Biology subjects

Dunstan, D. M.

Publications and source records attributed to Dunstan, D. M..

3 recordsLinked to original sources

bioRxiv2025

Dynamics-Informed Priors (DIP) for Neural Mass Modelling

Neural Mass Models (NMMs) are important mathematical tools for inferring hidden neural mechanisms that generate healthy and pathological brain activities. A critical step in the inference process is parameter estimation, which calibrates NMMs based on measured neuroimaging data. While parameter estimation can be conducted via various approaches, one of the most influential methods is Dynamic Causal Modelling (DCM). DCM adopts a Bayesian inference approach that relies on, and is sensitive to, the specification of prior parameter distributions reflecting a priori hypotheses about the causes of data. However, most parameters of NMMs encode neuronal properties that are not directly measurable. For this reason, in the absence of sufficient empirical data and well-founded prior beliefs, inference becomes increasingly susceptible to bias. Therefore, it was imperative to establish a comprehensive strategy for mapping model parameters to data. This study proposes a computational extension of DCM, named DCM with dynamics-informed priors (DIP-DCM), which adopts a genetic algorithm (GA) to map parameter values to model dynamics. Optimal sub-regions of the parameter space were subsequently selected and translated into groups of parameter priors for DCM. DIP-DCM was compared to the standard DCM inference and to the standalone GA, using two independent neuroimaging datasets. Results indicated that DIP-DCM models were the best predictors of data and captured key mechanistic signatures of psychiatric disease and pharmacological interventions. Overall, DIP-DCM addressed degeneracy, handled local minima, and explored diverse parameter regimes following trajectories informed directly by model dynamics and data. This study suggests that DIP-DCM is an advantageous route to parameter estimation when information is limited, enabling a data-driven derivation of parameter priors - or hypotheses - in exploratory studies, across different biological contexts and datasets.

systems biology↗

bioRxiv2025

Global search metaheuristics for neural mass model calibration

Neural mass models (NMMs) are often used to help understand the circuitry that underpins observed brain dynamics in basic and clinical research. A key step is to fuse models with data so that model parameter values can be inferred for a given data set--a process called model fitting or model calibration. This can shed light on putative physiological mechanisms underlying the observed signals. Calibration is notoriously challenging in biology since models are often non-identifiable, high-dimensional, and nonlinear. Established methods such as dynamic causal modelling (DCM) circumvent some of these issues, for example, by incorporating prior information and employing fast local search methods in the space of feasible parameter values ("parameter space"). However, it is pertinent to better understand the potential limitations of these methods so that we can increase our confidence in the use of models to interpret brain activity, and to develop new approaches as required. Here we use tools from dynamical systems theory to illustrate some of the complexities of model calibration in an archetypal NMM. We use this information to motivate the use of calibration methods that work across large regions of parameter space, rather than focusing on informative priors or localised search methods. We subsequently evaluate the performance of approximate Bayesian computation (ABC) and evolutionary search metaheuristics (ESMs) for mapping feasible sets of parameters for which an NMM can recreate electroen-cephalographic recordings during an eyes-closed resting state. Our results demonstrate the superiority of ESMs in terms of computational efficiency and accuracy. Furthermore, we elucidate potential reasons why ESMs are able to perform better than ABC, i.e. that they are less susceptible to biases induced by the complexity of underlying cost landscapes. These results highlight the importance of incorporating ESMs in future efforts to model brain dynamics.

neuroscience↗

bioRxiv2024

Longitudinal assessment of the conversion of mild cognitive impairment into Alzheimer's dementia: Observations and mechanisms from neuropsychological testing and electrophysiology

INTRODUCTIONElucidating and better understanding functional biomarkers of Alzheimers disease (AD) is crucial. By analysing a detailed longitudinal dataset, this study aimed to create a model-based toolset to characterise and understand the conversion of mild cognitive impairment (MCI) to AD. METHODSEEG, MRI, and neuropsychological data were collected from participants in San Marino: AD (n = 10), MCI (n = 20), and controls (n = 11). Across two additional years, MCI participants were classified as converters or non-converters. RESULTSWe identified the Stroop Color and Word Test as the largest differentiator for MCI conversion (ROC AUC = 0.795). This was underpinned by disconnectivity in working memory and attention networks. Unsupervised clustering of EEG spectra also differentiated MCI conversion (ROC AUC = 0.710) and was underpinned by reduced excitatory and enhanced inhibitory synaptic efficacy in (prodromal) AD. Combining electrophysiological and neuropsychological assessments increased the accuracy of the differentiation (ROC AUC = 0.880) in comparison to each measure considered individually. CONCLUSIONCombining electrophysiological and neuropsychological assessment with mathematical models can inform the development of non-invasive, low-cost tools for the early diagnosis of AD. HighlightsO_LIWe analysed longitudinal changes in EEG and neuropsychological assessments in MCI C_LIO_LIStroop Color and Word Test error scores were lower in MCI converters C_LIO_LIThe degree of impairment was found to be correlated with functional disconnectivity C_LIO_LIUnsupervised clustering of EEG spectra characterised patterns associated with disease C_LIO_LIMathematical modelling revealed reduced excitatory synaptic efficacy in (prodromal) AD C_LI Research in ContextSystematic review: The authors used PubMed to review the literature on the use of inexpensive modalities, including EEG and neurophysiological testing, for characterising the progression of MCI to AD. Although promising, existing work suggests the full potential of these methods as tools for understanding prodromal AD is still lacking. Interpretation: A novel application of a clustering algorithm to EEG spectra revealed different patient diagnoses could largely be characterised by their cluster assignment. We also found differences in a particular neuropsychological test, the Stroop Color and Word Test. Using mathematical modelling we found there were both network and synaptic mechanisms that underlie these differences. Future directions: Using the methods described herein to build markers for testing MCI to AD conversion on a large independent cohort will be crucial to understanding the full impact and applicability of these approaches. This may ultimately lead to a better characterisation and understanding of the diagnosis and prognosis of AD.

neuroscience↗