Publications by authors named "Ottavia Dipasquale"

Determining the effects of antipsychotics on MRI brain structural metrics without the potential confounding effects related to the natural course of a psychotic illness is challenging. However, it is crucial to understand these effects to interpret the results of cross-sectional and longitudinal studies in medicated patients and, ultimately, to understand better the biological mechanisms driving antipsychotics' effects. In this work, we aim to determine whether exposure to antipsychotics is associated with alterations in brain MRI structural metrics in the absence of disease effects.

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Background: Fatigue in Parkinson's disease (PD) is a prevalent and debilitating non-motor symptom. Despite its significant impact on quality of life, the underlying neurochemical and network-based mechanisms remain poorly understood.

Objectives: This observational study applied a multimodal imaging approach to explore potential links between the functional connectivity of neurotransmitter-specific circuits and fatigue in a sample of patients with PD.

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Differentiating brain radionecrosis (RN) from tumor progression (TP) is a persistent clinical difficulty. Here, we compared the diagnostic accuracy of leakage-corrected relative cerebral blood volume (rCBV) and fluid-suppressed amide proton transfer-weighted (APTw) imaging in distinguishing between RN and TP in metastases. Subjects with enlarging lesions after stereotactic radiosurgery were prospectively examined at 3T.

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Lysergic acid diethylamide (LSD) is a classic serotonergic psychedelic that induces a profoundly altered conscious state. In conjunction with psychological support, it is currently being explored as a treatment for generalized anxiety disorder and depression. The dorsolateral prefrontal cortex (DLPFC) is a brain region that is known to be involved in mood regulation and disorders; hypofunction in the left DLPFC is associated with depression.

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Molecular neuroimaging techniques, like PET and SPECT, offer invaluable insights into the brain's in-vivo biology and its dysfunction in neuropsychiatric patients. However, the transition of molecular neuroimaging into diagnostics and precision medicine has been limited to a few clinical applications, hindered by issues like practical feasibility, high costs, and high between-subject heterogeneity of neuroimaging measures. In this study, we explore the use of normative modelling (NM) to identify individual patient alterations by describing the physiological variability of molecular functions.

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Background: The brain integrates multiple scales of description, from the level of cells and molecules to large-scale networks and behavior. Understanding relationships across these scales may be fundamental to advancing understanding of brain function in health and disease. Recent neuroimaging research has shown that functional brain alterations that are associated with schizophrenia spectrum disorders (SSDs) are already present in young adults at clinical high risk for psychosis (CHR-P), but the cellular and molecular determinants of these alterations remain unclear.

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Article Synopsis
  • Advanced methods like REACT integrate fMRI with the brain's receptor landscape, offering new insights into the brain's multi-scale organization.
  • Normative modeling enables neuroscience to assess individual health deviations instead of just group averages, enhancing our understanding of mental disorders.
  • This study combines these methods to analyze functional networks related to neurotransmitter systems in patients with schizophrenia, bipolar disorder, and ADHD, revealing overlapping symptoms and potential biomarkers for more targeted treatments.
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Abnormalities in functional brain networks (functional connectome) are increasingly implicated in people at Clinical High Risk for Psychosis (CHR-P). Intranasal oxytocin, a potential novel treatment for the CHR-P state, modulates network topology in healthy individuals. However, its connectomic effects in people at CHR-P remain unknown.

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Background: Selective serotonin reuptake inhibitors (SSRIs) potentiate serotonergic neurotransmission by blocking the serotonin transporter (5-HTT), but the functional brain response to SSRIs involves neural circuits beyond regions with high 5-HTT expression. Currently, it is unclear whether and how changes in 5-HTT availability after SSRI administration modulate brain function of key serotoninergic circuits, including those characterized by high availability of the serotonin 1A receptor (5-HT1AR).

Aim: We investigated the association between 5-HTT availability and 5-HTT- and 5-HT1AR-enriched functional connectivity (FC) after an acute citalopram challenge.

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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.

