Biology subjects

Iijima, K.

Publications and source records attributed to Iijima, K..

11 recordsLinked to original sources

bioRxiv2026

Spatial transcriptomics identifies L6 corticothalamic and L6b subplate-like heterotopic neurons in an epileptogenic SLC35A2-associated brain malformation.

Increased white matter (WM) heterotopic neurons are a pathological feature observed in various neurological and psychiatric disorders. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a drug-resistant epilepsy-associated cortical malformation characterized by increased WM heterotopic neurons and OLIG2-positive cells and frequently associated with somatic SLC35A2 mutations. However, the precise cellular identity of these heterotopic neurons remains unclear. Using imaging-based spatial transcriptomics (iST) of SLC35A2-mutated MOGHE tissues, we found that most WM heterotopic neurons exhibited molecular signatures of excitatory neurons. Further analyses revealed that these heterotopic excitatory neurons included prominent populations with layer 6 corticothalamic (CT)-like and layer 6b subplate neuron (SpN)-like molecular features. These findings were further supported by human immunohistochemistry and a Slc35a2 conditional knockout (cKO) mouse model. Together, our results provide a cellular characterization of WM heterotopic neurons in MOGHE and suggest a new perspective on disease pathophysiology centered on deep-layer excitatory neuronal populations.

neuroscience↗

bioRxiv2026

Subsecond whole-brain neural dynamics identified by hidden Markov modeling reflect value-based decision making in humans

Value-based decision making emerges from coordinated neural dynamics across distributed brain networks. Recent studies using noninvasive whole-brain measurements in humans have highlighted the importance of neural activity in the 2-10 Hz frequency band for value-based decision making. Using magnetoencephalography and hidden Markov model (HMM) analysis, we examined whether and how whole-brain neural dynamics in this frequency band, evolving on a timescale of a few hundred milliseconds, reflect value-based decision processes. Thirty-five healthy adults (females and males) made binary choices between risky and sure options. Trial-wise subjective values were estimated using behavioral economic modeling based on prospect theory. We found that HMM-derived trial-by-trial whole-brain neural dynamics (defined by 2-10 Hz amplitude envelopes in distributed brain regions and their interregional coupling) were associated with the subjective values of choice options in a manner distinct from simple perceptual- or motor-evoked activity. Notably, these trial-by-trial whole-brain dynamics covaried with the difference in subjective values between the chosen and unchosen options when the neural data were time-locked to participants responses, but not when time-locked to option onset. These findings revealed a crucial link between subsecond whole-brain neural dynamics and trial-by-trial decision variables, providing insights into how value-based decision processes unfold over time in the human brain.

neuroscience↗

bioRxiv2026

Kinetic design of reversible probe exchange enables continuous single-molecule tracking beyond the photobleaching limit

Single-molecule fluorescence imaging enables direct tracking of molecular dynamics. Prolonged observation, however, is limited by photobleaching, restricting access to rare events and slow transitions. Exchangeable fluorogenic labeling has been developed to overcome this limitation, yet continuous single-molecule tracking has not been achieved. We define two quantitative kinetic conditions for continuous tracking: pre-bleach dissociation and within-frame rebinding. Mapping reported systems onto a kinetic landscape delineates the regime required for continuous tracking. To reach this regime, we turned to odorant-binding proteins, whose biological role favors rapid ligand capture and release. We paired this scaffold with high-contrast fluorogenic probes to maximize rebinding capacity while preserving rapid dissociation. The resulting system, EverGreen, sustains uninterrupted single-molecule observation for over 24 hours and establishes a general kinetic design framework beyond the photobleaching limit.

biophysics↗

bioRxiv2026

Comprehensive transcriptomic and proteomic profiling of mTOR-related epilepsy

Malformations of cortical development (MCDs) are a major cause of drug-resistant epilepsy (DRE) in children. A subset of MCDs, including focal cortical dysplasia type II, tuberous sclerosis complex, and hemimegalencephaly, shares characteristic histopathological features and somatic mutations in genes within the PI3K-AKT-mTOR signaling cascade, and is termed mTORopathies. However, the molecular mechanisms that drive epileptogenesis and consequent uncontrollable seizures in these disorders remain poorly understood. Here, we performed integrated genomic, transcriptomic, and proteomic analyses of 60 surgical brain specimens from 42 patients with MCDs and 18 with mesial temporal lobe epilepsy. Targeted genomic sequencing identified 19 somatic mutations in PI3K-AKT-mTOR pathway genes, including novel variants in AKT3 (L51H) and MTOR (A512T). RNA sequencing comparing mTORopathy brains with controls, along with cross-validation using an independent public dataset, identified 287 consistently differentially expressed genes that were consistently altered. Downregulated genes were enriched in oxidative phosphorylation (OXPHOS) and mitochondrial metabolic pathways, whereas upregulated genes were associated with gliogenesis and cellular senescence. Proteomic profiling identified 44 differentially expressed proteins, including significant reductions in OXPHOS-related proteins (COX5B, NDUFS4, GOT2, RAB27B, and DKK3). Our study provides a patient-matched, multi-omics dataset of human mTOR-related epilepsies from a single-institution cohort. Integrated analyses across transcriptomic and proteomic layers highlight impairment of OXPHOS as a molecular hallmark of mTORopathies, Integrated transcriptomic and proteomic analyses identified impaired OXPHOS as a molecular hallmark, potentially contributing to focal hypometabolism in mTORopathy. These findings offer mechanistic insights into epileptogenesis and provide a valuable resource for understanding molecular pathologies and developing mechanism-based therapies for mTOR-related epilepsy.

