Right limbic FDG-PET hypometabolism correlates with emotion recognition and attribution in probable behavioral variant of frontotemporal dementia patients

The behavioural variant of frontotemporal dementia (bvFTD) is a rare disease mainly affecting the social brain. FDG-PET fronto-temporal hypometabolism is a supportive feature for the diagnosis. It may also provide specific functional metabolic signatures for altered socio-emotional processing. In this study, we evaluated the emotion recognition and attribution deficits and FDG-PET cerebral metabolic patterns at the group and individual levels in a sample of sporadic bvFTD patients, exploring the cognitive-functional correlations. Seventeen probable mild bvFTD patients (10 male and 7 female; age 67.8±9.9) were administered standardized and validated version of social cognition tasks assessing the recognition of basic emotions and the attribution of emotions and intentions (i.e., Ekman 60-Faces test-Ek60F and Story-based Empathy task-SET). FDG-PET was analysed using an optimized voxel-based SPM method at the single-subject and group levels. Severe deficits of emotion recognition and processing characterized the bvFTD condition. At the group level, metabolic dysfunction in the right amygdala, temporal pole, and middle cingulate cortex was highly correlated to the emotional recognition and attribution performances. At the single-subject level, however, heterogeneous impairments of social cognition tasks emerged, and different metabolic patterns, involving limbic structures and prefrontal cortices, were also observed. The derangement of a right limbic network is associated with altered socio-emotional processing in bvFTD patients, but different hypometabolic FDG-PET patterns and heterogeneous performances on social tasks at an individual level exist

Different FDG-PET metabolic patterns at single-subject level in the behavioral variant of fronto-temporal dementia.

BACKGROUND: The diagnosis of probable behavioral variant of fronto-temporal dementia (bvFTD) according to current criteria requires the imaging evidence of frontal and/or anterior temporal atrophy or hypoperfusion/hypometabolism. Different variants of this pattern of brain involvement may, however, be found in individual cases, supporting the presence of heterogeneous phenotypes. OBJECTIVE: We examined in a case-by-case approach the FDG-PET metabolic patterns of patients fulfilling clinical criteria for probable bvFTD, assessing the presence and frequency of specific FDG-PET features. MATERIALS AND METHODS: Fifty two FDG-PET scans of probable bvFTD patients were retrospectively analyzed together with clinical and neuropsychological data. Neuroimaging experts rated the FDG-PET hypometabolism maps obtained at the single-subject level with optimized voxel-based Statistical Parametric Mapping (SPM). The functional metabolic heterogeneity was further tested by hierarchical cluster analysis and principal component analysis (PCA). RESULTS: Both the SPM maps and cluster analysis identified two major variants of cerebral hypometabolism, namely the "frontal" and the "temporo-limbic", which were correlated with different cognitive profiles. Executive and language deficits were the cognitive hallmark in the "frontal" subgroup, while poor encoding and recall on long-term memory tasks was typical of the "temporo-limbic" subgroup. DISCUSSION: SPM single-subject analysis indicates distinct patterns of brain dysfunction in bvFTD, coupled with specific clinical features, suggesting different profiles of neurodegenerative vulnerability. These findings have important implications for the early diagnosis of bvFTD and for the application of the recent international consensus criteria

Brain Hemodynamic Intermediate Phenotype Links Vitamin B12 to Cognitive Profile of Healthy and Mild Cognitive Impaired Subjects

Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders’ mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects’ neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated ( cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects’ visual search and attention abilities (), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders’ cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype

Default and Control Networks Connectivity Dynamics Track the Stream of Affect at Multiple Timescales

In everyday life, the stream of affect results from the interaction between past experiences, expectations and the unfolding of events. How the brain represents the relationship between time and affect has been hardly explored, as it requires modeling the complexity of everyday life in the laboratory setting. Movies condense into hours a multitude of emotional responses, synchronized across subjects and characterized by temporal dynamics alike real-world experiences. Here, we use time-varying intersubject brain synchronization and real-time behavioral reports to test whether connectivity dynamics track changes in affect during movie watching. The results show that polarity and intensity of experiences relate to the connectivity of the default mode and control networks and converge in the right temporoparietal cortex. We validate these results in two experiments including four independent samples, two movies and alternative analysis workflows. Finally, we reveal chronotopic connectivity maps within the temporoparietal and prefrontal cortex, where adjacent areas preferentially encode affect at specific timescales

Brain topography, connectivity dynamics and coding mechanisms underlying the subjective experience of affective states

The present dissertation focuses on the behavioral and neural substrates of socio-affective abilities involved in the subjective emotional experience. Socio-affective abilities are the building blocks of the more general domain of social cognition, which represents the cornerstone of human interactions. In particular, understanding, predicting and responding to others’ emotional signals are fundamental aspects necessary for the optimal functioning of human’s daily life. Emotions are pervasively present in dyadic interactions, give color to individual experiences, and can rapidly change over time, as they are the consequence of an active interplay between an individual and the environment. Despite their relevance, however, emotions are still an open question for researchers. Indeed, which mechanisms link descriptions of affective states to brain activity is still unclear, with evidence supporting either local or distributed processing. Moreover, the majority of neuroimaging studies so far did not take into account the dynamism of affective states and their unfolding over time. For this reason, how the temporal characteristics of emotions (e.g., duration, onset, resurgence) are represented in the brain, with the dynamics between specific regions related to different emotional experiences is an open question. In light of all this, the studies reported in the present dissertation aimed to overcome previous limitations and answer these questions. In the first study we used brain hemodynamic activity evoked by an emotionally charged movie and continuous ratings of the perceived emotion intensity to reveal the topographic organization of affective states. In the second study, we explored the dynamic interplay between different brain regions throughout a naturalistic situation. To do so, we related continuous ratings of the perceived intensity of various emotional states to changes in functional connectivity among distinct brain regions during the watching of the same movie employed before. Our results showed that moment-by-moment ratings of perceived emotions explain brain activity recorded in independent subjects. Most importantly, we demonstrated the existence of orthogonal and spatially overlapping right temporo-parietal gradients encoding emotion dimensions, a mechanism that we named emotionotopy. We also unveiled the central role of the right precentral sulcus during the subjective emotional experience, with changes in the functional connectivity dynamics of this region being modulated by three cardinal emotion dimensions