Biology subjects

Sonoda, M.

Publications and source records attributed to Sonoda, M..

11 recordsLinked to original sources

bioRxiv2025

Whole-Brain Millisecond-Scale Effective Connectivity Atlas of Auditory and Visual Naming

Neurobiological models suggest that speech relies on interactions among distant cortical regions interconnected by white matter pathways. Prior studies have shown that speech-related functional coactivation--simultaneous high-gamma augmentation across distributed regions--reflects underlying neural interactions, as validated by electrical stimulation mapping. However, it remains unclear at the whole-brain level when, for how long, and in which directions cortical regions transmit information, and how dynamic information flows contribute to speech. Here, we investigated the causal roles of directional neural information flow during auditory and visual naming using intracranial EEG from 9,526 artifact-free nonepileptic sites across 127 patients. Information flow, estimated by transfer entropy-based effective connectivity, was classified as excitatory when high-gamma acceleration in one region predicted subsequent acceleration in another, and inhibitory when deceleration predicted downstream deceleration. Following stimulus onset, excitatory flows emerged from modality-specific sensory cortices and propagated to higher-order regions, later becoming bidirectional as functional coactivation developed. Each excitatory flow event was transient (<500 ms), typically followed by inhibitory flows and decreased coactivation, during which excitatory flows often emerged along new pathways. During auditory naming, faster response times were associated with stronger excitatory flows in left perisylvian regions; during visual naming, faster responses were linked to stronger flows in bilateral basal temporal cortices. Stronger excitatory flows at specific time points predicted a higher probability of stimulation-induced symptoms (Spearmans rho: 0.54-0.81; p<0.00001), whereas associations with inhibitory flows peaked later. Excitatory flows near visual naming response onset were particularly associated with stimulation-induced speech arrest and face sensorimotor symptoms, whereas functional coactivation alone failed to reveal comparable associations. These findings demonstrate that transient acceleration of directional neural interactions through white matter supports successive stages of speech processing. As activity within one pathway decelerates, excitatory flow accelerates along another, enabling functional transitions critical for naming. By establishing the causal contribution of temporally precise, anatomically specific white matter pathways, this study substantiates and extends existing neurobiological models of speech. To facilitate replication and dynamic whole-brain visualization, we provide open access to the full dataset (62.15 GB) and analysis code.

neuroscience↗

bioRxiv2025

Normative high-frequency oscillation phase-amplitude coupling and effective connectivity under sevoflurane

Resective surgery for pediatric drug-resistant focal epilepsy often requires extraoperative intracranial electroencephalography recording to accurately localize the epileptogenic zone. This procedure entails multiple neurosurgeries, intracranial electrode implantation and explantation, and days of invasive inpatient evaluation. There is a need for methods to reduce diagnostic burden and introduce objective epilepsy biomarkers. Our preliminary studies aimed to address these issues by using sevoflurane anesthesia to rapidly and reversibly activate intraoperative phase-amplitude coupling between delta and high-frequency activities, as well as high-frequency activity-based effective connectivity. Phase-amplitude coupling can serve as a proxy for spike-and-wave discharges, and effective connectivity describes the spatiotemporal dynamics of neural information flow among regions. Notably, sevoflurane activated these interictal electrocorticography biomarkers most robustly in areas whose resection led to seizure freedom. However, they were also increased in normative brain regions that did not require removal for seizure control. Before using these electrocorticography biomarkers prospectively to guide resection, we should understand their endogenous distribution and propagation pathways, at different anesthetic stages. In the current study, we highlighted the normative distribution of delta and high-frequency activity phase-amplitude coupling and effective connectivity under sevoflurane. Normative data was derived from nineteen patients, whose ages ranged from four to eighteen years and included eleven males. All achieved seizure control following focal resection. Electrocorticography was recorded at an isoflurane baseline, during stepwise increases in sevoflurane concentration, and also during extraoperative slow-wave sleep without anesthesia. Normative electrode sites were then mapped onto a standard cortical surface for anatomical visualization. Dynamic tractography traced white matter pathways that connected sites with significantly augmented biomarkers. Finally, we analyzed all sites --regardless of normal or abnormal status -- to determine whether sevoflurane-enhanced biomarker values could intraoperatively localize the epileptogenic sites. We found that normative electrocorticography biomarkers increased as a function of sevoflurane concentration, especially in bilateral frontal and parietal lobe regions (Bonferroni-corrected p-values <0.05). Callosal fibers directly connected homotopic Rolandic regions exhibiting elevated phase-amplitude coupling. The superior longitudinal fasciculus linked frontal and parietal association cortices showing augmented effective connectivity. Higher biomarker values, particularly at three to four volume percent sevoflurane, characterized epileptogenicity and seizure-onset zone status (Bonferroni-corrected p-values <0.05). Supplementary analysis showed that epileptogenic sites exhibited less augmentation in delta-based effective connectivity. This study helps clarify the normative distribution of, and plausible propagation pathways supporting, sevoflurane enhanced electrocorticographic biomarkers. Future work should confirm that sevoflurane-activated electrocorticography biomarkers can predict postoperative seizure outcomes in larger cohorts, to establish their clinical utility.

