Extreme-groups designs (EGDs) are common in psychopathology research, often using diagnostic category as an independent variable. Continuous-variable analysis strategies drawing from a general linear model framework can be applied to such designs. The growing emphasis on dimensional examinations of psychological constructs, encouraged by the National Institute of Mental Health Research Domain Criteria framework, encourages continuous-variable analytic strategies. However, the interpretative implications of applying these strategies to various types of populations and sample score distributions, including those used in EGDs, are not always recognized. Appropriateness and utility of EGDs depend in part on whether the goal is to determine whether a relationship exists between 2 variables or to determine its strength. Whereas the literature investigating EGDs has emphasized symmetrical thresholds for defining extreme groups (e.g., bottom 10% vs. top 10%), psychopathologists often employ asymmetric thresholds (e.g., above a diagnostic threshold vs. a broader range of scores in a healthy comparison group). The present article selectively reviews literature on EGDs and extends it with simulations of symmetric and asymmetric selection criteria. Results indicate that including a wide range of scores in EGDs substantially mitigates problems (e.g., inflation of effect size) that arise when using statistical methods classically employed for continuous variables.

Objectives Studies of HIV-associated brain atrophy often focus on a priori brain regions of interest, which can introduce bias. A data-driven, minimally-biased approach was used to analyze changes in brain volumetrics associated with HIV and their relationship to aging, viral factors, and combination antiretroviral therapy (cART), as well as gender and smoking. Design A cross-sectional study of 51 HIV-uninfected (HIV−) and 146 HIV-infected (HIV+) participants. Methods Structural MRI of participants was analyzed using principal component analysis (PCA) to reduce dimensionality and determine topographies of volumetric changes. Neuropsychological (NP) assessment was examined using global and domain-specific scores. The effects of HIV disease factors (e.g. viral load, CD4, etc.) on brain volumes and NP were investigated using penalized regression (LASSO). Results Two components of interest were visualized using PCA. An aging effect predominated for both components. The first component, a cortically-weighted topography, accounted for a majority of variance across participants (43.5% of variance) and showed independent effects of HIV as well as smoking. A secondary, subcortically-weighted topography (4.6%) showed HIV-status accentuated age-related volume loss. In HIV+ patients, the cortical topography correlated with global NP scores and nadir CD4, while subcortical volume loss was associated with recent viral load. Conclusions Cortical regions showed the most prominent volumetric changes due to aging and HIV. Within HIV+ participants, cortical volumes were associated with immune history while subcortical changes correlated with current immune function. Cognitive function was primarily associated with cortical volume changes. Observed volumetric changes in chronic HIV+ patients may reflect both past infection history and current viral status.

Accurate perception of the emotional content of vocalisations is essential for successful social communication and interaction. However, it is not clear whether our ability to perceive emotional cues from vocal signals is specific to human signals, or can be applied to other species' vocalisations. Here, we address this issue by evaluating the perception and neural response to affective vocalisations from different primate species (humans, chimpanzees and macaques). We found that the ability of human participants to discriminate emotional valence varied as a function of phylogenetic distance between species. Participants were most accurate at discriminating the emotional valence of human vocalisations, followed by chimpanzee vocalisations. They were, however, unable to accurately discriminate the valence of macaque vocalisations. Next, we used fMRI to compare human brain responses to human, chimpanzee and macaque vocalisations. We found that regions in the superior temporal lobe that are closely associated with the perception of complex auditory signals, showed a graded response to affective vocalisations from different species with the largest response to human vocalisations, an intermediate response to chimpanzees, and the smallest response to macaques. Together, these results suggest that neural correlates of differences in the perception of different primate affective vocalisations are found in auditory regions of the human brain and correspond to the phylogenetic distances between the species.

Individuals infected with HIV are living longer due to effective treatment with combination antiretroviral therapy (cART). Despite these advances, HIV-associated neurocognitive disorders (HAND) remain prevalent. In this study, we analyzed resting state functional connectivity (rs-fc) data from HIV-infected and matched HIV-uninfected adults aged 60 years and older to determine associations between HIV status, neuropsychological performance, and clinical variables. HIV-infected participants with detectable plasma HIV RNA exhibited decreased rs-fc within the salience (SAL) network compared to HIV-infected participants with suppressed plasma HIV RNA. We did not identify differences in rs-fc within HIV-infected individuals by HAND status. Our analysis identifies focal deficits in the SAL network that may be mitigated with suppression of plasma virus. However, these findings suggest that rs-fc may not be sensitive as a marker of HAND among individuals with suppressed plasma viral loads.

Individuals higher in trait worry exhibit increased activation in Broca’s area during inhibitory processing tasks. To identify whether such activity represents an adaptive mechanism supporting top-down control, we investigated functional and effective connectivity of Broca’s area during a task of inhibitory control. Functional MRI data obtained from 106 participants performing an emotion-word Stroop task were examined using psychophysiological interaction and Granger causality (GC) analyses. Findings revealed greater directed connectivity from Broca’s area to amygdala in the presence of emotional distraction. Furthermore, a predictive relationship was observed between worry and the asymmetry in effective connectivity; worriers exhibited greater directed connectivity from Broca’s area to amygdala. When performing the task, worriers with greater GC directional asymmetry were more accurate than worriers with less asymmetry. Present findings indicate that individuals with elevated trait worry use a mechanism of top-down control in which communication from Broca’s area to amygdala fosters successful compensation for interference effects.