Publications by authors named "Hartwig Siebner"

Dopaminergic nigrostriatal denervation in Parkinson's disease (PD) disrupts the functional balance between striatal projecting neurons, leading to aberrant activity in the cortico-basal ganglia circuit and characteristic motor symptoms. While genetic and toxin-based animal models are commonly used to mimic PD pathology and behaviour, they have limitations when combined with circuit manipulation tools. This highlights the need for complementary approaches, particularly when combined with viral-based circuit targeting of specific neuronal subpopulations involved in PD circuit dysfunction.

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Intratelencephalic neurons are a crucial class of cortical principal neurons that heavily innervate the striatum and cortical areas bilaterally. Their extensive cortico-cortical and cortico-striatal connectivity enables sensorimotor integration within the telencephalon, but their role in motor control remains poorly understood. Here, we used a chemogenetic approach to explore the role of intratelencephalic neurons in spontaneous locomotor activity.

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Parkinson's disease (PD) can be effectively treated with levodopa and dopamine agonists but leads to levodopa-induced dyskinesia (LID) in most patients in the long run. Various functional brain mapping techniques are used to explore alterations in motor networks associated with LID. This pre-registered review (PROSPERO: CRD42022320830) summarizes the motor network abnormalities reported in functional brain mapping studies of patients with LID.

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Transcranial magnetic stimulation (TMS) triggers time-locked cortical activity that can be recorded with electroencephalography (EEG). Transcranial evoked potentials (TEPs) are widely used to probe brain responses to TMS. Here, we systematically reviewed 137 published experiments that studied TEPs elicited from TMS to the human primary motor cortex (M1) in healthy individuals to investigate the impact of methodological choices.

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Article Synopsis
  • The ETLAS-2 trial investigates the effectiveness of tadalafil, a medication that enhances blood flow in the brain, on patients with cerebral small vessel disease, a leading cause of strokes and vascular dementia.* -
  • It is a phase 2 double-blind study involving 100 patients, focusing on changes in brain health over three months of treatment and utilizing MRI and cognitive testing to assess outcomes.* -
  • Currently involving 64 patients, the trial aims to improve treatment options for small vessel disease and is expected to conclude in 2024.*
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Background: Schizophrenia and bipolar disorder are characterized by social cognitive impairments, and recent research has identified alterations of the social brain. However, it is unknown whether familial high risk (FHR) of these disorders is associated with neurobiological alterations already present in childhood.

Methods: As part of the Danish High Risk and Resilience Study-VIA 11, we examined children at FHR of schizophrenia (n = 121, 50% female) or bipolar disorder (n = 75, 47% female) and population-based control children (PBCs) (n = 128, 48% female).

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Introduction: In patients with inflammatory bowel disease (IBD), co-occurring spondyloarthritis (SpA) leads to poorer outcomes and impaired quality of life, highlighting the importance of early detection and effective treatment. This is the first study to assess the prevalence and distribution of axial symptoms and magnetic resonance imaging (MRI)-detected involvement of the spine and sacroiliac joints (SIJs) in early IBD.

Methods: Newly diagnosed patients with IBD from a prospective, population-based cohort were consecutively recruited.

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Background: Intrahepatic triacylglycerol (liver TG) content is associated with hepatic insulin resistance and dyslipidemia. Liver TG content can be modulated within days under hypocaloric conditions.

Objectives: We hypothesized that 4 d of eucaloric low-carbohydrate/high-fat (LC) intake would decrease liver TG content, whereas a high-carbohydrate/low-fat (HC) intake would increase liver TG content, and further that alterations in liver TG would be linked to dynamic changes in hepatic glucose and lipid metabolism.

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Background: Transcranial evoked potentials (TEPs) measured via electroencephalography (EEG) are widely used to study the cortical responses to transcranial magnetic stimulation (TMS). Immediate transcranial evoked potentials (i-TEPs) have been obscured by pulse and muscular artifacts. Thus, the TEP peaks that are commonly reported have latencies that are too long to be caused by direct excitation of cortical neurons.

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Background And Objectives: Cortical lesions contribute to disability in multiple sclerosis (MS), but their impact on regional neurotransmitter levels remains to be clarified. We tested the hypothesis that cortical lesions are associated with regional glutamate and gamma-aminobutyric acid (GABA) concentrations within the affected cortical region.

Methods: In this cross-sectional study, we used structural 7T MRI to segment cortical lesions and 7T proton MR-spectroscopy of the bilateral sensorimotor hand areas to quantify regional GABA, glutamate, -acetylaspartate, and myoinositol concentrations in patients with MS (inclusion criteria: diagnosis of relapsing-remitting [RR] or secondary progressive MS [SPMS]; age 18-80 years) and age and sex-matched healthy controls.

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Manual motor performance declines with age, but the extent to which age influences the acquisition of new skills remains a topic of debate. Here, we examined whether older healthy adults show less training-dependent performance improvements during a single session of a bimanual pinch task than younger adults. We also explored whether physical and cognitive factors, such as grip strength or motor-cognitive ability, are associated with performance improvements.

