Distinct impacts of sodium channel blockers on the strength–duration properties of human motor cortex neurons
Bibliographic record
Abstract
OBJECTIVE: This study was undertaken to determine how voltage-gated sodium channel (VGSC) blockers modulate cortical excitability in vivo. VGSCs are critical for regulating axonal excitability, yet the effects of sodium channel-blocking medications on human cortical neurons remain poorly characterized. We aimed to address this gap using transcranial magnetic stimulation (TMS)-derived strength-duration measures as a noninvasive index of VGSC function. METHODS: Thirteen healthy adults received single doses of either carbamazepine, lacosamide, or placebo in a crossover design. TMS was used to assess changes in resting motor threshold and strength-duration properties, including rheobase and the strength-duration time constant, as indices of VGSC function. RESULTS: Both medications elevated resting motor thresholds compared to placebo, indicating reduced excitability; however, their impacts varied according to TMS pulse width. Carbamazepine raised thresholds proportionally across all pulse widths, whereas lacosamide disproportionately influenced thresholds. Crucially, lacosamide reduced the strength-duration time constant and increased rheobase, whereas carbamazepine had minimal effects on both measures. SIGNIFICANCE: These results reveal subtle and unexpected differences in cortical neuron behavior following VGSC-blocking medication administration. Lacosamide's response aligns with the proposed mechanism of sodium conductance blockade, whereas carbamazepine's effects suggest distinct VGSC interactions or potential off-target effects. Our findings advance the understanding of VGSC-blocking medication interactions in the human cortex and underscore the importance of employing specific TMS measures to gain deeper insights into medication mechanisms of action in vivo. Such measures could serve as valuable adjuncts in medication development and patient monitoring.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".