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Background Processing of linguistic negation has been associated to inhibitory brain mechanisms. However, no study has tapped this link via multimodal measures in patients with core inhibitory alterations, a critical approach to reveal direct neural correlates and potential disease markers. Methods Here we examined oscillatory, neuroanatomical, and functional connectivity signatures of a recently reported Go/No-go negation task in healthy controls and behavioral variant frontotemporal dementia (bvFTD) patients, typified by primary and generalized inhibitory disruptions. To test for specificity, we also recruited persons with Alzheimer's disease (AD), a disease involving frequent but nonprimary inhibitory deficits. Results In controls, negative sentences in the No-go condition distinctly involved frontocentral delta (2–3 Hz) suppression, a canonical inhibitory marker. In bvFTD patients, this modulation was selectively abolished and significantly correlated with the volume and functional connectivity of regions supporting inhibition (e.g. precentral gyrus, caudate nucleus, and cerebellum). Such canonical delta suppression was preserved in the AD group and associated with widespread anatomo-functional patterns across non-inhibitory regions. Discussion These findings suggest that negation hinges on the integrity and interaction of spatiotemporal inhibitory mechanisms. Moreover, our results reveal potential neurocognitive markers of bvFTD, opening a new agenda at the crossing of cognitive neuroscience and behavioral neurology.

Consciousness impairments have been described as a cornerstone of epilepsy. Generalized seizures are usually characterized by a complete loss of consciousness, while focal seizures have more variable degrees of responsiveness. In addition to these impairments that occur during ictal episodes, alterations of consciousness have also been repeatedly observed between seizures (i.e., during interictal periods). In this opinion paper, we review evidence supporting the novel hypothesis that epilepsy produces consciousness impairments which remain present interictally. Then, we discuss therapies aimed to reduce seizure frequency, which may modulate consciousness between epileptic seizures. We conclude with a consideration of relevant pathophysiological mechanisms. In particular, the thalamocortical network seems to be involved in both seizure generation and interictal consciousness impairments, which could inaugurate a promising translational agenda for epilepsy studies. Fil: Moguilner, Sebastian Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencias Cognitivas y Traslacional; Argentina. Fundación Escuela de Medicina Nuclear; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina Fil: García, Adolfo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencias Cognitivas y Traslacional; Argentina. Universidad Nacional de Cuyo. Facultad de Educación Elemental y Especial; Argentina Fil: Mikulan, Ezequiel Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencias Cognitivas y Traslacional; Argentina Fil: García, Maria del Carmen. Hospital Italiano; Argentina Fil: Vaucheret, Esteban. Hospital Italiano; Argentina Fil: Amarillo Gómez, Yimy. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bekinchstein, Tristán. University of Cambridge; Reino Unido Fil: Ibáñez Barassi, Agustín Mariano. Universidad Autonoma del Caribe; Colombia. Universidad Adolfo Ibañez; Chile. Australian Research Council; Australia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencias Cognitivas y Traslacional; Argentina