Multimodal Neurocognitive Markers of Naturalistic Discourse Typify Diverse Neurodegenerative Diseases.

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.

Interoception Primes Emotional Processing: Multimodal Evidence from Neurodegeneration.

Recent frameworks in cognitive neuroscience and behavioral neurology underscore interoceptive priors as core modulators of negative emotions. However, the field lacks experimental designs manipulating the priming of emotions via interoception and exploring their multimodal signatures in neurodegenerative models. Here, we designed a novel task that involves interoceptive and control-exteroceptive priming conditions followed by post-interoception and post-exteroception facial emotion recognition (FER). We recruited 114 participants, including healthy controls (HCs) as well as patients with behavioral variant frontotemporal dementia (bvFTD), Parkinson's disease (PD), and Alzheimer's disease (AD). We measured online EEG modulations of the heart-evoked potential (HEP), and associations with both brain structural and resting-state functional connectivity patterns. Behaviorally, post-interoception negative FER was enhanced in HCs but selectively disrupted in bvFTD and PD, with AD presenting generalized disruptions across emotion types. Only bvFTD presented impaired interoceptive accuracy. Increased HEP modulations during post-interoception negative FER was observed in HCs and AD, but not in bvFTD or PD patients. Across all groups, post-interoception negative FER correlated with the volume of the insula and the ACC. Also, negative FER was associated with functional connectivity along the (a) salience network in the post-interoception condition, and along the (b) executive network in the post-exteroception condition. These patterns were selectively disrupted in bvFTD (a) and PD (b), respectively. Our approach underscores the multidimensional impact of interoception on emotion, while revealing a specific pathophysiological marker of bvFTD. These findings inform a promising theoretical and clinical agenda in the fields of nteroception, emotion, allostasis, and neurodegeneration.SIGNIFICANCE STATEMENT We examined whether and how emotions are primed by interoceptive states combining multimodal measures in healthy controls and neurodegenerative models. In controls, negative emotion recognition and ongoing HEP modulations were increased after interoception. These patterns were selectively disrupted in patients with atrophy across key interoceptive-emotional regions (e.g., the insula and the cingulate in frontotemporal dementia, frontostriatal networks in Parkinson's disease), whereas persons with Alzheimer's disease presented generalized emotional processing abnormalities with preserved interoceptive mechanisms. The integration of both domains was associated with the volume and connectivity (salience network) of canonical interoceptive-emotional hubs, critically involving the insula and the anterior cingulate. Our study reveals multimodal markers of interoceptive-emotional priming, laying the groundwork for new agendas in cognitive neuroscience and behavioral neurology.

Heart-brain interactions during social and cognitive stress in hypertensive disease: A multidimensional approach.

Hypertensive disease (HTD), a prominent risk factor for cardiovascular and cerebrovascular diseases, is characterized by elevated stress-proneness. Since stress levels are underpinned by both cardiac and neural factors, multidimensional insights are required to robustly understand their disruption in HTD. Yet, despite their crucial relevance, heart rate variability (HRV) and multimodal neurocognitive markers of stress in HTD remain controversial and unexplored respectively. To bridge this gap, we studied cardiodynamic as well as electrophysiological and neuroanatomical measures of stress in HTD patients and healthy controls. Both groups performed the Trier Social Stress Test (TSST), a validated stress-inducing task comprising a baseline and a mental stress period. During both stages, we assessed a sensitive HRV parameter (the low frequency/high frequency [LF/HF ratio]) and an online neurophysiological measure (the heartbeat-evoked potential [HEP]). Also, we obtained neuroanatomical data via voxel-based morphometry (VBM) for correlation with online markers. Relative to controls, HTD patients exhibited increased LF/HF ratio and greater HEP modulations during baseline, reduced changes between baseline and stress periods, and lack of significant stress-related HRV modulations associated with the grey matter volume of putative frontrostriatal regions. Briefly, HTD patients presented signs of stress-related autonomic imbalance, reflected in a potential basal stress overload and a lack of responsiveness to acute psychosocial stress, accompanied by neurophysiological and neuroanatomical alterations. These multimodal insights underscore the relevance of neurocognitive data for developing innovations in the characterization, prognosis and treatment of HTD and other conditions with autonomic imbalance. More generally, these findings may offer new insights into heart-brain interactions.

Multilevel convergence of interoceptive impairments in hypertension: New evidence of disrupted body-brain interactions.

