Publications by authors named "David E J Linden"

There is a growing interest in using machine learning (ML) models to perform automatic diagnosis of psychiatric conditions; however, generalising the prediction of ML models to completely independent data can lead to sharp decrease in performance. Patients with different psychiatric diagnoses have traditionally been studied independently, yet there is a growing recognition of neuroimaging signatures shared across them as well as rare genetic copy number variants (CNVs). In this work, we assess the potential of multi-task learning (MTL) to improve accuracy by characterising multiple related conditions with a single model, making use of information shared across diagnostic categories and exposing the model to a larger and more diverse dataset.

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Background: 22q11.2 deletion syndrome (22q11DS) is a genetic disorder characterised by a wide range of physical, cognitive, and psychiatric symptoms. Current knowledge on 22q11DS highlights considerable variation in cognitive outcomes, but the role of environmental factors in shaping these trajectories over time remains poorly understood.

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Background: Genetic studies have shown associations between genetic risk for schizophrenia and brain imaging phenotypes. However, prior studies focused on a single neuroimaging modality and/or employed methods that do not fully elucidate the shared genetic architecture between them, limiting our understanding of their complex genetic relationship.

Study Design: We used genome-wide association study summary statistics for schizophrenia alongside 37 brain measurements, selected based on adequate SNP-based heritability and representing structural, microstructural, and functional brain features derived from T1, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI).

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Introduction: In Parkinson's disease (PD) patients, modulation of the fibre tracts of the cortico-basal ganglia-thalamo-cortical loop is the presumed mechanism of action of deep brain stimulation (DBS) of the subthalamic nucleus (STN). Therefore, we explored patient-individual cortical structural connectivity of the volume of tissue activated (VTA), as well as DBS-induced modulation of fibre tracts connecting the STN with cortical and subcortical nodes, and their correlation with therapeutic effects.

Methods: A retrospective cohort of n = 69 PD patients treated with bilateral DBS of the STN was analysed.

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Cumulative evidence suggests neurodevelopmental disorders are closely related. The risk of these disorders is increased by a series of copy number variant syndromes - phenotypically heterogeneous genetic disorders, present in a minority of the population. Recent models suggest that a disruption in the balance between excitatory and inhibitory neural activity may contribute to the aetiology of neurodevelopmental disorders, and may be additionally disturbed in copy number variant syndromes.

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Background: Copy number variants (CNVs) may increase the risk for neurodevelopmental conditions. The neurobiological mechanisms that link these high-risk genetic variants to clinical phenotypes are largely unknown. An important question is whether brain abnormalities in individuals who carry CNVs are associated with their degree of penetrance.

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Genetic studies have identified common and rare variants increasing the risk for neurodevelopmental and psychiatric disorders (NPDs). These risk variants have also been shown to influence the structure of the cerebral cortex. However, it is unknown whether cortical differences associated with genetic variants are linked to the risk they confer for NPDs.

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Background: A previous study successfully identified 148 of 23,098 exposures associated with any psychotic experiences (PEs) in the UK Biobank using an exposome-wide association study (XWAS). Furthermore, research has shown that the polygenic risk score for schizophrenia (PRS-SCZ) is associated with PEs. However, the interaction of these exposures with PRS-SCZ remains unknown.

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Altered sensory feedback processing and attention control are assumed to contribute to auditory verbal hallucinations, which are experienced by the general population and patients with psychosis, implying a continuum of hallucination proneness (HP). However, the interaction of altered sensory feedback processing and attention control along this HP continuum remains unclear. We tested this interaction using electroencephalography while forty participants varying on HP, self-generated (via a button-press) and passively listened to their own voices.

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The present study analyzes habituation, sensitization, and nocebo effects based on individual differences in response to painful stimulation. Habituation and sensitization to pain show two opposite patterns that may occur during repeated painful stimulation. Negative expectations such as a nocebo manipulation have been shown to increase pain ratings, but it is unclear to what extent they can influence habituation and sensitization to pain.

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Objective: Coronavirus disease 2019 (COVID-19) is known to have adverse effects on the brain's vasculature in some patients. After recovery of the infection, vascular abnormalities may persist, but it remains unclear which pathological pathways play a role in post-COVID vascular and cognitive dysfunction and may contribute to post-COVID cognitive complaints.

Methods: In this observational cohort study, 108 previously hospitalized COVID-19 survivors (general ward: n = 53; intensive care unit (ICU): n = 55) were compared.