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Background: Surgical skills acquisition is under continuous development due to the emergence of new technologies, and there is a need for assessment tools to develop along with these. A range of neuroimaging modalities has been used to map the functional activation of brain networks while surgeons acquire novel surgical skills. These have been proposed as a method to provide a deeper understanding of surgical expertise and offer new possibilities for the personalized training of future surgeons.

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We recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in patients with Parkinson's disease compared to age- and sex-matched healthy controls. Since both groups showed substantial inter-individual variations, we extended the cohort of controls with a group of young individuals to investigate possible age-related effects. Seventeen healthy young subjects aged < 30 years and 17 elderly subjects aged > 50 years underwent serial PC-MRI to measure the postprandial blood flow response in the SMA after ingestion of a standardized liquid test meal (∼400 kcal).

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Background: Despite advances in the etiology of anorexia nervosa (AN), a large subgroup of individuals does not profit optimally from treatment. Perfectionism has been found to be a risk factor predicting the onset, severity, and duration of AN episodes. To date, perfectionism has been studied predominantly by the use of self-report questionnaires, a useful approach that may, however, be impacted by demand characteristics, or other distortions of introspective or metacognitive access.

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Background: The mechanisms underlying memory deficits after electroconvulsive therapy (ECT) remain unclear but altered functional interactions between hippocampus and neocortex may play a role.

Objectives: To test whether ECT reduces functional connectivity between hippocampus and posterior regions of the default mode network (DMN) and to examine whether altered hippocampal-neocortical functional connectivity correlates with memory impairment. A secondary aim was to explore if these connectivity changes are present 6 months after ECT.

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Background And Objectives: Reliable detection of white matter hyperintensities (WMH) is crucial for studying the impact of diffuse white-matter pathology on brain health and monitoring changes in WMH load over time. However, manual annotation of 3D high-dimensional neuroimages is laborious and can be prone to biases and errors in the annotation procedure. In this study, we evaluate the performance of deep learning (DL) segmentation tools and propose a novel volumetric segmentation model incorporating self-attention via a transformer-based architecture.

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The modeling of transcranial magnetic stimulation (TMS)-induced electric fields (E-fields) is a versatile technique for evaluating and refining brain targeting and dosing strategies, while also providing insights into dose-response relationships in the brain. This review outlines the methodologies employed to derive E-field estimations, covering TMS physics, modeling assumptions, and aspects of subject-specific head tissue and coil modeling. We also summarize various numerical methods for solving the E-field and their suitability for various applications.

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Background: Several studies have applied resting-state functional MRI to examine whether functional brain connectivity is altered in migraine with aura patients. These studies had multiple limitations, including small sample sizes, and reported conflicting results. Here, we performed a large, cross-sectional brain imaging study to reproduce previous findings.

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Background And Hypotheses: Impaired executive control is a potential prognostic and endophenotypic marker of schizophrenia (SZ) and bipolar disorder (BP). Assessing children with familial high-risk (FHR) of SZ or BP enables characterization of early risk markers and we hypothesize that they express impaired executive control as well as aberrant brain activation compared to population-based control (PBC) children.

Study Design: Using a flanker task, we examined executive control together with functional magnetic resonance imaging (fMRI) in 11- to 12-year-old children with FHR of SZ (FHR-SZ) or FHR of BP (FHR-BP) and PBC children as part of a register-based, prospective cohort-study; The Danish High Risk and Resilience study-VIA 11.

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Creatine transporter deficiency (CTD), caused by pathogenic variants in SLC6A8, is the second most common cause of X-linked intellectual disability. Symptoms include intellectual disability, epilepsy, and behavioral disorders and are caused by reduced cerebral creatine levels. Targeted treatment with oral supplementation is available, however the treatment efficacy is still being investigated.

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Modifiable lifestyle factors have been shown to promote healthy brain ageing. However, studies have typically focused on a single factor at a time. Given that lifestyle factors do not occur in isolation, multivariable analyses provide a more realistic model of the lifestyle-brain relationship.

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Introduction: With longer life expectancy in people living with HIV (PLWH) on antiretroviral therapy, cardiovascular disease (CVD) has become a common cause of mortality among them. Abacavir has been associated with an increased risk of myocardial infarction, but the mechanism is unknown. Additionally, abacavir may be obesogenic which could mediate an additional risk factor of CVD.

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Background: Non-alcoholic fatty liver disease (NAFLD), and particularly liver fibrosis, has been suggested as a risk factor of chronic kidney disease (CKD). Given that NAFLD affects every fourth person globally, better insight is needed. Our aim was to investigate the association between hepatic fibrosis and CKD in patients with type 2 diabetes and to compare different methods for diagnosing liver fibrosis in this study population.

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Article Synopsis
  • Quantum sensors using solid state qubits, particularly those based on diamond colour centres, have shown exceptional sensitivity to magnetic fields, making them suitable for biological applications.
  • This study successfully utilized a quantum sensor to non-invasively record electrical activity from neurons in living brain tissue, specifically tracking ionic currents in mouse axons.
  • The passive and remote nature of this sensing technique allows for a new method to understand neuronal circuits and disease mechanisms, possibly leading to future advancements in imaging brain activity in live mammals.
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