Mutant torsinA in the heterozygous DYT1 state compromises HSV propagation in infected neurons and fibroblasts.

Most cases of early onset torsion dystonia (DYT1) are caused by a 3-base pair deletion in one allele of the TOR1A gene causing loss of a glutamate in torsinA, a luminal protein in the nuclear envelope. This dominantly inherited neurologic disease has reduced penetrance and no other medical manifestations. It has been challenging to understand the neuronal abnormalities as cells and mouse models which are heterozygous (Het) for the mutant allele are quite similar to wild-type (WT) controls.

Insulo-opercular cortex generates oroalimentary automatisms in temporal seizures.

Objective: Oroalimentary automatisms (OAAs) resembling normal alimentary behavior are stereotyped complex movements that may occur during epileptic seizures. They are considered common clinical signs in temporal lobe seizures, but their anatomofunctional mechanisms are not established. We took the opportunity of presurgical intracerebral recordings to study the relations between the occurrence of OAAs and temporal/spatial features of ictal activities.

Efficacy and safety of SQJZ herbal mixtures on nonmotor symptoms in Parkinson disease patients: Protocol for a randomized, double-blind, placebo-controlled trial.

Background: As a multisystemic neurodegenerative disorder, Parkinson disease (PD) has a broad spectrum of symptoms including motor and nonmotor symptoms (NMS). As shown in studies, NMS can also impact patient's quality of life, and many of them often go untreated. Chinese herbal medicines with multiconstituent may alleviate NMS in PD patients.

Novel botanical drug DA-9803 prevents deficits in Alzheimer's mouse models.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by deposition of amyloid plaques and disruption of neural circuitry, leading to cognitive decline. Animal models of AD deposit senile plaques and exhibit structural and functional deficits in neurons and neural networks. An effective treatment would prevent or restore these deficits, including calcium dyshomeostasis observed with in-vivo imaging.

Hippocampal LTP and contextual learning require surface diffusion of AMPA receptors.

Long-term potentiation (LTP) of excitatory synaptic transmission has long been considered a cellular correlate for learning and memory. Early LTP (less than 1 h) had initially been explained either by presynaptic increases in glutamate release or by direct modification of postsynaptic AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor function. Compelling models have more recently proposed that synaptic potentiation can occur by the recruitment of additional postsynaptic AMPA receptors (AMPARs), sourced either from an intracellular reserve pool by exocytosis or from nearby extra-synaptic receptors pre-existing on the neuronal surface.

Low statistical power in biomedical science: a review of three human research domains.

Studies with low statistical power increase the likelihood that a statistically significant finding represents a false positive result. We conducted a review of meta-analyses of studies investigating the association of biological, environmental or cognitive parameters with neurological, psychiatric and somatic diseases, excluding treatment studies, in order to estimate the average statistical power across these domains. Taking the effect size indicated by a meta-analysis as the best estimate of the likely true effect size, and assuming a threshold for declaring statistical significance of 5%, we found that approximately 50% of studies have statistical power in the 0-10% or 11-20% range, well below the minimum of 80% that is often considered conventional.

Poor replication validity of biomedical association studies reported by newspapers.

Objective: To investigate the replication validity of biomedical association studies covered by newspapers.

Methods: We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases.

Assessment of Early Evidence of Multiple Sclerosis in a Prospective Study of Asymptomatic High-Risk Family Members.

Importance: Subclinical inflammatory demyelination and neurodegeneration often precede symptom onset in multiple sclerosis (MS).

Objective: To investigate the prevalence of brain magnetic resonance imaging (MRI) and subclinical abnormalities among asymptomatic individuals at risk for MS.

Design, Setting, And Participants: The Genes and Environment in Multiple Sclerosis (GEMS) project is a prospective cohort study of first-degree relatives of people with MS.

Optogenetic Restoration of Disrupted Slow Oscillations Halts Amyloid Deposition and Restores Calcium Homeostasis in an Animal Model of Alzheimer's Disease.

Slow oscillations are important for consolidation of memory during sleep, and Alzheimer's disease (AD) patients experience memory disturbances. Thus, we examined slow oscillation activity in an animal model of AD. APP mice exhibit aberrant slow oscillation activity.

Immunotherapy with Aducanumab Restores Calcium Homeostasis in Tg2576 Mice.