neuroscience↗

bioRxiv2026

Single-cell-resolved spatial multi-omics identifies mTOR-driven neuronal and astroglial pathogenicity underlying epileptogenic focal cortical dysplasia

Focal cortical dysplasia type II (FCDII) is a malformation of cortical development caused by somatic mutations in the mTOR signaling pathway. Two hallmark pathological cell types in FCDII, dysmorphic neurons (DNs) and balloon cells (BCs), arise as a result of somatic mutations in the mTOR signaling pathway and are implicated in the pathophysiology of drug-resistant epilepsy. However, how these somatic mutations reshape cell states within the human cortex remains poorly understood. Here, we integrate imaging-based spatial transcriptomics (iST), single-nucleus RNA sequencing, and proteomics of surgically resected FCDIIb tissue to define the transcriptional and proteomic profiles of DNs and BCs. Spatial mapping of iST data resolved transcriptional signatures in histologically validated DNs and BCs within FCDIIb sections. Integrative omics analysis further revealed that DNs show upregulation of PI3K-AKT-mTOR and p53-CROT metabolic programs accompanied by suppression of synaptic signaling, whereas BCs exhibit transcriptional signatures of reactive astrocytes with increased phagocytic and immune-like activity. These data delineate cell-type-specific consequences of somatic mTOR pathway mutations at single-cell resolution and reveal previously unrecognized metabolic and immunoregulatory mechanisms contributing to epileptogenesis in drug-resistant epilepsy. Our study establishes a spatial multi-omics framework for dissecting human cortical malformations and highlights potential therapeutic targets for drug-resistant epilepsy.

neuroscience↗

bioRxiv2025

Visualization of functional and effective connectivity underlying auditory descriptive naming

ObjectiveWe visualized functional and effective connectivity within specific white matter networks in response to auditory descriptive questions. MethodsWe investigated 40 Japanese-speaking patients with focal epilepsy and estimated connectivity measures using cortical high-gamma dynamics and MRI tractography. ResultsHearing a wh-interrogative at question onset enhanced inter-hemispheric functional connectivity, with left-to-right callosal facilitatory flows between the superior-temporal gyri, contrasted by functional connectivity diminution with right-to-left callosal suppressive flows between dorsolateral prefrontal regions. Processing verbs associated with concrete objects or adverbs increased left intra-hemispheric connectivity, with bidirectional facilitatory flows through extensive white matter pathways. Questions beginning with what, compared to where, induced greater neural engagement in the left posterior inferior-frontal gyrus at question offset, linked to enhanced functional connectivity and bidirectional facilitatory flows to the temporal lobe neocortex via the arcuate fasciculus. During overt responses, inter-hemispheric functional connectivity was enhanced, with bidirectional callosal flows between Rolandic areas, and individuals with higher IQ scores exhibited less prolonged neural engagement in the left posterior middle frontal gyrus. ConclusionsVisualization of directional neural interactions within white matter networks during overt naming is feasible. SignificancePhrase order may influence network dynamics in listeners, even when presented with auditory descriptive questions conveying similar meanings.

neuroscience↗

bioRxiv2023

Diverse Configurations of Erroneous Predictive Coding Across Brain Hierarchies in a Non-Human Primate Model of Autism Spectrum Disorder

In autism spectrum disorder (ASD), atypical sensory experiences are often associated with irregularities in predictive coding, which proposes that the brain creates hierarchical sensory models via a bidirectional process of predictions and prediction errors. However, it remains unclear how these irregularities manifest across different functional hierarchies in the brain. To address this, we used high-density electrocorticography (ECoG) in a non-human primate model of ASD during an auditory task with two layers of temporal control, and applied a quantitative model to quantify the integrity of predictive coding across two distinct hierarchies. Our results demonstrate that ASD is characterized by sensory hypersensitivity and unstable predictions across two brain hierarchies, and reveal the associated spatio-spectro-temporal neural signatures. Importantly, we observe diverse configurations of underestimation or overestimation of sensory regularities within these hierarchies. This work provides a multi-layered biomarker for ASD, contributing to our understanding of its diverse symptoms.

