Sophie Rivaud-Péchoux - Academia.edu (original) (raw)

Papers by Sophie Rivaud-Péchoux

Journal of …, 1999

Behavioral studies in monkeys and humans suggest that systematic and variable errors of memory-gu... more Behavioral studies in monkeys and humans suggest that systematic and variable errors of memory-guided saccades reflect distinct neuronal computations in primate spatial memory. We recorded memory-guided saccades with a 2-s delay in three patients with ...

Therapeutic advances in neurological disorders, 2012

Vitamin D could play a protective role in multiple sclerosis. In an observational, uncontrolled s... more Vitamin D could play a protective role in multiple sclerosis. In an observational, uncontrolled study, vitamin D3 supplementation (3010 IU/day on average) was given to 156 consecutive patients with relapsing-remitting multiple sclerosis, under first-line immunomodulatory therapy and with initial 25-OH-D serum level lower than 100 nmol/l (40 ng/ml). Relapses were determined for 29.1 ± 8.4 months during vitamin D and 29.8 ± 10.1 months before supplementation. The 25-OH-D level was measured before supplementation and several times during supplementation. The incidence rate of relapses before and during supplementation was estimated using negative binomial regression models with follow-up durations as offset terms. The incidence rate and incidence rate ratio of relapses at various 25-OH-D levels were also calculated using negative binomial regression models. In 76 patients, immunomodulatory therapy preceded vitamin D supplementation (by 4.2 ± 2.7 years) and in 80 patients both treatment...

Neurology, Jan 9, 2014

The aim of this study was to establish the frequency of ATXN2 polyglutamine (polyQ) expansion in ... more The aim of this study was to establish the frequency of ATXN2 polyglutamine (polyQ) expansion in large cohorts of patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP), and to evaluate whether ATXN2 could act as a modifier gene in patients carrying the C9orf72 expansion. We screened a large cohort of French patients (1,144 ALS, 203 FTD, 168 FTD-ALS, and 109 PSP) for ATXN2 CAG repeat length. We included in our cohort 322 carriers of the C9orf72 expansion (202 ALS, 63 FTD, and 57 FTD-ALS). We found a significant association with intermediate repeat size (≥29 CAG) in patients with ALS (both familial and sporadic) and, for the first time, in patients with familial FTD-ALS. Of interest, we found the co-occurrence of pathogenic C9orf72 expansion in 23.2% of ATXN2 intermediate-repeat carriers, all in the FTD-ALS and familial ALS subgroups. In the cohort of C9orf72 carriers, 3.1% of patients also carried an intermediate AT...

Journal of Alzheimer's Disease, 2013

Neurobiology of Aging, 2014

a b s t r a c t TMEM106B was identified as a risk factor for frontotemporal lobar degeneration (F... more a b s t r a c t TMEM106B was identified as a risk factor for frontotemporal lobar degeneration (FTD) with TAR DNAbinding protein 43 kDa inclusions. It has been reported that variants in this gene are genetic modifiers of the disease and that this association is stronger in patients carrying a GRN mutation or a pathogenic expansion in chromosome 9 open reading frame 72 (C9orf72) gene. Here, we investigated the contribution of TMEM106B polymorphisms in cohorts of FTD and FTD with amyotrophic lateral sclerosis patients from France and Italy. Patients carrying the C9orf72 expansion (n ¼ 145) and patients with GRN mutations (n ¼ 76) were compared with a group of FTD patients (n ¼ 384) negative for mutations and to a group of healthy controls (n ¼ 552). In our cohorts, the presence of the C9orf72 expansion did not correlate with TMEM106B genotypes but the association was very strong in individuals with pathogenic GRN mutations (p ¼ 9.54 Â 10 À6 ). Our data suggest that TMEM106B genotypes differ in FTD patient cohorts and strengthen the protective role of TMEM106B in GRN carriers. Further studies are needed to determine whether TMEM106B polymorphisms are associated with other genetic causes for FTD, including C9orf72 repeat expansions.

