The ventrointermediate nucleus of the thalamus (VIM) is implicated in motor sequence learning, yet the underlying neural mechanisms remain unclear. We recorded intracranial activity from the human VIM during a serial reaction time task to determine how neural dynamics support learning. Participants responded faster during repeating than randomized sequences. Beta-to-low-gamma activity was greater during repeating sequences and elevated relative to the prestimulus baseline, consistent with emergence and stabilization of learned motor representations. In contrast, beta-phase modulation of high-frequency activity decreased progressively from rest to random to repeated sequence execution. Stronger phase–amplitude coupling was associated with faster responses, reaching significance in the random condition. These findings reveal a dissociation between power and cross-frequency coupling. Together they suggest that thalamic dynamics contribute to motor learning through multiple mechanisms: beta-band power reflects the emergence of learned motor representations, whereas beta–high-frequency coupling is enhanced when the context is less predictable.
Angela Voegtle, L. Buentjen, Stefan Repplinger et al.· bioRxiv· 0 citations
Objective. Non-invasive brain stimulation (NIBS) techniques are increasingly used to modulate brain activity in basic and translational research. Kilohertz transcranial magnetic perturbation (kTMP) is a recently developed NIBS approach that uses magnetic induction to generate subthreshold electric fields in the brain. kTMP has been shown to modulate cortical excitability while producing no perceptible sensation at the stimulation site. However, its safety and tolerability have not yet been systematically evaluated—a gap this study aims to address. Approach. We conducted sham-controlled experiments, within-subject comparisons, and patient feasibility studies with kTMP, entailing 433 sessions across 143 individuals. Participants rated annoyance, muscle activation, and pain on a 0–10 scale after each session. With primary motor cortex (M1) as the target, we compared active stimulation (∼8 V m−1 cortical field) to sham (0 V m−1) in healthy adults and chronic stroke patients. In healthy adults, we compared active vs. sham stimulation applied to dorsolateral prefrontal cortex, superior temporal gyrus, and cerebellum. Additional datasets examined tolerability across active kTMP parameters and multi-session feasibility in stroke patients. Safety monitoring included continuous observation for abnormal motor activity and EMG recording in initial experiments. Main results. No device-related adverse reactions occurred across 433 sessions. EMG monitoring revealed no artifacts, and no participants exhibited involuntary muscle contractions or signs of abnormal cortical excitation. kTMP was well tolerated, with mean ratings for active and sham stimulation remaining below 1.5 (where ‘2’ indicates just-noticeable sensation). Permutation tests showed no significant active–sham differences and bootstrapped 95% confidence intervals consistently fell within the ±1 equivalence margin. When auditory masking was used, participants could not distinguish active from sham stimulation. Significance. kTMP achieves cortical E-fields an order of magnitude higher than conventional subthreshold tES while maintaining robust safety margins and tolerability indistinguishable from sham, supporting its use for rigorous double-blind studies and translational settings. Trial Registration: ClinicalTrials.gov Identifier: NCT06317194.
Christina M. Merrick, Guy Avraham, Philipp Reber et al.· Journal of Neural Engineerin...· 0 citations
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