Psychiatric phenotype in neurodevelopmental myoclonus-dystonia is underpinned by abnormality of cerebellar modulation on the cerebral cortex.

Psychiatric symptoms are common in neurodevelopmental movement disorders, including some types of dystonia. However, research has mainly focused on motor manifestations and underlying circuits. Myoclonus-dystonia is a rare and homogeneous neurodevelopmental condition serving as an illustrative paradigm of childhood-onset dystonias, associated with psychiatric symptoms.

Graded exposure therapy for adults with persistent symptoms after mTBI: A historical comparison study.

Fear avoidance behaviour is associated with slow recovery from mild traumatic brain injury (mTBI). This study is a preliminary evaluation of graded exposure therapy (GET), which directly targets fear avoidance behaviour, for reducing post-concussion symptoms (PCS) and disability following mTBI. In a historical comparison design, we compared two groups from independent randomized trials.

Modeling the progression of neuropsychiatric symptoms in Alzheimer's disease with PET-based Braak staging.

In Alzheimer's disease (AD), neuropsychiatric symptoms (NPS) correlate with tau deposition in the brain. Here, we investigated the association of PET-based Braak stages with NPS and assessed whether they predict annual changes in NPS. We evaluated 231 individuals in the aging and AD continuum.

Adaptive Trials in Stroke: Current Use and Future Directions.

Inclusion of adaptive design features in a clinical trial provides preplanned flexibility to dynamically modify a trial during its conduct while preserving validity and integrity. Adaptive trials are needed to accelerate the conduct of more efficient, informative, and ethical clinical research in the field of neurology. Stroke is a natural candidate for adoption of these innovative approaches to trial design.

Comparison of patient-reported outcomes between alternative care provider-led and physician-led care for severe sleep disordered breathing: secondary analysis of a randomized clinical trial.

Background: Previous research has suggested that alternative (respiratory) care providers (ACP) may provide affordable, accessible care for sleep-disordered breathing (SDB) that decreases wait-times and improves clinical outcomes. The objective of this study was to compare ACP-led and sleep physician-led care for SDB on patient reported outcome and experiences, with a focus on general and health-related quality of life, sleepiness, and patient satisfaction.

Methods: We conducted a secondary analysis of a randomized trial in which participants with severe SDB were assigned to either ACP-led or physician-led management.

Criticality and universality in neuronal cultures during "up" and "down" states.

The brain can be seen as a self-organized dynamical system that optimizes information processing and storage capabilities. This is supported by studies across scales, from small neuronal assemblies to the whole brain, where neuronal activity exhibits features typically associated with phase transitions in statistical physics. Such a critical state is characterized by the emergence of scale-free statistics as captured, for example, by the sizes and durations of activity avalanches corresponding to a cascading process of information flow.

Contribution of hypothalamic orexin (hypocretin) circuits to pathologies of motivation.

The orexin (also known as hypocretin) system, consisting of neuropeptides orexin-A and orexin-B, was discovered over 25 years ago and was immediately identified as a central regulator of sleep and wakefulness. These peptides interact with two G-protein coupled receptors, orexin 1 (OX) and orexin 2 (OX) receptors which are capable of coupling to all heterotrimeric G-protein subfamilies, but primarily transduce increases in calcium signalling. Orexin neurons are regulated by a variety of transmitter systems and environmental stimuli that signal reward availability, including food and drug related cues.

Transcriptional re-programming of liver-resident iNKT cells into T-regulatory type-1-like liver iNKT cells involves extensive gene de-methylation.

Unlike conventional CD4+ T cells, which are phenotypically and functionally plastic, invariant NKT (iNKT) cells generally exist in a terminally differentiated state. Naïve CD4+ T cells can acquire alternative epigenetic states in response to different cues, but it remains unclear whether peripheral iNKT cells are epigenetically stable or malleable. Repetitive encounters of liver-resident iNKT cells (LiNKTs) with alpha-galactosylceramide (αGalCer)/CD1d-coated nanoparticles (NPs) can trigger their differentiation into a LiNKT cell subset expressing a T regulatory type 1 (TR1)-like (LiNKTR1) transcriptional signature.