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Major depressive disorder (MDD) is a complex psychiatric disorder that affects the lives of hundreds of millions of individuals around the globe. Even today, researchers debate if morphological alterations in the brain are linked to MDD, likely due to the heterogeneity of this disorder. The application of deep learning tools to neuroimaging data, capable of capturing complex non-linear patterns, has the potential to provide diagnostic and predictive biomarkers for MDD.

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Background: Studies focusing on the treatment of neuropsychiatric symptoms (NPS) in Huntington's disease (HD) are scarce and show a wide variation in design, outcome measures and methodological quality. The effectiveness of pharmacological treatment of NPS in HD has not been systematically reviewed so far.

Objective: To provide an overview of the available literature on the effectiveness of pharmacological treatment of NPS in HD.

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Extinction learning is regarded as a core mechanism underlying exposure therapy. Under this assumption, studies have looked at the predictive value of the extinction learning paradigm for exposure therapy outcomes. However, predicting factors of long-term exposure therapy success have not been established.

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47,XXX (Triple X syndrome) is a sex chromosome aneuploidy characterized by the presence of a supernumerary X chromosome in affected females, and has been associated with a variable cognitive, behavioral, and psychiatric phenotype. Alterations in brain gray matter structure and function have been reported, but less is known about white matter (WM) organization in 47,XXX. Therefore, we conducted 7 T diffusion tensor imaging and characterized fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity of 22 adult women with 47,XXX and 22 age-matched typically developing females using tract-based spatial statistics.

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Stress-related disorders are among the biggest global health challenges. Despite significant progress in understanding their neurocognitive basis, the promise of applying insights from fundamental research to prevention and treatment remains largely unfulfilled. We argue that neurofeedback - a method for training voluntary control over brain activity - has the potential to fill this translational gap.

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47,XXX (Triple X syndrome) is a sex chromosome aneuploidy characterized by the presence of a supernumerary X chromosome in affected females and is associated with a variable cognitive, behavioral, and psychiatric phenotype. The effect of a supernumerary X chromosome in affected females on intracortical microstructure is currently unknown. Therefore, we conducted 7 Tesla structural MRI and compared T1 (ms), as a proxy for intracortical myelin (ICM), across laminae of 21 adult women with 47,XXX and 22 age-matched typically developing females using laminar analyses.

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Objectives: Aberrant movement-related cortical activity has been linked to impaired motor function in Parkinson's disease (PD). Dopaminergic drug treatment can restore these, but dosages and long-term treatment are limited by adverse side-effects. Effective non-pharmacological treatments could help reduce reliance on drugs.

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Background: Sensory suppression occurs when hearing one's self-generated voice, as opposed to passively listening to one's own voice. Quality changes in sensory feedback to the self-generated voice can increase attentional control. These changes affect the self-other voice distinction and might lead to hearing voices in the absence of an external source (ie, auditory verbal hallucinations).

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Background: Neurological complications in COVID-19 patients admitted to an intensive care unit (ICU) have been previously reported. As the pandemic progressed, therapeutic strategies were tailored to new insights. This study describes the incidence, outcome, and types of reported neurological complications in invasively mechanically ventilated (IMV) COVID-19 patients in relation to three periods during the pandemic.

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Background: Resting state (RS) brain activity is inherently non-stationary. Hidden semi-Markov Models (HsMM) can characterize continuous RS data as a sequence of recurring and distinct brain states along with their spatio-temporal dynamics.

New Method: Recent explorations suggest that HsMM state dynamics in the alpha frequency band link to auditory hallucination proneness (HP) in non-clinical individuals.

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Asymmetry between the left and right hemisphere is a key feature of brain organization. Hemispheric functional specialization underlies some of the most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variants, which typically exert small effects on brain-related phenotypes.

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Objectives: Schizophrenia genetics is intricate, with common and rare variants' contributions not fully understood. Certain copy number variations (CNVs) elevate risk, pivotal for understanding mental disorder models. Despite CNVs' genome-wide distribution and variable gene and protein effects, we must explore beyond affected genes to interaction partners and molecular pathways.

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The mechanisms by which genomic risks contribute to the onset of neuropsychiatric conditions remain a key challenge and a prerequisite for successful development of effective therapies. 15q11.2 copy number variation (CNV) containing the CYFIP1 gene is associated with autism and schizophrenia.

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