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↗

bioRxiv2025

Dynamic Causal Tractography Analysis of Auditory Descriptive Naming:An Intracranial Study of 106 Patients

Humans understand and respond to spoken questions through coordinated activity across distributed cortical networks. However, the causal roles of connectivity engagements alternating across multiple white matter bundles remain understudied at the whole-brain scale. Using intracranial high-gamma activity recorded from 7,792 non-epileptic electrode sites in 106 epilepsy patients who underwent direct cortical stimulation mapping, we constructed an atlas visualizing the millisecond-scale dynamics of functional connectivity during a naming task in response to auditory questions. This atlas, the Dynamic Causal Tractography Atlas, identified functional connectivity patterns at specific time windows most strongly associated with stimulation-induced language- and speech-related manifestations (p-value range: 2.5 x 10-5 to 6.6 x 10-14; rho range: +0.54 to +0.82). The atlas revealed that no single intra-hemispheric fasciculus was consistently engaged in all naming stages; instead, each fasciculus supported specific stages, with multiple distinct major fasciculi simultaneously contributing to each stage. Additionally, this atlas identified the specific linguistic stages and fasciculi where handedness effects became evident. Our findings clarify the dynamics and causal roles of alternating, coordinated neural activity through specific fasciculi during auditory descriptive naming, advancing current neurobiological models of speech network organization. Additionally, we have made our white matter streamline template and intracranial EEG data available as open-source material, enabling investigators to construct personalized dynamic tractography atlases.

neuroscience↗

bioRxiv2022

Reprogramming of lactate metabolism is linked to the oncogenesis of the virus-induced leukemia

Acceleration of glycolysis is a common trait of cancer. A key metabolite, lactate, is properly secreted from cancer cells, since its accumulation is toxic. Here, we report that a viral oncogene, HTLV-1 bZIP factor (HBZ), bimodally upregulates TAp73 to promote lactate excretion from adult T-cell leukemia-lymphoma (ATL) cells. HBZ protein binds to EZH2 and reduces its occupancy of the TAp73 promoter. Meanwhile, HBZ RNA activates TAp73 transcription via the BATF3-IRF4 machinery. TAp73 upregulates the lactate transporters MCT1 and MCT4. Inactivation of TAp73 leads to intracellular accumulation of lactate, inducing cell death in ATL cells. Furthermore, TAp73 knockout diminished development of inflammation in HBZ-transgenic mice. An MCT1/4 inhibitor, syrosingopine, decreased the growth of ATL cells in vitro and in vivo. MCT1/4 expression was positively correlated with TAp73 in many cancers, and their upregulations were associated with dismal prognosis. Activation of the TAp73-MCT1/4 pathway could be a common mechanism contributing to oncogenesis.