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  • This study investigates the effects of ketamine on brain connectivity in individuals with remitted depression, focusing specifically on changes occurring 2 hours post-infusion, when symptoms aren't actively improving.
  • A total of 35 participants underwent a double-blind trial, revealing decreased connectivity between key brain regions (specifically the sgACC and amygdala) after ketamine administration compared to a placebo.
  • The results suggest that ketamine alters brain connectivity related to cognitive and emotional processes, potentially indicating the drug's impact on neural plasticity.
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  • REACT is a method that combines fMRI data with information about neurotransmitter distribution in the brain, enhancing the analysis of functional connectivity by providing biological context.* -
  • The study applied REACT to simultaneous ASL (Arterial Spin Labeling) and BOLD (Blood Oxygen Level Dependent) imaging methods in 29 healthy subjects, examining the functional connectivity related to six molecular systems.* -
  • Results indicated that ASL provides similar functional circuit information as BOLD, showing moderate overlap between their connectivity maps, and both methods offer complementary insights into brain function.*
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  • The study aimed to understand the neuropharmacological changes in visual snow syndrome (VSS) by using receptor target maps and resting fMRI to identify involved neurotransmitters.* -
  • Researchers compared functional connectivity (FC) in patients with VSS, healthy controls, and migraine patients, finding reduced FC in glutamatergic and serotonergic networks specifically in VSS patients.* -
  • The findings suggest that altered glutamate and serotonin connectivity in VSS might share similarities with migraine with aura, indicating a possible shared biological mechanism between the two conditions.*
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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.

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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.

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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.

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Placing a patient in a state of anaesthesia is crucial for modern surgical practice. However, the mechanisms by which anaesthetic drugs, such as propofol, impart their effects on consciousness remain poorly understood. Propofol potentiates GABAergic transmission, which purportedly has direct actions on cortex as well as indirect actions via ascending neuromodulatory systems.

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  • * Neuroimaging studies showed that MB reduced cerebral blood flow (CBF) and metabolic rates for oxygen in humans and glucose in rats, contradicting expectations that MB would boost these metrics.
  • * The unexpected results may be due to the dose used, suggesting that higher concentrations of MB could inhibit metabolism rather than enhance it, especially in healthy individuals with normal brain function.
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  • Dynamic functional connectivity (dFC) in resting-state fMRI has potential as a clinical biomarker, but its reliability and interpretation are still debated.
  • The research used a complexity-science approach to explore various dFC metrics, revealing meaningful relationships that can enhance understanding and predictive modeling of brain information.
  • Findings suggest that resting-state fMRI dynamics exhibit a unique complexity profile for each individual, indicating that personal history could be more valuable for understanding brain function than average results across a population.
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Competing and complementary models of resting-state brain dynamics contribute to our phenomenological and mechanistic understanding of whole-brain coordination and communication, and provide potential evidence for differential brain functioning associated with normal and pathological behaviour. These neuroscientific theories stem from the perspectives of physics, engineering, mathematics and psychology and create a complicated landscape of domain-specific terminology and meaning, which, when used outside of that domain, may lead to incorrect assumptions and conclusions within the neuroscience community. Here, we review and clarify the key concepts of connectivity, computation, criticality and coherence-the 4C's-and outline a potential role for metastability as a common denominator across these propositions.

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Background: Alterations in the serotonergic control of brain pathways responsible for facial emotion processing in people with autism spectrum disorder (ASD) may be a target for intervention. However, the molecular underpinnings of autistic-neurotypical serotonergic differences are challenging to access in vivo. Receptor-Enriched Analysis of functional Connectivity by Targets (REACT) has helped define molecular-enriched functional magnetic resonance imaging (fMRI) brain networks based on a priori information about the spatial distribution of neurochemical systems from available PET templates.

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The integration of neuroimaging and transcriptomics data, , is becoming increasingly popular but standardized workflows for its implementation are still lacking. We describe the Imaging Transcriptomics toolbox, a new package that implements a full imaging transcriptomics pipeline using a user-friendly, command line interface. This toolbox allows the user to identify patterns of gene expression which correlates with a specific neuroimaging phenotype and perform gene set enrichment analyses to inform the biological interpretation of the findings using up-to-date methods.

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Rationale: LSD is the prototypical psychedelic. Despite a clear central role of the 5HT receptor in its mechanism of action, the contributions of additional receptors for which it shows affinity and agonist activity remain unclear.

Objectives: We employed receptor-enriched analysis of functional connectivity by targets (REACT) to explore differences in functional connectivity (FC) associated with the distributions of the primary targets of LSD-the 5HT, 5HT, 5HT, D1 and D2 receptors.

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