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International audience; Background: The potential of non-invasive repetitive transcranial magnetic stimulation (rTMS) to improve auditory verbal hallucinations (AVH) in schizophrenia patients has been increasingly explored over the past decade. Despite highly promising results, high inter-individual variability of clinical response and ineffective outcomes in a significant number of patients underscored the need to identify factors associated with the clinical response to rTMS. It should help improve the efficacy of rTMS in patients with medication-resistant AVH, and allow a better understanding of its neural impact. Here, we describe an exploratory study protocol which aims to identify structural and functional brain biomarkers associated with clinical response after an rTMS treatment for medication-resistant AVH in schizophrenia.; Contexte: Le potentiel de la stimulation magnétique transcrânienne répétitive non invasive (SMTr) pour améliorer les hallucinations verbales auditives (AVH) chez les patients schizophrènes a été de plus en plus exploré au cours de la dernière décennie. Malgré des résultats très prometteurs, la forte variabilité interindividuelle de la réponse clinique et les résultats inefficaces chez un nombre important de patients ont souligné la nécessité d'identifier les facteurs associés à la réponse clinique à la SMTr. Il devrait aider à améliorer l'efficacité de la SMTr chez les patients atteints d'AVH résistant aux médicaments et permettre une meilleure compréhension de son impact neuronal. Ici, nous décrivons un protocole d'étude exploratoire qui vise à identifier les biomarqueurs cérébraux structurels et fonctionnels associés à la réponse clinique après un traitement rTMS pour AVH résistant aux médicaments dans la schizophrénie.

Attention and Saccadic Adaptation (SA) are critical components of visual perception, the former enhancing sensory processing of selected objects, the latter maintaining the eye movements accuracy towards them. Also, a similar dichotomy could be applied to both: voluntary saccades and endogenous attentional shifts follow internal goals while reactive saccades and exogenous shifts are elicited by sudden changes in the environment. Further, their neural substrates partially overlap and they impact each other behaviorally. This PhD work investigates the hypothesis of a functional coupling linking attention and SA in healthy humans. Our experimental contributions all rely on the measurement of attentional performances before and after an exposure to SA (or control). In the first study, we recorded brain magnetic fields to investigate neurophysiological bases of the reactive/exogenous coupling. In the second study, we compared exogenous orienting measured in a Posner-like paradigm before and after reactive SA. Finally, using the same design, the third experiment investigated the voluntary/endogenous modality. We found that SA increased gamma band activity and boosted the orienting of spatial attention. We thus propose that this functional coupling relies on neuronal populations co-activated by both oculomotor plasticity and attention in the Posterior Parietal Cortex (PPC). The initial activation would emerge from a dual effect of the cerebellum inhibiting the left PPC and activating the right PPC. This effect would increase the right hemispheric dominance and the leftward attentional bias. This work opens new perspectives for the rehabilitation of visuoattentional deficits, L’attention et l’Adaptation Saccadique (AS) sont des composants essentiels de la perception visuelle, le premier renforce le traitement sensoriel des items sélectionnés, le second maintient la précision des mouvements des yeux vers ceux-ci. Ils partagent aussi une dichotomie : les saccades volontaires et l’orientation endogène de l’attention suivent nos buts internes tandis que les saccades réactives et l’orientation exogène répondent aux changements soudains dans l’espace visuel. Leurs substrats neuronaux se superposent en partie. Enfin, chacun impacte l’autre au niveau comportemental. Ce travail de doctorat étudie l’hypothèse d’un couplage fonctionnel entre attention et AS.Toutes nos études chez l’humain sain reposent sur la mesure des performances attentionnelles avant et après l’exposition à l’AS (ou contrôle). Dans la première nous avons exploré les bases neurophysiologiques du couplage réactif/exogène en magnétoencéphalographie. Dans la suivante nous avons comparé l’orientation exogène mesurée par un paradigme de Posner avant et après AS réactive. La dernière, basée sur le même modèle, explorait la modalité volontaire/endogène. Nos résultats montrent que l’AS augmente l’activité oscillatoire gamma et renforce l’orientation de l’attention spatiale. Nous proposons que le couplage repose sur la co-activation de populations neuronales par la plasticité oculomotrice et l’attention au niveau du Cortex Pariétal Postérieur (CPP). Cette activation émerge initialement d’un double effet du cervelet qui inhibe le CPP gauche et active le CPP droit. Cet effet augmente la dominance hémisphérique droite et le biais attentionnel vers la gauche. Notre travail ouvre des perspectives de rééducation des déficits visuo-attentionels