cancer biology↗

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↗

bioRxiv2021

Spontaneous modulations of high frequency cortical activity

ObjectiveWe clarified the clinical and mechanistic significance of physiological modulations of high-frequency broadband cortical activity associated with spontaneous saccadic eye movements during a resting state. MethodsWe studied 30 patients who underwent epilepsy surgery following extraoperative electrocorticography and electrooculography recordings. We determined whether high-gamma activity at 70-110 Hz preceding saccade onset would predict upcoming ocular behaviors. We assessed how accurately the model incorporating saccade-related high-gamma modulations would localize the primary visual cortex defined by electrical stimulation. ResultsThe whole-brain level dynamic atlas demonstrated transient high-gamma suppression in the striatal region before saccade onset and high-gamma augmentation subsequently involving the widespread posterior brain regions. More intense striatal high-gamma suppression predicted the upcoming saccade directed to the ipsilateral side and lasting longer in duration. The bagged-tree-ensemble model demonstrated that intense saccade-related high-gamma modulations localized the visual cortex with an accuracy of 95%. ConclusionsWe successfully animated the neural dynamics supporting saccadic suppression, a principal mechanism minimizing the perception of blurred vision during rapid eye movements. The primary visual cortex per se may prepare actively in advance for massive image motion expected during upcoming prolonged saccades. SignificanceMeasuring saccade-related electrocorticographic signals may help localize the visual cortex and avoid misperceiving physiological high-frequency activity as epileptogenic. Highlights- The whole-brain level dynamic atlas animated spontaneous high gamma modulations associated with saccadic eye movements. - Preceding high gamma activity in the striatal cortex predicted the direction and duration of the upcoming saccades. - Saccade-related high-gamma modulations localized the stimulation-defined visual cortex with an accuracy of 95%.

neuroscience↗

bioRxiv2021

Naming-related spectral responses predict neuropsychological outcome after epilepsy surgery

This prospective study determined the utility of intracranially-recorded spectral responses during naming tasks in predicting neuropsychological performance following epilepsy surgery. We recruited 65 patients with drug-resistant focal epilepsy who underwent preoperative neuropsychological assessment and intracranial EEG (iEEG) recording. The Clinical Evaluation of Language Fundamentals (CELF) evaluated the baseline and postoperative language function. During extraoperative iEEG recording, we assigned patients to undergo auditory and picture naming tasks. Time-frequency analysis determined the spatiotemporal characteristics of naming-related amplitude modulations, including high gamma augmentation (HGA) at 70-110 Hz. We surgically removed the presumed epileptogenic zone based on the extent of iEEG and MRI abnormalities while maximally preserving the eloquent areas defined by electrical stimulation mapping (ESM). The multivariate regression model incorporating auditory naming-related HGA predicted the postoperative changes in Core Language Score (CLS) on CELF with r2 of 0.37 (p = 0.015) and in Expressive Language Index (ELI) with r2 of 0.32 (p = 0.047). Independently of the effects of epilepsy and neuroimaging profiles, higher HGA at the resected language-dominant hemispheric area predicted a more severe postoperative decline in CLS (p = 0.004) and ELI (p = 0.012). Conversely, the model incorporating picture naming-related HGA predicted the change in Receptive Language Index (RLI) with r2 of 0.50 (p < 0.001). Higher HGA independently predicted a more severe postoperative decline in RLI (p = 0.03). Ancillary regression analysis indicated that naming-related low gamma augmentation as well as alpha/beta attenuation likewise independently predicted a more severe CLS decline. The machine learning-based prediction model, referred to as the boosted tree ensemble model, suggested that naming-related HGA, among all spectral responses utilized as predictors, most strongly contributed to the improved prediction of patients showing a >5-point CLS decline (reflecting the lower 25 percentile among patients). We generated the model-based atlas visualizing sites, which, if resected, would lead to such a CLS decline. The auditory naming-based model predicted patients who developed the CLS decline with an accuracy of 0.80. The model indicated that virtual resection of an ESM-defined language site would have increased the relative risk of the CLS decline by 5.28 (95%CI: 3.47 to 8.02). Especially, that of an ESM-defined receptive language site would have maximized it to 15.90 (95%CI: 9.59-26.33). In summary, naming-related spectral responses predict objectively-measured neuropsychological outcome after epilepsy surgery. We have provided our prediction model as an open-source material, which will indicate the postoperative language function of future patients and facilitate external validation at tertiary epilepsy centers.

