Biology subjects

Lythgoe, D.

Publications and source records attributed to Lythgoe, D..

4 recordsLinked to original sources

bioRxiv2026

Multimodal imaging suggests potential immune-vascular contributions to altered regional brain perfusion and oxygen metabolism in Post-COVID-19 Syndrome

Post-COVID-19 Syndrome (PCS) frequently presents with persistent fatigue, cognitive impairment, and emotional symptoms. Although structural brain changes remain subtle, growing evidence implicates functional and metabolic disruptions in ongoing symptomatology. We used multimodal MRI to investigate cerebral perfusion and oxygen metabolism in PCS and examined their associations with cognitive function and peripheral biomarkers. We enrolled 40 individuals with prior mild SARS-CoV-2 infection, including 20 with persistent fatigue and 20 recovered controls matched for age, sex, BMI, and acute COVID-19 severity. Participants underwent structural MRI, arterial spin labelling (ASL) to quantify regional cerebral blood flow (CBF), and asymmetric spin echo imaging to estimate oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO{square}). We assessed cognition using an online battery and measured serum levels of TNF-, IL-6, IL-8, IL-13, IFN-{gamma}, GFAP, and S100{beta}, alongside blood routine tests. We performed ANCOVAs on predefined regions of interest (hippocampus, anterior cingulate cortex [ACC], insula, amygdala, striatum), followed by Bayesian inference and exploratory whole-brain analyses. PCS participants showed increased CMRO{square} in the hippocampus and decreased CMRO{square} in the ACC. Subfield analysis revealed elevated OEF and CMRO{square} across most hippocampal regions, excluding the entorhinal cortex. Whole-brain analyses identified increased perfusion in salience-related regions (insula, ACC, thalamus) and decreased perfusion in posterior cortical and cerebellar areas, in the absence of grey matter volume differences. Higher hippocampal metabolism positively correlated with cognitive performance, suggesting compensatory adaptation to sustain function. In contrast, lower ACC CMRO{square} correlated with depressive symptoms, reduced motivation, and elevated TNF- and GFAP, consistent with neurovascular uncoupling possibly driven by immune-glial activation. These findings reveal distinct physiological disruptions in PCS, with potential implications for stratified, metabolism-focused interventions.

neuroscience↗

bioRxiv2022

Functional MRS studies of GABA and Glutamate/Glx: a systematic review and meta-analysis

Functional magnetic resonance spectroscopy (fMRS) can be used to investigate neurometabolic responses to external stimuli in-vivo, but findings are inconsistent. We performed a systematic review and meta-analysis on fMRS studies of the primary neurotransmitters Glutamate (Glu), Glx (Glutamate + Glutamine), and GABA. Data were extracted, grouped by metabolite, stimulus domain, and brain region, and analysed by determining standardized effect sizes. The quality of individual studies was rated. When results were analysed by metabolite type small to moderate effect sizes of 0.29-0.47 (p < 0.05) were observed for changes in Glu and Glx regardless of stimulus domain and brain region, but no significant effects were observed for GABA. Further analysis suggests that Glu, Glx and GABA responses differ by stimulus domain or task and vary depending on the time course of stimulation and data acquisition. Here, we establish effect sizes and directionality of GABA, Glu and Glx response in fMRS. This work highlights the importance of standardised reporting and minimal best practice for fMRS research.

neuroscience↗

bioRxiv2022

Erbb4 deletion from fast-spiking interneurons causes psychosis-relevant neuroimaging phenotypes

Converging lines of evidence suggest that dysfunction of cortical parvalbumin-expressing (PV+) GABAergic interneurons is a core feature of psychosis. This dysfunction is thought to underlie neuroimaging abnormalities commonly found in patients with psychosis, particularly in the hippocampus. These include increases in resting cerebral blood flow (CBF) and levels of glutamatergic metabolites, and decreases in binding of GABAA 5 receptors and the synaptic density marker synaptic vesicle glycoprotein 2A (SV2A). However, direct links between PV+ interneuron dysfunction and these neuroimaging readouts have yet to be established. Conditional deletion of a schizophrenia susceptibility gene, the tyrosine kinase receptor Erbb4, from cortical and hippocampal PV+ interneurons leads to several synaptic, behavioral and cognitive phenotypes relevant to psychosis in mice. Here, we investigated how this PV+ interneuron disruption affects the hippocampal in vivo neuroimaging readouts in the Erbb4 model. Adult Erbb4 conditional mutant mice (Lhx6-Cre;Erbb4F/F, n=12) and their wild-type littermates (Erbb4F/F, n=12) were scanned in a 9.4T magnetic resonance scanner to quantify CBF and glutamatergic metabolite levels (glutamine, glutamate, GABA). Subsequently, we assessed GABAA receptors and SV2A density using quantitative autoradiography. Erbb4 mutant mice showed significantly elevated CBF and glutamine levels, as well as decreased SV2A density compared to wild-type littermates. No significant GABAA receptor density differences were identified. These findings demonstrate that specific disruption of cortical PV+ interneurons in mice recapitulate some of the key neuroimaging findings in psychosis patients, and link PV+ interneuron deficits to non-invasive, translational measures of brain function and neurochemistry that can be used across species.

neuroscience↗

bioRxiv2020

Daily and Intermittent Smoking Decrease Gray Matter Volume and Concentrations of Glutamate, Creatine, Myo-Inositol and N-acetylaspartate in the Prefrontal Cortex

Cigarette smoking is still the largest contributor to disease and death worldwide. Successful cessation is hindered by decreases in prefrontal glutamate concentrations and gray matter volume due to daily smoking. Because non-daily, intermittent smoking also contributes greatly to disease and death, understanding whether infrequent tobacco use is associated with reductions in prefrontal glutamate concentrations and gray matter volume may aid public health. Eighty-five young participants (41 non-smokers, 24 intermittent smokers, 20 daily smokers, mean age ~23 years old), underwent 1H-magnetic resonance spectroscopy of the medial prefrontal cortex, as well as structural MRI to determine whole-brain gray matter volume. Compared to non-smokers, both daily and intermittent smokers exhibited lower concentrations of glutamate, creatine, N-acetylaspartate and myo-inositol in the medial prefrontal cortex, and lower gray matter volume in the right inferior frontal gyrus; these measures of prefrontal metabolites and structure did not differ between daily and intermittent smokers. Finally, medial prefrontal metabolite concentrations and right inferior frontal gray matter volume were positively correlated, but these relationships were not influenced by smoking status. This study provides the first evidence that both daily and intermittent smoking are associated with low concentrations of glutamate, creatine, N-acetylaspartate and myo-inositol, and low gray matter volume in the prefrontal cortex. Future tobacco cessation efforts should not ignore potential deleterious effects of intermittent smoking by considering only daily smokers. Finally, because low glutamate concentrations hinder cessation, treatments that can normalize tonic levels of prefrontal glutamate, such as N-acetylcysteine, may help intermittent and daily smokers to quit.

neuroscience↗