Biology subjects

Yamada, E.

Publications and source records attributed to Yamada, E..

7 recordsLinked to original sources

bioRxiv2026

Simulation-informed low-current anodal tDCS accelerates early motor recovery after photochemically induced cortical stroke in rats

Animal transcranial direct current stimulation (tDCS) studies typically use intensities exceeding clinical levels, and the off-line behavioral effects of weak electric fields in rodents remain unclear. We examined whether repeated anodal tDCS, calibrated by electric-field simulation to approximate human-equivalent weak fields, facilitates motor recovery after focal photothrombotic ischemic stroke (PIT) in rats. Simulation estimated that 50 A produced a maximum field of [~]1.96 V/m in the targeted motor cortex, matching clinically relevant intensities. Under isoflurane anesthesia, rats received anodal tDCS at 50 A, 250 A, or 1 mA (5 min/day, 5 days/week, 2 weeks), or sham; motor recovery was assessed weekly by beam-walking for 4 weeks. A linear mixed-effects model revealed significant time, group, and time x group effects. The 50 A group outperformed the PIT group at 1 week, and the 1 mA group at 2 weeks, with no differences thereafter. Low-current tDCS accelerates early post-stroke motor recovery, supporting weak-field neuromodulation.

neuroscience↗

bioRxiv2026

Evaluation of Neuronal Activation Thresholds for Low-Frequency Electromagnetic Exposure Using Morphologically Realistic Neuron Models

International guidelines for low-frequency electromagnetic field exposure (LF EMF) are primarily intended to prevent substantiated adverse effects. In the frameworks, limits on internal electric fields are linked to external exposure levels through computational dosimetry. However, the relationship between internal electric fields and these adverse effects remains incompletely understood. In particular, current approaches often overlook the morphological complexity and diversity of cortical neurons, which may limit the realism of neuronal activation estimates used to support these assessments. This study evaluates LF EMF-induced neural activation using 25 morphologically realistic neuron models spanning all cortical layers, embedded within 11 detailed human head models. The internal electric fields were simulated for uniform magnetic field exposures (100 Hz-100 kHz) along the three anatomical directions, and excitation thresholds were computed using a multi-scale framework combining voxel-based dosimetry with biophysical neuron simulations. A real-world exposure scenario involving a child near an acousto-magnetic article-surveillance deactivator was also analyzed. Thresholds varied across cell type, morphology, cortical location, subject anatomy, frequency, and exposure direction, with L2/3 pyramidal, L4 basket, and L5 thick-tufted pyramidal cells showing the lowest thresholds. Despite this variability, all simulated thresholds were conservative with respect to the basic restrictions and dosimetric reference limits set by IEEE ICES and ICNIRP. The smallest margin occurred at 100 kHz, where the threshold remained a factor of 2.8 above the corresponding limit. These findings indicate that current LF EMF exposure limits remain conservative when evaluated using highly detailed, morphology-based CNS activation models.

neuroscience↗

bioRxiv2026

MEG correlates of empty subjects in Japanese control and raising constructions

Empty categories are unpronounced elements with syntactic properties that play a central role in theories of sentence structure. Although there are several types within these categories, the neural basis for distinguishing among them remains unclear. Using magnetoencephalography, we investigate whether the brain distinguishes between two Japanese sentence structures: Control and raising. Although these constructions appear similar on the surface, they are argued to involve different types of empty categories. In theoretical analyses, the control-type empty category, which is called PRO, is often treated as an anaphoric element, similar to reflexives such as himself and herself, whereas the raising-type empty category is a noun phrase trace. Twenty-six native Japanese speakers participated in a reading task under three experimental conditions: Control, raising, and baseline. Source estimates were computed, and condition differences were tested using spatiotemporal cluster-based permutation t-tests. We observed late left-hemispheric differences at approximately 700-800 ms after the critical verb. The control condition elicited larger responses than the raising condition, with activity centered in the temporal cortex spanning the middle temporal gyrus and the superior temporal sulcus and gyrus and extending into the anterior insula and the supramarginal gyrus. In addition, the control condition elicited larger late responses than the baseline condition in a broader left fronto-temporal distribution, including the inferior frontal cortex, anterior temporal cortex, and insula. These results provide source-level evidence that brain activity in the left language network differs between the control and raising conditions in Japanese during online sentence comprehension. Furthermore, they suggest that we can distinguish empty category types in the brain.

