Biology subjects

Rothermel, R.

Publications and source records attributed to Rothermel, R..

5 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

Dynamic Causal White Matter Atlas of Auditory and Visual Speech Networks at Millisecond Resolution: Intracranial Evidence from 125 Patients

Background and ObjectivesSince the era of Penfield, invasive neurophysiology has laid a lasting foundation for functional neuroscience by elucidating brain regions necessary for speech. However, whole-brain investigations have yet to distinguish the millisecond-scale dynamics and specific white matter pathways that support rapid naming in the auditory and visual domains. MethodsIn this observational study, we constructed a whole-brain Dynamic Causal Tractography atlas using intracranial neurophysiological data from 125 neurosurgical patients. The resulting video atlas captured local cortical high-gamma activity and cortico-cortical coactivation via white matter tracts during rapid and delayed auditory and picture naming. Direct electrical stimulation was employed to assess the causal significance of the observed neural dynamics. ResultsThe atlas revealed white matter coactivation intensity patterns at specific 5-millisecond time windows that best aligned with sensorimotor and language symptoms elicited by electrical stimulation (Spearmans {rho} = 0.58-0.91; p = 4.8 x 10cc to 1.6 x 10c{superscript 2}c). Rapid auditory naming was associated with deactivation of the right rostral middle frontal gyrus and increased coactivation along the left arcuate fasciculus, linked to stimulation-induced receptive and expressive aphasia. In contrast, delayed auditory naming correlated with a late surge in bifrontal coactivation. Rapid picture naming involved early coactivation between cortices connected via the bilateral inferior longitudinal fasciculi--associated with stimulation-induced visual distortions--coinciding with transient co-inactivation of Brocas area. DiscussionThese findings delineate dissociable white matter-mediated mechanisms supporting rapid naming in the auditory and visual domains. Reduced inhibitory monitoring by the right dorsolateral prefrontal cortex may facilitate efficient lexical retrieval via left perisylvian pathways during auditory naming. In contrast, excessive bifrontal interaction may underlie delayed auditory naming. Rapid visual object recognition appears to rely on early occipitotemporal coactivation with minimal involvement of Brocas area. The resulting atlas--accompanied by a publicly available dataset (61.2 GB) and analysis code--serves as a valuable resource for students and trainees studying the network dynamics underlying speech, as well as for presurgical language mapping in patients undergoing cortical or subcortical intervention.

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↗

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↗