The Effects of Propofol Anaesthesia on Molecular-enriched Networks During Resting-state and Naturalistic Stimulation

Lawn, Timothy; Martins, Daniel; O’Daly, Owen; Williams, Steven; Howard, Matthew A.; Dipasquale, Ottavia

doi:10.1101/2022.05.24.493298

Cited by 2 publications

(3 citation statements)

References 105 publications

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“…Using this output, a second GLM is then used to estimate the subject-specific, molecular-enriched functional connectivity map. REACT has been used in studies related to 3,4-methylenedioxymethamphetamine (MDMA) [70], methylphenidate [71], multiple sclerosis [72], lysergic acid diethylamide (LSD) [73], chronic pain [74], autism spectrum disorder [75], and anesthesia [76 ▪ ]. Interestingly, REACT was recently extended to include five neurotransmitter receptors from postmortem autoradiography with multiple in-vivo neuroimaging modalities (tau, amyloid-β and FDG PET, and structural, functional and arterial spin labeling MRI) to obtain a personalized, generative, whole-brain disease-related alteration model in individuals suffering from Alzheimer's disease [77], which may ultimately lead to personalized treatments.…”

Section: Synergy Of Molecular and Functional Connectivitymentioning

confidence: 99%

PET-based brain molecular connectivity in neurodegenerative disease

Hanania,

Reimers,

Bevington

et al. 2024

Current Opinion in Neurology

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Purpose of review Molecular imaging has traditionally been used and interpreted primarily in the context of localized and relatively static neurochemical processes. New understanding of brain function and development of novel molecular imaging protocols and analysis methods highlights the relevance of molecular networks that co-exist and interact with functional and structural networks. Although the concept and evidence of disease-specific metabolic brain patterns has existed for some time, only recently has such an approach been applied in the neurotransmitter domain and in the context of multitracer and multimodal studies. This review briefly summarizes initial findings and highlights emerging applications enabled by this new approach. Recent findings Connectivity based approaches applied to molecular and multimodal imaging have uncovered molecular networks with neurodegeneration-related alterations to metabolism and neurotransmission that uniquely relate to clinical findings; better disease stratification paradigms; an improved understanding of the relationships between neurochemical and functional networks and their related alterations, although the directionality of these relationships are still unresolved; and a new understanding of the molecular underpinning of disease-related alteration in resting-state brain activity. Summary Connectivity approaches are poised to greatly enhance the information that can be extracted from molecular imaging. While currently mostly contributing to enhancing understanding of brain function, they are highly likely to contribute to the identification of specific biomarkers that will improve disease management and clinical care.

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Section: Synergy Of Molecular and Functional Connectivitymentioning

confidence: 99%

PET-based brain molecular connectivity in neurodegenerative disease

Hanania,

Reimers,

Bevington

et al. 2024

Current Opinion in Neurology

View full text Add to dashboard Cite

show abstract

“…These are group average templates derived from healthy cohorts separate to the functional imaging datasets examined here. These have been widely utilised in our previous work (41)(42)(43)(61)(62)(63)(64)(65), as well as by the broader imaging community (66,67). Here, we chose to use transporters for the neuromodulatory systems as these provide a general measure of the innervation and influence of a given receptor system over a given region (40).…”

Section: Population-based Molecular Templatesmentioning

confidence: 99%

“…Whilst much work has focussed on how bridging the gap between molecular and systems level mechanisms can help us better understand the inherent architecture of the brain, this work is especially well suited to provide novel biomarkers that link neuropathology through to pharmacotherapy in a mechanistic and data driven manner (40). For example, Receptor-Enriched Analysis of functional Connectivity by Targets (REACT) has proven useful in characterising the complex psychopharmacological effects of various drugs (40)(41)(42)(43). Furthermore, it is increasingly being applied to clinical conditions, with recent proof of concept papers demonstrating its potential to stratify patients with osteoarthritis who may respond preferentially to placebo or duloxetine (Martins et al, 2022) as well as normalise aberrant serotonergic processing associated with an emotional task in individuals with autism spectrum disorder (Wong et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Normative Modelling of Molecular-based Functional Neurocircuits Captures Clinical Heterogeneity Transdiagnostically in Neuropsychiatric Patients

Lawn,

Giacomel,

Martins

et al. 2023

Preprint

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Clinical neuroscience principally aims to delineate the neurobiology underpinning the symptoms of various disorders, with the ultimate goal of developing mechanistically informed treatments for these conditions. This has been hindered by the complex hierarchical organisation of the brain and extreme heterogeneity of neuropsychiatric disorders. However, recent advances in multimodal analytic techniques - such as Receptor Enriched Analysis of Connectivity by Targets (REACT) - have allowed to integrate the functional dynamics seen in fMRI with the brain's receptor landscape, providing novel trans-hierarchical insights. Similarly, normative modelling of brain features has allowed translational neuroscience to move beyond group average differences between patients and controls and characterise deviations from health at an individual level. Here, we bring these novel methods together for the first time in order to address these two longstanding translational barriers in clinical neuroscience. REACT was used create functional networks enriched with the main modulatory (noradrenaline, dopamine, serotonin, acetylcholine), inhibitory (GABA), and excitatory (glutamate) neurotransmitter systems in a large group of healthy participants [N=607]. Next, we generated normative models of these networks across the spectrum of healthy ageing and demonstrated that these capture deviations within and across patients with Schizophrenia, Bipolar-disorder, and ADHD [N=119]. Our results align with prior accounts of excitatory-inhibitory imbalance in schizophrenia and bipolar disorder, with the former also related to deviations within the cholinergic system. Our transdiagnostic analyses also emphasised the substantial overlap in symptoms and deviations across these disorders. Altogether, this work provides impetus for the development of novel biomarkers that characterise both molecular- and systems-level dysfunction at the individual level, helping facilitate the transition towards mechanistically targeted treatments.

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The Effects of Propofol Anaesthesia on Molecular-enriched Networks During Resting-state and Naturalistic Stimulation

Cited by 2 publications

References 105 publications

PET-based brain molecular connectivity in neurodegenerative disease

PET-based brain molecular connectivity in neurodegenerative disease

Normative Modelling of Molecular-based Functional Neurocircuits Captures Clinical Heterogeneity Transdiagnostically in Neuropsychiatric Patients

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