie Coutant,
Anne Rovelet-Lecrux,
Solenn Legallic,
Stéphane Rousseau,
Yvan Vaschalde,
Lucie Guyant-Maréchal,
Jérôme Augustin, [......],
Pierre Krystkowiak, Jérémie Pariente,
Michel Clanet,
Pierre Labauge,
Xavier Ayrignac,
Romain Lefaucheur,
Isabelle Le Ber,
Thierry Frébourg,
Didier Hannequin,
Dominique Campion
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ABSTRACT: OBJECTIVES: To identify a new idiopathic basal ganglia calcification (IBGC)-causing gene. METHODS: In a 3-generation family with no SLC20A2 mutation, we performed whole exome sequencing in 2 affected first cousins, once removed. Nonsynonymous coding variants, splice acceptor and donor site variants, and frameshift coding indels (NS/SS/I) were filtered against dbSNP131, the HapMap Project, 1000 Genomes Project, and our in-house database including 72 exomes. RESULTS: Seventeen genes were affected by identical unknown NS/SS/I variations in the 2 patients. After screening the relatives, the p.Leu658Pro substitution within the PDGFRB gene remained the sole unknown mutation segregating with the disease in the family. This variation, which is predicted to be highly damaging, was present in 13 of 13 affected subjects and absent in 8 relatives without calcifications. Sequencing PDGFRB of 19 other unrelated IBGC cases allowed us to detect another potentially pathogenic substitution within PDGFRB, p.Arg987Trp, also predicted to be highly damaging. PDGFRB encodes a protein involved in angiogenesis and in the regulation of inorganic phosphate (Pi) transport in vascular smooth muscle cells via Pit-1, a Pi transporter encoded by SLC20A1. CONCLUSION: Mutations of PDGFRB further support the involvement of this biological pathway in IBGC pathophysiology.
Neurology 12/2012; · 8.31 Impact Factor
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Isabelle Le Ber,
Agnès Camuzat,
Lena Guillot-Noel,
Didier Hannequin,
Lucette Lacomblez,
Véronique Golfier,
Michèle Puel,
Olivier Martinaud,
Vincent Deramecourt,
Sophie Rivaud-Pechoux, [......],
Karl Mondon,
Elisabeth Tournier-Lasserve,
Cyril Goizet,
Marie Fleury,
Gabriel Viennet,
Patrice Verpillat,
Vincent Meininger,
Charles Duyckaerts,
Bruno Dubois,
Alexis Brice
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ABSTRACT: Frontotemporal dementia (FTD) refers to a disease spectrum including the behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), progressive supranuclear palsy/corticobasal degeneration syndrome (PSP/CBDS), and FTD with amyotrophic lateral sclerosis (FTD-ALS). A GGGGCC expansion in C9ORF72 is a major cause of FTD and ALS. C9ORF72 was analyzed in 833 bvFTD, FTD-ALS, PPA, and PSP/CBDS probands; 202 patients from 151 families carried an expansion. C9ORF72 expansions were much more frequent in the large subgroup of patients with familial FTD-ALS (65.9%) than in those with pure FTD (12.8%); they were even more frequent than in familial pure ALS, according to estimated frequencies in the literature (23-50%). The frequency of carriers in non-familial FTD-ALS (12.7%) indicates that C9ORF72 should be analyzed even when family history is negative. Mutations were detected in 6.8% of PPA patients, and in 3.2% of patients with a clinical phenotype of PSP, thus enlarging the phenotype spectrum of C9ORF72. Onset was later in C9ORF72 (57.4 years, 95%CI: 55.9-56.1) than in MAPT patients (46.8, 95%CI: 43.0-50.6; p = 0.00001) and the same as in PGRN patients (59.6 years; 95%CI: 57.6-61.7; p = 0.4). ALS was more frequent in C9ORF72 than in MAPT and PGRN patients; onset before age 50 and parkinsonism were indicative of MAPT mutations, whereas hallucinations were indicative of PGRN mutations; prioritization of genetic testing is thus possible. Penetrance was age- and gender-dependent: by age 50, 78% of male carriers were symptomatic, but only 52% of females. This can also guide genetic testing and counseling. A flowchart for genetic testing is thus proposed.
