Functional brain neuroimaging-guided repetitive transcranial magnetic stimulation in neurodevelopmental disorders: The case of a schizencephaly-related spastic dystonia

International audienceSpastic dystonia is defined as tonic involuntary muscle activation at rest superimposed over spastic paresis [1]. It occurs in different pathological conditions, ranging from dopamine-dependent dystonia [2] to post-stroke deforming spastic hemiparesis [1]. Even though important burden is associated to spastic dystonia, therapeutic options are scarce and mostly limited to intramuscular botulinum toxin injection and surgical partial nerve section. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as an interesting therapeutic option, but with inconsistent results [3]. We suggest that optimized targeting based on functional brain imaging could enhance the results of rTMS in schizencephaly-related dystonia and improve our knowledge about the technical procedure to become more widely applicable in neurodevelopmental disorders

Serotonin 3A Receptor Subtype as an Early and Protracted Marker of Cortical Interneuron Subpopulations

To identify neocortical neurons expressing the type 3 serotonergic receptor, here we used transgenic mice expressing the enhanced green fluorescent protein (GFP) under the control of the 5-HT3A promoter (5-HT3A:GFP mice). By means of whole-cell patch-clamp recordings, biocytin labeling, and single-cell reversed-transcriptase polymerase chain reaction on acute brain slices of 5-HT3A:GFP mice, we identified 2 populations of 5-HT3A-expressing interneurons within the somatosensory cortex. The first population was characterized by the frequent expression of the vasoactive intestinal peptide and a typical bipolar/bitufted morphology, whereas the second population expressed predominantly the neuropeptide Y and exhibited more complex dendritic arborizations. Most interneurons of this second group appeared very similar to neurogliaform cells according to their electrophysiological, molecular, and morphological properties. The combination of 5-bromo-2-deoxyuridine injections with 5-HT3A mRNA detection showed that cortical 5-HT3A interneurons are generated around embryonic day 14.5. Although at this stage the 5-HT3A receptor subunit is expressed in both the caudal ganglionic eminence and the entopeduncular area, homochronic in utero grafts experiments revealed that cortical 5-HT3A interneurons are mainly generated in the caudal ganglionic eminence. This protracted expression of the 5-HT3A subunit allowed us to study specific cortical interneuron populations from their birth to their final functional phenotype

Neural correlates of affective and cognitive theory of mind in schizophrenia : an fMRI study

L’objectif de cette thèse est d’étudier de manière comparative les théories de l’esprit affective et cognitive et les réseaux cérébraux qui les soutiennent dans la schizophrénie et troubles apparentés. Notre travail expérimental s’articule autour d’une tâche validée et adaptée à notre population permettant d’explorer les théories de l’esprit affective (ToMA) et cognitive (ToMC) comparativement à la causalité physique en imagerie cérébrale fonctionnelle qui a été réalisé dans trois études distinctes : 1) comparaison de patients schizophrènes aux témoins sains ; 2) étude de corrélation entre le score total de l’échelle explorant les traits de personnalité schizotypique (SPQ) et les données de l’imagerie fonctionnelle dans un groupe de participants sains, 3) comparaison de patients atteints de schizophrénie, de trouble bipolaire et des témoins sains. Nous avons observé une augmentation de l’activation cérébrale dans le pôle temporal droit pendant la ToMA et une diminution de l’activité de gyrus temporal supérieur droit pendant la ToMC dans la schizophrénie. Le score total SPQ a corrélé avec l’activation de gyrus temporal moyen gauche et les structures adjacentes, suggérant un possible lien entre la vulnérabilité à la schizophrénie et la créativité. Enfin, l’étude 3 apporte les arguments neurofonctionnels en faveur d’une distinction neurobiologiques entre le trouble bipolaire et la schizophrénie en ce qui concerne leur activation cérébrale au cours de la tâche expérimentale. Ces corrélats cérébraux relatifs au déficit de mentalisation dans la schizophrénie peuvent devenir des cibles thérapeutiques, accessibles aux techniques de neuromodulation non invasives.Schizophrenia is highly disabling neurodevelopmental disorder. Theory of mind, the ability to attribute the mental states to others, is the best predictor of social functioning. The aim of this thesis is to comparatively explore neural correlates of affective and cognitive theories of the mind in schizophrenia and related disorders. We adapted a validated experimental visual task that explored distinctly affective (ToMA) and cognitive (ToMC) theory of mind in comparison to the physical causality during functional brain scanning. We carried out three separate studies: 1) comparison of schizophrenia patients with healthy controls; 2) correlation study between the total Schizotypal Personality Questionnaire (SPQ) score and functional imaging data in a group of healthy participants, 3) comparison of patients with schizophrenia, bipolar disorder and healthy controls matched for age, education level and gender. We observed increased brain activation in the right temporal pole during ToMA and decreased right superior temporal gyrus activity during ToMC in schizophrenia. The SPQ total score correlated with activation of the left middle temporal gyrus and adjacent structures, suggesting a possible link between vulnerability to schizophrenia and creativity. Finally, Study 3 provides neurofunctional arguments for a neurobiological distinction between bipolar disorder and schizophrenia with regard to their brain activation during the experimental task. These cerebral correlates of theories of mind deficits in schizophrenia may become therapeutic targets, accessible to non-invasive neuromodulation techniques like repetitive Transcranial Magnetic Stimulation (rTMS)

