Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macroscale neuroanatomy and how they shape emergent function remains poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography scans in >1,200 healthy individuals to construct a whole-brain 3-D normative atlas of 18 receptors and transporters across 9 different neurotransmitter systems. We find that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncover a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we find both expected and novel associations between receptor distributions and cortical thinning patterns across 13 disorders. We replicate all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization.

Multiple neonicotinoids in children’s cerebro-spinal fluid, plasma, and urine

Background Neonicotinoids (NN) are selective neurotoxic pesticides that bind to insect but also mammal nicotinic acetycholine receptors (nAChRs). As the most widely used class of insecticides worldwide, they are ubiquitously found in the environment, wildlife, and foods, and thus of special concern for their impacts on the environment and human health. nAChRs are vital to proper brain organization during the prenatal period and play important roles in various motor, emotional, and cognitive functions. Little is known on children’s contamination by NN. In a pilot study we tested the hypothesis that children’s cerebro-spinal fluid (CSF) can be contaminated by NN. Methods NN were analysed in leftover CSF, blood, and urine samples from children treated for leukaemias and lymphomas and undergoing therapeutic lumbar punctions. We monitored all neonicotinoids approved on the global market and some of their most common metabolites by ultra-high performance liquid chromatography-tandem mass spectrometry. Results From August to December 2020, 14 children were consecutively included in the study. Median age was 8 years (range 3–18). All CSF and plasma samples were positive for at least one NN. Nine (64%) CSF samples and 13 (93%) plasma samples contained more than one NN. Thirteen (93%) CSF samples had N-desmethyl-acetamiprid (median concentration 0.0123, range 0.0024–0.1068 ng/mL), the major metabolite of acetamiprid. All but one urine samples were positive for ≥ one NN. A statistically significant linear relationship was found between plasma/urine and CSF N-desmethyl-acetamiprid concentrations. Conclusions We have developed a reliable analytical method that revealed multiple NN and/or their metabolites in children’s CSF, plasma, and urine. Our data suggest that contamination by multiple NN is not only an environmental hazard for non-target insects such as bees but also potentially for children.

Disrupted stepwise functional brain organization in overweight individuals

Functional hierarchy establishes core axes of the brain, and overweight individuals show alterations in the networks anchored on these axes, particularly in those involved in sensory and cognitive control systems. However, quantitative assessments of hierarchical brain organization in overweight individuals are lacking. Capitalizing stepwise functional connectivity analysis, we assess altered functional connectivity in overweight individuals relative to healthy weight controls along the brain hierarchy. Seeding from the brain regions associated with obesity phenotypes, we conduct stepwise connectivity analysis at different step distances and compare functional degrees between the groups. We find strong functional connectivity in the somatomotor and prefrontal cortices in both groups, and both converge to transmodal systems, including frontoparietal and default-mode networks, as the number of steps increased. Conversely, compared with the healthy weight group, overweight individuals show a marked decrease in functional degree in somatosensory and attention networks across the steps, whereas visual and limbic networks show an increasing trend. Associating functional degree with eating behaviors, we observe negative associations between functional degrees in sensory networks and hunger and disinhibition-related behaviors. Our findings suggest that overweight individuals show disrupted functional network organization along the hierarchical axis of the brain and these results provide insights for behavioral associations.

Dyslexia and Cerebral Dysfunction

Children with slow visual-motor responses to visual-temporal response tests also have brain dysfunctions in the mobile and motor areas (6, 4). If the left parietal cortex does not participate in these dysfunctions, then this child will also have difficulties in reading. Furthermore, we could say that the brain dysfunctions that are detected by visual-motor tests and that the performance in them is low, are accompanied by difficulties in reading. Aim: In this study we want to show the function of the child's brain in dyslexia. Method: We followed the most up-to-date literature on the subject: neuropsychology and dyslexia. Conclusions: brain organization and its relationship to dyslexia is a major problem for Neuropsychology and Neurolinguistics.

Dyslexia and Cerebral Dysfunction

Children with slow visual-motor responses to visual-temporal response tests also have brain dysfunctions in the mobile and motor areas [6,4]. If the left parietal cortex does not participate in these dysfunctions, then this child will also have difficulties in reading. Furthermore, we could say that the brain dysfunctions that are detected by visual-motor tests and that the performance in them is low, are accompanied by difficulties in reading. Aim: In this study we want to show the function of the child’s brain in dyslexia. Method: We followed the most up-to-date literature on the subject: neuropsychology and dyslexia. Conclusions: brain organization and its relationship to dyslexia is a major problem for Neuropsychology and Neurolinguistics.

Scaffolding layered control architectures through constraint closure: insights into brain evolution and development

The functional organization of the mammalian brain can be considered to form a layered control architecture, but how this complex system has emerged through evolution and is constructed during development remains a puzzle. Here we consider brain organization through the framework of constraint closure, viewed as a general characteristic of living systems, that they are composed of multiple sub-systems that constrain each other at different timescales. We do so by developing a new formalism for constraint closure, inspired by a previous model showing how within-lifetime dynamics can constrain between-lifetime dynamics, and we demonstrate how this interaction can be generalized to multi-layered systems. Through this model, we consider brain organization in the context of two major examples of constraint closure—physiological regulation and visual orienting. Our analysis draws attention to the capacity of layered brain architectures to scaffold themselves across multiple timescales, including the ability of cortical processes to constrain the evolution of sub-cortical processes, and of the latter to constrain the space in which cortical systems self-organize and refine themselves. This article is part of the theme issue ‘Systems neuroscience through the lens of evolutionary theory’.

