Faculty Bibliography

When patients seek professional help for mental disorders, they often do so because of troubling subjective affective experiences. While these subjective states are at the center of the patient's symptomatology, scientific tools for studying them and their cognitive antecedents are limited. Here, we explore the use of concepts and analytic tools from the science of consciousness, a field of research that has faced similar challenges in having to develop robust empirical methods for addressing a phenomenon that has been considered difficult to pin down experimentally. One important strand is the operationalization of some relevant processes in terms of metacognition and confidence ratings, which can be rigorously studied in both humans and animals. By assessing subjective experience with similar approaches, we hope to develop new scientific approaches for studying affective processes and promoting psychological resilience in the face of debilitating emotional experiences.

Sleep problems are common in neurological conditions for which ketogenic dietary therapies (KDTs) are recognised as an effective intervention (drug-resistant epilepsy, autism spectrum disorder, and migraine). Given the composite framework of action of ketogenic dietary therapies, the prevalence of sleep disturbance, and the importance of sleep regulation, the present scoping review aimed at identifying and mapping available evidence of the effects of ketogenic dietary therapies on sleep. A comprehensive web-based literature search was performed retrieving publications published to June 2023 using PubMed and Scopus, yielding to 277 records. Twenty papers were finally selected and included in the review. Data were abstracted by independent coders. High variability was identified in study design and sleep outcome evaluation among the selected studies. Several changes in sleep quality and sleep structure under ketogenic dietary therapies were found, namely an improvement of overall sleep quality, improvement in the difficulty falling asleep and nighttime awakenings, improvement in daytime sleepiness and an increase of REM sleep. The relevance and possible physiological explanations of these changes, clinical recommendations, and future directions in the field are discussed.

KBG syndrome is a rare genetic disorder caused by heterozygous pathogenic variants in ANKRD11. Affected individuals have developmental delay, short stature, characteristic facial features, and other dysmorphic findings. To date, a spectrum of unspecific neuroradiological defects has been reported in KBG patients, such as cortical defects, white matter abnormalities, corpus callosum, and cerebellar vermis hypoplasia.Deep clinical and neuroradiological phenotyping and genotype of a patient presenting with mild cognitive and behavioral problems were obtained after written informed consent.We herein describe the first KBG patient presenting with cerebellar heterotopia, a heterogeneous malformation characterized by the presence of clusters of neurons within the white matter of cerebellar hemispheres.This novel association broadens the neuroradiological spectrum of KBG syndrome, and further prompts to investigate the potential functions of ANKRD11 in cerebellar development.

Early-life stress has been linked to multiple neurodevelopmental and neuropsychiatric deficits. Our previous studies have linked maternal presence/absence from the nest in developing rat pups to changes in prefrontal cortex (PFC) activity. Furthermore, we have shown that these changes are modulated by serotonergic signaling. Here we test whether changes in PFC activity during early life affect the developing cortex leading to behavioral alterations in the adult. We show that inhibiting the PFC of mouse pups leads to cognitive deficits in the adult comparable to those seen following maternal separation. Moreover, we show that activating the PFC during maternal separation can prevent these behavioral deficits. To test how maternal separation affects the transcriptional profile of the PFC we performed single-nucleus RNA-sequencing. Maternal separation led to differential gene expression almost exclusively in inhibitory neurons. Among others, we found changes in GABAergic and serotonergic pathways in these interneurons. Interestingly, both maternal separation and early-life PFC inhibition led to changes in physiological responses in prefrontal activity to GABAergic and serotonergic antagonists that were similar to the responses of more immature brains. Prefrontal activation during maternal separation prevented these changes. These data point to a crucial role of PFC activity during early life in behavioral expression in adulthood.

INTRODUCTION/BACKGROUND:Access to care for children and adolescents affected by ADHD in France remains below the levels attained in most industrialised countries. To contribute to improving ADHD care in France, we assessed existing ADHD knowledge among medical doctors (MDs) and described associated care pathways in two large French regions in 2021. We produced tools to evaluate the regional impact of implementing a stepped-care pathway for ADHD. METHODS:A SurveyMonkey® study was sent to professionals from two regions in France accounting for 14 million inhabitants, allowing them to describe their role in child/adolescent ADHD, as well as their representations and knowledge about the disorder. RESULTS:Around 9.4% of all MDs potentially involved with children took part in the study; 34.9% considered themselves untrained, 40.5% were involved in ADHD care at a first-tier level, and 19.6% at a second-tier level. Access to a second or third-tier service for ADHD was associated with mean waiting times of 5.7 and 8.5 months, respectively. Initiation of stimulant therapy remained mainly restricted to second or third-tier MDs, and adaptation of dosage or change in the galenic formulation was rarely performed by first-tier MDs (27.2% and 18%, respectively). Training in neurodevelopmental disorders and tier-level were the strongest determinants of knowledge, attitudes and self-assessed expertise about ADHD. CONCLUSIONS:This study provides insight into training needs for MDs regarding healthcare pathways in ADHD and should support the implementation of health policies, such as a stepped healthcare access for ADHD. The study design and dissemination have been validated and will be available in France and other countries facing similar obstacles in care pathways for ADHD. Official recommendations on ADHD in children and adults are being updated in France, and our data and the survey design will be a starting point for their implementation.

