5-HT1A gene promoter polymorphism and [18F]MPPF binding potential in healthy subjects: a PET study

<p>Abstract</p> <p>Background</p> <p>Previous Positron Emission Tomography (PET) studies of 5-HT_1Areceptors have shown an influence of several genetic factors, including the triallelic serotonin transporter gene-linked polymorphic region on the binding potential (BP_ND) of these receptors. The aim of our study was to investigate the relationship between a 5-HT_1Apromoter polymorphism and the binding potential of another selective 5-HT_1Areceptor antagonist, [¹⁸F]MPPF, in healthy subjects.</p> <p>Methods</p> <p>Thirty-five volunteers, including 23 women, underwent an [¹⁸F]MPPF scan and were genotyped for both the C(-1019)G 5-HT_1Apromoter polymorphism and the triallelic serotonin transporter gene-linked polymorphic region. We used a simplified reference tissue model to generate parametric images of BP_ND. Whole brain Statistical Parametric Mapping and raphe nuclei region of interest analyses were performed to look for an association of [¹⁸F]MPPF BP_NDwith the C(-1019)G 5-HT_1Apromoter polymorphism.</p> <p>Results</p> <p>Among the 35 subjects, 5-HT_1Apromoter genotypes occurred with the following frequencies: three G/G, twenty-one G/C, and eleven C/C. No difference of [¹⁸F]MPPF BP_NDbetween groups was observed, except for two women who were homozygote carriers for the G allele and showed greater binding potential compared to other age-matched women over the frontal and temporal neocortex. However, the biological relevance of this result remains uncertain due to the very small number of subjects with a G/G genotype. These findings were not modified by excluding individuals carrying the S/S genotype of the serotonin transporter gene-linked polymorphic region.</p> <p>Conclusions</p> <p>We failed to observe an association between the C(-1019)G 5-HT_1Apromoter polymorphism and [¹⁸F]MPPF binding in healthy subjects. However our data suggest that the small number of women homozygote for the G allele might have greater [¹⁸F]MPPF BP_NDrelative to other individuals. This finding should be confirmed in a larger sample.</p

Candidate socioemotional remediation program for individuals with intellectual disability

The authors developed a computerized program, Vis-à-Vis (VAV), to improve socioemotional functioning and working memory in children with developmental disabilities. The authors subsequently tested whether participants showed signs of improving the targeted skills. VAV is composed of three modules: Focus on the Eyes, Emotion Recognition and Understanding, and Working Memory. Ten children with idiopathic developmental delay completed four 20-min weekly sessions of VAV for 12 weeks with an adult. Participants were evaluated before (Time 0) and after (Time 1) training and 6 months after remediation (Time 2). Subjects improved on all three modules during training and on emotion recognition and nonverbal reasoning post-VAV. These gains were still present at Time 2. VAV is a promising new tool for working on socioemotional impairments in hard-to-treat pediatric populations

Gamma oscillations in V1 are correlated with GABAA receptor density: A multi-modal MEG and Flumazenil-PET study

International audienceHigh-frequency oscillations in the gamma-band reflect rhythmic synchronization of spike timing in active neural networks. The modulation of gamma oscillations is a widely established mechanism in a variety of neurobiological processes, yet its neurochemical basis is not fully understood. Modeling, in-vitro and in-vivo animal studies suggest that gamma oscillation properties depend on GABAergic inhibition. In humans, search for evidence linking total GABA concentration to gamma oscillations has led to promising -but also to partly diverging- observations. Here, we provide the first evidence of a direct relationship between the density of GABA A receptors and gamma oscillatory gamma responses in human primary visual cortex (V1). By combining Flumazenil-PET (to measure resting-levels of GABA A receptor density) and MEG (to measure visually-induced gamma oscillations), we found that GABA A receptor densities correlated positively with the frequency and negatively with amplitude of visually-induced gamma oscillations in V1. Our findings demonstrate that gamma-band response profiles of primary visual cortex across healthy individuals are shaped by GABA A -receptor-mediated inhibitory neurotransmission. These results bridge the gap with in-vitro and animal studies and may have future clinical implications given that altered GABAergic function, including dysregulation of GABA A receptors, has been related to psychiatric disorders including schizophrenia and depression

Gamma oscillations in V1 are correlated with GABAA receptor density: A multi-modal MEG and Flumazenil-PET study

