The association of regional cerebral blood flow and glucose metabolism in normative ageing and insulin resistance.

Rising rates of insulin resistance and an ageing population are set to exact an increasing toll on individuals and society. Here we examine the contribution of age and insulin resistance to the association of cerebral blood flow and glucose metabolism; both critical process in the supply of energy for the brain. Thirty-four younger (20-42 years) and 41 older (66-86 years) healthy adults underwent a simultaneous resting state MR/PET scan, including arterial spin labelling. Rates of cerebral blood flow and glucose metabolism were derived using a functional atlas of 100 brain regions. Older adults had lower cerebral blood flow than younger adults in 95 regions, reducing to 36 regions after controlling for cortical atrophy and blood pressure. Lower cerebral blood flow was also associated with worse working memory and slower reaction time in tasks requiring cognitive flexibility and response inhibition. Younger and older insulin sensitive adults showed small, negative correlations between relatively high rates of regional cerebral blood flow and glucose metabolism. This pattern was inverted in insulin resistant older adults, who showed hypoperfusion and hypometabolism across the cortex, and a positive correlation. In insulin resistant younger adults, the association showed inversion to positive correlations, although not to the extent seen in older adults. Our findings suggest that the normal course of ageing and insulin resistance alter the rates of and associations between cerebral blood flow and glucose metabolism. They underscore the criticality of insulin sensitivity to brain health across the adult lifespan.

Neural mechanisms of psychedelic visual imagery.

Visual alterations under classic psychedelics can include rich phenomenological accounts of eyes-closed imagery. Preclinical evidence suggests agonism of the 5-HT2A receptor may reduce synaptic gain to produce psychedelic-induced imagery. However, this has not been investigated in humans. To infer the directed connectivity changes to visual connectivity underlying psychedelic visual imagery in healthy adults, a double-blind, randomised, placebo-controlled, cross-over study was performed, and dynamic causal modelling was applied to the resting state eyes-closed functional MRI scans of 24 subjects after administration of 0.2 mg/kg of the serotonergic psychedelic drug, psilocybin (magic mushrooms), or placebo. The effective connectivity model included the early visual area, fusiform gyrus, intraparietal sulcus, and inferior frontal gyrus. We observed a pattern of increased self-inhibition of both early visual and higher visual-association regions under psilocybin that was consistent with preclinical findings. We also observed a pattern of reduced inhibition from visual-association regions to earlier visual areas that indicated top-down connectivity is enhanced during visual imagery. The results were analysed with behavioural measures taken immediately after the scans, suggesting psilocybin-induced decreased sensitivity to neural inputs is associated with the perception of eyes-closed visual imagery. The findings inform our basic and clinical understanding of visual perception. They reveal neural mechanisms that, by affecting balance, may increase the impact of top-down feedback connectivity on perception, which could contribute to the visual imagery seen with eyes-closed during psychedelic experiences.

Localized Changes in Dentate Nucleus Shape and Magnetic Susceptibility in Friedreich Ataxia.

BACKGROUND: The dentate nuclei of the cerebellum are key sites of neuropathology in Friedreich ataxia (FRDA). Reduced dentate nucleus volume and increased mean magnetic susceptibility, a proxy of iron concentration, have been reported by magnetic resonance imaging studies in people with FRDA. Here, we investigate whether these changes are regionally heterogeneous. METHODS: Quantitative susceptibility mapping data were acquired from 49 people with FRDA and 46 healthy controls. The dentate nuclei were manually segmented and analyzed using three dimensional vertex-based shape modeling and voxel-based assessments to identify regional changes in morphometry and susceptibility, respectively. RESULTS: Individuals with FRDA, relative to healthy controls, showed significant bilateral surface contraction most strongly at the rostral and caudal boundaries of the dentate nuclei. The magnitude of this surface contraction correlated with disease duration, and to a lesser extent, ataxia severity. Significantly greater susceptibility was also evident in the FRDA cohort relative to controls, but was instead localized to bilateral dorsomedial areas, and also correlated with disease duration and ataxia severity. CONCLUSIONS: Changes in the structure of the dentate nuclei in FRDA are not spatially uniform. Atrophy is greatest in areas with high gray matter density, whereas increases in susceptibility-reflecting iron concentration, demyelination, and/or gliosis-predominate in the medial white matter. These findings converge with established histological reports and indicate that regional measures of dentate nucleus substructure are more sensitive measures of disease expression than full-structure averages. Biomarker development and therapeutic strategies that directly target the dentate nuclei, such as gene therapies, may be optimized by targeting these areas of maximal pathology. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Neurodesk: an accessible, flexible and portable data analysis environment for reproducible neuroimaging.

Neuroimaging research requires purpose-built analysis software, which is challenging to install and may produce different results across computing environments. The community-oriented, open-source Neurodesk platform ( https://www.neurodesk.org/ ) harnesses a comprehensive and growing suite of neuroimaging software containers. Neurodesk includes a browser-accessible virtual desktop, command-line interface and computational notebook compatibility, allowing for accessible, flexible, portable and fully reproducible neuroimaging analysis on personal workstations, high-performance computers and the cloud.

Neural Mechanisms of Resting-State Networks and the Amygdala Underlying the Cognitive and Emotional Effects of Psilocybin.

BACKGROUND: Serotonergic psychedelics, such as psilocybin, alter perceptual and cognitive systems that are functionally integrated with the amygdala. These changes can alter cognition and emotions that are hypothesized to contribute to their therapeutic utility. However, the neural mechanisms of cognitive and subcortical systems altered by psychedelics are not well understood. METHODS: We used resting-state functional magnetic resonance images collected during a randomized, double-blind, placebo-controlled clinical trial of 24 healthy adults under 0.2 mg/kg psilocybin to estimate the directed (i.e., effective) changes between the amygdala and 3 large-scale resting-state networks involved in cognition. These networks are the default mode network, the salience network, and the central executive network. RESULTS: We found a pattern of decreased top-down effective connectivity from these resting-state networks to the amygdala. Effective connectivity decreased within the default mode network and salience network but increased within the central executive network. These changes in effective connectivity were statistically associated with behavioral measures of altered cognition and emotion under the influence of psilocybin. CONCLUSIONS: Our findings suggest that temporary amygdala signal attenuation is associated with mechanistic changes to resting-state network connectivity. These changes are significant for altered cognition and perception and suggest targets for research investigating the efficacy of psychedelic therapy for internalizing psychiatric disorders. More broadly, our study suggests the value of quantifying the brain's hierarchical organization using effective connectivity to identify important mechanisms for basic cognitive function and how they are integrated to give rise to subjective experiences.