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.

Behavioral and neurophysiological signatures of interoceptive enhancements following vagus nerve stimulation.

An accruing body of research has shown that interoception (the sensing of signals from the body's internal milieu) relies on both a direct route (afforded by the vagus nerve) and a secondary route (supported by somatosensory mechanisms). However, no study has causally tested the differential role of these pathways, let alone via direct stimulation. To bridge this gap, we tested whether multidimensional signatures of interoception are modulated by noninvasive vagus nerve stimulation (nVNS). Sixty-three participants were divided into an nVNS and a sham-stimulation group. Before and after stimulation, both groups performed a validated heartbeat detection (HBD) task including a genuinely interoceptive condition (monitoring one's own heartbeat) and a control exteroceptive condition (tracking an aurally presented heartbeat). Electroencephalographic signals were obtained during both conditions to examine modulations of the heartbeat-evoked potential (HEP). Moreover, before and after stimulation, participants were asked to complete a somatosensory heartbeat localization task. Results from the interoceptive condition revealed that, after treatment, only the nVNS group exhibited improved performance and greater HEP modulations. No behavioral differences were found for the exteroceptive control condition, which was nonetheless associated with significant HEP modulations. Finally, no between-group differences were observed regarding the localization of the heartbeat sensations or relevant cardiodynamic variables (heart rate and or heart rate variability). Taken together, these results constitute unprecedented evidence that the vagus nerve plays a direct role in neurovisceral integration during interoception. This finding can constrain mechanistic models of the domain while informing a promising transdiagnostic agenda for interoceptive impairments across neuropsychiatric conditions.

A multidimensional and multi-feature framework for cardiac interoception.

Interoception (the sensing of inner-body signals) is a multi-faceted construct with major relevance for basic and clinical neuroscience research. However, the neurocognitive signatures of this domain (cutting across behavioral, electrophysiological, and fMRI connectivity levels) are rarely reported in convergent or systematic fashion. Additionally, various controversies in the field might reflect the caveats of standard interoceptive accuracy (IA) indexes, mainly based on heartbeat detection (HBD) tasks. Here we profit from a novel IA index (md) to provide a convergent multidimensional and multi-feature approach to cardiac interoception. We found that outcomes from our IA-md index are associated with -and predicted by- canonical markers of interoception, including the hd-EEG-derived heart-evoked potential (HEP), fMRI functional connectivity within interoceptive hubs (insular, somatosensory, and frontal networks), and socio-emotional skills. Importantly, these associations proved more robust than those involving current IA indexes. Furthermore, this pattern of results persisted when taking into consideration confounding variables (gender, age, years of education, and executive functioning). This work has relevant theoretical and clinical implications concerning the characterization of cardiac interoception and its assessment in heterogeneous samples, such as those composed of neuropsychiatric patients.

At the Heart of Neurological Dimensionality: Cross-Nosological and Multimodal Cardiac Interoceptive Deficits.

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.

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.

The roles of interoceptive sensitivity and metacognitive interoception in panic.

BACKGROUND: Interoception refers to the ability to sense body signals. Two interoceptive dimensions have been recently proposed: (a) interoceptive sensitivity (IS) -objective accuracy in detecting internal bodily sensations (e.g., heartbeat, breathing)-; and (b) metacognitive interoception (MI) -explicit beliefs and worries about one's own interoceptive sensitivity and internal sensations. Current models of panic assume a possible influence of interoception on the development of panic attacks. Hypervigilance to body symptoms is one of the most characteristic manifestations of panic disorders. Some explanations propose that patients have abnormal IS, whereas other accounts suggest that misinterpretations or catastrophic beliefs play a pivotal role in the development of their psychopathology. Our goal was to evaluate these theoretical proposals by examining whether patients differed from controls in IS, MI, or both. Twenty-one anxiety disorders patients with panic attacks and 13 healthy controls completed a behavioral measure of IS motor heartbeat detection (HBD) and two questionnaires measuring MI. FINDINGS: Patients did not differ from controls in IS. However, significant differences were found in MI measures. Patients presented increased worries in their beliefs about somatic sensations compared to controls. These results reflect a discrepancy between direct body sensing (IS) and reflexive thoughts about body states (MI). CONCLUSION: Our findings support the idea that hypervigilance to body symptoms is not necessarily a bottom-up dispositional tendency (where patients are hypersensitive about bodily signals), but rather a metacognitive process related to threatening beliefs about body/somatic sensations.