International audienceHigh-frequency oscillations in the gamma-band reflect rhythmic synchronization of spike timing in active neural networks. The modulation of gamma oscillations is a widely established mechanism in a variety of neurobiological processes, yet its neurochemical basis is not fully understood. Modeling, in-vitro and in-vivo animal studies suggest that gamma oscillation properties depend on GABAergic inhibition. In humans, search for evidence linking total GABA concentration to gamma oscillations has led to promising -but also to partly diverging- observations. Here, we provide the first evidence of a direct relationship between the density of GABA A receptors and gamma oscillatory gamma responses in human primary visual cortex (V1). By combining Flumazenil-PET (to measure resting-levels of GABA A receptor density) and MEG (to measure visually-induced gamma oscillations), we found that GABA A receptor densities correlated positively with the frequency and negatively with amplitude of visually-induced gamma oscillations in V1. Our findings demonstrate that gamma-band response profiles of primary visual cortex across healthy individuals are shaped by GABA A -receptor-mediated inhibitory neurotransmission. These results bridge the gap with in-vitro and animal studies and may have future clinical implications given that altered GABAergic function, including dysregulation of GABA A receptors, has been related to psychiatric disorders including schizophrenia and depression

An examination of the efficacy and safety of fenfluramine in adults, children, and adolescents with Dravet syndrome in a real-world practice setting: a report from the fenfluramine European Early Access Program

Objective: To examine the efficacy and safety of fenfluramine in patients with Dravet syndrome (DS) in three age groups: &lt;6, 6 to 17, and ≥18 years old, treated in a real-world setting. Methods: Patients with DS were treated with fenfluramine in the European Union Early Access Program (EAP). Following a 28-day baseline period to establish the pretreatment monthly convulsive seizure frequency (MCSF), fenfluramine was started at a dose chosen by the treating physician and gradually titrated based on efficacy and tolerability up to a maximum of 0.7 mg/kg/day. Seizure incidence was recorded in a written diary, and adverse events (AEs) were reported at each patient visit. Cardiovascular safety was assessed by transthoracic echocardiography before treatment started and at least every 6 months thereafter. Results: A total of 149 patients have enrolled in the EAP and 63 were &lt;6 years old, 62 were 6 to 17 years old, and 24 were ≥18 years old. After 3 months of treatment 62%, 53%, and 50% of patients demonstrated ≥75% reduction in MCSF in the &lt;6, 6-17, and ≥18-year-old groups, respectively. This pattern of response was sustained through 12 months of treatment with 55%, 46%, and 80% of the &lt;6, 6-17, and ≥18-year-old groups, respectively, experiencing a ≥75% reduction in MCSF. Most common AEs were loss of appetite (21%) and somnolence (16%). No valvular heart disease or pulmonary artery hypertension was observed. Significance: The magnitude, consistency, and durability of the response to add-on fenfluramine is consistent across age groups in patients with Dravet Syndrome

White matter development in children with Benign Childhood Epilepsy with Centro-Temporal Spikes

International audienc

Inclusion en contexte de diversité ethnoculturelle : pratiques institutionnelles et points de vue des apprenants sur leurs expériences scolaires

Ce numéro montre que la mise en œuvre d’une éducation inclusive constitue un défi de taille inachevé, tant au plan systémique que du travail sur soi. Cette démarche de changement des pratiques, questionnant de manière continue la responsabilité de l’école à l’égard de la (re)production des inégalités, de l’exclusion et de rapports sociaux inégaux, est parsemée d’obstacles, de situations non prévisibles et d’émotions fortes. Les chercheurs soulignent notamment que de nombreux mécanismes systémiques de la culture scolaire contribuent à reproduire et à réifier des expériences scolaires hiérarchisées et à exacerber des processus de discrimination institutionnelle en défaveur des élèves issus de l’immigration et/ou racisés. Les recherches empiriques présentées mettent également en exergue la pensée déficitaire (deficit thinking) du personnel scolaire vis-à-vis des élèves issus de l’immigration et de leurs parents. Les résultats montrent que des intervenants tendent à utiliser les écarts linguistiques et culturels entre les élèves et le système scolaire pour expliciter l’échec scolaire. Quoi qu’il en soit, les chercheurs ainsi que les acteurs scolaires et les élèves interrogés dans les articles du numéro suggèrent des pistes fécondes pour améliorer l’inclusion en contexte scolaire, soulignant l’importance de donner la voix aux divers acteurs pour tendre vers des transformations institutionnelles. This issue reveals that the implementation of inclusive education is an unfinished challenge, both within the system and for individual self-improvement. This process of changing practices, by continually questioning the school’s responsibility for the (re)production of inequalities, exclusion and unequal social relations, is riddled with obstacles, unpredictable situations and strong emotions. In particular, the researchers point out that many systemic mechanisms of school culture contribute to replicating and reifying hierarchical school experiences and exacerbating processes of institutional discrimination against immigrant background and/or racialized students. The empirical research presented also highlights the deficit thinking of school staff toward immigrant students and their parents. The results show that staff tend to use linguistic and cultural gaps between students and the school system to explain academic failure. Be that as it may, the researchers as well as the school actors and students interviewed in this issue suggest fertile ways to improve inclusion in the school context, stressing the importance of giving voice to the various actors in order to move toward institutional transformation