Early alterations of functional connectivity, regional brain volumes and astrocyte markers in the beta-sitosterol beta-d-glucoside (BSSG) rat model of parkinsonism.

The β-sitosterol-β-ᴅ-glucoside (BSSG) rat model of experimental parkinsonism develops pathological behaviour and motor changes that progress over time. The purpose of this study was to identify early changes in structure and function of the brain of rats treated with BSSG using both structural and resting-state functional MRI. BSSG and non-BSSG rats were fed five days a week for sixteen weeks, then underwent in vivo MRI scans and an assessment of motor performance 2 and 8 weeks later (18 and week 24 from BSSG).

Estimating the energy of dissipative neural systems.

There is, at present, a lack of consensus regarding precisely what is meant by the term 'energy' across the sub-disciplines of neuroscience. Definitions range from deficits in the rate of glucose metabolism in consciousness research to regional changes in neuronal activity in cognitive neuroscience. In computational neuroscience virtually all models define the energy of neuronal regions as a quantity that is in a continual process of dissipation to its surroundings.

Metastability demystified - the foundational past, the pragmatic present and the promising future.

Healthy brain function depends on balancing stable integration between brain areas for effective coordinated functioning, with coexisting segregation that allows subsystems to express their functional specialization. Metastability, a concept from the dynamical systems literature, has been proposed as a key signature that characterizes this balance. Building on this principle, the neuroscience literature has leveraged the phenomenon of metastability to investigate various aspects of brain function in health and disease.

Extra-axial inflammatory signal and its relationship to peripheral and central immunity in depression.

Although both central and peripheral inflammation have been observed consistently in depression, the relationship between the two remains obscure. Extra-axial immune cells may play a role in mediating the connection between central and peripheral immunity. This study investigates the potential roles of calvarial bone marrow and parameningeal spaces in mediating interactions between central and peripheral immunity in depression.

ASCHOPLEX: A generalizable approach for the automatic segmentation of choroid plexus.

Background: The Choroid Plexus (ChP) plays a vital role in brain homeostasis, serving as part of the Blood-Cerebrospinal Fluid Barrier, contributing to brain clearance pathways and being the main source of cerebrospinal fluid. Since the involvement of ChP in neurological and psychiatric disorders is not entirely established and currently under investigation, accurate and reproducible segmentation of this brain structure on large cohorts remains challenging. This paper presents ASCHOPLEX, a deep-learning tool for the automated segmentation of human ChP from structural MRI data that integrates existing software architectures like 3D UNet, UNETR, and DynUNet to deliver accurate ChP volume estimates.

Physically informed deep neural networks for metabolite-corrected plasma input function estimation in dynamic PET imaging.

Introduction: We propose a novel approach for the non-invasive quantification of dynamic PET imaging data, focusing on the arterial input function (AIF) without the need for invasive arterial cannulation.

Methods: Our method utilizes a combination of three-dimensional depth-wise separable convolutional layers and a physically informed deep neural network to incorporatea priori knowledge about the AIF's functional form and shape, enabling precise predictions of the concentrations of [C]PBR28 in whole blood and the free tracer in metabolite-corrected plasma.

Results: We found a robust linear correlation between our model's predicted AIF curves and those obtained through traditional, invasive measurements.

Synaptic changes in psychiatric and neurological disorders: state-of-the art of in vivo imaging.

Synapses are implicated in many neuropsychiatric illnesses. Here, we provide an overview of in vivo techniques to index synaptic markers in patients. Several positron emission tomography (PET) tracers for synaptic vesicle glycoprotein 2 A (SV2A) show good reliability and selectivity.

A blood-free modeling approach for the quantification of the blood-to-brain tracer exchange in TSPO PET imaging.

Introduction: Recent evidence suggests the blood-to-brain influx rate ( ) in imaging as a promising biomarker of blood-brain barrier () permeability alterations commonly associated with peripheral inflammation and heightened immune activity in the brain. However, standard compartmental modeling quantification is limited by the requirement of invasive and laborious procedures for extracting an arterial blood input function. In this study, we validate a simplified blood-free methodologic framework for estimation by fitting the early phase tracer dynamics using a single irreversible compartment model and an image-derived input function ().

Brain Fluid Clearance After Traumatic Brain Injury Measured Using Dynamic Positron Emission Tomography.

Brain fluid clearance by pathways including the recently described paravascular glymphatic system is a critical homeostatic mechanism by which metabolic products, toxins, and other wastes are removed from the brain. Brain fluid clearance may be especially important after traumatic brain injury (TBI), when blood, neuronal debris, inflammatory cells, and other substances can be released and/or deposited. Using a non-invasive dynamic positron emission tomography (PET) method that models the rate at which an intravenously injected radiolabeled molecule (in this case C-flumazenil) is cleared from ventricular cerebrospinal fluid (CSF), we estimated the overall efficiency of brain fluid clearance in humans who had experienced complicated-mild or moderate TBI 3-6 months before neuroimaging ( = 7) as compared to healthy controls ( = 9).

Altered dynamical integration/segregation balance during anesthesia-induced loss of consciousness.

In recent years, brain imaging studies have begun to shed light on the neural correlates of physiologically-reversible altered states of consciousness such as deep sleep, anesthesia, and psychedelic experiences. The emerging consensus is that normal waking consciousness requires the exploration of a dynamical repertoire enabling both global integration i.e.

Microglial activation, tau and amyloid deposition in TREM2 p.R47H carriers and mild cognitive impairment patients: a multi-modal/multi-tracer PET/MRI imaging study with influenza vaccine immune challenge.