We investigated whether SARS-CoV-2 infection is associated with short- and long-term neuropsychiatric sequelae. We used population-based cohorts from the Korean nationwide cohort (discovery; n = 10,027,506) and the Japanese claims-based cohort (validation; n = 12,218,680) to estimate the short-term (<30 days) and long-term (≥30 days) risks of neuropsychiatric outcomes after SARS-CoV-2 infection compared with general population groups or external comparators (people with another respiratory infection). Using exposure-driven propensity score matching, we found that both the short- and long-term risks of developing neuropsychiatric sequelae were elevated in the discovery cohort compared with the general population and those with another respiratory infection. A range of conditions including Guillain-Barré syndrome, cognitive deficit, insomnia, anxiety disorder, encephalitis, ischaemic stroke and mood disorder exhibited a pronounced increase in long-term risk. Factors such as mild severity of COVID-19, increased vaccination against COVID-19 and heterologous vaccination were associated with reduced long-term risk of adverse neuropsychiatric outcomes. The time attenuation effect was the strongest during the first six months after SARS-CoV-2 infection, and this risk remained statistically significant for up to one year in Korea but beyond one year in Japan. The associations observed were replicated in the validation cohort. Our findings contribute to the growing evidence base on long COVID by considering ethnic diversity.

Adolescence is a critical developmental period of biological and social change during which 1 in 3 youth experience significant anxiety symptoms. The social-emotional lives of the majority of adolescents are largely conducted via digital media use (DMU; e.g., social media, text messaging). Yet the past decade of research on DMU and anxiety has yielded mixed results (e.g., Keles et al., 2020 review), leaving the complex role that DMU might play in the emergence and maintenance of anxiety poorly understood. A key step forward is to leverage psychophysiology to identify individual differences in cognitive and emotional processes that confer vulnerability to potential negative effects of DMU. Further, given the ubiquity of DMU, a greater focus is needed on measurements that move beyond sheer frequency to capture DMU in comparison to face-to-face (FTF) social interactions. This study examined attention bias (AB), characterized by selective and exaggerated attention toward or away from threat, as a moderator of the link between DMU and anxiety in adolescents (N = 75; 42 female) aged 12-14 years (M = 13.28, SD = 0.87). AB was indexed during a dot probe task using reaction time metrics (i.e., trial-level bias) and via ERPs capturing attentional selection and discrimination (N170) and cognitive control (N2) to threat compared to neutral faces. AB moderated associations between DMU and anxiety. A greater preference to use DMU vs FTF predicted greater anxiety among those with a greater behavioral bias away from threat, blunted N170, and blunted N2 in the presence of threat. Future research should examine potential causal and bidirectional links between DMU and anxiety and explore whether preferences for technology-mediated interactions and individual differences in threat processing increase risk.

The implementation and potential of ketogenic dietary therapies (KDTs) have changed over time. The organization of KDT services, the availability of multidisciplinary teams, resources and support for patients and families still vary widely around the world. This diversity is reflected by a lack of consistency in reported outcomes, optimization of using KDT and KDT compliance. To highlight the unmet needs for KDT services, the ERN EpiCARE Ketogenic Dietary Therapy Special Interest Group (KDT SIG) conducted an online survey on KDT implementation and utilization, addressing the following topics: Use and completeness of guidelines and protocols; assessment of compliance and outcome parameters, sustainability and inclusivity in daily life. Consistently reported unmet needs included the lack of psychological support and resources to measure and improve adherence to KDT, the lack of inclusion strategies, and shared guidelines and protocols adapting to specific needs. Future interventions should focus primarily on educational and informative measures together with creation of shared protocols for complex care. PLAIN LANGUAGE SUMMARY: This study provides the results of a survey compiled by clinicians and patients representatives belonging to ERN Epicare, designed to unravel unmet needs from both patients' and healthcare practitioners' perspectives during ketogenic dietary therapies (KDT) provision. Importantly, results show the need to create new shared protocols and guidelines meant for KDT use in complex care situations and to develop future strategies initiatives to support patients improving their social inclusivity.