Neuroscience needs evolution

The nervous system is a product of evolution. That is, it was constructed through a long series of modifications, within the strong constraints of heredity, and continuously subjected to intense selection pressures. As a result, the organization and functions of the brain are shaped by its history. We believe that this fact, underappreciated in contemporary systems neuroscience, offers an invaluable aid for helping us resolve the brain's mysteries. Indeed, we think that the consideration of evolutionary history ought to take its place alongside other intellectual tools used to understand the brain, such as behavioural experiments, studies of anatomical structure and functional characterization based on recordings of neural activity. In this introduction, we argue for the importance of evolution by highlighting specific examples of ways that evolutionary theory can enhance neuroscience. The rest of the theme issue elaborates this point, emphasizing the conservative nature of neural evolution, the important consequences of specific transitions that occurred in our history, and the ways in which considerations of evolution can shed light on issues ranging from specific mechanisms to fundamental principles of brain organization. This article is part of the theme issue ‘Systems neuroscience through the lens of evolutionary theory’.

SARS-CoV-2 Exacerbates Beta-Amyloid Neurotoxicity, Inflammation and Oxidative Stress in Alzheimer’s Disease Patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the pandemic Coronavirus Disease 19 (COVID-19), causing millions of deaths. The elderly and those already living with comorbidity are likely to die after SARS-CoV-2 infection. People suffering from Alzheimer’s disease (AD) have a higher risk of becoming infected, because they cannot easily follow health roles. Additionally, those suffering from dementia have a 40% higher risk of dying from COVID-19. Herein, we collected from Gene Expression Omnibus repository the brain samples of AD patients who died of COVID-19 (AD+COVID-19), AD without COVID-19 (AD), COVID-19 without AD (COVID-19) and control individuals. We inspected the transcriptomic and interactomic profiles by comparing the COVID-19 cohort against the control cohort and the AD cohort against the AD+COVID-19 cohort. SARS-CoV-2 in patients without AD mainly activated processes related to immune response and cell cycle. Conversely, 21 key nodes in the interactome are deregulated in AD. Interestingly, some of them are linked to beta-amyloid production and clearance. Thus, we inspected their role, along with their interactors, using the gene ontologies of the biological process that reveals their contribution in brain organization, immune response, oxidative stress and viral replication. We conclude that SARS-CoV-2 worsens the AD condition by increasing neurotoxicity, due to higher levels of beta-amyloid, inflammation and oxidative stress.

Task-domain and hemisphere-asymmetry effects in cisgender and transmale individuals

The present research examined the extent to which transmale individuals’ functional brain organization resembles that of their assigned sex or gender identity. Cisgender-female, cisgender-male, and transmale participants, who were assigned female sex but did not have a female gender identity, were compared in terms of effects that have been observed in cisgender individuals: task-domain effects, in which males perform better than females on spatial tasks and females perform better than males on verbal tasks; and hemisphere-asymmetry effects, in which males show larger differences between the left and right hemispheres than females. In addition, the present research measured participants’ intelligence in order to control for potential moderating effects. Participants performed spatial (mental rotation) and verbal (lexical decision) tasks presented to each hemisphere using a divided-visual field paradigm, and then completed an intelligence assessment. In the mental-rotation task, cismale and transmale participants performed better than cisfemale participants, however this group difference was explained by intelligence scores, with higher scores predicting better performance. In the lexical-decision task, cismale and transmale participants exhibited a greater left-hemisphere advantage than cisfemales, and this difference was not affected by intelligence scores. Taken together, results do not support task-domain effects when intelligence is accounted for; however, they do demonstrate a hemisphere-asymmetry effect in the verbal domain that is moderated by gender identity and not assigned sex.

The gradient model of brain organization in decisions involving 'empathy for pain'

Recent meta-analytic studies of social cognition and the functional imaging of empathy have exposed the overlap between their neural substrates and heteromodal association areas. The 'gradient model' of cortical organization proposes a close relationship between these areas and highly connected hubs in the default mode network, a set of cortical areas deactivated by demanding tasks. Here, we used a decision-making task and representational similarity analysis with classic 'empathy for pain' visual stimuli to probe the relationship between high-level representations of imminent pain in others and the high end of the gradient of this model. High-level representations were found to co-localize with task deactivations or the transitions from activations to deactivations. These loci belonged to two groups: those that loaded on the high end of the principal cortical gradient and were associated by meta-analytic decoding with the default mode network, and those that appeared to accompany functional repurposing of somatosensory cortex in the presence of visual stimuli. In contrast to the nonspecific meta-analytic decoding of these loci, low-level representations, such as those of body parts involved in pain or of pain itself, were decoded with matching topics terms. These findings suggest that that task deactivations may set out cortical areas that host high-level representations, but whose functional characterization in terms of simple mappings is unlikely. We anticipate that an increased understanding of the cortical correlates of high-level representations may improve neurobiological models of social interactions and psychopathology.