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    Multidimensional inhibitory signatures of sentential negation in behavioral variant frontotemporal dementia
    (2022)
    Mariano N Díaz-Rivera
    ;
    Agustina Birba
    ;
    Sol Fittipaldi
    ;
    Débora Mola
    ;
    Yurena Morera
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Discussion</jats:title> <jats:p>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.</jats:p> </jats:sec>
    Scopus© Citations 18  4
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    Dysconnectivity in Schizophrenia Revisited: Abnormal Temporal Organization of Dynamic Functional Connectivity in Patients With a First Episode of Psychosis
    (2022)
    Juan P Ramirez-Mahaluf
    ;
    Ángeles Tepper
    ;
    Luz Maria Alliende
    ;
    Carlos Mena
    ;
    Carmen Paz Castañeda
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background and Hypothesis</jats:title> <jats:p>Abnormal functional connectivity between brain regions is a consistent finding in schizophrenia, including functional magnetic resonance imaging (fMRI) studies. Recent studies have highlighted that connectivity changes in time in healthy subjects. We here examined the temporal changes in functional connectivity in patients with a first episode of psychosis (FEP). Specifically, we analyzed the temporal order in which whole-brain organization states were visited.</jats:p> </jats:sec> <jats:sec> <jats:title>Study Design</jats:title> <jats:p>Two case-control studies, including in each sample a subgroup scanned a second time after treatment. Chilean sample included 79 patients with a FEP and 83 healthy controls. Mexican sample included 21 antipsychotic-naïve FEP patients and 15 healthy controls. Characteristics of the temporal trajectories between whole-brain functional connectivity meta-states were examined via resting-state functional MRI using elements of network science. We compared the cohorts of cases and controls and explored their differences as well as potential associations with symptoms, cognition, and antipsychotic medication doses.</jats:p> </jats:sec> <jats:sec> <jats:title>Study Results</jats:title> <jats:p>We found that the temporal sequence in which patients’ brain dynamics visited the different states was more redundant and segregated. Patients were less flexible than controls in changing their network in time from different configurations, and explored the whole landscape of possible states in a less efficient way. These changes were related to the dose of antipsychotics the patients were receiving. We replicated the relationship with antipsychotic medication in the antipsychotic-naïve FEP sample scanned before and after treatment.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>We conclude that psychosis is related to a temporal disorganization of the brain’s dynamic functional connectivity, and this is associated with antipsychotic medication use.</jats:p> </jats:sec>
    Scopus© Citations 17  1