The role of sleep quality in mediating the relationship between habenula volume and resilience.

Background: Our human volumetric MRI study (Dai et al., 2024) demonstrated that habenula (Hb) volume is associated with psychological resilience, a key protective factor against depression. However, the biological mechanisms underpinning this relationship remain unclear.

Alpha-synuclein inhibits the secretion of extracellular vesicles through disruptions in YKT6 lipidation.

Parkinson's disease is characterized by the presence of α-synuclein (α-syn) primarily containing Lewy bodies in neurons. Despite decades of extensive research on α-syn accumulation, its molecular mechanisms have remained largely unexplored. Recent studies by us and others have suggested that extracellular vesicles (EVs), especially exosomes, can mediate the release of α-syn from cells, and inhibiting this pathway could result in increased intracellular α-syn levels.

Task relevant autoencoding enhances machine learning for human neuroscience.

In human neuroscience, machine learning can help reveal lower-dimensional neural representations relevant to subjects' behavior. However, state-of-the-art models typically require large datasets to train, and so are prone to overfitting on human neuroimaging data that often possess few samples but many input dimensions. Here, we capitalized on the fact that the features we seek in human neuroscience are precisely those relevant to subjects' behavior rather than noise or other irrelevant factors.

Swimming Into Future Breakthroughs From Kyoto, Japan: Report of the 18th International Zebrafish Conference (IZFC2024).

The 18th International Zebrafish Conference (IZFC2024) took place from August 17 to 21, 2024, at Miyako Messe in Kyoto, Japan. This conference attracted 641 researchers from around the world along with 83 virtual participants, making it the largest gathering since the COVID-19 pandemic. The event featured two keynote lectures, three award lectures, 36 plenary talks, 90 oral presentations, and 374 poster presentations.

In vivo hyperphosphorylation of tau is associated with synaptic loss and behavioral abnormalities in the absence of tau seeds.

Tau pathology is a hallmark of several neurodegenerative diseases, including frontotemporal dementia and Alzheimer's disease. However, the sequence of events and the form of tau that confers toxicity are still unclear, due in large part to the lack of physiological models of tauopathy initiation and progression in which to test hypotheses. We have developed a series of targeted mice expressing frontotemporal-dementia-causing mutations in the humanized MAPT gene to investigate the earliest stages of tauopathy.

A neurocognitive mechanism for increased cooperation during group formation.

How do group size changes influence cooperation within groups? To examine this question, we performed a dynamic, network-based prisoner's dilemma experiment with fMRI. Across 83 human participants, we observed increased cooperation as group size increased. However, our computational modeling analysis of behavior and fMRI revealed that groups size itself did not increase cooperation.

The Utility of Long-Read Sequencing in Diagnosing Early Onset Parkinson's Disease.

Objective: Variants in PRKN and PINK1 are the leading cause of early-onset autosomal recessive Parkinson's disease, yet many cases remain genetically unresolved. We previously identified a 7 megabases complex structural variant in a pair of monozygotic twins using Oxford Nanopore Technologies (ONT) long-read sequencing. This study aims to determine if ONT long-read sequencing can detect a second variant in other unresolved early-onset Parkinson's disease (EOPD) cases with 1 heterozygous PRKN or PINK1 variant.

Association between microenvironment-related genes and prognosis of primary central nervous system lymphoma.

Background: Primary central nervous system lymphoma (PCNSL) is a rare lymphoid malignancy. Systemic profiling of the PCNSL tumor microenvironment (TME) was previously conducted through gene expression analysis. We investigated the prognostic impact of TME on survival to establish novel prognostic biomarkers in PCNSL patients.

Human-Induced Pluripotent Stem Cell-Derived Neural Organoids as a Novel In Vitro Platform for Developmental Neurotoxicity Assessment.

There has been a recent drive to replace in vivo studies with in vitro studies in the field of toxicity testing. Therefore, instead of conventional animal or planar cell culture models, there is an urgent need for in vitro systems whose conditions can be strictly controlled, including cell-cell interactions and sensitivity to low doses of chemicals. Neural organoids generated from human-induced pluripotent stem cells (iPSCs) are a promising in vitro platform for modeling human brain development.

The modulatory role of bone morphogenetic protein signaling in cerebellar synaptic plasticity.

Bone morphogenetic proteins (BMPs), regulators of bone formation, have been implicated in embryogenesis and morphogenesis of various tissues and organs. BMP signaling plays a role in the formation of appropriate synaptic connections and development of normal neural circuits in the brain. However, physiological roles of BMP signaling in postnatal neural functions, including synaptic plasticity, remain largely unknown.

Predicting the effect of micro-stimulation on macaque prefrontal activity based on spontaneous circuit dynamics.

