Facial expression recognition deficits in frontotemporal dementia and Alzheimer's disease: a meta-analytic investigation of effects of phenotypic variant, task modality, geographical region and symptomatic specificity.

Deficits in social cognition may be present in frontotemporal dementia (FTD) and Alzheimer's disease (AD). Here, we conduct a qualitative synthesis and meta-analysis of facial expression recognition studies in which we compare the deficits between both disorders. Furthermore, we investigate the specificity of the deficit regarding phenotypic variant, domain-specificity, emotion category, task modality, and geographical region. The results reveal that both FTD and AD are associated with facial expression recognition deficits, that this deficit is more pronounced in FTD compared to AD and that this applies for the behavioral as well as for language FTD-variants, with no difference between the latter two. In both disorders, overall emotion recognition was most frequently impaired, followed by recognition of anger in FTD and by fear in AD. Verbal categorization was the most frequently used task, although matching or intensity rating tasks may be more specific. Studies from Oceania revealed larger deficits. On the other hand, non-emotional control tasks were more impacted by AD than by FTD. The present findings sharpen the social cognitive phenotype of FTD and AD, and support the use of social cognition assessment in late-life neuropsychiatric disorders.

Neural compensation in manifest neurodegeneration: systems neuroscience evidence from social cognition in frontotemporal dementia.

BACKGROUND: It has been argued that symptom onset in neurodegeneration reflects the overload of compensatory mechanisms. The present study aimed to investigate whether neural functional compensation can be observed in the manifest neurodegenerative disease stage, by focusing on a core deficit in frontotemporal dementia, i.e. social cognition, and by combining psychophysical assessment, structural MRI and functional MRI with multidimensional neural markers that allow quantification of neural computations. METHODS: Nineteen patients with clinically manifest behavioral variant frontotemporal dementia (bvFTD) and 20 controls performed facial expression recognition tasks in the MRI-scanner and offline. Group differences in grey matter volume, neural response amplitude and neural patterns were assessed via a combination of voxel-wise whole-brain, searchlight, and ROI-analyses and these measures were correlated with psychophysical measures of emotion, valence and arousal ratings. RESULTS: Significant group effects were observed only outside task-relevant regions, converging in the caudate nucleus. This area showed a diagnostic neural pattern as well as hyperactivation and stronger neural representation of facial expressions in the bvFTD sample. Furthermore, response amplitude was associated with behavioral arousal ratings. CONCLUSIONS: The combined findings reveal converging support for compensatory processes in clinically manifest neurodegeneration, complementing accounts that clinical onset synchronizes with the breakdown of compensatory processes. Furthermore, active compensation may proceed along nodes in intrinsically connected networks, rather than along the more task-specific networks. The findings underscore the potential of distributed multidimensional functional neural characteristics that may provide a novel class of biomarkers with both diagnostic and therapeutic implications, including biomarkers for clinical trials.

Age Effects in Emotional Memory and Associated Eye Movements.

Mnemonic enhanced memory has been observed for negative events. Here, we investigate its association with spatiotemporal attention, consolidation, and age. An ingenious method to study visual attention for emotional stimuli is eye tracking. Twenty young adults and twenty-one older adults encoded stimuli depicting neutral faces, angry faces, and houses while eye movements were recorded. The encoding phase was followed by an immediate and delayed (48 h) recognition assessment. Linear mixed model analyses of recognition performance with group, emotion, and their interaction as fixed effects revealed increased performance for angry compared to neutral faces in the young adults group only. Furthermore, young adults showed enhanced memory for angry faces compared to older adults. This effect was associated with a shorter fixation duration for angry faces compared to neutral faces in the older adults group. Furthermore, the results revealed that total fixation duration was a strong predictor for face memory performance.

The neurobiological basis of affect is consistent with psychological construction theory and shares a common neural basis across emotional categories.