Revue Neurologique, 2006

ABSTRACT Introduction Autosomal recessive cerebellar ataxias (ARCA) comprise a phenotypically and... more ABSTRACT Introduction Autosomal recessive cerebellar ataxias (ARCA) comprise a phenotypically and genetically heterogeneous group of diseases. Recently, a subgroup of ARCA associated with oculomotor apraxia has been delineated. State of the art The ataxias with oculomotor apraxia (AOA) include four distinct genetic entities at least: ataxia-telangiectasia, ataxia telangiectasia-like disorder, ataxia with oculomotor apraxia type 1 (AOA1) and type 2 (AOA2). The responsible genes, ATM, MRE11, APTX and SETX respectively, are implicated in DNA-break repair mechanisms. Conclusion We describe the phenotypic and genetic characteristics of these ataxias, based on a review of the literature and a personal study of AOA1 and AOA2 patients.

Psychopharmacology, 2010

Background Ketamine, a non-competitive N-methyl-Daspartic acid antagonist, has been widely used f... more Background Ketamine, a non-competitive N-methyl-Daspartic acid antagonist, has been widely used for anaesthetic purposes. At sub-anaesthetic dosage, it induces a dissociative state similar to schizophrenia. The discovery of this effect on dissociative state has led to its use as a pharmacological model of schizophrenia and has also been responsible for its illegal use as a recreational drug. Whereas the former has provided invaluable information, the latter has demonstrated that repeated administration of ketamine induces tolerance. Surprisingly, a review of the relevant literature shows that tolerance to sub-anaesthetic doses of ketamine is largely unreported in neuropharmacological studies. Methods In order to investigate this caveat, we have performed a post hoc analysis of the behavioural effects induced by repeated injections of sub-anaesthetic doses of ketamine observed in five consecutive monkeys performing two oculomotor tasks. Ketamine effects were quantified by the animals' performances and latencies in a prosaccade and an antisaccade task, two oculomotor paradigms that are impaired after ketamine administration. Results Although the result of the initial injections confirmed a clear behavioural effect of ketamine injections in all monkeys, subsequent administrations showed that a tolerance eventually appeared in all monkeys. The profile of this tolerance exhibited however a large inter-subject variability.

PLoS ONE, 2009

High intraindividual performance variability is one of the most robust findings to emerge in cogn... more High intraindividual performance variability is one of the most robust findings to emerge in cognitive-experimental research of attention deficit hyperactivity disorder (ADHD). Evidences from studies incorporating structural or functional human brain mapping methods indicate that this increased intraindividual variability is not simply a sequel of general brain dysfunction, but is likely related to the functioning of neural circuits that engage the prefrontal cortex, particularly the dorsolateral areas (dlPFC). In order to examine further the anatomical and pharmacological substrate responsible for this high intraindividual variability disorder, we injected GABA A antagonist (bicuculline) or GABA A agonist (muscimol) in the dlPFC of monkeys performing a reflexive oculomotor task. Here we show that, whereas GABA A agonist injection induced no or minimal impairments, injection of GABA A antagonist dramatically increased the intraindividual variability of saccade response time and of saccade spatial accuracy (amplitude and direction). Overall, this study demonstrates that the balance between excitatory/inhibitory activities in the dlPFC is fragile but crucial, since local micro-injection of GABA A antagonist can induce marked behavioural effects. It also reveals that higher cognitive areas such as the dlPFC are markedly capable to influence the productions and metrics of reflexive movements. Altogether, this study provides promising perspectives for the development of new therapeutic strategies for the treatment of diseases in which high intravariability disorders are a prominent feature.

Neuroreport, 2002

Cortical stimulation is a useful way of elucidating the cortical control of eye movements.The aim... more Cortical stimulation is a useful way of elucidating the cortical control of eye movements.The aim of this study was to determine the type of eye movements evoked in response to intraoperative electrical stimulation of the frontal eye f|eld (FEF) region in a fully awake patient during surgery for a frontal lobe glioma. A train of low-intensity electrical pulses within an area in the precentral gyrus evoked contraversive smooth eye movements (SEM) recorded electro-oculographically. Stimulation of an anterior sub-region of this electrically determined FEF disclosed both SEM and suppression of self-paced saccades. However, electrical stimulation of this region evoked no saccades in agreement with pre-operative fMRI using a self-paced saccade paradigm, which did not show activation within the ipsilateral FEF. In humans, intraoperative FEF stimulation may elicit recordable contraversive SEM, and interfere with oculomotor behaviour, suppressing self-paced saccades.