Anomalies neurodéveloppementales et vulnérabilité à la schizophrénie

REIMS-BU Santé (514542104) / SudocSudocFranceF

Neural correlates of theory of mind and empathy in schizophrenia: An activation likelihood estimation meta-analysis

International audienceSocial cognition impairment predicts social functioning in schizophrenia. Several studies have found abnormal brain activation in patients with schizophrenia during social cognition tasks. Nevertheless, no coordinate-based meta-analysis comparing the neural correlates of theory of mind and empathy had been done in this population. Our aim was to explore neural correlates related to theory of mind and empathy in patients with schizophrenia compared to healthy controls, in order to identify abnormal brain activation related to emotional content during mental state attribution in schizophrenia. We performed a neural-coordinate-based Activation Likelihood Estimation (ALE) meta-analysis of existing neuroimaging data in the literature to distinguish between abnormal brain maps associated with emotional attribution and those associated with intention/belief inference. We found that brain activation in patients group was significantly decreased in the right ventrolateral prefrontal cortex (VLPFC) during emotional attribution, while there was a significant decrease in the left posterior temporo-parietal junction (TPJ) during intention/belief attribution. Using a meta-analytic connectivity modeling approach (MACM), we demonstrated that both regions are coactivated with other brain regions known to play a role in social cognition, including the bilateral anterior insula, right TPJ, left amygdala and dorsolateral prefrontal cortex. In addition, abnormal activation in both the left TPJ and right VLPFC was previously reported in association with verbal-auditory hallucinations and a "jumping to conclusions" cognitive bias. Thus, these regions could be valuable targets for therapeutic interventions in schizophrenia

How to project oneself without positive and integrated memories? Exploration of self-defining memories and future projections in bipolar disorder

International audienc

Higher Emotion-Related Distress in Patients with Fibromyalgia versus Chronic Neuropathic Pain and Healthy Controls: Is It a Primary Affective Disorder?

International audienceAbstract Schizophrenia, a severe psychiatric disorder, is associated with abnormal brain activation during theory of mind (ToM) processing. Researchers recently suggested that there is a continuum running from subclinical schizotypal personality traits to fully expressed schizophrenia symptoms. Nevertheless, it remains unclear whether schizotypal personality traits in a nonclinical population are associated with atypical brain activation during ToM tasks. Our aim was to investigate correlations between fMRI brain activation during affective ToM (ToMA) and cognitive ToM (ToMC) tasks and scores on the Schizotypal Personality Questionnaire (SPQ) and the Basic Empathy Scale in 39 healthy individuals. The total SPQ score positively correlated with brain activation during ToMA processing in clusters extending from the left medial temporal gyrus (MTG), lingual gyrus and fusiform gyrus to the parahippocampal gyrus (Brodmann area: 19). During ToMA processing, the right inferior occipital gyrus, right MTG, precuneus and posterior cingulate cortex negatively correlated with the emotional disconnection subscore and the total score of self-reported empathy. These posterior brain regions are known to be involved in memory and language, as well as in creative reasoning, in nonclinical individuals. Our findings highlight changes in brain processing associated with trait schizotypy in nonclinical individuals during ToMA but not ToMC processing

Neural substrates of mentalizing and hypomanic personality traits: How do you understand the others?

22nd Annual Conference of the International-Society-for-Bipolar-Disorders (ISBD), ELECTR NETWORK, JUN 18-21, 2020International audienc

Neural correlates of theory of mind in social interaction vs social observation in bipolar disorder

22nd Annual Conference of the International-Society-for-Bipolar-Disorders (ISBD), ELECTR NETWORK, JUN 18-21, 2020International audienc