Key Points Question Can metabolic brain changes be detected in presymptomatic individuals who are carriers of a hexanucleotide repeat expansion in the C9orf72 gene (preSxC9) using time-of-flight fluorine 18–labeled fluorodeoxyglucose positron emission tomographic imaging and magnetic resonance imaging, and what is the association between the mutation and clinical and fluid biomarkers of amyotrophic lateral sclerosis and frontotemporal dementia? Findings In a case-control study including 17 preSxC9 participants and 25 healthy controls, fluorine 18–labeled fluorodeoxyglucose positron emission tomographic imaging noted significant clusters of relative hypometabolism in frontotemporal regions, the insular cortices, basal ganglia, and thalami in the preSxC9 participants. Use of this strategy allowed detection of changes at an individual level. Meaning Glucose metabolic changes appear to occur early in the sequence of events leading to manifest amyotrophic lateral sclerosis and frontotemporal dementia. Fluorine 18–labeled fluorodeoxyglucose positron emission tomographic imaging may provide a sensitive biomarker of a presymptomatic phase of disease.

Personality reflects the set of psychological traits and mechanisms characteristic for an individual. The brain-trait association between personality and gray matter volume (GMv) has been well studied. However, a recent study has shown that brain structure-personality relationships are highly dependent on sex. In addition, the present study investigates the role of sex on the association between temperaments and regional GMv. Sixty-six participants (33 male) completed the Temperament and Character Inventory (TCI) and underwent structural magnetic resonance brain imaging. Mann-Whitney U tests showed a significant higher score on Novelty Seeking (NS) and Reward Dependence (RD) for females, but no significant group effects were found for Harm Avoidance (HA) and Persistence (P) score. Full factor model analyses were performed to investigate sex-temperament interaction effects on GMv. This revealed increased GMv for females in the superior temporal gyrus when linked to NS, middle temporal gyrus for HA, and the insula for RD. Males displayed increased GMv compared to females relating to P in the posterior cingulate gyrus, the medial superior frontal gyrus, and the middle cingulate gyrus, compared to females. Multiple regression analysis showed clear differences between the brain regions that correlate with female subjects and the brain correlates that correlate with male subjects. No overlap was observed between sex-specific brain-trait associations. These results increase the knowledge of the role of sex on the structural neurobiology of personality and indicate that sex differences reflect structural differences observed in the normal brain. Furthermore, sex hormones seem an important underlying factor for the found sex differences in brain-trait associations. The present study indicates an important role for sex in these brain structure-personality relationships, and implies that sex should not just be added as a covariate of no interest.

IntroductionBehavioral variant frontotemporal dementia (bvFTD) is associated with abnormal emotion recognition and moral processing.MethodsWe assessed emotion detection, discrimination, matching, selection, and categorization as well as judgments of nonmoral, moral impersonal, moral personal low‐ and high‐conflict scenarios.ResultsbvFTD patients gave more utilitarian responses on low‐conflict personal moral dilemmas. There was a significant correlation between a facial emotion processing measure derived through principal component analysis and utilitarian responses on low‐conflict personal scenarios in the bvFTD group (controlling for MMSE‐score and syntactic abilities). Voxel‐based morphometric multiple regression analysis in the bvFTD group revealed a significant association between the proportion of utilitarian responses on personal low‐conflict dilemmas and gray matter volume in ventromedial prefrontal areas (p height < .0001). In addition, there was a correlation between utilitarian responses on low‐conflict personal scenarios in the bvFTD group and resting‐state fractional Amplitude of Low Frequency Fluctuations (fALFF) in the anterior insula (p height < .005).ConclusionsThe results underscore the importance of emotions in moral cognition and suggest a common basis for deficits in both abilities, possibly related to reduced experience of emotional sensations. At the neural level abnormal moral cognition in bvFTD is related to structural integrity of the medial prefrontal cortex and functional characteristics of the anterior insula. The present findings provide a common basis for emotion recognition and moral reasoning and link them with areas in the default mode and salience network.

Theory of mind (ToM) refers to the ability to attribute mental states to others. Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterized by profound deficits in social cognition, including ToM. We investigate whether bvFTD affects intention attribution tendency while viewing abstract animations and whether this might represent a primary deficit. A sample of 15 bvFTD patients and 19 matched controls were assessed on cognition and performed an implicit ToM task. They were instructed to describe what they observed in movement patterns displayed by geometrical shapes (triangles). These movement patterns either represented animacy, goal-directed actions or manipulation of mental state (ToM). The responses were scored for both accuracy and intentionality attribution. Using Voxel-Based Morphometry, we investigated the structural neuroanatomy associated with intention attribution tendency. The behavioral results revealed deficits in the bvFTD group on intentionality attribution that were specific for the ToM condition after controlling for global cognitive functioning (MMSE-score), visual attention (TMT B-score), fluid intelligence (RCPMT-score) and confrontation naming (BNT-score). In the bvFTD sample, the intention attribution tendency on the ToM-condition was associated with grey matter volume of a cluster in the cerebellum, spanning the right Crus I, Crus II, VIIIb, IX, left VIIb, IX and vermal IX and X. The results reveal a specific, primary, implicit domain-general ToM deficit in bvFTD that cannot be explained by cognitive dysfunction. Furthermore, the findings point to a contribution of the cerebellum in the social-cognitive phenotype of bvFTD.

Repetition suppression (RS) reflects a neural attenuation during repeated stimulation. We used fMRI and the subsequent memory paradigm to test the predictive coding hypothesis for RS during visual memory processing by investigating the interaction between RS and differences due to memory in category-selective cortex (FFA, pSTS, PPA, and RSC). Fifty-six participants encoded face and house stimuli twice, followed by an immediate and delayed (48 h) recognition memory assessment. Linear Mixed Model analyses with repetition, subsequent recognition performance, and their interaction as fixed effects revealed that absolute RS during encoding interacts with probability of future remembrance in face-selective cortex. This effect was not observed for relative RS, i.e. when controlled for adapter-response. The findings also reveal an association between adapter response and RS, both for short and long term (48h) intervals, after controlling for the mathematical dependence between both measures. These combined findings are challenging for predictive coding models of visual memory and are more compatible with adapter-related and familiarity accounts.