Interoception, the sensing of visceral body signals, involves an interplay between neural and autonomic mechanisms. Clinical studies into this domain have focused on patients with neurological and psychiatric disorders, showing that damage to relevant brain mechanisms can variously alter interoceptive functions. However, the association between peripheral cardiac-system alterations and neurocognitive markers of interoception remains poorly understood. To bridge this gap, we examined multidimensional neural markers of interoception in patients with early stage of hypertensive disease (HTD) and healthy controls. Strategically, we recruited only HTD patients without cognitive impairment (as shown by neuropsychological tests), brain atrophy (as assessed with voxel-based morphometry), or white matter abnormalities (as evidenced by diffusion tensor imaging analysis). Interoceptive domains were assessed through (a) a behavioral heartbeat detection task; (b) measures of the heart-evoked potential (HEP), an electrophysiological cortical signature of attention to cardiac signals; and (c) neuroimaging recordings (MRI and fMRI) to evaluate anatomical and functional connectivity properties of key interoceptive regions (namely, the insula and the anterior cingulate cortex). Relative to controls, patients exhibited poorer interoceptive performance and reduced HEP modulations, alongside an abnormal association between interoceptive performance and both the volume and functional connectivity of the above regions. Such results suggest that peripheral cardiac-system impairments can be associated with abnormal behavioral and neurocognitive signatures of interoception. More generally, our findings indicate that interoceptive processes entail bidirectional influences between the cardiovascular and the central nervous systems.

Altered neural signatures of interoception in multiple sclerosis.

Multiple sclerosis (MS) patients present several alterations related to sensing of bodily signals. However, no specific neurocognitive impairment has yet been proposed as a core deficit underlying such symptoms. We aimed to determine whether MS patients present changes in interoception-that is, the monitoring of autonomic bodily information-a process that might be related to various bodily dysfunctions. We performed two studies in 34 relapsing-remitting, early-stage MS patients and 46 controls matched for gender, age, and education. In Study 1, we evaluated the heartbeat-evoked potential (HEP), a cortical signature of interoception, via a 128-channel EEG system during a heartbeat detection task including an exteroceptive and an interoceptive condition. Then, we obtained whole-brain MRI recordings. In Study 2, participants underwent fMRI recordings during two resting-state conditions: mind wandering and interoception. In Study 1, controls exhibited greater HEP modulation during the interoceptive condition than the exteroceptive one, but no systematic differences between conditions emerged in MS patients. Patients presented atrophy in the left insula, the posterior part of the right insula, and the right anterior cingulate cortex, with abnormal associations between neurophysiological and neuroanatomical patterns. In Study 2, controls showed higher functional connectivity and degree for the interoceptive state compared with mind wandering; however, this pattern was absent in patients, who nonetheless presented greater connectivity and degree than controls during mind wandering. MS patients were characterized by atypical multimodal brain signatures of interoception. This finding opens a new agenda to examine the role of inner-signal monitoring in the body symptomatology of MS.

A pre-registered, multi-lab non-replication of the action-sentence compatibility effect (ACE).

The Action-sentence Compatibility Effect (ACE) is a well-known demonstration of the role of motor activity in the comprehension of language. Participants are asked to make sensibility judgments on sentences by producing movements toward the body or away from the body. The ACE is the finding that movements are faster when the direction of the movement (e.g., toward) matches the direction of the action in the to-be-judged sentence (e.g., Art gave you the pen describes action toward you). We report on a pre-registered, multi-lab replication of one version of the ACE. The results show that none of the 18 labs involved in the study observed a reliable ACE, and that the meta-analytic estimate of the size of the ACE was essentially zero.

Towards affordable biomarkers of frontotemporal dementia: A classification study via network's information sharing.

Developing effective and affordable biomarkers for dementias is critical given the difficulty to achieve early diagnosis. In this sense, electroencephalographic (EEG) methods offer promising alternatives due to their low cost, portability, and growing robustness. Here, we relied on EEG signals and a novel information-sharing method to study resting-state connectivity in patients with behavioral variant frontotemporal dementia (bvFTD) and controls. To evaluate the specificity of our results, we also tested Alzheimer's disease (AD) patients. The classification power of the ensuing connectivity patterns was evaluated through a supervised classification algorithm (support vector machine). In addition, we compared the classification power yielded by (i) functional connectivity, (ii) relevant neuropsychological tests, and (iii) a combination of both. BvFTD patients exhibited a specific pattern of hypoconnectivity in mid-range frontotemporal links, which showed no alterations in AD patients. These functional connectivity alterations in bvFTD were replicated with a low-density EEG setting (20 electrodes). Moreover, while neuropsychological tests yielded acceptable discrimination between bvFTD and controls, the addition of connectivity results improved classification power. Finally, classification between bvFTD and AD patients was better when based on connectivity than on neuropsychological measures. Taken together, such findings underscore the relevance of EEG measures as potential biomarker signatures for clinical settings.