Multidimensional inhibitory signatures of sentential negation in behavioral variant frontotemporal dementia

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.

Automated summary

This study investigated the neural correlates of linguistic negation in healthy controls, behavioral variant frontotemporal dementia (bvFTD) patients, and Alzheimer's disease (AD) patients. The results showed that control participants displayed a delta suppression in frontocentral regions during negative sentences in a No-go condition, which is a marker of inhibition. In bvFTD patients, this suppression was selectively abolished and correlated with the volume and functional connectivity of regions involved in inhibition. This study provides insights into the neural mechanisms of negation and potential neurocognitive markers of bvFTD.