neuroscience↗

bioRxiv2021

Interpersonal Comparison of Utility by Measuring Neural Activity

Aggregating well-being across individuals to reach collective decisions is one of the most fundamental problems in our society. Interpersonal comparisons of utility are pivotal and inevitable for well-being aggregation, because if utility is not interpersonally comparable, there is no rational aggregation procedure that simultaneously satisfies even mild conditions for validity (Arrows impossibility theorem); however, there are as yet no scientific methods for interpersonal comparison of utility. In this study, we developed a method based on brain signals. We found that the anterior cingulate and its adjacent ventromedial prefrontal activity is correlated with changes in expected utility. The ratio of lower- and higher-income participants neural signals coincided with estimates of their psychological pleasure by "impartial spectators." We confirmed the validity of our interpersonal utility comparison method using an independent large-scale dataset and used the aggregated well-being from our experimental data to derive an optimal decision rule. These findings suggest that our interpersonal comparison method enables scientifically reasonable well-being aggregation by escaping Arrows impossibility and has implications for the fair distribution of economic goods. Our method can be used for evidence-based policy-making in nations that use cost-benefit analyses or optimal taxation theory for policy evaluation.

neuroscience↗

bioRxiv2020

Massive occurrence of benthic plastic debris at the abyssal seafloor beneath the Kuroshio Extension, the North West Pacific

The deep-sea is considered to be an ultimate sink for marine plastic debris. The abyssal (3500-6500 m) covers the bulk of the deep ocean floor yet little is known about the extent of plastic debris on the abyssal seafloor. We undertook a quantitative assessment of debris presents on the abyssal seafloor (5700-5800 m depth) beneath the Kuroshio Extension current system in the Northwest Pacific, which is one of the major transit points for massive amounts of debris sourced from Asia that are entering the North Pacific Ocean. The dominant type of debris was single-use plastics-mainly bags and food packaging. The density of plastic debris (average 4561 items km-2) in the abyssal zone was the highest recorded for an abyssal plain, suggesting that the deep-sea basin of the Northwest Pacific is a significant reservoir of plastic debris.

ecology↗

bioRxiv2019

Molecular Networks and Key Regulators of the Dysregulated Neuronal System in Alzheimer’s Disease

To study the molecular mechanisms driving the pathogenesis and identify novel therapeutic targets of late onset Alzheimers Disease (LOAD), we performed an integrative network analysis of whole-genome DNA and RNA sequencing profiling of four cortical areas, including the parahippocampal gyrus, across 364 donors spanning the full spectrum of LOAD-related cognitive and neuropathological disease severities. Our analyses revealed thousands of molecular changes and uncovered for the first-time multiple neuron specific gene subnetworks most dysregulated in LOAD. ATP6V1A, a critical subunit of vacuolar-type H+-ATPase (v-ATPase), was predicted to be a key regulator of one neuronal subnetwork and its role in disease-related processes was evaluated through CRISPR-based manipulation of human induced pluripotent stem cell derived neurons and RNAi-based knockdown in transgenic Drosophila models. This study advances our understanding of LOAD pathogenesis by providing the global landscape and detailed circuits of complex molecular interactions and regulations in several key brain regions affected by LOAD and the resulting network models provide a blueprint for developing next generation therapeutics against LOAD.

neuroscience↗

bioRxiv2019

Optical clearing of living brains with MAGICAL to extend in vivo imaging

To understand brain functions, it is important to observe directly how multiple neural circuits are performing in living brains. However, due to tissue opaqueness, observable depth and spatiotemporal resolution are severely degraded in vivo. Here, we propose an optical brain clearing method for in vivo fluorescence microscopy, termed MAGICAL (Magical Additive Glycerol Improves Clear Alive Luminance). MAGICAL enabled two-photon microscopy to capture vivid images with fast speed, at cortical layer V and hippocampal CA1 in vivo. Moreover, MAGICAL promoted conventional confocal microscopy to visualize finer neuronal structures including synaptic boutons and spines in unprecedented deep regions, without intensive illumination leading to phototoxic effects. Fluorescence Emission Spectrum Transmissive Analysis (FESTA) showed that MAGICAL improved in vivo transmittance of shorter wavelength light, which is vulnerable to optical scattering thus unsuited for in vivo microscopy. These results suggest that MAGICAL would transparentize living brains via scattering reduction.

neuroscience↗