Neuropsychologia, 2000

To study the temporal organisation of memory-guided saccade control we used single-pulse transcra... more To study the temporal organisation of memory-guided saccade control we used single-pulse transcranial magnetic stimulation (TMS) over the left posterior parietal (PPC) and prefrontal cortex (PFC) in eight healthy subjects. TMS was applied either following presentation of a visual target, i.e. 160, 260, and 360 ms after the¯ashed point, or during the period of memorisation, i.e. between 700 and 1500 ms, or ®nally 100 ms after extinguishing of the central ®xation point (i.e. 2100 ms after the target presentation). Latency of memory-guided saccades and the percentage of error in amplitude (PEA) was measured and compared with results without stimulation.

Neurobiology of Disease, 2012

Hereditary spastic paraplegias (HSPs) are rare neurological conditions caused by degeneration of ... more Hereditary spastic paraplegias (HSPs) are rare neurological conditions caused by degeneration of the long axons of the cerebrospinal tracts, leading to locomotor impairment and additional neurological symptoms. There are more than 40 different causative genes, 24 of which have been identified, including SPG11 and SPG15 mutated in complex clinical forms. Since the vast majority of the causative mutations lead to loss of function of the corresponding proteins, we made use of morpholino-oligonucleotide (MO)-mediated gene knock-down to generate zebrafish models of both SPG11 and SPG15 and determine how invalidation of the causative genes (zspg11 and zspg15) during development might contribute to the disease. Micro-injection of MOs targeting each gene caused locomotor impairment and abnormal branching of spinal cord motor neurons at the neuromuscular junction. More severe phenotypes with abnormal tail developments were also seen. Moreover, partial depletion of both proteins at sub-phenotypic levels resulted in the same phenotypes, suggesting for the first time, in vivo, a genetic interaction between these genes. In conclusion, the zebrafish orthologues of the SPG11 and SPG15 genes are important for proper development of the axons of spinal motor neurons and likely act in a common pathway to promote their proper path finding towards the neuromuscular junction.

Journal of Neurology, Neurosurgery & Psychiatry, 2011

Background Recent neuroimaging studies point to a possible pathophysiological role of cerebellar ... more Background Recent neuroimaging studies point to a possible pathophysiological role of cerebellar dysfunction in dystonia. The authors investigated the association between sensorimotor adaptation, cerebellar dysfunction and the myoclonusedystonia phenotype. Methods The authors prospectively analysed reactive saccade adaptation in a genetically homogeneous group of 14 patients with DYT11 dystonia owing to a mutation of the SGCE gene. The authors used a backward reactive saccade adaptation task, a well-characterised experimental oculomotor paradigm involving the cerebellum. The principle of this paradigm is to simulate a spatial error in saccade generation by systematically shifting a visual target during saccade execution. Repetition of this systematic error induces a gradual decrease in the initial saccade amplitude, reflecting an adaptive phenomenon. Results Saccade adaptation was significantly lower in the DYT11 patients than in healthy controls (mean value: 8.9%64.5% vs 21.6%64.5%; p¼8.3310 À6 ). The time course of adaptation also differed between the patients and controls (p¼0.002), reflecting the slower saccadic adaptation in the patients. Conclusions This study provides the first neurophysiological evidence of cerebellar dysfunction in DYT11 dystonia and supports a role of cerebellar dysfunction in the myoclonusedystonia phenotype.