Delving into the relationship between regular physical exercise and cardiac interoception in two cross-sectional studies.

Cardiac interoception, the ability to sense and process cardiac afferent signals, has been shown to improve after a single session of acute physical exercise. However, it remains unclear whether repetitive engagement in physical exercise over time leads to long-term changes in cardiac interoceptive accuracy. It is also unknown whether those changes affect the neural activity associated with the processing of afferent cardiac signals, assessed by the heart-evoked potential (HEP). In this study, we aimed to investigate this hypothesis through two cross-sectional studies, categorizing participants as active or inactive based on physical fitness (Study I; N = 45) or self-reported physical activity levels (Study II; N = 60). Interoception was assessed at rest using the HEP (Studies I and II), the Heartbeat Counting task (Study II), and the Rubber Hand Illusion (RHI) (Study II). Study I showed strong evidence of better cardiovascular fitness in the active group than in the inactive group as well as robust between-group differences in electrocardiogram (ECG) recordings. Study 2 replicated the clear differences in ECG as a function of regular physical activity. Those results were expected due to clear differences in physical activity habits. In contrast, our analysis revealed no robust differences between groups across cardiac interoception tasks and the RHI, although the direct relevance of these measures to interoception remains under investigation. In sum, our results do not provide convincing evidence to support a strong version of the notion that regular physical exercise is associated with an enhanced in cardiac interoception.

Thinking versus feeling: How interoception and cognition influence emotion recognition in behavioural-variant frontotemporal dementia, Alzheimer's disease, and Parkinson's disease.

Disease-specific mechanisms underlying emotion recognition difficulties in behavioural-variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), and Parkinson's disease (PD) are unknown. Interoceptive accuracy, accurately detecting internal cues (e.g., one's heart beating), and cognitive abilities are candidate mechanisms underlying emotion recognition. One hundred and sixty-eight participants (52 bvFTD; 41 AD; 24 PD; 51 controls) were recruited. Emotion recognition was measured via the Facial Affect Selection Task or the Mini-Social and Emotional Assessment Emotion Recognition Task. Interoception was assessed with a heartbeat detection task. Participants pressed a button each time they: 1) felt their heartbeat (Interoception); or 2) heard a recorded heartbeat (Exteroception-control). Cognition was measured via the Addenbrooke's Cognitive Examination-III or the Montreal Cognitive Assessment. Voxel-based morphometry analyses identified neural correlates associated with emotion recognition and interoceptive accuracy. All patient groups showed worse emotion recognition and cognition than controls (all P's ≤ .008). Only the bvFTD showed worse interoceptive accuracy than controls (P < .001). Regression analyses revealed that in bvFTD worse interoceptive accuracy predicted worse emotion recognition (P = .008). Whereas worse cognition predicted worse emotion recognition overall (P < .001). Neuroimaging analyses revealed that the insula, orbitofrontal cortex, and amygdala were involved in emotion recognition and interoceptive accuracy in bvFTD. Here, we provide evidence for disease-specific mechanisms for emotion recognition difficulties. In bvFTD, emotion recognition impairment is driven by inaccurate perception of the internal milieu. Whereas, in AD and PD, cognitive impairment likely underlies emotion recognition deficits. The current study furthers our theoretical understanding of emotion and highlights the need for targeted interventions.

Risk perception, but also political orientation, modulate behavioral response to COVID-19: A randomized survey experiment.

Prior work has shown that accurately perceiving the risk for COVID-19 is associated with higher adherence to protective health behaviors, like face mask use, and more acceptance of governmental restrictive measures such as partial or complete banning of indoor activities and social gatherings. In this study we explored these associations at the beginning of the second wave of COVID-19 in Argentina through a national representative probabilistic survey that evaluated personal and contextual risk perception, self-reported compliance with protective health behaviors, attitude to governmental restrictive measures, and political orientation and psychological distress as potential modulators. Also, going beyond measures of association, here we sought to test whether messages highlighting potential risks increased acceptance of restrictive measures. Three types of messages were randomized to the participants. Two messages conveyed risk-related content (either through emotional arousal or cognitive appraisal) and the third a prosocial, altruistic content. Between March 29th and 30th, 2021, 2,894 participants were recruited (57.57% female). 74.64% of those surveyed evaluated the current health situation as "quite serious" or "very serious" and 62.03% estimated that the situation will be "worse" or "much worse" in the following 3 months. The perception of personal risk and the level of adherence to protective behaviors gradually increased with age. Through a regression model, age, perceived personal risk, and contextual risk appraisal were the variables most significantly associated with protective behaviors. In the case of the acceptance of restrictive measures, political orientation was the most associated variable. We then found messages aimed at increasing risk perception (both emotionally or cognitively focused) had a significantly greater effect on increasing the acceptance of restrictive measures than the prosocial message, mainly for government supporters but also for non-supporters. However, the level of response was also modulated by the political orientation of the participants. We propose a mechanism of "ideological anchoring" to explain that participants were responsive to risk modulation, but within the limits established by their pre-existent political views. We conclude that messages highlighting risk can help reinforce the acceptance of restrictive measures even in the presence of polarized views, but must be calibrated by age and political orientation.