A crucial challenge in targeted manipulation of neural activity is to identify perturbation sites whose stimulation exerts significant effects downstream with high efficacy, a procedure currently achieved by labor-intensive and potentially harmful trial and error. Can one predict the effects of electrical stimulation on neural activity based on the circuit dynamics during spontaneous periods? Here we show that the effects of single-site micro-stimulation on ensemble activity in an alert monkey's prefrontal cortex can be predicted solely based on the ensemble's spontaneous activity. We first inferred the ensemble's causal flow based on the directed functional interactions inferred during spontaneous periods using convergent cross-mapping and showed that it uncovers a causal hierarchy between the recording electrodes.

Light-exercise-induced dopaminergic and noradrenergic stimulation in the dorsal hippocampus: Using a rat physiological exercise model.

Exercise activates the dorsal hippocampus that triggers synaptic and cellar plasticity and ultimately promotes memory formation. For decades, these benefits have been explored using demanding and stress-response-inducing exercise at moderate-to-vigorous intensities. In contrast, our translational research with animals and humans has focused on light-intensity exercise (light exercise) below the lactate threshold (LT), which almost anyone can safely perform with minimal stress.

Cyclin-dependent kinase inhibitor p18 regulates lineage transitions of excitatory neurons, astrocytes, and interneurons in the mouse cortex.

Neural stem cells (NSCs) can give rise to both neurons and glia, but the regulatory mechanisms governing their differentiation transitions remain incompletely understood. Here, we address the role of cyclin-dependent kinase inhibitors (CDKIs) in the later stages of dorsal cortical development. We find that the CDKIs p18 and p27 are upregulated at the onset of astrocyte generation.

Tensor dictionary-based heterogeneous transfer learning to study emotion-related gender differences in brain.

In practice, collecting auxiliary labeled data with same feature space from multiple domains is difficult. Thus, we focus on the heterogeneous transfer learning to address the problem of insufficient sample sizes in neuroimaging. Viewing subjects, time, and features as dimensions, brain activation and dynamic functional connectivity data can be treated as high-order heterogeneous data with heterogeneity arising from distinct feature space.

Decoding continuous motion trajectories of upper limb from EEG signals based on feature selection and nonlinear methods.

Brain-computer interface (BCI) system has emerged as a promising technology that provides direct communication and control between the human brain and external devices. Among the various applications of BCI, limb motion decoding has gained significant attention due to its potential for patients with motor impairment to regain independence and improve their quality of life. However, the reconstruction of continuous motion trajectories in BCI systems based on electroencephalography (EEG) signals remains a challenge in practical life.

Exposed Hsp70-binding site impacts yeast Sup35 prion disaggregation and propagation.

The dynamic balance between formation and disaggregation of amyloid fibrils is associated with many neurodegenerative diseases. Multiple chaperones interact with and disaggregate amyloid fibrils, which impacts amyloid propagation and cellular phenotypes. However, it remains poorly understood whether and how site-specific binding of chaperones to amyloids facilitates the concerted disaggregation process and modulates physiological consequences in vivo.

A multiwell plate approach to increase the sample throughput during tissue clearing.

Tissue clearing, coupled with immunostaining, enables the transition from two-dimensional to three-dimensional pathology and has the potential to substantially improve data quality for biomedical diagnostics. Nevertheless, the workflows are limited by the complex sample processing protocols. Approaches for the parallel processing of samples, to include tissue clearing, immunostaining, imaging and analysis can increase three-dimensional pathology throughput.

Regime switching in coupled nonlinear systems: Sources, prediction, and control-Minireview and perspective on the Focus Issue.

Regime switching, the process where complex systems undergo transitions between qualitatively different dynamical states due to changes in their conditions, is a widespread phenomenon, from climate and ocean circulation, to ecosystems, power grids, and the brain. Capturing the mechanisms that give rise to isolated or sequential switching dynamics, as well as developing generic and robust methods for forecasting, detecting, and controlling them is essential for maintaining optimal performance and preventing dysfunctions or even collapses in complex systems. This Focus Issue provides new insights into regime switching, covering the recent advances in theoretical analysis harnessing the reduction approaches, as well as data-driven detection methods and non-feedback control strategies.

ALS-linked mutant TDP-43 in oligodendrocytes induces oligodendrocyte damage and exacerbates motor dysfunction in mice.

Nuclear clearance and cytoplasmic aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) are pathological hallmarks of amyotrophic lateral sclerosis (ALS) and its pathogenic mechanism is mediated by both loss-of-function and gain-of-toxicity of TDP-43. However, the role of TDP-43 gain-of-toxicity in oligodendrocytes remains unclear. To investigate the impact of excess TDP-43 on oligodendrocytes, we established transgenic mice overexpressing the ALS-linked mutant TDP-43 in oligodendrocytes through crossbreeding with Mbp-Cre mice.