neuroscience↗

bioRxiv2026

Non-Canonical ERP Patterns in Second-language Sentence Processing: Evidence from Syntactic, Semantic, and Phonological Violations in Japanese Learners of English

Background/ObjectivesDespite notable advances in the neural mechanisms of second-language (L2) processing, few studies have systematically compared syntactic, semantic, and phonological processing of L2 within a single experimental design. We investigate the neurocognitive mechanisms underlying L2 sentence processing in native Japanese speakers with intermediate English proficiency. By integrating behavioral measures and event-related potentials (ERPs), we examined how syntactic, semantic, and phonological information influenced sentence comprehension. MethodsTwenty-seven participants completed an auditory sentence judgment task involving English sentences with a syntactic, semantic, or phonological error. ResultsBehavioral results revealed the highest accuracy in the control and semantic conditions, while syntactic and phonological violations led to significantly lower performance, indicating greater processing difficulty in these domains. Among the three linguistic violation types, phonological violations elicited the robust ERP negativities across both time 300-500 ms and 500-800 ms time windows, while syntactic and semantic violations evoked less consistent neural responses in this L2 auditory sentence judgment task. These results suggest that mismatches in expected phonological forms hinder lexical activation, triggering a negativity that resembles an N400 but reflects different underlying processes. ConclusionWe found non-canonical neural response patterns in L2 learners, characterized by sensitivity to phonological anomalies but minimal neural disruption for semantic or syntactic anomalies. The current study contributes to our understanding of L2 sentence processing in native Japanese speakers, particularly by aligning real-time neural responses with behavioral performance. This work offers implications for pedagogical practices and assessment strategies tailored to neurodiverse bilingual populations.

neuroscience↗

bioRxiv2025

Two Sites, Two Languages: Dual-site tDCS and EEG Evidence for L1 Feature Transfer in L2

The neural bases of syntactic and semantic processing remain unclear. While prior transcranial direct current stimulation (tDCS) studies have targeted either the inferior frontal gyrus (LIFG) or left superior temporal gyrus (LSTG), we test whether dual stimulation of both alters second language (L2) anomaly based on native language (L1). Chinese and Korean participants evaluated Japanese sentence correctness; Japanese shares morpho-syntax with Korean and semantic radicals with Chinese. For the N400, dual anodal tDCS elicited a significant interaction stimulation and L1 (F (1,960.7) = 5.48, p = 0.0194), stimulation and sentence type (F (5,960.7) = 2.28, p = .0448), and L1 and sentence type (F (5, 960) = 2.28, p = 0.045). For the P600, a significant effect of stimulation and L1 interaction (F (1,1303.1) = 9.86, p = 0.0017), and stimulation x sentence type (F (5,1303.1) = 2.35, p = 0.039), suggesting L1 typology affected semantic integration during dual-stimulation tDCS.

neuroscience↗

bioRxiv2022

SARS-CoV-2-specific T cells associate with reduced lung function and inflammation in pulmonary post-acute sequalae of SARS-CoV-2

