Biology subjects

Peattie, A. R. D.

Publications and source records attributed to Peattie, A. R. D..

5 recordsLinked to original sources

bioRxiv2023

Converging on consistent functional connectomics

Functional interactions between brain regions can be viewed as a network, empowering neuroscientists to leverage network science to investigate distributed brain function. However, obtaining a brain network from functional neuroimaging data involves multiple steps of data manipulation, which can drastically affect the organisation and validity of the estimated brain network and its properties. Here, we provide a systematic evaluation of 576 unique data-processing pipelines for functional connectomics from resting-state functional MRI, obtained from all possible recombinations of popular choices for brain atlas type and size, connectivity definition and selection, and global signal regression. We use the portrait divergence, an information-theoretic measure of differences in network topology across scales, to quantify the influence of analytic choices on the overall organisation of the derived functional connectome. We evaluate each pipeline across an entire battery of criteria, seeking pipelines that (i) minimise spurious test-retest discrepancies of network topology, while simultaneously (ii) mitigating motion confounds, and being sensitive to both (iii) inter-subject differences and (iv) experimental effects of interest, as demonstrated by propofol-induced general anaesthesia. Our findings reveal vast and systematic variability across pipelines suitability for functional connectomics. Choice of the wrong data-processing pipeline can lead to results that are not only misleading, but systematically so, distorting the functional connectome more drastically than the passage of several months. We also found that the majority of pipelines failed to meet at least one of our criteria. However, we identified 8 candidates satisfying all criteria across each of four independent datasets spanning minutes, weeks, and months, ensuring the generalisability of our recommendations. Our results also generalise to alternative acquisition parameters and preprocessing and denoising choices. By providing the community with a full breakdown of each pipelines performance across this multi-dataset, multi-criteria, multi-scale and multi-step approach, we establish a comprehensive set of benchmarks to inform future best practices in functional connectomics.

neuroscience↗

bioRxiv2022

Mapping Pharmacologically-induced Functional Reorganisation onto the Brain's Neurotransmitter Landscape

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brains rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, LSD, psilocybin, DMT, ayahuasca, MDMA, modafinil, and methylphenidate. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. The effects of both anaesthetics and psychedelics on brain function are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brains functional architecture.

neuroscience↗

bioRxiv2022

Reduced emergent character of neural dynamics in patients with a disrupted connectome

High-level brain functions are widely believed to emerge from the orchestrated activity of multiple neural systems. However, lacking a formal definition and practical quantification of emergence for experimental data, neuroscientists have been unable to empirically test this long-standing conjecture. Here we investigate this fundamental question by leveraging a recently proposed framework known as "Integrated Information Decomposition," which establishes a principled information-theoretic approach to operationalise and quantify emergence in dynamical systems -- including the human brain. By analysing functional MRI data, our results show that the emergent and hierarchical character of neural dynamics is significantly diminished in chronically unresponsive patients suffering from severe brain injury. At a functional level, we demonstrate that emergence capacity is positively correlated with the extent of hierarchical organisation in brain activity. Furthermore, by combining computational approaches from network control theory and whole-brain biophysical modelling, we show that the reduced capacity for emergent and hierarchical dynamics in severely brain-injured patients can be mechanistically explained by disruptions in the patients structural connectome. Overall, our results suggest that chronic unresponsiveness resulting from severe brain injury may be due to structural impairment of the fundamental neural infrastructures required for brain dynamics to support emergence.

neuroscience↗

bioRxiv2021

Searching for Consistent Brain Network Topologies Across the Garden of (Shortest) Forking Paths

The functional interactions between regions of the human brain can be viewed as a network, empowering neuroscientists to leverage tools such as graph theory to obtain insight about brain function. However, obtaining a brain network from functional neuroimaging data inevitably involves multiple steps of data manipulation, which can affect the organisation (topology) of the resulting network and its properties. Test-retest reliability is a gold standard for both basic research and clinical use: a suitable data-processing pipeline for brain networks should recover the same network topology across repeated scan sessions of the same individual. Analyzing resting-state functional Magnetic Resonance Imaging (rs-fMRI) recordings from two test-retest studies across short (45 minutes), medium (2-4 weeks) and long term delays (5-16 months), we investigated the reliability of network topologies constructed by applying 576 unique pipelines to the same fMRI data, obtained from considering combinations of atlas type and size, edge definition and thresholding, and use of global signal regression. We adopted the portrait divergence, an information-theoretic criterion to measure differences in network topology across all scales, enabling us to quantify the influence of different pipelines on the overall organisation of the resulting network. Remarkably, our findings reveal that the choice of pipeline plays a fundamental role in determining how reproducible an individuals brain network topology will be across different scans: there is large and systematic variability across pipelines, such that an inappropriate choice of pipeline can distort the resulting network more than an interval of several months between scans. Across datasets and time-spans, we also identify specific combinations of data-processing steps that consistently yield networks with reproducible topology, enabling us to make recommendations about best practices to ensure high-quality brain networks.

neuroscience↗

bioRxiv2021

Paths to Oblivion: Common Neural Mechanisms of Anaesthesia and Disorders of Consciousness

The human brain generates a rich repertoire of spatiotemporal dynamics during normal wakefulness, supporting a wide variety of conscious experiences and cognitive functions. However, neural dynamics are reconfigured, in comparable ways, when consciousness is lost either due to anaesthesia or disorders of consciousness (DOC). Here, leveraging a neurobiologically realistic whole-brain computational model informed by functional MRI, diffusion MRI, and PET, we sought to identify the neurobiological mechanisms that explain the common reconfiguration of neural dynamics observed both for transient pharmacological intervention and chronic neuroanatomical injury. Our results show that, by incorporating local inhibitory action through a PET-based GABA receptor density map, our model can reproduce the brain dynamics of subjects undergoing propofol anaesthesia, and that this effect depends specifically on the spatial distribution of GABA receptors across cortical regions. Additionally, using a structural connectome obtained from DOC patients, we demonstrate how the dynamics that characterise loss of consciousness can emerge from changes in neuroanatomical connectivity. Crucially, we find that each of these two interventions generalises across datasets: a model with increased GABA-mediated inhibition can reproduce the dynamics of DOC patients brains, and a model with a DOC connectome is also compatible with brain dynamics observed during propofol anaesthesia. These results demonstrate how increased inhibition and connectome randomisation represent different neurobiological paths towards the characteristic dynamics of the unconscious brain. Overall, the present findings begin to disentangle the neurobiological mechanisms by which highly dissimilar perturbations of the brains neurodynamics can lead to unconsciousness.

neuroscience↗