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.

Objective: Neurological nosology, based on categorical systems, has largely ignored dimensional aspects of neurocognitive impairments. Transdiagnostic dimensional approaches of interoception (the sensing of visceral signals) may improve the descriptions of cross-pathological symptoms at behavioral, electrophysiological, and anatomical levels. Alterations of cardiac interoception (encompassing multidimensional variables such as accuracy, learning, sensibility, and awareness) and its neural correlates (electrophysiological markers, imaging-based anatomical and functional connectivity) have been proposed as critical across disparate neurological disorders. However, no study has examined the specific impact of neural (relative to autonomic) disturbances of cardiac interoception or their differential manifestations across neurological conditions. Methods: Here, we used a computational approach to classify and evaluate which markers of cardiac interoception (behavioral, metacognitive, electrophysiological, volumetric, or functional) offer the best discrimination between neurological conditions and cardiac (hypertensive) disease (model 1), and among neurological conditions (Alzheimer’s disease, frontotemporal dementia, multiple sclerosis, and brain stroke; model 2). In total, the study comprised 52 neurological patients (mean [standard deviation] age = 55.1 [17.3] years; 37 women), 25 cardiac patients (age = 66.2 [9.1] years; 13 women), and 72 healthy controls (age = 52.65 [17.1] years; 50 women). Results: Cardiac interoceptive outcomes successfully classified between neurological and cardiac conditions (model 1: >80% accuracy) but not among neurological conditions (model 2: 53% accuracy). Behavioral cardiac interoceptive alterations, although present in all conditions, were powerful in differentiating between neurological and cardiac diseases. However, among neurological conditions, cardiac interoceptive deficits presented more undifferentiated and unspecific disturbances across dimensions. Conclusions: Our result suggests a diffuse pattern of interoceptive alterations across neurological conditions, highlighting their potential role as dimensional, transdiagnostic markers.

In construing meaning, the brain recruits multimodal (conceptual) systems and embodied (modality-specific) mechanisms. Yet, no consensus exists on how crucial the latter are for the inception of semantic distinctions. To address this issue, we combined electroencephalographic (EEG) and intracranial EEG (iEEG) to examine when nouns denoting facial body parts (FBPs) and nonFBPs are discriminated in face-processing and multimodal networks. First, FBP words increased N170 amplitude (a hallmark of early facial processing). Second, they triggered fast (~100 ms) activity boosts within the face-processing network, alongside later (~275 ms) effects in multimodal circuits. Third, iEEG recordings from face-processing hubs allowed decoding ~80% of items before 200 ms, while classification based on multimodal-network activity only surpassed ~70% after 250 ms. Finally, EEG and iEEG connectivity between both networks proved greater in early (0–200 ms) than later (200–400 ms) windows. Collectively, our findings indicate that, at least for some lexico-semantic categories, meaning is construed through fast reenactments of modality-specific experience.

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. 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. 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. 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.

Impairments of action semantics (a cognitive domain that critically engages motor brain networks) are pervasive in early Parkinson’s disease (PD). However, no study has examined whether action semantic skills in persons with this disease can be influenced by non-invasive neuromodulation. Here, we recruited 22 PD patients and performed a five-day randomized, blinded, sham-controlled study to assess whether anodal transcranial direct current stimulation (atDCS) over the primary motor cortex, combined with cognitive training, can boost action–concept processing. On day 1, participants completed a picture–word association (PWA) task involving action-verb and object-noun conditions. They were then randomly assigned to either an atDCS (n = 11, 2 mA for 20 m) or a sham tDCS (n = 11, 2 mA for 30 s) group and performed an online PWA practice over three days. On day 5, they repeated the initial protocol. Relative to sham tDCS, the atDCS group exhibited faster reaction times for action (as opposed to object) concepts in the post-stimulation test. This result was exclusive to the atDCS group and held irrespective of the subjects’ cognitive, executive, and motor skills, further attesting to its specificity. Our findings suggest that action-concept deficits in PD are distinctively grounded in motor networks and might be countered by direct neuromodulation of such circuits. Moreover, they provide new evidence for neurosemantic models and inform a thriving agenda in the embodied cognition framework.

Persons with autism spectrum disorder (ASD) have impaired mentalizing skills. In this study, a group of persons with ASD traits (high-AQ scores) initially received sham tDCS before completing a pre-test in two mentalizing tasks: false belief and self-other judgments. Over the next week, on four consecutive days, they received sessions of anodal electrical stimulation (a-tDCS) over the right temporo-parietal junction (rTPJ), a region frequently associated with the theory of mind. On the last day, after the stimulation session, they completed a new set of mentalizing tasks. A control group (with low-AQ scores) matched in age, education and intelligence received just sham stimulation and completed the same pre-test and post-test. The results showed that the high-AQ group improved their performance (faster responses), after a-tDCS, in the false belief and in the self-other judgments of mental features, whereas they did not change performance in the false photographs or the self-other judgments of physical features. These selective improvements cannot be attributed to increased familiarity with the tasks, because the performance of the low-AQ control group remained stable about one week later. Therefore, our study provides initial proof that tDCS could be used to improve mentalizing skills in persons with ASD traits.