Journal of Alzheimer's disease: JAD 12/2012; · 3.74 Impact Factor
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Laure Saint-Aubert,
Pierre Payoux,
Didier Hannequin,
Emmanuel J Barbeau,
Dominique Campion,
Marie-Bernadette Delisle,
Mathieu Tafani,
Gérard Viallard,
Patrice Péran,
Michèle Puel,
François Chollet,
Jean-François Demonet, Jérémie Pariente
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ABSTRACT: We report the case of a 37-year-old man suffering from insidious visual agnosia and spastic paraparesis due to a PSEN1 mutation. His mother was diagnosed with Alzheimer disease after a biopsy. He was assessed by multimodal neuroimaging, including new in vivo positron emission tomography amyloid imaging (F-AV45). His data were compared with those from healthy participants and patients with sporadic predemential Alzheimer disease. He exhibited posterior cortical thickness reduction, posterior hypometabolism, and increased amyloid ligand uptake in the posterior cortex and the striatum. We show that F-AV45 positron emission tomography allows visualization of the unusual pattern of amyloid deposits that co-localize with cortical atrophy in this genetic form of Alzheimer disease.
Alzheimer disease and associated disorders 04/2012; · 2.88 Impact Factor
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David Wallon,
Stéphane Rousseau,
Anne Rovelet-Lecrux,
Muriel Quillard-Muraine,
Lucie Guyant-Maréchal,
Olivier Martinaud, Jérémie Pariente,
Michèle Puel,
Adeline Rollin-Sillaire,
Florence Pasquier, [......],
François Sellal,
Mathilde Sauvée,
Annie Laquerrière,
Charles Duyckaerts,
Marie-Bernadette Delisle,
Nathalie Streichenberger,
Béatrice Lannes,
Thierry Frebourg,
Didier Hannequin,
Dominique Campion
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ABSTRACT: We describe 56 novel autosomal dominant early-onset Alzheimer disease (ADEOAD) families with PSEN1, PSEN2, and AβPP mutations or duplications, raising the total of families with mutations on known genes to 111 (74 PSEN1, 8 PSEN2, 16 AβPP, and 13 AβPP duplications) in the French series. In 33 additional families (23% of the series), the genetic determinism remained uncharacterized after this screening. Cerebrospinal fluid (CSF) biomarker levels were obtained for patients of 58 families (42 with known mutations and 16 without genetic characterization). CSF biomarkers profile was consistent with an AD diagnosis in 90% of families carrying mutations on known genes. In families without mutation, CSF biomarkers were consistent with AD diagnosis in 14/16 cases. Overall, these results support further genetic heterogeneity in the determinism of ADEOAD and suggest that other major genes remain to be characterized.
Journal of Alzheimer's disease: JAD 04/2012; 30(4):847-56. · 3.74 Impact Factor
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Anne Rovelet-Lecrux,
Solenn Legallic,
David Wallon,
Jean-Michel Flaman,
Olivier Martinaud,
Stéphanie Bombois,
Adeline Rollin-Sillaire,
Agnès Michon,
Isabelle Le Ber, Jérémie Pariente,
Michèle Puel,
Claire Paquet,
Bernard Croisile,
Catherine Thomas-Antérion,
Martine Vercelletto,
Richard Lévy,
Thierry Frébourg,
Didier Hannequin,
Dominique Campion
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ABSTRACT: Studying rare extreme forms of Alzheimer disease (AD) may prove to be a useful strategy in identifying new genes involved in monogenic determinism of AD. Amyloid precursor protein (APP), PSEN1, and PSEN2 mutations account for only 85% of autosomal dominant early-onset AD (ADEOAD) families. We hypothesised that rare copy number variants (CNVs) could be involved in ADEOAD families without mutations in known genes, as well as in rare sporadic young-onset AD cases. Using high-resolution array comparative genomic hybridisation, we assessed the presence of rare CNVs in 21 unrelated ADEOAD cases, having no alteration on known genes, and 12 sporadic AD cases, with an age of onset younger than 55 years. The analysis revealed the presence of 7 singleton CNVs (4 in ADEOAD and 3 in sporadic cases) absent in 1078 controls and 912 late-onset AD cases. Strikingly, 4 out of 7 rearrangements target genes (KLK6, SLC30A3, MEOX2, and FPR2) encoding proteins that are tightly related to amyloid-β peptide metabolism or signalling. Although these variants are individually rare and restricted to particular subgroups of patients, these findings support the causal role, in human pathology, of a set of genes coding for molecules suspected for a long time to modify Aβ metabolism or signalling, and for which animal or cellular models have already been developed.