International audience; • Atomoxetine decreases reaction time of the most prevalent trials. • Atomoxetine modulates the accumulation rate of sensory information. • Atomoxetine adapts the response strategy to the context. The role of norepinephrine (NE) in visuo-spatial attention remains poorly understood. Our goal was to identify the attentional processes influenced by atomoxetine (ATX) injections, a NE-reuptake inhibitor that boosts the level of NE in the brain, and to characterize these influences. We tested the effects of ATX injections, on seven monkeys performing a saccadic cued task in which cues and distractors were used to manipulate spatial attention. We found that when the cue accurately predicted the location of the upcoming cue in 80% of the trials, ATX consistently improved attentional orienting, as measured from reaction times (RTs). These effects were best accounted for by a faster accumulation rate in the valid trials, rather than by a change in the decision threshold. By contrast, the effect of ATX on alerting and distractor interference was more inconsistent. Finally, we also found that, under ATX, RTs to non-cued targets were longer when these were presented separately from cued targets. This suggests that the impact of NE on visuo-spatial attention depends on the context, such that the adaptive changes elicited by the highly informative value of the cues in the most frequent trials were accompanied by a cost in the less frequent trials.

May white matter connectivity influence rhythmic brain activity underlying visual cognition? We here employed diffusion imaging to reconstruct the fronto-parietal white matter pathways in a group of healthy participants who displayed frequency-specific ameliorations of visual sensitivity during the entrainment of high-beta oscillatory activity by rhythmic transcranial magnetic stimulation over their right frontal eye field. Our analyses reveal a strong tract-specific association between the volume of the first branch of the superior longitudinal fasciculus and improvements of conscious visual detection driven by frontal beta oscillation patterns. These data indicate that the architecture of specific white matter pathways has the ability to influence the distributed effects of rhythmic spatio-temporal activity, and suggest a potentially relevant role for long-range connectivity in the synchronization of oscillatory patterns across fronto-parietal networks subtending the modulation of conscious visual perception.

International audience; The causal ability of pre-target FEF activity to modulate visual detection for perithreshold stimuli has been recently demonstrated in humans by means of non-invasive neurostimulation. Yet in spite of the network-distributed effects of these type of techniques, the white matter (WM) tracts and distant visual nodes contributing to such behavioral impact remain unknown. We hereby used individual data from a group of healthy human subjects, who received time-locked pulses of active or sham Transcranial Magnetic Stimulation (TMS) to the right Frontal Eye Field (FEF) region, and experienced increases in visual detection sensitivity. We then studied the extent to which interindividual differences in visual modulation might be dependent on the WM patterns linking the targeted area to other regions relevant for visuo-attentional behaviors. We report a statistically significant correlation between the probability of connection in a right fronto-tectal pathway (FEF-Superior Colliculus) and the modulation of visual sensitivity during a detection task. Our findings support the potential contribution of this pathway and the superior colliculus in the mediation of visual performance from frontal regions in humans. Furthermore, we also show the ability of a TMS/DTI correlational approach to contribute to the disambiguation of the specific long-range pathways driving network-wide neurostimulatory effects on behavior, anticipating their future role in guiding a more efficient use of focal neurostimulation.

The aim of this project was to examine with event related potentials ventral (involved in expertise for print) and dorsal (involved in phonological and attentional processes) pathways implication in visual word recognition in dyslexic adults. The specificity of dyslexics was determined by comparing them to age-matched controls (i.e., expert readers) and reading-level matched controls (i.e., poor readers). Results showed impaired expertise for print, decoding abilities and conflict detection which were specific to dyslexics. Our data also revealed impaired expertise for familiar words and attention orienting in both dyslexics and poor readers. Results are discussed in the context of the LCD model, the phonological mapping theory and an early involvement of attention orienting in reading., L’objectif de ces travaux a été d’étudier, à partir des potentiels évoqués, l’implication des voies ventrale (qui sous-tend le traitement expert de l’écrit) et dorsale (qui sous-tend des processus phonologiques et attentionnels) lors de la reconnaissance visuelle des mots chez des adultes dyslexiques. Les spécificités des sujets dyslexiques ont été isolées en les comparant à deux groupes contrôles, appariés sur : l’âge (i.e., des lecteurs experts) et sur le niveau de lecture (i.e., des mauvais lecteurs). Les résultats montrent des déficits du traitement expert de l’écrit, phonologiques et de la détection du conflit spécifiques aux sujets dyslexiques. Nos données montrent aussi des déficits du traitement expert des mots familiers et d’orientation de l’attention communs aux sujets dyslexiques et mauvais lecteurs. Les résultats sont discutés dans le cadre du modèle LCD, de la théorie du mapping phonologique et d’une implication précoce de l’orientation attentionnelle dans la lecture.