Psychological symptoms, mental fatigue and behavioural adherence after 72 continuous days of strict lockdown during the COVID-19 pandemic in Argentina.

BACKGROUND: An early and prolonged lockdown was adopted in Argentina during the first wave of COVID-19. Early reports evidenced elevated psychological symptoms. AIMS: To explore if the prolonged lockdown was associated with elevated anxiety and depressive symptoms; if mental fatigue was associated with lockdown adherence (a phenomenon called 'behavioural fatigue'); and if financial concerns were associated with lockdown adherence and emotional symptoms. METHOD: The survey included standardised questionnaires to assess depressive (PHQ-9) and anxious (GAD-7) symptoms, mental fatigue, risk perception, lockdown adherence, financial concerns, daily stress, loneliness, intolerance to uncertainty, negative repetitive thinking and cognitive problems. LASSO regression analyses were carried out to predict depression, anxiety and lockdown adherence. RESULTS: The survey reached 3617 adults (85.2% female) from all provinces of Argentina after 72 days of lockdown. Data were collected between 21 May 2020 and 4 June 2020. In that period, Argentina had an Oxford stringency index of 85/100. Of those surveyed, 45.6% and 27% met the cut-offs for depression and anxiety, respectively. Mental fatigue, cognitive failures and financial concerns were correlated with psychological symptoms, but not with adherence to lockdown. In regression models, mental fatigue, cognitive failures and loneliness were the most important variables to predict depression, intolerance to uncertainty and lockdown difficulty were the most important for anxiety, and perceived threat was the most important for predicting lockdown adherence. CONCLUSIONS: During the extended lockdown, psychological symptoms increased, being enhanced by mental fatigue, cognitive difficulties and financial concerns. We found no evidence of behavioural fatigue. Thus, feeling mentally fatigued is not the same as being behaviourally fatigued.

Multicentric evidence of emotional impairments in hypertensive heart disease.

The mechanisms underlying emotional alterations constitute a key research target in neuroscience. Emerging evidence indicates that these disruptions can be related to abnormal interoception (i.e., the sensing of visceral feelings), as observed in patients with cardiodynamic deficits. To directly assess these links, we performed the first multicenter study on emotion recognition and interoception in patients with hypertensive heart disease (HHD). Participants from two countries completed a facial emotion recognition test, and a subsample additionally underwent an interoception protocol based on a validated heartbeat detection task. HHD patients from both countries presented deficits in the recognition of overall and negative emotions. Moreover, interoceptive performance was impaired in the HHD group. In addition, a significant association between interoceptive performance and emotion recognition was observed in the control group, but this relation was abolished in the HHD group. All results survived after covariance with cognitive status measures, suggesting they were not biased by general cognitive deficits in the patients. Taken together, these findings suggest that emotional recognition alterations could represent a sui generis deficit in HHD, and that it may be partially explained by the disruption of mechanisms subserving the integration of neuro-visceral signals.

Social neuroscience: undoing the schism between neurology and psychiatry.

Multiple disorders once jointly conceived as "nervous diseases" became segregated by the distinct institutional traditions forged in neurology and psychiatry. As a result, each field specialized in the study and treatment of a subset of such conditions. Here we propose new avenues for interdisciplinary interaction through a triangulation of both fields with social neuroscience. To this end, we review evidence from five relevant domains (facial emotion recognition, empathy, theory of mind, moral cognition, and social context assessment), highlighting their common disturbances across neurological and psychiatric conditions and discussing their multiple pathophysiological mechanisms. Our proposal is anchored in multidimensional evidence, including behavioral, neurocognitive, and genetic findings. From a clinical perspective, this work paves the way for dimensional and transdiagnostic approaches, new pharmacological treatments, and educational innovations rooted in a combined neuropsychiatric training. Research-wise, it fosters new models of the social brain and a novel platform to explore the interplay of cognitive and social functions. Finally, we identify new challenges for this synergistic framework.

