Pharmacological mechanisms of focused ultrasound for human motor cortical plasticity
Bibliographic record
Abstract
Abstract Transcranial focused ultrasound (TUS) is a novel brain stimulation technique which has been shown to induce immediate (‘online’) and prolonged (‘offline’) changes in cortical excitability. Although animal and cell studies have inferred the mechanisms of this technique, its mechanism of action in the human brain is unknown. A popular hypothesis posits that sonication waves deliver perturbations, which act on mechanosensitive voltage-gated ion channels. Additionally, paired-pulse measures of transcranial magnetic stimulation (TMS) in the human motor cortex (M1) has found that TUS is able to modulate glutamatergic and GABAergic intracortical circuits. The purpose of the present study is to determine the mechanisms of online inhibitory and offline excitatory TUS stimulation in the human motor cortex. This is done by delivering TUS together with administration of approved brain-active drugs, to determine the effects of the drugs on TUS induced changes. This is a within-subjects randomized, double-blind, cross-over study, where subjects were administered on separate sessions: carbamazepine (Na+ channel blocker), nimodipine (Ca2+ channel blocker), lorazepam (GABAA receptor positive allosteric modulator), dextromethorphan (NMDA receptor antagonist), or placebo. In each session, participants take the drug and after 1.5 hours, they participate in online coupled TUS-TMS stimulation, where TMS is delivered at the last 10 ms of a 500 ms TUS sonication over M1. This is followed by delivery of a theta-burst TUS over M1, where pre-stimulation TMS measures are compared offline to post-stimulation measures at several timepoints. The effects of the pharmacological agents on TUS-induced plasticity are compared to that of placebo. This study will elucidate the mechanisms of TUS neuromodulation in the human motor cortex. This will be a crucial step in the development of TUS as a novel non-invasive treatment for neurological and psychiatric disorders. We intend to present preliminary data of our study at the conference. Keywords: Focused Ultrasound, Neurophysiology, Neuropharmacology
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.005 |
| 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) | 0.000 | 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 teacher head, 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".