Fear Extinction-Based Inter-Individual and Sex Differences in Pain-Related Vocalizations and Anxiety-like Behaviors but Not Nocifensive Reflexes

Inter-individual and sex differences in pain responses are recognized but their mechanisms are not well understood. This study was intended to provide the behavioral framework for analyses of pain mechanisms using fear extinction learning as a predictor of phenotypic and sex differences in sensory (mechanical withdrawal thresholds) and emotional-affective aspects (open field tests for anxiety-like behaviors and audible and ultrasonic components of vocalizations) of acute and chronic pain. In acute arthritis and chronic neuropathic pain models, greater increases in vocalizations were found in females than males and in females with poor fear extinction abilities than females with strong fear extinction, particularly in the neuropathic pain model. Female rats showed higher anxiety-like behavior than males under baseline conditions but no inter-individual or sex differences were seen in the pain models. No inter-individual and sex differences in mechanosensitivity were observed. The data suggest that vocalizations are uniquely suited to detect inter-individual and sex differences in pain models, particularly in chronic neuropathic pain, whereas no such differences were found for mechanosensitivity, and baseline differences in anxiety-like behaviors disappeared in the pain models.

Gene, the Sexual Brain, and Cognition: Machine-Predicted Brain Sex Score Explains Individual Differences in Cognitive Development and Genetic Influence.

Sex impacts the development of the brain and cognition differently across individuals. We investigated the biological underpinnings of the individual variability of sexual dimorphism in the brain and its impact on cognitive development. In prepubertal children (N=9,658, ages 9~10 years old; the Adolescent Brain Cognitive Development study), we tested whether the individual difference in brain sex development was related to that in cognitive development, known to be influenced by genetic factors. We estimated an individual’s brain sex score from machine learning models trained on brain morphometry and diffusion white matter connectomes that accurately classified the biological sex with a test ROC-AUC of 93.32%. A greater brain sex score correlated significantly with greater intelligence (Pfdr<0.001, ηp2=0.034~0.050; adjusted for covariates) and higher cognitive genome-wide polygenic scores (GPSs) (Pfdr<0.001, ηp2<0.005). Structural equation models revealed that the GPS-intelligence association was modulated by the brain sex score, such that a brain with a higher maleness score (or a lower femaleness score) mediated a positive GPS effect on intelligence (indirect effects=0.006~0.009; P=0.002~0.022; sex-stratified analysis). The novel gene-brain-cognition relationship reported in this study presents a biological pathway to the individual and sex differences in the brain and cognitive development in preadolescence.

Age-related change in adult chimpanzee social network integration

Background: Social isolation is a key risk factor for the onset and progression of age-related disease and mortality in humans, yet older people commonly have narrowing social networks. Few models explain why human networks shrink with age, despite the risk that small networks and isolation pose. We evaluate models grounded in a life history perspective by studying social aging in wild chimpanzees, which are long-lived and show physical decline with age. Methodology: We applied social network analysis to examine age-related changes in social integration in a 7+ year mixed-longitudinal dataset comprised of 38 wild adult chimpanzees (22 F, 16 M) in the Kanyawara community in the Kibale National Park, Uganda. Metrics of social integration included social attractivity and overt effort (directed degree and strength), gregariousness (undirected strength), social roles (betweenness and local transitivity), and embeddedness (eigenvector centrality) in grooming and spatial association networks. Results: Males reduced overt social effort yet increased in attractivity, roles in cliques, and embeddedness. Females were overall less integrated than males, and their decreased integration with age suggested social avoidance. Effects of age were largely independent of rank. Both sexes maintained highly repeatable inter-individual differences in several aspects of integration, particularly among mixed-sex partners. Conclusions and implications: As in humans, chimpanzees experience age-related declines in social effort. However, important facets of integration aged more similarly to humans in non-industrialized vs. industrialized societies, suggesting an evolutionary social mismatch between conserved declines in effort and dynamics of industrialized society. Lastly, individual and sex differences have the potential to be important mediators of successful social aging in chimpanzees, as in humans.