European journal of human genetics: EJHG 12/2011; 20(6):613-7. · 3.56 Impact Factor
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Laure Saint-Aubert,
Mélanie Planton,
Didier Hannequin,
Jean-François Albucher,
Marie-Bernadette Delisle,
Pierre Payoux,
Anne Hitzel,
Gérard Viallard,
Patrice Péran,
Dominique Campion,
Annie Laquerrière,
Emmanuel J Barbeau,
Michéle Puel,
Nicolas Raposo,
François Chollet, Jérémie Pariente
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ABSTRACT: We report the case of a 62-year-old asymptomatic carrier of AβPP gene duplication. He was investigated by MRI and the amyloid ligand (18)F-AV45, and compared to Alzheimer's disease patients (n = 11) and healthy controls (n = 11). The neuropsychological examination was normal. Cortical thickness and AV45 retention were comparable to Alzheimer's disease patients. AβPP duplication was diagnosed because cerebral amyloid angiopathy and Alzheimer's disease pathology were found on the neuropathological examination of his youngest brother, who died at 42 from intracerebral hemorrhage. This is the first description of a pre-symptomatic AβPP duplication carrier over 60, despite widespread cerebral amyloid angiopathy, "Alzheimer's like" atrophy, and amyloid deposition.
Journal of Alzheimer's disease: JAD 12/2011; 28(4):877-83. · 3.74 Impact Factor
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ABSTRACT: Little is known about the outcome and recovery mechanisms of visual perception after a focal lesion of the occipital lobe in humans, especially after stroke. In this study, the authors aimed to describe the clinical course and the neural substrates of conscious perceptive visual deficit after posterior cerebral artery infarct.
The authors prospectively included 8 patients (7 men and 1 woman; mean age, 64.6 ± 18 years) with visual deficit induced by partial damage of the striate cortex related to acute posterior cerebral artery infarct. Conscious perception of color and motion was assessed from the acute phase to the third month. Functional magnetic resonance imaging was performed to investigate neural substrates of visual recovery.
In the acute phase of stroke, visual deficiency was global (3/8 patients), selective to color (4/8 patients), or selective to motion (1/8 patients). During the follow-up, visual performance increased with respect to color (from 29% to 70%; P < .005) and with respect to motion (from 47% to 74%; P < .005). Despite a lack of ipsilesional V1 area activation in the acute phase, activations in this area and in the contralesional extrastriate cortex were obtained during follow-up. Both ipsilesional and contralesional V4 activations were correlated with better outcome.
Extensive visual recovery occurs early after partial acute posterior cerebral artery infarct. Spared islands in ipsilesional V1 area and transcallosal pathways might be involved in poststroke visual recovery.
Neurorehabilitation and neural repair 06/2011; 25(8):703-10. · 4.49 Impact Factor
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François Chollet,
Jean Tardy,
Jean-François Albucher,
Claire Thalamas,
Emilie Berard,
Catherine Lamy,
Yannick Bejot,
Sandrine Deltour,
Assia Jaillard,
Philippe Niclot,
Benoit Guillon,
Thierry Moulin,
Philippe Marque, Jérémie Pariente,
Catherine Arnaud,
Isabelle Loubinoux
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ABSTRACT: Hemiplegia and hemiparesis are the most common deficits caused by stroke. A few small clinical trials suggest that fluoxetine enhances motor recovery but its clinical efficacy is unknown. We therefore aimed to investigate whether fluoxetine would enhance motor recovery if given soon after an ischaemic stroke to patients who have motor deficits.
In this double-blind, placebo-controlled trial, patients from nine stroke centres in France who had ischaemic stroke and hemiplegia or hemiparesis, had Fugl-Meyer motor scale (FMMS) scores of 55 or less, and were aged between 18 years and 85 years were eligible for inclusion. Patients were randomly assigned, using a computer random-number generator, in a 1:1 ratio to fluoxetine (20 mg once per day, orally) or placebo for 3 months starting 5-10 days after the onset of stroke. All patients had physiotherapy. The primary outcome measure was the change on the FMMS between day 0 and day 90 after the start of the study drug. Participants, carers, and physicians assessing the outcome were masked to group assignment. Analysis was of all patients for whom data were available (full analysis set). This trial is registered with ClinicalTrials.gov, number NCT00657163.
118 patients were randomly assigned to fluoxetine (n=59) or placebo (n=59), and 113 were included in the analysis (57 in the fluoxetine group and 56 in the placebo group). Two patients died before day 90 and three withdrew from the study. FMMS improvement at day 90 was significantly greater in the fluoxetine group (adjusted mean 34·0 points [95% CI 29·7-38·4]) than in the placebo group (24·3 points [19·9-28·7]; p=0·003). The main adverse events in the fluoxetine and placebo groups were hyponatraemia (two [4%] vs two [4%]), transient digestive disorders including nausea, diarrhoea, and abdominal pain (14 [25%] vs six [11%]), hepatic enzyme disorders (five [9%] vs ten [18%]), psychiatric disorders (three [5%] vs four [7%]), insomnia (19 [33%] vs 20 [36%]), and partial seizure (one [<1%] vs 0).
