Biology subjects

Soh, C.

Publications and source records attributed to Soh, C..

6 recordsLinked to original sources

bioRxiv2026

A domain-general basal ganglia mechanism for inhibitory control during language comprehension

Whether controlled language processing involves domain-general or language-specific neural circuits is subject of controversial debate. We tested whether the inhibitory control of linguistic activity shares a common neural process with motor inhibition in twenty humans undergoing intra- and extracranial neural field potential recordings and deep-brain stimulation. Engaging motor and linguistic inhibition simultaneously resulted in a significant behavioral cost, suggesting a shared underlying neural process. Indeed, neural decoders trained during motor inhibition were able to decode linguistic inhibition and vice versa. Depth-electrode recordings from the subthalamic nucleus (STN), a key basal ganglia area for inhibitory control, showed increased {beta}-band (13-30 Hz) activity during both linguistic and motor inhibition. Finally, disrupting the STN via deep-brain stimulation impaired behavioral and neural signatures of both linguistic and motor inhibition. Together, these findings show that the inhibitory control of language and movement share a domain-general mechanism implemented via the subthalamic nucleus of the basal ganglia.

neuroscience↗

bioRxiv2026

Cortico-basal ganglia dynamics of global and selective response inhibition in humans

Response inhibition is an important cognitive control mechanism, which enables flexible behavior by stopping inappropriate actions. Intracranial recordings across species have identified a neural circuit that implements response inhibition via the subthalamic nucleus of the basal ganglia. However, this work has been limited to simple tasks, in which unequivocal, salient "stop"-signals require the inhibition of all ongoing responses. Notably, response inhibition in the real world is substantially different. Real-world response inhibition is selective: it occurs only after specific salient signals ( stimulus-selectivity) and stops only specific movements, while others continue ( response-selectivity). If and how the fronto-subthalamic system implements selective inhibition is largely unknown. Here, we recorded subthalamic local field potentials and scalp-EEG in humans performing a novel, selective inhibition task. Salient signals either required stopping all initiated responses (global inhibition), stopping only some responses (response-selective inhibition), or continuing all responses - i.e., ignoring the signal (which ensures stimulus-selectivity). All three signals initially triggered a common fronto-subthalamic inhibitory process, signified by a rapid increase in {beta}-burst activity. During global inhibition, subthalamic {beta}-bursting subsequently increased above baseline, persisting for over a second. During response-selective inhibition, this activity was delayed, which enabled a second bout of disinhibition and allowed appropriate responses to continue. Throughout this period, frontal cortical and subthalamic {beta}-band activity was tightly coupled. This shows that selective inhibition is implemented through rapid, context-dependent engagement and release of fronto-subthalamic inhibition. Moreover, subthalamic activity lasted substantially longer than assumed by classic behavioral-computational models. This supports recent theoretical models that assume protracted response inhibition during action-stopping.

neuroscience↗

bioRxiv2025

A First-in-Class Therapy Targeting Transcription-Replication Conflicts Drives Synthetic Lethality in Homologous Recombination Deficient Cancers

Hidden beneath the layer of tumor malignancy lies unchecked proliferation driven by hyperactive transcription, which fosters the formation of RNA:DNA hybrids. These structural intermediates precipitate collisions between the transcription and replication machineries. Central to mitigating this genomic threat is interleukin enhancer-binding factor 2 (ILF2), which orchestrates the recruitment of RNA:DNA helicases to resolve R-loops and, in doing so, reveals cancer cells dependency on stress-mitigating mechanisms to avert genome catastrophe. Our discovery of Molephantin and its lead derivative, NYH0002 is the outcome of delineating ILF2s function. NYH002 exerts direct binding to the ILF2 complex and disrupts RNA:DNA helicase activity to elicit genome-wide DNA breakages. Tumors with elevated cyclin E and E2F1 expression are sensitive to NYH002, while those deficient in homologous recombination repair exhibit lethality. Collectively, these findings position ILF2 as a key regulator of R-loop homeostasis and reveal a therapeutic vulnerability that NYH002 exploits to suppress tumor malignancy.