Journal of Neurology, Neurosurgery & Psychiatry, 2000

Recent studies in the monkey suggest that the subthalamic nucleus (STN) is involved in control of... more Recent studies in the monkey suggest that the subthalamic nucleus (STN) is involved in control of eye movement, yet its functional significance in humans is unknown. Saccadic eye movements were studied in eight parkinsonian patients treated by bilateral electrical stimulation of the STN. STN stimulation improved the accuracy of memory guided saccades but not of reflexive visually guided saccades and had no eVect on the antisaccade task. This study shows that, by contrast with levodopa, STN stimulation improves memory guided saccade deficits, and illustrates for the first time in humans the role of the STN in the control of purposive saccades. (J Neurol Neurosurg Psychiatry 2000;68:381-384)

Journal of Cognitive Neuroscience, 2008

The presentation of saccadic and smooth pursuit eye movements as two separate systems has recentl... more The presentation of saccadic and smooth pursuit eye movements as two separate systems has recently been reconsidered: The two subsystems share a number of anatomical structures, and recent data suggest that this sharing also extends to physiological processes. The aim of our study was first to test whether these two subsystems share a common predictive process. We designed a new predictive smooth pursuit paradigm that requires the triggering of unpredictable saccades, performed either during low (ongoing pursuit) or high (pursuit direction reversal) predictive behavior. Saccade latency was used as a probe to reveal a possible sharing of prediction between the two subsystems. The main finding was that saccade latencies were markedly decreased when triggered around pursuit direction reversal and performed in the direction of the predicted pursuit. The aim of the second part of this study was to determine the neural substrate of this common predictive process. According to previous studies, the supplementary eye field (SEF) would be involved in the control of predictive pursuit. The same subjects therefore performed the same tasks, and transcranial magnetic stimulation (TMS) was applied over this area: Decreased saccade latencies were no longer observed, whereas it continued to be observed when applied over the occipital cortex. These results are consistent with (1) The existence of a common predictive process shared by both oculomotor subsystems; (2) The view of the SEF not as a primary oculomotor area but as a higher order structure able to elaborate complex processes, such as prediction, independently of the oculomotor output.

Investigative Ophthalmology & Visual Science, 2003

PURPOSE. The prefrontal cortex (PFC) is known to inhibit unwanted saccades through its connection... more PURPOSE. The prefrontal cortex (PFC) is known to inhibit unwanted saccades through its connections to the superior colliculus (SC). Indeed, transcranial magnetic stimulation (TMS) of the PFC decreases saccade latency by increasing the rate of express saccades. This study examined whether a similar phenomenon exists for vergence. METHODS. In a gap paradigm, six healthy subjects were asked to look at LEDs placed in a horizontal plane and to make lateral saccades, pure convergence along the median plane, and combined eye movements. Eye movements were recorded binocularly. TMS was applied over the right (r)PFC synchronously with the onset of the target. In a control condition, TMS was applied over the motor cortex (MC). RESULTS. TMS over the MC had no effect on the latency of any type of eye movements. In contrast, TMS over the rPFC (1) decreased significantly (P ϭ 0.00367) the latency of contralateral pure saccades, (2) had no effect on the latency of pure convergence, (3) and caused a mild decrease in the latency of both the saccadic and the convergence components of combined eye movements, and the effect was bilateral. Decreased latencies were mainly due to an increase of the rate of express movements. CONCLUSIONS. The inhibition exerted by PFC over SC and preventing express movements from occurring is presumably a saccade-specific mechanism. When the saccade is combined with convergence, the express triggering can be transferred to a certain extent to the convergence. (Invest Ophthalmol Vis Sci. 2003;44:600 -609)

Experimental Brain Research, 1991

Memory-guided saccades were electro-oculographically recorded in 30 patients with limited unilate... more Memory-guided saccades were electro-oculographically recorded in 30 patients with limited unilateral cerebral infarction, documented by computerized tomographic scan and/or magnetic resonance imaging. The lesions affected either (1) the posterior parietal cortex (PPC), (2) the dorsolateral frontal cortex (DLFC), involving the frontal eye field (FEF) and/or the prefrontal cortex (PFC) (area 46 of Brodmann), or (3) the supplementary motor area in the dorsomedial frontal cortex (DMFC). Patients were divided into 6 groups according to the location (PPC, DLFC, DMFC) and side of the lesions. Both latency and accuracy (expressed as percentage of error in amplitude) of memory-guided saccades were compared in each group of patients to values obtained from 20 age-matched normal subjects. Latency was significantly increased, for both directions of saccades in the two DLFC groups and in the right PPC group, and for leftward saccades in the left PPC group. The percentage of error in amplitude was also significantly increased for both directions of saccades in the right PPC group and the left DLFC group, and for leftward saccades in the right DLFC group. Results were near the normal values in patients with lesions affecting the DMFC. Thus, both the PPC (essentially on the right side) and the DLFC appear to play a role in the control of memory-guided saccades. It is suggested that the cortical pathway involved in these saccades includes the PPC, the PFC and the FEF, successively. The PPC could have a dual role: visuospatial integration, and early selection and preparation of certain collicular cells by pre-excitation. Both functions could be ensured by two different types of cells, corresponding, in the monkey, to area 7a and to lateral intraparietal area, respectively. The DLFC could also have a dual role: memorization of visuospatial information by the PFC, and triggering of memory-guided saccades by the FEF.

