Biology subjects

Adams, N. E.

Publications and source records attributed to Adams, N. E..

3 recordsLinked to original sources

bioRxiv2024

Asymmetric gene flow maintains an abundant range center

Species are restricted to finite ranges, and when they are in demographic equilibrium with the environment this implies a failure to adapt at the range periphery. There are several competing evolutionary hypotheses for the maintenance and persistence of range edges. One hypothesis is gene swamping of edge populations, in which migrants from the center carrying alleles adapted to the range center but maladaptive along the edge hamper local adaptation. A competing explanation is dispersal limitation, in which reduced migration to the periphery keeps edge populations small, causing drift to dominate over selection. It has proven difficult to assess these potential generative scenarios due to the inherent complexity of species ranges. In this study, we leverage range-wide genomic sequencing data to investigate the evolution of range edges in an empirical system - Haustorius canadensis, the Canadian shovel bug. We find increased genetic drift and inbreeding on the range edges and detect signatures of asymmetric migration towards the range center. The inferred directionality of migration is consistent with the direction of the dominant current regimes in the North Atlantic. We conclude that anisotropic dispersal towards the range center leaves progressively fewer migrants to replenish peripheral populations, consistent with the migration limitation hypothesis, and generates the appearance of an abundant center.

evolutionary biology↗

bioRxiv2022

Neurochemistry-enriched dynamic causal models of magnetoencephalography, using magnetic resonance spectroscopy

We present a hierarchical and empirical Bayesian framework for testing hypotheses about synaptic neurotransmission, based on the integration of ultra-high field magnetic resonance spectroscopy (7T-MRS) and magnetoencephalography data (MEG). A first level dynamic causal modelling of cortical microcircuits is used to infer the connectivity parameters of a generative model of individuals neurophysiological observations. At the second level, individuals 7T-MRS estimates of regional neurotransmitter concentration supply empirical priors on synaptic connectivity. We compare the group-wise evidence for alternative empirical priors, defined by monotonic functions of spectroscopic estimates, on subsets of synaptic connections. For efficiency and reproducibility, we used Bayesian model reduction (BMR), parametric empirical Bayes and variational Bayesian inversion. In particular, we used Bayesian model reduction to compare models of how spectroscopic neurotransmitter measures inform estimates of synaptic connectivity. This identifies the subset of synaptic connections that are influenced by neurotransmitter levels, as measured by 7T-MRS. We demonstrate the method using resting-state MEG (i.e., task-free recording) and 7T-MRS data from healthy adults. We perform cross-validation using split-sampling of the MEG dataset. Our results confirm the hypotheses that GABA concentration influences local recurrent inhibitory intrinsic connectivity in deep and superficial cortical layers, while glutamate influences the excitatory connections between superficial and deep layers and connections from superficial to inhibitory interneurons. The method is suitable for applications with magnetoencephalography or electroencephalography, and is well-suited to reveal the mechanisms of neurological and psychiatric disorders, including responses to psychopharmacological interventions.

neuroscience↗

bioRxiv2019

GABA-ergic dynamics in human frontotemporal networks confirmed by pharmaco-magnetoencephalography.

To bridge the gap between preclinical cellular models of disease and in vivo imaging of human cognitive network dynamics, there is a pressing need for informative biophysical models. Here we assess dynamic causal models (DCM) of cortical network responses, inverted to magnetoencephalographic observations during an auditory oddball roving paradigm in healthy adults. This paradigm induces robust perturbations that permeate frontotemporal networks, including an evoked mismatch negativity response and transiently induced oscillations. Here, we probe GABAergic influences of the networks using double-blind placebo-controlled randomised-crossover administration of the GABA re-uptake inhibitor, tiagabine (oral, 10mg) in healthy older adults. We demonstrate the facility of conductance-based neural mass mean-field models, incorporating local synaptic connectivity, to investigate laminar-specific and GABAergic mechanisms of the auditory response. The neuronal model accurately recapitulated the observed magnetoencephalographic data. Using parametric empirical Bayes for optimal model inversion across both sessions, we identify the effect of tiagabine on GABAergic modulation of deep pyramidal and interneuronal cell populations. Moreover, in keeping with the hierarchical coding of beliefs and sensory evidence, we found a transition of the main GABAergic drug effects from auditory cortex in standard trials to prefrontal cortex in deviant trials. The successful integration of pharmaco-magnetoencephalography with dynamic causal models of frontotemporal networks provides a potential platform on which to evaluate the effects of disease and pharmacological interventions.\n\nSignificance StatementUnderstanding human brain function and developing new treatments require good models of brain function. We tested a detailed generative model of cortical microcircuits that accurately reproduced human magnetoencephalography, to quantify network dynamics and connectivity in frontotemporal cortex. This approach correctly identified the effect of a test drug (tiagabine) on neuronal function (GABA-ergic dynamics), opening the way for psychopharmacological studies in health and disease with the mechanistic precision afforded by generative models of the brain.

neuroscience↗