HarmonyTM: multi-center data harmonization applied to distributed learning for Parkinson's disease classification.

Purpose: Distributed learning is widely used to comply with data-sharing regulations and access diverse datasets for training machine learning (ML) models. The traveling model (TM) is a distributed learning approach that sequentially trains with data from one center at a time, which is especially advantageous when dealing with limited local datasets. However, a critical concern emerges when centers utilize different scanners for data acquisition, which could potentially lead models to exploit these differences as shortcuts.

Responding to the Growing Need for Medical Experts in Testamentary and Estate Related Capacities: A Course for Physicians.

Objectives: The objective of this continuing medical education course was to improve the knowledge and skills of physicians in the assessment of testamentary and related capacities.

Methods: We developed, conducted, and evaluated an accredited medical education course focusing on the role and responsibilities of medical experts in estate litigation and held in Toronto, Ontario, Canada in June 2022.

Results: Participants reported a 65% and 35% improvement in confidence in conducting retrospective and contemporaneous assessments of testamentary capacity, respectively.

Incorporating individual differences into a mechanistic embodied cognitive neuroscience.

The review article proposes that the embodied cognition framework can be applied to develop mechanistic explanations for cognitive neuroscience phenomena. In our commentary we argue that any mechanistic explanation of such phenomena must be able to account for individual differences in cognition that are an inevitable consequence of the varied brain-body-environment experiences that comprise embodied cognition. We propose that, while mechanistic accounts may be able to model individual differences, the definition of mechanistic models may limit their application to the study of individual differences.

Understanding physician preferences about combined thrombolysis and thrombectomy in patients with large vessel occlusion: An international cross-sectional survey.

Background: A recently published individual participant-level meta-analysis found that EVT alone was not non-inferior to combined intravenous thrombolysis (IVT) and EVT. Our aim was to determine factors that influence physicians' treatment choice of IVT-alone versus EVT-alone versus a combined approach.

Methods: We performed an international, structured, invite-only survey among physicians treating patients presenting with AIS.

Excess health care use is significantly and persistently reduced following diagnosis of late-onset epilepsy.

Objective: The incidence of late-onset epilepsy (LOE) is rising, and these patients may use an excess of health care resources. This study aimed to measure pre-/post-diagnostic health care use (HCU) for patients with LOE compared to controls.

Methods: This was an observational open cohort study covering years 1998-2019 using UK population-based linked primary care (Clinical Practice Research Datalink [CPRD]) and hospital (HES) electronic health records.

Reduced Stroke Volume and Brain Perfusion Drive Postural Hyperventilation in Postural Orthostatic Tachycardia Syndrome.

Postural hyperventilation has been implicated as a cause of postural orthostatic tachycardia syndrome (POTS), yet the precise mechanisms underlying the heightened breathing response remain unclear. This study challenges current hypotheses by revealing that exaggerated peripheral chemoreceptor activity is not the primary driver of postural hyperventilation. Instead, significant contributions from reduced stroke volume and compromised brain perfusion during orthostatic stress were identified.

Remote electrical neuromodulation to treat children and adolescents with migraine in the emergency department: A randomized double-dummy pilot trial.

Objective: Using a double-dummy pilot randomized controlled trial design, we aimed to determine the feasibility and acceptability of comparing remote electrical neuromodulation (REN) to typical care intravenous pharmacologic interventions for the treatment of children and adolescents visiting the emergency department (ED) with migraine, and to compare parallel-group versus crossover trial designs.

Background: There are limited data to guide the management of migraine in the ED. Children and adolescents are interested in neuromodulation, and specifically REN, for treatment in this setting, but there are no existing data on this approach.

The Canadian Prospective Cohort Study to understand progression in multiple sclerosis: baseline characteristics.

Background: Disease progression is observed across the spectrum of people with multiple sclerosis (MS) and identification of effective treatment strategies to halt progression remains one of the greatest unmet clinical needs.

Objectives: The Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) was designed to evaluate a wide range of factors associated with the onset and rate of clinical disease progression in MS and to describe the interplay between these factors.

Design: A prospective cohort study.