cancer biology↗

bioRxiv2021

Towards a two-stage model of action-stopping: Attentional capture explains motor inhibition during early stop-signal processing

The ability to stop an already initiated action is paramount to adaptive behavior. Most scientific debate in the field of human action-stopping currently focuses on two interrelated questions. First: Which mental and neural processes underpin the implementation of inhibitory control, and which reflect the attentional detection of salient stop-signals instead? Second: Why do physiological signatures of inhibition occur at two different latencies after stop-signals (for visual signals, either before or after [~]150ms)? Here, we address both questions via two pre-registered experiments that combined transcranial magnetic stimulation, electromyography, and multi-variate pattern analysis of whole-scalp electroencephalography. Using a stop-signal task that also contained a second type of salient signal that did not require stopping, we found that both signals induced equal amounts of early-latency inhibitory activity, whereas only later signatures (after 175ms) distinguished the two. These findings resolve ongoing debates in the literature and strongly suggest a two-step model of action-stopping.

neuroscience↗

bioRxiv2020

Latency and amplitude of the stop-signal P3 event-related potential are related to inhibitory GABAa activity in primary motor cortex

By stopping actions even after their initiation, humans can adapt their ongoing behavior rapidly to changing environmental circumstances. The neural processes underlying the implementation of rapid action-stopping are still controversially discussed. In the early 1990s, a fronto-central P3 event-related potential (ERP) was identified in the human EEG response following stop-signals in the classic stop-signal task, accompanied by the proposal that this ERP reflects the "inhibitory" side of the purported horse-race underlying successful action-stopping. Later studies have lent support to this interpretation by finding that the amplitude and onset of the stop-signal P3 relate to both overt behavior and to movement-related EEG activity in ways predicted by the race model. However, such studies are limited by the ability of EEG to allow direct inferences about the presence (or absence) of true, physiologically inhibitory signaling at the neuronal level. To address this, we here present a cross-modal individual differences investigation of the relationship between the features stop-signal P3 ERP and GABAergic neurotransmission in primary motor cortex (M1, as measured by paired-pulse transcranial magnetic stimulation). Following recent work, we measured short-interval intracortical inhibition (SICI), a marker of inhibitory GABAa activity in M1, in a group of 41 human participants who also performed the stop-signal task while undergoing EEG recordings. In line with the P3-inhibition hypothesis, we found that subjects with stronger inhibitory GABA activity in M1 also showed both faster onsets and larger amplitudes of the stop-signal P3. This provides direct evidence linking the properties of this ERP to a true physiological index of motor system inhibition. We discuss these findings in the context of recent theoretical developments and empirical findings regarding the neural implementation of inhibitory control during action-stopping.

neuroscience↗

bioRxiv2020

Unexpected sounds non-selectively inhibit active visual stimulus representations

The brains capacity to process unexpected events is key to cognitive flexibility. The most well-known effect of unexpected events is the interruption of attentional engagement (distraction). We tested whether unexpected events interrupt attentional representations by activating a neural mechanism for inhibitory control. This mechanism is most well-characterized within the motor system. However, recent work showed that it is automatically activated by unexpected events and can explain some of their non-motor effects (e.g., on working memory representations). Here, human participants attended to lateralized flickering visual stimuli, producing steady-state visual evoked potentials (SSVEP) in the scalp-electroencephalogram. After unexpected sounds, the SSVEP was rapidly suppressed. Using a functional localizer (stop-signal) task and independent component analysis, we then identified a fronto-central EEG source whose activity indexes inhibitory motor control. Unexpected sounds in the SSVEP task also activated this source. Using single-trial analyses, we found that sub-components of this source differentially relate to sound-related SSVEP changes: while its N2 component predicted the subsequent suppression of the attended-stimulus SSVEP, the P3 component predicted the suppression of the SSVEP to the unattended stimulus. These results shed new light on the processes underlying fronto-central control signals and have implications for phenomena such as distraction and the attentional blink.

neuroscience↗