Sickness behaviors across vertebrate taxa: proximate and ultimate mechanisms

ABSTRACT There is nothing like a pandemic to get the world thinking about how infectious diseases affect individual behavior. In this respect, sick animals can behave in ways that are dramatically different from healthy animals: altered social interactions and changes to patterns of eating and drinking are all hallmarks of sickness. As a result, behavioral changes associated with inflammatory responses (i.e. sickness behaviors) have important implications for disease spread by affecting contacts with others and with common resources, including water and/or sleeping sites. In this Review, we summarize the behavioral modifications, including changes to thermoregulatory behaviors, known to occur in vertebrates during infection, with an emphasis on non-mammalian taxa, which have historically received less attention. We then outline and discuss our current understanding of the changes in physiology associated with the production of these behaviors and highlight areas where more research is needed, including an exploration of individual and sex differences in the acute phase response and a greater understanding of the ecophysiological implications of sickness behaviors for disease at the population level.

Individual and Sex Differences

The chapter summarizes current research on individual and sex differences in personality and cognitive abilities and reviews the main evolutionary processes that produce and maintain individual variation. Since psychopathology is inextricably linked to normal variation in personality and cognition, a unified approach to mental disorders must incorporate a sophisticated understanding of both individual and sex differences. The chapter describes the structure of personality and cognitive ability and examines their evolutionary and neurobiological underpinnings. The final section considers the interplay of genetic and environmental factors in the development of individual differences and discusses recent models of developmental plasticity and genotype–environment interactions.

Automatic measurement of prosody in behavioral variant FTD

Objective:To help understand speech changes in behavioral variant frontotemporal dementia (bvFTD), we developed and implemented automatic methods of speech analysis for quantification of prosody, and evaluated clinical and anatomical correlations.Methods:We analyzed semi-structured, digitized speech samples from 32 patients with bvFTD (21 male, mean age 63 ± 8.5, mean disease duration 4 ± 3.1 years) and 17 matched healthy controls (HC). We automatically extracted fundamental frequency (f0, the physical property of sound most closely correlating with perceived pitch) and computed pitch range on a logarithmic scale (semitone) that controls for individual and sex differences. We correlated f0 range with neuropsychiatric tests, and related f0 range to gray matter (GM) atrophy using 3T T1 MRI.Results:We found significantly reduced f0 range in patients with bvFTD (mean 4.3 ± 1.8 ST) compared to HC (5.8 ± 2.1 ST; p = 0.03). Regression related reduced f0 range in bvFTD to GM atrophy in bilateral inferior and dorsomedial frontal as well as left anterior cingulate and anterior insular regions.Conclusions:Reduced f0 range reflects impaired prosody in bvFTD. This is associated with neuroanatomic networks implicated in language production and social disorders centered in the frontal lobe. These findings support the feasibility of automated speech analysis in frontotemporal dementia and other disorders.

Sex-Specific Conditions, Gender, and Evaluation Using the AMA Guides

Concerns about potential sex and gender bias during impairment and disability evaluations have been raised; this article reviews ways in which sex and gender contribute to the unique presentation, manifestations, treatment, and functional outcome of medical conditions and how these differences can be appropriately addressed using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition. Sex differences are objective and are based on biochemical and biological factors; gender refers to cultural attitudes that are learned and vary by culture, history, and ethnicity. The AMA Guides acknowledges individual variations and advocates a flexible approach: Physicians can choose among sections of the AMA Guides those best suited to account for individual and sex differences. The AMA Guides does not advocate different evaluation of medical conditions based on sex, except for sex-specific disorders (eg, unique male or female reproductive organs). The health care system is striving to eliminate gender and sex bias, and impairment and disability are following by attempting to eliminate bias by offering individualized assessments of how impairment affects the injured organ, use of unique rating methods to fully characterize the impairment, use of rating ranges to account for individual variability and sex, and by ascribing equal values to gender-ascribed activities of daily living.