Biology subjects

Mitsuhashi, T.

Publications and source records attributed to Mitsuhashi, T..

5 recordsLinked to original sources

bioRxiv2026

Co-targeting an AMPK--MAPK axis reprograms CAFs and suppresses PDAC

Pancreatic ductal adenocarcinoma (PDAC) is a fatal cancer characterized by limited therapeutic options and a highly treatment-resistant tumor microenvironment. Beyond tumor-intrinsic genetic alterations, growing evidence indicates that host-microbiome interactions influence cancer progression through microbial metabolites. However, how microbiome-derived metabolites influence oncogenic signaling in PDAC remains unclear. Here, integrated profiling revealed a consistent reduction of the microbial metabolite acetic acid in fecal samples from treatment-naive patients with PDAC and in a genetically defined Drosophila model recapitulating key PDAC driver alterations. Acetic acid activates AMP-activated protein kinase, and pharmacological activation of this pathway together with inhibition of mitogen-activated protein kinase signaling suppressed tumor growth in fly and mouse models. Combined pathway targeting restored AMPK activity and suppressed cancer-associated fibroblast activation. These findings identify a microbiome-associated metabolic vulnerability in PDAC and suggest that coordinated targeting of metabolic and oncogenic signaling may restrain tumor progression and improve therapeutic strategies.

cancer biology↗

bioRxiv2024

Speech Synthesis from Electrocorticogram During Imagined Speech Using a Transformer-Based Decoder and Pretrained Vocoder

Synthesizing speech from Electrocorticogram (ECoG) signals recorded during imagined speech remains a challenge due to the absence of synchronized audio signals for training. To address this, we propose a training framework that utilizes audio recorded during overt speech tasks as a surrogate ground truth for imagined speech signals, based on the consistency of the linguistic content. We employed a Transformer-based decoder to generate log-mel spectrograms from imagined speech ECoG, which were then converted into waveform audio using a pre-trained Parallel WaveGAN. In experiments involving ECoG recordings from 13 participants, the synthesized speech achieved dynamic time warping-aligned Pearson correlation coefficients ranging from 0.74 to 0.84 with the proxy targets. These results demonstrate that overt speech audio can serve as an effective training target for reconstructing imagined speech, offering a viable solution for training decoders in the absence of behavioral output.

neuroscience↗

bioRxiv2024

Feasibility of decoding covert speech in ECoG with aTransformer trained on overt speech

Several attempts for speech brain-computer interfacing (BCI) have been made to decode phonemes, sub-words, words, or sentences using invasive measurements, such as the electrocorticogram (ECoG), during auditory speech perception, overt speech, or imagined (covert) speech. Decoding sentences from covert speech is a challenging task. Sixteen epilepsy patients with intracranially implanted electrodes participated in this study, and ECoGs were recorded during overt speech and covert speech of eight Japanese sentences, each consisting of three tokens. In particular, Transformer neural network model was applied to decode text sentences from covert speech, which was trained using ECoGs obtained during overt speech. We first examined the proposed Transformer model using the same task for training and testing, and then evaluated the models performance when trained with overt task for decoding covert speech. The Transformer model trained on covert speech achieved an average token error rate (TER) of 46.6% for decoding covert speech, whereas the model trained on overt speech achieved a TER of 46.3% (p > 0.05; d = 0.07). Therefore, the challenge of collecting training data for covert speech can be addressed using overt speech. The performance of covert speech can improve by employing several overt speeches.

neuroscience↗

bioRxiv2022

Dynamic cortical and tractography atlases of proactive and reactive alpha and high-gamma activities

Alpha waves - posterior-dominant rhythms at 8-12 Hz reactive to eye opening and closure - are among the most fundamental EEG findings in clinical practice and research since Hans Berger first documented them in the early 20th century. Yet, the exact network dynamics of alpha waves in regard to eye movements remains unknown. High-gamma activity at 70-110 Hz is also reactive to eye movements and a summary measure of local cortical activation supporting sensorimotor or cognitive function. We aimed to build the first-ever brain atlases directly visualizing the network dynamics of eye movement-related alpha and high-gamma modulations, at cortical and white matter levels. We studied 28 patients (age: 5-20 years) who underwent intracranial EEG and electrooculography recordings. We measured alpha and high-gamma modulations at 2,170 electrode sites outside the seizure onset zone, interictal spike-generating areas, and MRI-visible structural lesions. Dynamic tractography animated white matter streamlines modulated significantly and simultaneously beyond chance, on a millisecond scale. Before eye closure onset, significant alpha augmentation occurred at the occipital and frontal cortices. After eye closure onset, alpha-based functional connectivity was strengthened, while high gamma-based connectivity was weakened extensively in both intrahemispheric and interhemispheric pathways involving the central visual areas. The inferior fronto-occipital fasciculus supported the strengthened alpha coaugmentation-based functional connectivity between occipital and frontal lobe regions, whereas the posterior corpus callosum supported the interhemispheric functional connectivity between the occipital lobes. After eye opening offset, significant high gamma augmentation and alpha attenuation occurred at occipital, fusiform, and inferior parietal cortices. High gamma coaugmentation-based functional connectivity was strengthened, whereas alpha-based connectivity was weakened in the posterior interhemispheric and intrahemispheric white matter pathways involving central and peripheral visual areas. Proactive and reactive alpha waves involve extensive, distinct white matter networks that include the frontal lobe cortices, along with low- and high-order visual areas. High-gamma co-attenuation coupled to alpha co-augmentation in shared brain circuitry after eye closure supports the notion of an idling role for alpha waves during eye closure. These dynamic tractography atlases may improve understanding of the significance of EEG alpha waves in assessing the functional integrity of brain networks in clinical practice; they also may help elucidate the effects of eye movements on task-related brain network measures observed in cognitive neuroscience research.

neuroscience↗

bioRxiv2020

Four-dimensional tractography animates neural propagations via distinct interhemispheric pathways

ObjectiveTo visualize and validate the dynamics of interhemispheric neural propagations induced by single-pulse electrical stimulation (SPES). MethodsThis methodological study included three patients with drug-resistant focal epilepsy who underwent measurement of cortico-cortical spectral responses (CCSRs) during bilateral stereo-electroencephalography recording. We delivered SPES to 83 electrode pairs and analyzed CCSRs recorded at 268 nonepileptic electrode sites. Diffusion-weighted imaging (DWI) tractography localized the interhemispheric white matter pathways as streamlines directly connecting two electrode sites. We localized and visualized the putative SPES-related fiber activation, at each 1-ms time window, based on the propagation velocity defined as the DWI-based streamline length divided by the early CCSR peak latency. ResultsThe resulting movie, herein referred to as four-dimensional tractography, delineated the spatiotemporal dynamics of fiber activation via the corpus callosum and anterior commissure. Longer streamline length was associated with delayed peak latency and smaller amplitude of CCSRs. The cortical regions adjacent to each fiber activation site indeed exhibited CCSRs at the same time window. ConclusionsOur four-dimensional tractography successfully animated neural propagations via distinct interhemispheric pathways. SignificanceOur novel animation method has the potential to help investigators in addressing the mechanistic significance of the interhemispheric network dynamics supporting physiological function.

neuroscience↗