Auditory Stimulation-Evoked Frontoparietal Theta Asymmetry for Subtype Classification and Long-Term Prognosis
Chen Chen1,2,3, Yajuan Hu1,2,3,4,5,6, Sifan Wang1,2,3
1Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
Abstract:
Background: Quantitative electroencephalography (qEEG) facilitates the objective assessment of residual brain function in patients with disorders of consciousness (DOC), which addresses the intrinsic limitations of behavioral assessment methods. Nevertheless, the characteristics of frontoparietal neural oscillation asymmetry between resting state and auditory stimulation state have not been fully elucidated, and its incremental prognostic value for DOC subtype classification and outcome prediction remains to be confirmed. Methods: Fifty-seven patients with DOC and 23 healthy controls completed qEEG recordings at baseline and during auditory stimulation. Interhemispheric asymmetry indices of the frontal lobe and parietal lobe were calculated for the theta band and alpha band. Linear mixed-effects models (LMMs) were adopted to test the main effects and interaction effects of diagnosis, brain region and stimulation condition. The correlations between asymmetry indicators, Coma Recovery Scale-Revised (CRS-R) scores and 6-month Glasgow Outcome Scale (GOS) scores were analyzed. Nested logistic regression and Receiver Operating Characteristic (ROC) analysis were performed to quantify the incremental prognostic value of oscillatory asymmetry beyond conventional clinical variables; odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for all predictive indicators. Internal leave-one-out cross-validation and external cohort validation were performed to assess the generalizability and robustness of the final prognostic model. Results: Significant diagnosis × region interaction effects were observed in both frequency bands. Vegetative state (VS) patients presented with frontal-dominant asymmetry, while minimally conscious state (MCS) patients showed parietal-dominant asymmetry; this dissociative pattern was significantly amplified after auditory stimulation. Only stimulation-evoked theta asymmetry showed consistent correlations with clinical status and prognosis: frontal theta asymmetry was negatively correlated with CRS-R scores, while parietal theta asymmetry was positively correlated with CRS-R scores and 6-month GOS outcomes. Incorporating stimulated frontoparietal theta asymmetry significantly improved prognostic performance, and the area under the curve (AUC) of the optimal model reached 0.930. Conclusions: VS and MCS present distinct frontoparietal oscillatory asymmetry phenotypes, which are specifically enhanced by auditory stimulation. Stimulation-evoked theta band asymmetry can reflect residual conscious function and provides incremental prognostic value for long-term functional recovery, with robust generalizability verified by internal and external validation.