Affective experience colours everyday perception and cognition, yet its fundamental and neurobiological basis is poorly understood. The current debate essentially centers around the communalities and specificities across individuals, events, and emotional categories like anger, sadness, and happiness. Using fMRI during the experience of these emotions, we critically compare the two dominant conflicting theories on human affect. Basic emotion theory posits emotions as discrete universal entities generated by dedicated emotion category-specific neural circuits, while psychological construction theory claims emotional events as unique, idiosyncratic, and constructed by psychological primitives like core affect and conceptualization, which underlie each emotional event and operate in a predictive framework. Based on the findings of 8 a priori-defined model-specific prediction tests on the neural response amplitudes and patterns, we conclude that the neurobiological basis of affect is primarily characterized by idiosyncratic mechanisms and a common neural basis shared across emotion categories, consistent with psychological construction theory. The findings provide further insight into the organizational principles of the neural basis of affect and brain function in general. Future studies in clinical populations with affective symptoms may reveal the corresponding underlying neural changes from a psychological construction perspective.

Long term fMRI adaptation depends on adapter response in face-selective cortex.

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.

Use of Multimodal Imaging and Clinical Biomarkers in Presymptomatic Carriers of C9orf72 Repeat Expansion.

Importance: During a time with the potential for novel treatment strategies, early detection of disease manifestations at an individual level in presymptomatic carriers of a hexanucleotide repeat expansion in the C9orf72 gene (preSxC9) is becoming increasingly relevant. Objectives: To evaluate changes in glucose metabolism before symptom onset of amyotrophic lateral sclerosis or frontotemporal dementia in preSxC9 using simultaneous fluorine 18-labeled fluorodeoxyglucose ([18F]FDG positron emission tomographic (PET) and magnetic resonance imaging as well as the mutation's association with clinical and fluid biomarkers. Design, Setting, and Participants: A prospective, case-control study enrolled 46 participants from November 30, 2015, until December 11, 2018. The study was conducted at the neuromuscular reference center of the University Hospitals Leuven, Leuven, Belgium. Main Outcomes and Measures: Neuroimaging data were spatially normalized and analyzed at the voxel level at a height threshold of P < .001, cluster-level familywise error-corrected threshold of P < .05, and statistical significance was set at P < .05 for the volume-of-interest level analysis, using Benjamini-Hochberg correction for multiple correction. W-score maps were computed using the individuals serving as controls as a reference to quantify the degree of [18F]FDG PET abnormality. The threshold for abnormality on the W-score maps was designated as an absolute W-score greater than or equal to 1.96. Neurofilament levels and performance on cognitive and neurologic examinations were determined. All hypothesis tests were 1-sided. Results: Of the 42 included participants, there were 17 with the preSxC9 mutation (12 women [71%]; mean [SD] age, 51 [9] years) and 25 healthy controls (12 women [48%]; mean [SD] age, 47 [10] years). Compared with control participants, significant clusters of relative hypometabolism were found in frontotemporal regions, basal ganglia, and thalami of preSxC9 participants and relative hypermetabolism in the peri-Rolandic region, superior frontal gyrus, and precuneus cortex. W-score frequency maps revealed reduced glucose metabolism with local maxima in the insular cortices, central opercular cortex, and thalami in up to 82% of preSxC9 participants and increased glucose metabolism in the precentral gyrus and precuneus cortex in up to 71% of preSxC9 participants. Other findings in the preSxC9 group were upper motor neuron involvement in 10 participants (59%), cognitive abnormalities in 5 participants (29%), and elevated neurofilament levels in 3 of 16 individuals (19%) who underwent lumbar puncture. Conclusions and Relevance: The results suggest that [18F]FDG PET can identify glucose metabolic changes in preSxC9 at an individual level, preceding significantly elevated neurofilament levels and onset of symptoms.

Non-overlapping and Inverse Associations Between the Sexes in Structural Brain-Trait Associations.

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.

Reduced tendency to attribute mental states to abstract shapes in behavioral variant frontotemporal dementia links with cerebellar structural integrity.

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.

Gray Matter Volume of a Region in the Thalamic Pulvinar Is Specifically Associated with Novelty Seeking.

Personality reflects the set of psychological traits and mechanisms characteristic for an individual. Geno-neuro-biologically inspired personality accounts have proposed a set of temperaments and characters that jointly compose personality profiles. The present study addresses the link between neurobiology and personality and investigates the association between temperament traits and regional gray matter volume. Furthermore, the specificity of these associations as well as the underlying components that drive the association are addressed. One hundred and four participants completed the Temperament and Character Inventory (TCI) and underwent structural magnetic resonance brain imaging. The participants included premanifest carriers of Huntington's disease, as this population is associated with temperament-related neuropsychiatric symptoms. Whole brain voxel-based multiple regression analyses on gray matter volume revealed a significant specific positive correlation between a region in the left thalamic pulvinar and novelty seeking score, controlled for the other traits (Pheight < 0.05, FWE-corrected). No significant associations were observed for the other temperament traits. Region of interest analyses showed that this association is driven by the subscale NS2: impulsiveness. The results increase the knowledge of the structural neurobiology of personality and indicate that individual differences in novelty seeking reflect the structural differences observed in the brain in an area that is widely and densely connected, which is in line with the typically domain-general behavioral influence of personality traits on a wide range of affective, perceptual, mnemotic, executive, and other cognitive functions.