As of January 2022, at least 60 million individuals are estimated to develop post-acute sequelae of SARS-CoV-2 (PASC) after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While elevated levels of SARS-CoV-2-specific T cells have been observed in non-specific PASC, little is known about their impact on pulmonary function which is compromised in the majority of these individuals. This study compares frequencies of SARS-CoV-2-specific T cells and inflammatory markers with lung function in participants with pulmonary PASC and resolved COVID-19 (RC). Compared to RC, participants with respiratory PASC had up to 34-fold higher frequencies of IFN-{gamma}- and TNF--producing SARS-CoV-2-specific CD4+ and CD8+ T cells in peripheral blood and elevated levels of plasma CRP and IL-6. Importantly, in PASC participants the frequency of TNF--producing SARS-CoV-2-specific CD4+ and CD8+ T cells, which exhibited the highest levels of Ki67 indicating they were activity dividing, correlated positively with plasma IL-6 and negatively with measures of lung function, including forced expiratory volume in one second (FEV1), while increased frequencies of IFN-{gamma}-producing SARS-CoV-2-specific T cells associated with prolonged dyspnea. Statistical analyses stratified by age, number of comorbidities and hospitalization status demonstrated that none of these factors affect differences in the frequency of SARS-CoV-2 T cells and plasma IL-6 levels measured between PASC and RC cohorts. Taken together, these findings demonstrate elevated frequencies of SARS-CoV-2-specific T cells in individuals with pulmonary PASC are associated with increased systemic inflammation and decreased lung function, suggesting that SARS-CoV-2-specific T cells contribute to lingering pulmonary symptoms. These findings also provide mechanistic insight on the pathophysiology of PASC that can inform development of potential treatments to reduce symptom burden. Author SummaryLong COVID-19 or post-acute sequelae of SARS-CoV-2 (PASC) impacts 20-30% of those infected with SARS-CoV-2 and is characterized by COVID-19 symptoms exceeding 4 weeks from symptom onset. While those with PASC experience a wide variety of persistent symptoms including shortness of breath, cough, chest pain, irregular heartbeat, brain fog, fatigue, and intermittent fever, lung-related conditions are the most common. Although, infection with SARS-CoV-2 is clearly the inciting factor for PASC, the mechanisms responsible for long-term lung dysfunction are unclear and current treatments are ineffective at resolving pulmonary symptoms. Generalized PASC has been associated with SARS-CoV-2-specific T cells, a component of adaptive immunity, suggesting that residual virus may persist. Here, we investigated the frequency and function of virus-specific T cells in the blood of individuals with pulmonary PASC and correlated their presence with systemic inflammation and lung function. Our findings demonstrated that T cells specific for SARS-CoV-2 are elevated in the blood of those with pulmonary PASC and are associated with increased IL-6, a cytokine strongly associated with COVID-19 severity, and decreased lung function. These findings provide mechanistic insight into the pathophysiology of pulmonary PASC needed for the development of new treatments to improve quality of life for those affected.

immunology↗

bioRxiv2017

Differential activation of Fyn kinase distinguishes saturated and unsaturated fats in mouse macrophages

Diet-induced obesity is associated with increased adipose tissue activated macrophage numbers. Yet, how macrophages integrate fatty acid (FA) signals remains unclear. We previously demonstrated that Fyn deficiency (FynKO) protects against high fat diet-induced adipose tissue macrophage accumulation. Herein, we show that inflammatory markers and reactive oxygen species are not induced in FynKO bone marrow-derived macrophages exposed to the saturated FA palmitate, suggesting that Fyn regulates macrophage function in response to FA signals. Saturated palmitate activates Fyn and re-localizes Fyn into the nucleus of RAW264.7, J774 and wild-type bone marrow-derived macrophages. Similarly, Fyn activity is increased in cells of AT stromal vascular fraction of high fat-fed control mice, with Fyn protein being located in the nucleus of these cells. We demonstrate that Fyn modulates palmitate-dependent oxidative stress in macrophages. Moreover, Fyn catalytic activity is necessary for its nuclear re-localization and downstream effects, as Fyn pharmacological inhibition abolishes palmitate-induced Fyn nuclear redistribution and palmitate-dependent increase of oxidative stress markers. Importantly, mono-or polyunsaturated FAs do not activate Fyn, and fail to re-localize Fyn to the nucleus. Together these data demonstrate that macrophages integrate nutritional FA signals via a differential activation of Fyn that distinguishes, at least partly, the effects of saturated versus unsaturated fats.

cell biology↗