In patients with ischaemic stroke and moderate to severe motor deficit, the early prescription of fluoxetine with physiotherapy enhanced motor recovery after 3 months. Modulation of spontaneous brain plasticity by drugs is a promising pathway for treatment of patients with ischaemic stroke and moderate to severe motor deficit.
Public French National Programme for Clinical Research.
The Lancet Neurology 02/2011; 10(2):123-30. · 23.46 Impact Factor
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ABSTRACT: There is an ongoing debate regarding the respective role of anterior subhippocampal structures and the hippocampus in recognition memory. Here, we report a double anatomo-functional dissociation observed in two brain-damaged patients, FRG and JMG. They both suffered from complete destruction of left MTL structures. In the right hemisphere however, FRG sustained extensive lesions to the hippocampus sparing anterior subhippocampal structures, while JMG suffered from the reversed pattern of lesion, i.e., extensive damage to anterior subhippocampal structures but preserved hippocampus. FRG was severely amnesic and failed all recall tasks involving visual material, but exhibited normal performance at a large battery of visual recognition memory tasks. JMG was not amnesic and showed the opposite pattern of performance. These results strongly support the view that right anterior subhippocampal structures are a critical relay for visual recognition memory in the human.
Hippocampus 11/2010; 21(9):929-34. · 5.18 Impact Factor
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ABSTRACT: Brain atrophy measured by magnetic resonance structural imaging has been proposed as a surrogate marker for the early diagnosis of Alzheimer's disease. Studies on large samples are still required to determine its practical interest at the individual level, especially with regards to the capacity of anatomical magnetic resonance imaging to disentangle the confounding role of the cognitive reserve in the early diagnosis of Alzheimer's disease. One hundred and thirty healthy controls, 122 subjects with mild cognitive impairment of the amnestic type and 130 Alzheimer's disease patients were included from the ADNI database and followed up for 24 months. After 24 months, 72 amnestic mild cognitive impairment had converted to Alzheimer's disease (referred to as progressive mild cognitive impairment, as opposed to stable mild cognitive impairment). For each subject, cortical thickness was measured on the baseline magnetic resonance imaging volume. The resulting cortical thickness map was parcellated into 22 regions and a normalized thickness index was computed using the subset of regions (right medial temporal, left lateral temporal, right posterior cingulate) that optimally distinguished stable mild cognitive impairment from progressive mild cognitive impairment. We tested the ability of baseline normalized thickness index to predict evolution from amnestic mild cognitive impairment to Alzheimer's disease and compared it to the predictive values of the main cognitive scores at baseline. In addition, we studied the relationship between the normalized thickness index, the education level and the timeline of conversion to Alzheimer's disease. Normalized thickness index at baseline differed significantly among all the four diagnosis groups (P < 0.001) and correctly distinguished Alzheimer's disease patients from healthy controls with an 85% cross-validated accuracy. Normalized thickness index also correctly predicted evolution to Alzheimer's disease for 76% of amnestic mild cognitive impairment subjects after cross-validation, thus showing an advantage over cognitive scores (range 63-72%). Moreover, progressive mild cognitive impairment subjects, who converted later than 1 year after baseline, showed a significantly higher education level than those who converted earlier than 1 year after baseline. Using a normalized thickness index-based criterion may help with early diagnosis of Alzheimer's disease at the individual level, especially for highly educated subjects, up to 24 months before clinical criteria for Alzheimer's disease diagnosis are met.
Brain 05/2009; 132(Pt 8):2036-47. · 9.46 Impact Factor
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ABSTRACT: The first objective of the study was to determine whether functional magnetic resonance imaging (fMRI) signal was correlated with motor performance at different stages of poststroke recovery. The second objective was to assess the existence of prognostic factors for recovery in early functional MR images. Eight right-handed patients with pure motor deficit secondary to a first lacunar infarct localized on the pyramidal tract were included. This study concerned moderately impaired patients and recovery of handgrip strength and finger-tapping speed. The fMRI task was a calibrated flexion-extension movement. Ten healthy subjects served as a control group. The intensity of the activation in the "classical" motor network (ipsilesional S1M1, ipsilesional ventral premotor cortex [BA 6], contralesional cerebellum) 20 days after stroke was indicative of the performance (positive correlation). The cluster in M1 was posterior and circumscribed to BA 4p. No area was associated with bad performance (negative correlation). No correlation was found 4 and 12 months after stroke. Prognosis factors were evidenced. The higher early the activation in the ipsilesional M1 (BA 4p), S1, and insula, the better the recovery 1 year after stroke. Although the lesions partly deefferented the primary motor cortex, patients who activated the posterior primary motor cortex early had a better recovery of hand function. This suggests that there is benefit in increasing ipsilesional M1 activity shortly after stroke as a rehabilitative approach in mildly impaired patients.
