Single-channel EEG captures tDCS-induced changes in neural reactivity: a pilot study in disorders of consciousness patients and healthy controls.

Background: Understanding and enhancing neural recovery in disorders of consciousness
(DoC) remains a critical challenge in clinical care. Clinical scales such as the Coma Recovery
Scale–Revised (CRS-R) are essential, but reflect behavioral responsiveness and may not fully
capture subtle neurophysiological changes. Transcranial direct current stimulation (tDCS) has
shown promise, yet objective biomarkers to assess treatment response are needed.

Objectives: This proof-of-concept study explores the feasibility and sensitivity of combining a
compact single-channel EEG with noninvasive brain stimulation to assess changes in neural
reactivity in individuals with DoC.Design: Pilot observational study with DoC patients undergoing intervention; healthy controls were assessed to provide a physiological reference benchmark for interpreting mismatch
negativity (MMN) responses and assess the specificity of EEG biomarkers relative to DoC
patients.

Methods: Six DoC patients underwent a 2-week open-label anodal tDCS protocol targeting
the left dorsolateral prefrontal cortex. Neural activity was tracked using a compact threeelectrode EEG alongside traditional 19-electrode EEG. To capture treatment-induced changes, three complementary biomarkers were analyzed: MMN, reflecting pre-attentive auditory discrimination function; Beta oscillatory activity, associated with global attentional processes; and L1, a machine-learning-derived biomarker of cognitive engagement. CRS-R, auditory event-related potentials, and EEG-based machine learning biomarkers were recorded at
baseline and immediately post-intervention. Healthy controls underwent the same baseline
EEG assessments without receiving stimulation.Results: MMN, Beta, and L1 demonstrated task-related modulation in healthy participants across cognitive load levels. In DoC patients, changes were observed following tDCS in MMN, Beta activity, and L1 as well, with patients demonstrating complex heterogeneous response
patterns. Two patients showed behavioral improvement (CRS-R), while others exhibited
increased EEG reactivity without corresponding behavioral gains.

Conclusion: These findings highlight the feasibility and potential value of integrating compact
EEG systems with neuromodulation protocols to monitor neural reactivity in DoC patients, with
the potential to inform and refine tDCS treatment strategies over time.