Unlabelled: Calcium homeostasis plays a major role in maintaining neuronal function under physiological conditions. Amyloid-β (Aβ) initiates pathological processes that include disruption in intracellular calcium levels, so amelioration of the calcium alteration could serve as an indirect functional indicator of treatment efficacy. Therefore, calcium dynamics were used as a measure of functional outcome.

Formation, release, and internalization of stable tau oligomers in cells.

Tau is a neuronal microtubule-binding protein that, in Alzheimer's disease and other neurodegenerative diseases, can form oligomeric and large fibrillar aggregates, which deposit in neurofibrillary tangles. Tau's physiological state of multimerization appears to vary across conditions, and a stable dimeric form of soluble tau has been suggested from experiments using recombinant tau in vitro. We tested if tau dimerization or oligomerization, also occurs in cells, and if soluble tau oligomers are relevant for the release and internalization of tau.

Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases.

Context: There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems.

Objective: Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and "others").

Methods: We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases).

How Health Professionals Conceptualize and Represent Placebo Treatment in Clinical Trials and How Their Patients Understand It: Impact on Validity of Informed Consent.

Context: Previous studies suggested that many patients, who have given their informed consent to participate in randomized controlled trials (RCT), have somewhat limited understanding of what a placebo treatment is. We hypothesized that the relationship between patients and their health professionals plays a central role in this understanding.

Methods: We interviewed 12 patients included in RCTs (nine suffering from Parkinson's disease and three from Huntington's disease) and 18 health professionals involved with RCTs (eight principal investigators, four associated physicians and six clinical research associates).

Graph theory network function in Parkinson's disease assessed with electroencephalography.

Objectives: To determine what differences exist in graph theory network measures derived from electroencephalography (EEG), between Parkinson's disease (PD) patients who are cognitively normal (PD-CN) and matched healthy controls; and between PD-CN and PD dementia (PD-D).

Methods: EEG recordings were analyzed via graph theory network analysis to quantify changes in global efficiency and local integration. This included minimal spanning tree analysis.

Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach.

Background: Therapeutic treatments for schizophrenia do not alleviate symptoms for all patients and efficacy is limited by common, often severe, side-effects. Genetic studies of disease can identify novel drug targets, and drugs for which the mechanism has direct genetic support have increased likelihood of clinical success. Large-scale genetic studies of schizophrenia have increased the number of genes and gene sets associated with risk.

Leveraging Large-scale Behavioral Profiling in Zebrafish to Explore Neuroactive Polypharmacology.

Many psychiatric drugs modulate the nervous system through multitarget mechanisms. However, systematic identification of multitarget compounds has been difficult using traditional in vitro screening assays. New approaches to phenotypic profiling in zebrafish can help researchers identify novel compounds with complex polypharmacology.

Precompetitive Data Sharing as a Catalyst to Address Unmet Needs in Parkinson's Disease.

Parkinson's disease is a complex heterogeneous disorder with urgent need for disease-modifying therapies. Progress in successful therapeutic approaches for PD will require an unprecedented level of collaboration. At a workshop hosted by Parkinson's UK and co-organized by Critical Path Institute's (C-Path) Coalition Against Major Diseases (CAMD) Consortiums, investigators from industry, academia, government and regulatory agencies agreed on the need for sharing of data to enable future success.

Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations.

Progressive neuronal cell loss in a small subset of brainstem and mesencephalic nuclei and widespread aggregation of the α-synuclein protein in the form of Lewy bodies and Lewy neurites are neuropathological hallmarks of Parkinson's disease. Most cases occur sporadically, but mutations in several genes, including SNCA, which encodes α-synuclein, are associated with disease development. The discovery and development of therapeutic strategies to block cell death in Parkinson's disease has been limited by a lack of understanding of the mechanisms driving neurodegeneration.

Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission.

Control of the glutamate time course in the synapse is crucial for excitatory transmission. This process is mainly ensured by astrocytic transporters, high expression of which is essential to compensate for their slow transport cycle. Although molecular mechanisms regulating transporter intracellular trafficking have been identified, the relationship between surface transporter dynamics and synaptic function remains unexplored.

Wireless neurosensor for full-spectrum electrophysiology recordings during free behavior.

Brain recordings in large animal models and humans typically rely on a tethered connection, which has restricted the spectrum of accessible experimental and clinical applications. To overcome this limitation, we have engineered a compact, lightweight, high data rate wireless neurosensor capable of recording the full spectrum of electrophysiological signals from the cortex of mobile subjects. The wireless communication system exploits a spatially distributed network of synchronized receivers that is scalable to hundreds of channels and vast environments.