Background: Microglia are increasingly understood to play an important role in the pathogenesis of Alzheimer's disease. The rs75932628 (p.R47H) TREM2 variant is a well-established risk factor for Alzheimer's disease.

Two human brain systems micro-structurally associated with obesity.

The relationship between obesity and human brain structure is incompletely understood. Using diffusion-weighted MRI from ∼30,000 UK Biobank participants, we test the hypothesis that obesity (waist-to-hip ratio, WHR) is associated with regional differences in two micro-structural MRI metrics: isotropic volume fraction (ISOVF), an index of free water, and intra-cellular volume fraction (ICVF), an index of neurite density. We observed significant associations with obesity in two coupled but distinct brain systems: a prefrontal/temporal/striatal system associated with ISOVF and a medial temporal/occipital/striatal system associated with ICVF.

Establishing brain states in neuroimaging data.

The definition of a brain state remains elusive, with varying interpretations across different sub-fields of neuroscience-from the level of wakefulness in anaesthesia, to activity of individual neurons, voltage in EEG, and blood flow in fMRI. This lack of consensus presents a significant challenge to the development of accurate models of neural dynamics. However, at the foundation of dynamical systems theory lies a definition of what constitutes the 'state' of a system-i.

Mapping acute neuroinflammation in vivo with diffusion-MRI in rats given a systemic lipopolysaccharide challenge.

It is becoming increasingly apparent that neuroinflammation plays a critical role in an array of neurological and psychiatric disorders. Recent studies have demonstrated the potential of diffusion MRI (dMRI) to characterize changes in microglial density and morphology associated with neuroinflammation, but these were conducted mostly ex vivo and/or in extreme, non-physiological animal models. Here, we build upon these studies by investigating the utility of well-established dMRI methods to detect neuroinflammation in vivo in a more clinically relevant animal model of sickness behavior.

The relationship between striatal dopamine and anterior cingulate glutamate in first episode psychosis changes with antipsychotic treatment.

The neuromodulator dopamine and excitatory neurotransmitter glutamate have both been implicated in the pathogenesis of psychosis, and dopamine antagonists remain the predominant treatment for psychotic disorders. To date no study has measured the effect of antipsychotics on both of these indices together, in the same population of people with psychosis. Striatal dopamine synthesis capacity (Ki) and anterior cingulate glutamate were measured using 18F-DOPA positron emission tomography and proton magnetic resonance spectroscopy respectively, before and after at least 5 weeks' naturalistic antipsychotic treatment in people with first episode psychosis (n = 18) and matched healthy controls (n = 20).

Histological examination of choroid plexus epithelia changes in schizophrenia.

Background: The choroid plexus (CP) produces and secretes most of the cerebrospinal fluid (CSF) of the central nervous system. The CP is suggested to be regulated by descending neurons and by circulating factors and is involved in the interaction between central and peripheral inflammation. Quantitative imaging has demonstrated volumetric CP changes in psychosis, schizophrenia and depression.

From neurotransmitters to networks: Transcending organisational hierarchies with molecular-informed functional imaging.

The human brain exhibits complex interactions across micro, meso-, and macro-scale organisational principles. Recent synergistic multi-modal approaches have begun to link micro-scale information to systems level dynamics, transcending organisational hierarchies and offering novel perspectives into the brain's function and dysfunction. Specifically, the distribution of micro-scale properties (such as receptor density or gene expression) can be mapped onto macro-scale measures from functional MRI to provide novel neurobiological insights.

Sickness behaviour and depression: An updated model of peripheral-central immunity interactions.

Current research into mood disorders indicates that circulating immune mediators participating in the pathophysiology of chronic somatic disorders have potent influences on brain function. This paradigm has brought to the fore the use of anti-inflammatory therapies as adjunctive to standard antidepressant therapy to improve treatment efficacy, particularly in subjects that do not respond to standard medication. Such new practice requires biomarkers to tailor these new therapies to those most likely to benefit but also validated mechanisms of action describing the interaction between peripheral immunity and brain function to optimize target intervention.

Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease.

Neuroinflammation is an important component of many neurodegenerative diseases, whether as a primary cause or a secondary outcome. For that reason, either as diagnostic tools or to monitor progression and/or pharmacological interventions, there is a need for robust biomarkers of neuroinflammation in the brain. Mitochondrial TSPO (18 kDa Translocator protein) is one of few available biomarkers of neuroinflammation for which there are clinically available PET imaging agents.

An automatic analysis framework for FDOPA PET neuroimaging.

In this study we evaluate the performance of a fully automated analytical framework for FDOPA PET neuroimaging data, and its sensitivity to demographic and experimental variables and processing parameters. An instance of XNAT imaging platform was used to store the King's College London institutional brain FDOPA PET imaging archive, alongside individual demographics and clinical information. By re-engineering the historical Matlab-based scripts for FDOPA PET analysis, a fully automated analysis pipeline for imaging processing and data quantification was implemented in Python and integrated in XNAT.

Metastability as a candidate neuromechanistic biomarker of schizophrenia pathology.

The disconnection hypothesis of schizophrenia proposes that symptoms of the disorder arise as a result of aberrant functional integration between segregated areas of the brain. The concept of metastability characterizes the coexistence of competing tendencies for functional integration and functional segregation in the brain, and is therefore well suited for the study of schizophrenia. In this study, we investigate metastability as a candidate neuromechanistic biomarker of schizophrenia pathology, including a demonstration of reliability and face validity.