European Journal of Neuroscience, 2007

In the anti-saccade paradigm, subjects are instructed not to make a reflexive saccade to an appea... more In the anti-saccade paradigm, subjects are instructed not to make a reflexive saccade to an appearing lateral target but to make an intentional saccade to the opposite side instead. The inhibition of reflexive saccade triggering is under the control of the dorsolateral prefrontal cortex (DLPFC). The critical time interval at which this inhibition takes place during the paradigm, however, is not exactly known. In the present study, we used single-pulse transcranial magnetic stimulation (TMS) to interfere with DLPFC function in 15 healthy subjects. TMS was applied over the right DLPFC either 100 ms before the onset of the visual target (i.e. )100 ms), at target onset (i.e. 0 ms) or 100 ms after target onset (i.e. +100 ms). Stimulation 100 ms before target onset significantly increased the percentage of anti-saccade errors to both sides, while stimulation at, or after, target onset had no significant effect. All three stimulation conditions had no significant influence on saccade latency of correct or erroneous anti-saccades. These findings show that the critical time interval at which the DLPFC controls the suppression of a reflexive saccade in the anti-saccade paradigm is before target onset. In addition, the results suggest the view that the triggering of correct anti-saccades is not under direct control of the DLPFC.

European Journal of Neurology, 2007

The efficacy of gabapentin on motor, oculomotor and frontal lobe symptoms was evaluated in patien... more The efficacy of gabapentin on motor, oculomotor and frontal lobe symptoms was evaluated in patients with progressive supranuclear palsy (PSP) in a pilot study. Fourteen patients were included and seven of them received gabapentin. Clinical evaluation and horizontal eye movement recordings were performed at inclusion and 5-weeks later. Motor score and saccade latency in the visually guided saccade (VGS) task were identical in the two groups. However, the error rate in the antisaccade task was significantly decreased in the gabapentin group. This preliminary study shows that gabapentin improves reflexive saccade inhibition in patients with PSP but does not improve the latency of VGSs.

Cortex, 2011

Computational model a b s t r a c t Diagonistic dyspraxia (DD) is a behavioural disorder encounte... more Computational model a b s t r a c t Diagonistic dyspraxia (DD) is a behavioural disorder encountered in split-brain subjects in which the left arm acts against the subject's will, deliberately counteracting what the right arm does. We report here an oculomotor and computational study of a patient with a long lasting form of DD. A first series of oculomotor paradigms revealed marked and unprecedented saccade impairments. We used a computational model in order to provide information about the impaired decision-making process: the analysis of saccade latencies revealed that variations of decision times were explained by adjustments of response criterion. This result and paradoxical impairments observed in additional oculomotor paradigms allowed to propose that this adjustment of the criterion level resulted from the co-existence of counteracting oculomotor programs, consistent with the existence of antagonist programs in homotopic cortical areas. In the intact brain, trans-hemispheric inhibition would allow suppression of these counter programs. Depending on the topography of the disconnected areas, various motor and/or behavioural impairments would arise in split-brain subjects. In motor systems, such conflict would result in increased criteria for desired movement execution (oculomotor system) or in simultaneous execution of counteracting movements (skeletal motor system). At higher cognitive levels, it may result in conflict of intentions. ª (B. Gaymard). a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / c o r t e x c o r t e x 4 7 ( 2 0 1 1 ) 4 7 3 e4 8 3 0010-9452/$ e see front matter ª