Multimodal neurocognitive markers of naturalistic discourse typify diverse neurodegenerative diseases

Abstract

Neurodegeneration has multiscalar impacts, including behavioral, neuroanatomical, and neurofunctional disruptions. Can disease-differential alterations be captured across such dimensions using naturalistic stimuli? To address this question, we assessed comprehension of four naturalistic stories, highlighting action, nonaction, social, and nonsocial events, in Parkinson’s disease (PD) and behavioral variant frontotemporal dementia (bvFTD) relative to Alzheimer’s disease patients and healthy controls. Text-specific correlates were evaluated via voxel-based morphometry, spatial (fMRI), and temporal (hd-EEG) functional connectivity. PD patients presented action–text deficits related to the volume of action–observation regions, connectivity across motor-related and multimodal-semantic hubs, and frontal hd-EEG hypoconnectivity. BvFTD patients exhibited social–text deficits, associated with atrophy and spatial connectivity patterns along social-network hubs, alongside right frontotemporal hd-EEG hypoconnectivity. Alzheimer’s disease patients showed impairments in all stories, widespread atrophy and spatial connectivity patterns, and heightened occipitotemporal hd-EEG connectivity. Our framework revealed disease-specific signatures across behavioral, neuroanatomical, and neurofunctional dimensions, highlighting the sensitivity and specificity of a single naturalistic task. This investigation opens a translational agenda combining ecological approaches and multimodal cognitive neuroscience for the study of neurodegeneration.

Social concepts and the cerebellum: behavioural and functional connectivity signatures in cerebellar ataxic patients

“…Crucially, the emergence of category-specific deficits with a naturalistic text would strongly support their relation with damaged brain regions, as contextual information facilitates linguistic performance [38] and enhances cognitive outcomes in patients [39]. Importantly, in other atrophy models, this task has revealed that selective difficulties in grasping social (as opposed to non-social) concepts are associated with cerebello-cortical functional connectivity [8], attesting to its relevance to the present hypothesis.…”

“…This question can be explored in persons with cerebellar ataxia (CA), a disorder typified by cerebellar atrophy [30][31][32] and abnormal cerebello-cortical connectivity [33,34], as well as disruptions of socio-cognitive domains-such as emotion attribution, mental state recognition and theory of mind [25,35,36]. To address the issue, we leveraged a novel textlevel protocol [8] involving two naturalistic stories: a social text (highlighting interpersonal events) and a non-social text (focused on a single person's actions), each accompanied with comprehension questionnaires.…”

“…While both accounts ascribe these features to abstract concepts at large, 1 social concepts constitute a distinct cluster in semantic memory [6] and account for inter-individual brain similarities during processing abstract concept features [7]. More particularly, and in line with both situated and embodied tenets, social concepts would be distinctly rooted in the same brain circuitry subserving socio-cognitive functions at large [8]. This embodied view aligns with evidence that other abstract concepts engage the same mechanisms which subserve relevant non-verbal experiences, including reactivation of emotional circuits by threatening words [9], inhibitory mechanisms by negation markers [10,11] and motor networks by action verbs [12].…”

Functional connectivity in behavioral variant frontotemporal dementia

“…In addition to the above‐mentioned studies, there are investigations of other variables in bvFTD. For instance, reports of association between FC and mind‐wandering (O'Callaghan et al., 2019 ), autonomic nervous system activity (Sturm et al., 2018 ), heartbeat evoked potential (Birba et al., 2022 ), comprehension of text containing social information (Birba et al., 2021 ), and cognitive reserve (Premi et al., 2013 ). The main findings are listed in Fact box 2.…”

The neurocognitive impact of loneliness and social networks on social adaptation

“…The resulting functional connectivity (FC) correlation coe cients between all pairs of regions (AAL atlas) were used to perform Spearman's correlations with the scores of each predictor: loneliness (UCLA score), and social network (LSNS-R score). Following procedures from recent research [50][51][52] signi cance thresholding of neuroimaging results was set to p ≤ .001 (uncorrected). Uncorrected statistical threshold has been used previously to avoid the detrimental effects of liberal primary thresholds on false positives (especially in modest sample sizes such as ours) [53][54][55] .…”