Resting state changes in aging and Parkinson's disease are shaped by underlying neurotransmission - a normative modeling study.

BACKGROUND: Human healthy and pathological aging is linked to a steady decline in brain resting state activity and connectivity measures. The neurophysiological mechanisms underlying these changes remain poorly understood. METHODS: Making use of recent developments in normative modeling and availability of in vivo maps for various neurochemical systems, we test in the UK Biobank cohort (N=25917) if and how age- and Parkinson's disease related resting state changes in commonly applied local and global activity and connectivity measures co-localize with underlying neurotransmitter systems. RESULTS: We find the distributions of several major neurotransmitter systems including serotonergic, dopaminergic, noradrenergic, and glutamatergic neurotransmission to correlate with age-related changes as observed across functional activity and connectivity measures. Co-localization patterns in Parkinson's disease deviate from normative aging trajectories for these, as well as for cholinergic and GABAergic, neurotransmission. The deviation from normal co-localization of brain function and GABAa correlates with disease duration. CONCLUSIONS: These findings provide new insights into molecular mechanisms underlying age- and Parkinson's related brain functional changes by extending the existing evidence elucidating the vulnerability of specific neurochemical attributes to normal aging and Parkinson's disease. The results particularly indicate that alongside dopamine and serotonin, increased vulnerability of glutamatergic, cholinergic, and GABAergic systems may also contribute to Parkinson's disease-related functional alterations. Combining normative modeling and neurotransmitter mapping may aid future research and drug development through deeper understanding of neurophysiological mechanisms underlying specific clinical conditions.

Sex-dependent clinical presentation, body image, and endocrine status in long-term remitted anorexia nervosa.

OBJECTIVE: Although anorexia nervosa (AN) in males has recently gained attention, knowledge of its psychological and physiological outcomes is still scarce. We explore sex-specific characteristics of long-term remitted AN with respect to residual eating disorder (ED) psychopathology, body image, and endocrinology. METHOD: We recruited 33 patients with AN in remission for at least 18 months (24 women, 9 men) and 36 matched healthy controls (HCs). Eating disorder psychopathology and body image ideals were assessed via clinical interviews, questionnaires, and an interactive 3D body morphing tool. Plasma levels of leptin, free triiodothyronine, cortisol, and sex hormones were quantified. Univariate models controlled for age and weight were used to test for the effects of diagnosis and sex. RESULTS: Both patient groups showed residual ED psychopathology but normal weight and hormone levels relative to HCs. Male remitted patients demonstrated significantly stronger muscularity-focused body image ideals, evident in interviews, self-reports, and behavioural data, than both female patients and HCs. CONCLUSIONS: Sex-specific body image characteristics in patients with remitted AN point towards the need to adjust test instruments and diagnostic criteria to male-specific psychopathology. In the future, sufficiently powered studies should evaluate the risk of men with AN developing muscle dysmorphia in the long term.

Beware 'persuasive communication devices' when writing and reading scientific articles.

Authors rely on a range of devices and techniques to attract and maintain the interest of readers, and to convince them of the merits of the author's point of view. However, when writing a scientific article, authors must use these 'persuasive communication devices' carefully. In particular, they must be explicit about the limitations of their work, avoid obfuscation, and resist the temptation to oversell their results. Here we discuss a list of persuasive communication devices and we encourage authors, as well as reviewers and editors, to think carefully about their use.

Human cortex development is shaped by molecular and cellular brain systems.

Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cerebral cortex development unfolds along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial distributions of dopaminergic receptors, inhibitory neurons, glial cell populations, and brain-metabolic features explain up to 50% of variance associated with regional cortical thickness trajectories. Adult cortical change patterns are best explained by cholinergic and glutamatergic neurotransmission. These relationships are supported by developmental gene expression trajectories and translate to longitudinal data from over 8,000 adolescents, explaining up to 59% of developmental change at population- and 18% at single-subject level. Integrating multilevel brain atlases with normative modeling and population neuroimaging provides a biologically meaningful path to understand typical and atypical brain development in living humans.

Revealing the neurobiology underlying interpersonal neural synchronization with multimodal data fusion.

Humans synchronize with one another to foster successful interactions. Here, we use a multimodal data fusion approach with the aim of elucidating the neurobiological mechanisms by which interpersonal neural synchronization (INS) occurs. Our meta-analysis of 22 functional magnetic resonance imaging and 69 near-infrared spectroscopy hyperscanning experiments (740 and 3721 subjects) revealed robust brain regional correlates of INS in the right temporoparietal junction and left ventral prefrontal cortex. Integrating this meta-analytic information with public databases, biobehavioral and brain-functional association analyses suggested that INS involves sensory-integrative hubs with functional connections to mentalizing and attention networks. On the molecular and genetic levels, we found INS to be associated with GABAergic neurotransmission and layer IV/V neuronal circuits, protracted developmental gene expression patterns, and disorders of neurodevelopment. Although limited by the indirect nature of phenotypic-molecular association analyses, our findings generate new testable hypotheses on the neurobiological basis of INS.

Recovery-Associated Resting-State Activity and Connectivity Alterations in Anorexia Nervosa.

BACKGROUND: Previous studies provided controversial insight on the impact of starvation, disease status, and underlying gray matter volume (GMV) changes on resting-state functional magnetic resonance imaging alterations in anorexia nervosa (AN). Here, we adapt a combined longitudinal and cross-sectional approach to disentangle the effects of these factors on resting-state alterations in AN. METHODS: Overall, 87 female subjects were included in the study: adolescent patients with acute AN scanned at inpatient admission (n = 22, mean age 15.3 years) and at discharge (n = 21), patients who recovered from AN (n = 21, mean age 22.3 years), and two groups of healthy age-matched control subjects (both n = 22, mean age 16.0 and 22.5 years, respectively). Whole-brain measures of resting-state activity and functional connectivity were computed (network-based statistics, global correlation, integrated local correlation, and fractional amplitude of low-frequency fluctuations) to assess resting-state functional magnetic resonance imaging alterations over the course of AN treatment before and after controlling for underlying GMV. RESULTS: Patients with acute AN displayed strong and widespread prefrontal, sensorimotor, parietal, temporal, precuneal, and insular reductions of resting-state connectivity and activity. All alterations were independent of GMV and were largely normalized in short-term recovered AN and absent in long-term recovered patients. CONCLUSIONS: Resting-state functional magnetic resonance imaging alterations in AN constitute acute and GMV-independent, presumably starvation-related, phenomena. The majority of alterations found here normalized over the course of recovery without evidence for possible preexisting trait- or remaining "scar" effects.