A Fragile Balance: Perturbation of GABA Mediated Circuit in Prefrontal Cortex Generates High Intraindividual Performance Variability

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 GABAA antagonist (bicuculline) or GABAA agonist (muscimol) in the dlPFC of monkeys performing a reflexive oculomotor task. Here we show that, whereas GABAA agonist injection induced no or minimal impairments, injection of GABAA 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 GABAA 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

Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies

Ataxia with ocular motor apraxia type 1 (AOA1) is an autosomal recessive cerebellar ataxia (ARCA) associated with oculomotor apraxia, hypoalbuminaemia and hypercholesterolaemia. The gene APTX, which encodes aprataxin, has been identified recently. We studied a large series of 158 families with non‐Friedreich progressive ARCA. We identified 14 patients (nine families) with five different missense or truncating mutations in the aprataxin gene (W279X, A198V, D267G, W279R, IVS5+1), four of which were new. We determined the relative frequency of AOA1 which is 5%. Mutation carriers underwent detailed neurological, neuropsychological, electrophysiological, oculographic and biological examinations, as well as brain imaging. The mean age at onset was 6.8± 4.8 years (range 2-18 years). Cerebellar ataxia with cerebellar atrophy on MRI and severe axonal sensorimotor neuropathy were present in all patients. In contrast, oculomotor apraxia (86%), hypoalbuminaemia (83%) and hypercholesterolaemia (75%) were variable. Choreic movements were frequent at onset (79%), but disappeared in the course of the disease in most cases. However, a remarkably severe and persistent choreic phenotype was associated with one of the mutations (A198V). Cognitive impairment was always present. Ocular saccade initiation was normal, but their duration was increased by the succession of multiple hypometric saccades that could clinically be confused with ‘slow saccades'. We emphasize the phenotypic variability over the course of the disease. Cerebellar ataxia and/or chorea predominate at onset, but later on they are often partially masked by severe neuropathy, which is the most typical symptom in young adults. The presence of chorea, sensorimotor neuropathy, oculomotor anomalies, biological abnormalities, cerebellar atrophy on MRI and absence of the Babinski sign can help to distinguish AOA1 from Friedreich's ataxia on a clinical basis. The frequency of chorea at onset suggests that this diagnosis should also be considered in children with chorea who do not carry the IT15 mutation responsible for Huntington's diseas

Frontal Non-Invasive Neurostimulation Modulates Antisaccade Preparation in Non-Human Primates

A combination of oculometric measurements, invasive electrophysiological recordings and microstimulation have proven instrumental to study the role of the Frontal Eye Field (FEF) in saccadic activity. We hereby gauged the ability of a non-invasive neurostimulation technology, Transcranial Magnetic Stimulation (TMS), to causally interfere with frontal activity in two macaque rhesus monkeys trained to perform a saccadic antisaccade task. We show that online single pulse TMS significantly modulated antisaccade latencies. Such effects proved dependent on TMS site (effects on FEF but not on an actively stimulated control site), TMS modality (present under active but not sham TMS on the FEF area), TMS intensity (intensities of at least 40% of the TMS machine maximal output required), TMS timing (more robust for pulses delivered at 150 ms than at 100 post target onset) and visual hemifield (relative latency decreases mainly for ipsilateral AS). Our results demonstrate the feasibility of using TMS to causally modulate antisaccade-associated computations in the non-human primate brain and support the use of this approach in monkeys to study brain function and its non-invasive neuromodulation for exploratory and therapeutic purposes

La crise américaine d’aujourd’hui comparée à la crise japonaise des années 1990

Sicsic Michaël, Rivaud Sophie. La crise américaine d’aujourd’hui comparée à la crise japonaise des années 1990 . In: Économie & prévision, n°192, 2010-1. pp. 131-139

Reprise américaine : quel contenu en emplois ?

Our study does not challenge the mainly cyclical nature of the net job losses observed in the U.S. in the 2007-2009 crisis. However , we show that the U.S. labor market’s responsiveness to post-crisis GDP changes is relatively similar to the pattern observed in the “ jobless recoveries ” after the 1990 and 2001 recessions. This econometric result is supported by the available data on flows into and out of unemployment, on part-time work, and on the number of hours worked. A breakdown by economic sector shows that the phenomenon is partly due to the decline in the share of manufacturing jobs in total employment. This leaves the service sector, which is less cyclical, as the main source of job creation during recoveries.Sans remettre en cause le caractère principalement cyclique des destructions nettes d’emplois observées lors de la crise de 2007-2009, cette étude montre que la réactivité du marché du travail américain à l’activité constatée depuis est relativement similaire à celle observée lors des « reprises sans emploi » (après les récessions de 1990 et 2001). Ce résultat économétrique est conforté par les données disponibles sur les flux d’entrée et sortie du chômage, l’emploi à temps partiel et le nombre d’heures travaillées. Une décomposition par secteurs permet d’expliquer en partie ce phénomène par la baisse de la part de l’emploi manufacturier dans l’emploi total, laissant le secteur des services, moins cyclique, comme principale source de création d’emplois en période de reprise.Rivaud Sophie, Grossmann-Wirth Vincent. Reprise américaine : quel contenu en emplois ? . In: Économie & prévision, n°195-196, 2010-4-5. pp. 165-171

Les effets du ralentissement immobilier sur la consommation aux États-Unis

Rivaud Sophie, Fortin Aurélien, Eyraud Luc. Les effets du ralentissement immobilier sur la consommation aux États-Unis. In: Économie & prévision, n°183-184, 2008-2-3. pp. 257-264

Comprendre la formation de la bulle immobilière américaine et son éclatement

Grossmann-Wirth Vincent, Rivaud Sophie, Sorbe Stéphane. Comprendre la formation de la bulle immobilière américaine et son éclatement. In: Economie et statistique, n°438-440, 2010. pp. 151-171

Short-term temporal memory in idiopathic and Parkin-associated Parkinson's disease.

In a rapidly changing environment, we often know when to do something before we have to do it. This preparation in the temporal domain is based on a 'perception' of elapsed time and short-term memory of previous stimulation in a similar context. These functions could be perturbed in Parkinson's disease. Therefore, we investigated their role in eye movement preparation in sporadic Parkinson's disease and in a very infrequent variant affecting the Parkin gene. We used a simple oculomotor task where subjects had to orient to a visual target and movement latency was measured. We found that in spite of an increased average reaction time, the influence of elapsed time on movement preparation was similar in controls and the two groups of PD patients. However, short-term temporal memory of previous stimulation was severely affected in sporadic PD patients either ON or OFF dopaminergic therapy. We conclude that the two different contributions to temporal preparation could be dissociated. Moreover, a short-term temporal memory deficit might underlie temporal cognition deficits previously observed in PD