Characterising cortical perturbation-recovery dynamics using TMS-EEG: The Brain Dynamic Toolbox

Objective: To adapt dynamical measures used in computational and experimental perturbation models to human transcranial magnetic stimulation and electroencephalography (TMS-EEG) and determine whether analysis of the extended post-stimulation trajectory reveals additional features of the cortical response to long-interval intracortical inhibition (LICI). Methods: Single pulse and paired pulse LICI TMS-EEG responses from the bilateral dorsolateral prefrontal cortex were re-analysed in 16 healthy adults. At the stimulation site, 75 single-pulse and 75 paired-pulse trials were delivered; paired pulses comprised conditioning and test stimuli separated by 100 ms. Responses from 20 frontocentral EEG channels were analysed from 50-950 ms following TMS using the open source Brain Dynamic Metric Toolbox. Perturbative Integration Latency Index (PILI) indexed cortical resilience via response energy and recovery, Autocorrelation Function Width (ACFW) captured temporal memory, and Lyapunov Exponent (LE) indicated the dynamical stability. Linear mixed-effects models examined temporal, spectral, and time-frequency effects from the measured metrics. Results: LICI altered the temporal evolution of the dynamical measures. PILI distinguished conditions in the earliest post-stimulation window before converging, whereas ACFW differences persisted across a broader early interval. LE showed weaker and less consistent discrimination. Spectral effects were most evident for ACFW, while time-frequency analyses revealed later, frequency-specific LICI effects for PILI and ACFW but not LE. Conclusions: The extended post-stimulation trajectory revealed LICI-related differences in cortical resilience and temporal memory with distinct temporal and spectral profiles, while effects on dynamical stability were less consistent. Significance: The Brain Dynamic Metric Toolbox provides a reproducible framework for quantifying perturbation-recovery dynamics in TMS-EEG and demonstrates that the extended perturbational response contains information about LICI not captured by discrete early response measures.