Cerebral Cortex 12/2007; 17(12):2980-7. · 6.54 Impact Factor
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Jean Tardy, Jérémie Pariente,
Anne Leger,
Sophie Dechaumont-Palacin,
Angélique Gerdelat,
Vincent Guiraud,
Fabrice Conchou,
Jean-François Albucher,
Philippe Marque,
Xavier Franceries,
Christophe Cognard,
Olivier Rascol,
François Chollet,
Isabelle Loubinoux
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ABSTRACT: We hypothesized that a single dose of methylphenidate (MP) would modulate cerebral motor activation and behavior in patients having suffered a subcortical stroke.
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.
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.
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.
NeuroImage 12/2006; 33(3):913-22. · 5.89 Impact Factor
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Jérémie Pariente,
Susanna Cole,
Richard Henson,
Linda Clare,
Angus Kennedy,
Martin Rossor,
Lisa Cipoloti,
Michèle Puel,
Jean Francois Demonet,
Francois Chollet,
Richard S J Frackowiak
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ABSTRACT: We conducted an event-related functional magnetic resonance imaging experiment to better understand the potentially compensatory alternative brain networks activated by a clinically relevant face-name association task in Alzheimer's disease (AD) patients and matched control subjects. We recruited 17 healthy subjects and 12 AD patients at an early stage of the disease. They underwent functional magnetic resonance imaging scanning in four sessions. Each of the sessions combined a "study" phase and a "test" phase. Face/name pairs were presented in each study phase, and subjects were asked to associate faces with names. In the test phase, a recognition task, faces seen in the study phase were presented each with four different names. The task required selection of appropriate previously associated names from the study phase. Responses were recorded for post hoc classification into those successfully or unsuccessfully encoded. There were significant differences between the groups in accuracy and reaction time. Comparison of correctly versus incorrectly encoded and recognized pairs in the two groups indicated bilateral hippocampal hypoactivation both when encoding and recognizing in the AD group. Moreover, patients showed bilateral hyperactivation of parts of the parietal and frontal lobes. We discuss whether hyperactivation of a frontoparietal network reflects compensatory strategies for failing associative memory in AD patients.
Annals of Neurology 01/2006; 58(6):870-9. · 11.09 Impact Factor
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ABSTRACT: 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.
NeuroImage 08/2005; 27(2):299-313. · 5.89 Impact Factor
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ABSTRACT: Both specific and non-specific factors may play a role in acupuncture therapy for pain. We explored the cerebral consequences of needling and expectation with real acupuncture, placebo acupuncture and skin-prick, using a single-blind, randomized crossover design with 14 patients suffering from painful osteoarthritis, who were scanned with positron emission tomography (PET). The three interventions, all of which were sub-optimal acupuncture treatment, did not modify the patient's pain. The insula ipsilateral to the site of needling was activated to a greater extent during real acupuncture than during the placebo intervention. Real acupuncture and placebo (with the same expectation of effect as real acupuncture) caused greater activation than skin prick (no expectation of a therapeutic effect) in the right dorsolateral prefrontal cortex, anterior cingulate cortex, and midbrain. These results suggest that real acupuncture has a specific physiological effect and that patients' expectation and belief regarding a potentially beneficial treatment modulate activity in component areas of the reward system.
NeuroImage 06/2005; 25(4):1161-7. · 5.89 Impact Factor
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ABSTRACT: 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.
NeuroImage 12/2004; 23(3):827-39. · 5.89 Impact Factor
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ABSTRACT: 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.
NeuroImage 01/2004; 20(4):2166-80. · 5.89 Impact Factor
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ABSTRACT: 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.
Bulletin de l'Académie nationale de médecine 02/2002; 186(6):1015-23; discussion 1023-4. · 0.25 Impact Factor
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ABSTRACT: 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.
NeuroImage 02/2002; 15(1):26-36. · 5.89 Impact Factor
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ABSTRACT: 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.
Neuropsychologia 02/2002; 40(11):1815-21. · 3.64 Impact Factor