Moral processing deficit in behavioral variant frontotemporal dementia is associated with facial emotion recognition and brain changes in default mode and salience network areas.

Introduction: Behavioral variant frontotemporal dementia (bvFTD) is associated with abnormal emotion recognition and moral processing. Methods: We assessed emotion detection, discrimination, matching, selection, and categorization as well as judgments of nonmoral, moral impersonal, moral personal low- and high-conflict scenarios. Results: bvFTD 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 (pheight < .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 (pheight < .005). Conclusions: The 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.

Co-evolution of atmospheres, life, and climate.

After Earth's origin, our host star, the Sun, was shining 20-25% less brightly than today. Without greenhouse-like conditions to warm the atmosphere, our early planet would have been an ice ball, and life may never have evolved. But life did evolve, which indicates that greenhouse gases must have been present on early Earth to warm the planet. Evidence from the geological record indicates an abundance of the greenhouse gas CO(2). CH(4) was probably present as well; and, in this regard, methanogenic bacteria, which belong to a diverse group of anaerobic prokaryotes that ferment CO(2) plus H(2) to CH(4), may have contributed to modification of the early atmosphere. Molecular oxygen was not present, as is indicated by the study of rocks from that era, which contain iron carbonate rather than iron oxide. Multicellular organisms originated as cells within colonies that became increasingly specialized. The development of photosynthesis allowed the Sun's energy to be harvested directly by life-forms. The resultant oxygen accumulated in the atmosphere and formed the ozone layer in the upper atmosphere. Aided by the absorption of harmful UV radiation in the ozone layer, life colonized Earth's surface. Our own planet is a very good example of how life-forms modified the atmosphere over the planets' lifetime. We show that these facts have to be taken into account when we discover and characterize atmospheres of Earth-like exoplanets. If life has originated and evolved on a planet, then it should be expected that a strong co-evolution occurred between life and the atmosphere, the result of which is the planet's climate.

Deciphering spectral fingerprints of habitable exoplanets.

We discuss how to read a planet's spectrum to assess its habitability and search for the signatures of a biosphere. After a decade rich in giant exoplanet detections, observation techniques have advanced to a level where we now have the capability to find planets of less than 10 Earth masses (M(Earth)) (so-called "super Earths"), which may be habitable. How can we characterize those planets and assess whether they are habitable? This new field of exoplanet search has shown an extraordinary capacity to combine research in astrophysics, chemistry, biology, and geophysics into a new and exciting interdisciplinary approach to understanding our place in the Universe. The results of a first-generation mission will most likely generate an amazing scope of diverse planets that will set planet formation, evolution, and our planet into an overall context.

Stellar aspects of habitability--characterizing target stars for terrestrial planet-finding missions.

We present and discuss the criteria for selecting potential target stars suitable for the search for Earth-like planets, with a special emphasis on the stellar aspects of habitability. Missions that search for terrestrial exoplanets will explore the presence and habitability of Earth-like exoplanets around several hundred nearby stars, mainly F, G, K, and M stars. The evaluation of the list of potential target systems is essential in order to develop mission concepts for a search for terrestrial exoplanets. Using the Darwin All Sky Star Catalogue (DASSC), we discuss the selection criteria, configuration-dependent subcatalogues, and the implication of stellar activity for habitability.

A roadmap for the detection and characterization of other Earths.