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↗

bioRxiv2020

Scalp EEG interictal high frequency oscillations as an objective EEG biomarker of infantile spasms

ObjectiveTo investigate the diagnostic utility of high frequency oscillations (HFOs) via scalp electroencephalogram (EEG) in infantile spasms. MethodsWe retrospectively analyzed interictal slow-wave sleep EEGs sampled at 2,000 Hz recorded from 30 consecutive patients who were suspected of having infantile spasms. We measured the rate of HFOs (80-500 Hz) and the strength of the cross-frequency coupling between HFOs and slow-wave activity (SWA) at 3-4 Hz and 0.5-1 Hz as quantified with modulation indices (MIs). ResultsTwenty-three patients (77%) exhibited active spasms during the overnight EEG recording. Although the HFOs were detected in all children, increased HFO rate and MIs correlated with the presence of active spasms (p < 0.001 by HFO rate; p < 0.01 by MIs at 3-4 Hz; p = 0.02 by MIs at 0.5-1 Hz). The presence of active spasms was predicted by the logistic regression models incorporating HFO-related metrics (AUC: 0.80-0.98) better than that incorporating hypsarrhythmia (AUC: 0.61). The predictive performance of the best model remained favorable (87.5% accuracy) after a cross-validation procedure. ConclusionsIncreased rate of HFOs and coupling between HFOs and SWA are associated with active epileptic spasms. SignificanceScalp-recorded HFOs may serve as an objective EEG biomarker for active epileptic spasms. HighlightsO_LIObjective analyses of scalp high frequency oscillations and its coupling with slow-wave activity in infantile spasms were feasible. C_LIO_LIIncreased rate of high frequency oscillations and its coupling with slow-wave activity correlated with active epileptic spasms. C_LIO_LIThe scalp high frequency oscillations were also detected in neurologically normal children (although at the low rate). C_LI

neuroscience↗

bioRxiv2019

Two Y chromosome-encoded genes determine sex in kiwifruit

Dioecy, the presence of male and female individuals, has evolved independently in multiple flowering plant lineages. Although theoretical models for the evolution of dioecy, such as the \"two-mutation\" model, are well established, little is known about the specific genes determining sex and their evolutionary history. Kiwifruit, a major tree crop consumed worldwide, is a dioecious species. In kiwifruit, we had previously identified a Y-encoded sex-determinant candidate gene acting as the suppressor of feminization (SuF), named Shy Girl (SyGI). Here, we identified a second Y-encoded sex-determinant that we named Friendly boy (FrBy), which exhibits strong expression in tapetal cells. Gene-editing and complementation analyses in Arabidopsis thaliana and Nicotiana tabacum indicated that FrBy acts for the maintenance of male (M) functions, independently of SyGI, and that these functions are conserved across angiosperm species. We further characterized the genomic architecture of the small (< 1 Mb) male specific region of the Y-chromosome (MSY), which harbors only two genes significantly expressed in developing gynoecia and androecia, respectively: SyGI and FrBy. Resequencing of the genome of a natural hermaphrodite kiwifruit revealed that this individual is genetically male but carries deletion(s) of parts of the Y-chromosome, including SyGI. Additionally, expression of FrBy in female kiwifruit resulted in hermaphrodite plants. These results clearly indicate that Y-encoded SyGI and FrBy act independently as the SuF and M factors in kiwifruit, respectively, and provide insight into the evolutionary path leading to a two-factor sex determination system but also a new breeding approach for dioecious species.

plant biology↗