Feeling, learning from and being aware of inner states: interoceptive dimensions in neurodegeneration and stroke.

Interoception is a complex process encompassing multiple dimensions, such as accuracy, learning and awareness. Here, we examined whether each of those dimensions relies on specialized neural regions distributed throughout the vast interoceptive network. To this end, we obtained relevant measures of cardiac interoception in healthy subjects and patients offering contrastive lesion models of neurodegeneration and focal brain damage: behavioural variant fronto-temporal dementia (bvFTD), Alzheimer's disease (AD) and fronto-insular stroke. Neural correlates of the three dimensions were examined through structural and functional resting-state imaging, and online measurements of the heart-evoked potential (HEP). The three patient groups presented deficits in interoceptive accuracy, associated with insular damage, connectivity alterations and abnormal HEP modulations. Interoceptive learning was differentially impaired in AD patients, evidencing a key role of memory networks in this skill. Interoceptive awareness results showed that bvFTD and AD patients overestimated their performance; this pattern was related to abnormalities in anterior regions and associated networks sub-serving metacognitive processes, and probably linked to well-established insight deficits in dementia. Our findings indicate how damage to specific hubs in a broad fronto-temporo-insular network differentially compromises interoceptive dimensions, and how such disturbances affect widespread connections beyond those critical hubs. This is the first study in which a multiple lesion model reveals fine-grained alterations of body sensing, offering new theoretical insights into neuroanatomical foundations of interoceptive dimensions.This article is part of the themed issue 'Interoception beyond homeostasis: affect, cognition and mental health'.

How do you feel when you can't feel your body? Interoception, functional connectivity and emotional processing in depersonalization-derealization disorder.

Depersonalization-Derealization Disorder (DD) typically manifests as a disruption of body self-awareness. Interoception -defined as the cognitive processing of body signals- has been extensively considered as a key processing for body self-awareness. In consequence, the purpose of this study was to investigate whether there are systematic differences in interoception between a patient with DD and controls that might explain the disembodiment symptoms suffered in this disease. To assess interoception, we utilized a heartbeat detection task and measures of functional connectivity derived from fMRI networks in interoceptive/exteroceptivo/mind-wandering states. Additionally, we evaluated empathic abilities to test the association between interoception and emotional experience. The results showed patient's impaired performance in the heartbeat detection task when compared to controls. Furthermore, regarding functional connectivity, we found a lower global brain connectivity of the patient relative to controls only in the interoceptive state. He also presented a particular pattern of impairments in affective empathy. To our knowledge, this is the first experimental research that assesses the relationship between interoception and DD combining behavioral and neurobiological measures. Our results suggest that altered neural mechanisms and cognitive processes regarding body signaling might be engaged in DD phenomenology. Moreover, our study contributes experimental data to the comprehension of brain-body interactions and the emergence of self-awareness and emotional feelings.

Structural neuroimaging of social cognition in progressive non-fluent aphasia and behavioral variant of frontotemporal dementia.

Social cognition impairments are pervasive in the frontotemporal dementias (FTD). These deficits would be triggered by (a) basic emotion and face recognition processes as well as by (b) higher level social cognition (e.g., theory of mind, ToM). Both emotional processing and social cognition impairments have been previously reported in the behavioral variant of FTD (bvFTD) and also in other versions of FTDs, including primary progressive aphasia. However, no neuroanatomic comparison between different FTD variants has been performed. We report selective behavioral impairments of face recognition, emotion recognition, and ToM in patients with bvFTD and progressive non-fluent aphasia (PNFA) when compared to controls. Voxel-based morphometry (VBM) shows a classical impairment of mainly orbitofrontal (OFC), anterior cingulate (ACC), insula and lateral temporal cortices in patients. Comparative analysis of regional gray matter related to social cognition deficits (VBM) reveals a differential pattern of fronto-insulo-temporal atrophy in bvFTD and an insulo-temporal involvement in PNFA group. Results suggest that in spite of similar social cognition impairments reported in bvFTD and PNFA, the former represents an inherent ToM affectation whereas in the PNFA these deficits could be related to more basic processes of face and emotion recognition. These results are interpreted in the frame of the fronto-insulo-temporal social context network model (SCNM).