The European Space Agency and other space agencies such as NASA recognize that the question with regard to life beyond Earth in general, and the associated issue of the existence and study of exoplanets in particular, is of paramount importance for the 21(st) century. The new Cosmic Vision science plan, Cosmic Vision 2015-2025, which is built around four major themes, has as its first theme: "What are the conditions for planet formation and the emergence of life?" This main theme is addressed through further questions: 1) How do gas and dust give rise to stars and planets? 2) How will the search for and study of exoplanets eventually lead to the detection of life outside Earth (biomarkers)? 3) How did life in the Solar System arise and evolve? Although ESA has busied itself with these issues since the beginning of the Darwin study in 1996, it has become abundantly clear that, as these topics have evolved, only a very large effort, addressed from the ground and from space with the utilization of different instruments and space missions, can provide the empirical results required for a complete understanding. The good news is that the problems can be addressed and solved within a not-too-distant future. In this short essay, we present the present status of a roadmap related to projects that are related to the key long-term goal of understanding and characterizing exoplanets, in particular Earth-like planets.

The far future of exoplanet direct characterization.

We describe future steps in the direct characterization of habitable exoplanets subsequent to medium and large mission projects currently underway and investigate the benefits of spectroscopic and direct imaging approaches. We show that, after third- and fourth-generation missions have been conducted over the course of the next 100 years, a significant amount of time will lapse before we will have the capability to observe directly the morphology of extrasolar organisms.

The search for worlds like our own.

The direct detection of Earth-like exoplanets orbiting nearby stars and the characterization of such planets-particularly, their evolution, their atmospheres, and their ability to host life-constitute a significant problem. The quest for other worlds as abodes of life has been one of mankind's great questions for several millennia. For instance, as stated by Epicurus approximately 300 BC: "Other worlds, with plants and other living things, some of them similar and some of them different from ours, must exist." Demokritos from Abdera (460-370 BC), the man who invented the concept of indivisible small parts-atoms-also held the belief that other worlds exist around the stars and that some of these worlds may be inhabited by life-forms. The idea of the plurality of worlds and of life on them has since been held by scientists like Johannes Kepler and William Herschel, among many others. Here, one must also mention Giordano Bruno. Born in 1548, Bruno studied in France and came into contact with the teachings of Nicolas Copernicus. He wrote the book De l'Infinito, Universo e Mondi in 1584, in which he claimed that the Universe was infinite, that it contained an infinite amount of worlds like Earth, and that these worlds were inhabited by intelligent beings. At the time, this was extremely controversial, and eventually Bruno was arrested by the church and burned at the stake in Rome in 1600, as a heretic, for promoting this and other equally confrontational issues (though it is unclear exactly which idea was the one that ultimately brought him to his end). In all the aforementioned cases, the opinions and results were arrived at through reasoning-not by experiment. We have only recently acquired the technological capability to observe planets orbiting stars other than 6 our Sun; acquisition of this capability has been a remarkable feat of our time. We show in this introduction to the Habitability Primer that mankind is at the dawning of an age when, by way of the scientific method and 21(st)-century technology, we will be able to answer this fascinating controversial issue that has persisted for at least 2500 years.

Origin and formation of planetary systems.

To estimate the occurrence of terrestrial exoplanets and maximize the chance of finding them, it is crucial to understand the formation of planetary systems in general and that of terrestrial planets in particular. We show that a reliable formation theory should not only explain the formation of the Solar System, with small terrestrial planets within a few AU and gas giants farther out, but also the newly discovered exoplanetary systems with close-in giant planets. Regarding the presently known exoplanets, we stress that our current knowledge is strongly biased by the sensitivity limits of current detection techniques (mainly the radial velocity method). With time and improved detection methods, the diversity of planets and orbits in exoplanetary systems will definitely increase and help to constrain the formation theory further. In this work, we review the latest state of planetary formation in relation to the origin and evolution of habitable terrestrial planets.

Dynamical habitability of planetary systems.

The problem of the stability of planetary systems, a question that concerns only multiplanetary systems that host at least two planets, is discussed. The problem of mean motion resonances is addressed prior to discussion of the dynamical structure of the more than 350 known planets. The difference with regard to our own Solar System with eight planets on low eccentricity is evident in that 60% of the known extrasolar planets have orbits with eccentricity e > 0.2. We theoretically highlight the studies concerning possible terrestrial planets in systems with a Jupiter-like planet. We emphasize that an orbit of a particular nature only will keep a planet within the habitable zone around a host star with respect to the semimajor axis and its eccentricity. In addition, some results are given for individual systems (e.g., Gl777A) with regard to the stability of orbits within habitable zones. We also review what is known about the orbits of planets in double-star systems around only one component (e.g., gamma Cephei) and around both stars (e.g., eclipsing binaries).