Antipsychotics reverse abnormal EEG complexity in drug-naive schizophrenia: a multiscale entropy analysis

Abstract

Multiscale entropy (MSE) analysis is a novel entropy-based approach for measuring dynamical complexity in physiological systems over a range of temporal scales. To evaluate this analytic approach as an aid to elucidating the pathophysiologic mechanisms in schizophrenia, we examined MSE in EEG activity in drug-naive schizophrenia subjects pre- and post-treatment with antipsychotics in comparison with traditional EEG analysis. We recorded eyes-closed resting-state EEG from frontal, temporal, parietal, and occipital regions in drug-naive 22 schizophrenia and 24 age-matched healthy control subjects. Fifteen patients were re-evaluated within 2-8 weeks after the initiation of antipsychotic treatment. For each participant, MSE was calculated on one continuous 60-s epoch for each experimental session. Schizophrenia subjects showed significantly higher complexity at higher time scales (lower frequencies) than did healthy controls in fronto-centro-temporal, but not in parieto-occipital regions. Post-treatment, this higher complexity decreased to healthy control subject levels selectively in fronto-central regions, while the increased complexity in temporal sites remained higher. Comparative power analysis identified spectral slowing in frontal regions in pre-treatment schizophrenia subjects, consistent with previous findings, whereas no antipsychotic treatment effect was observed. In summary, multiscale entropy measures identified abnormal dynamical EEG signal complexity in anterior brain areas in schizophrenia that normalized selectively in fronto-central areas with antipsychotic treatment. These findings show that entropy-based analytic methods may serve as a novel approach for characterizing and understanding abnormal cortical dynamics in schizophrenia and elucidating the therapeutic mechanisms of antipsychotics.

Fig. 1

Results of the MSE analysis for simulated pure sinusoidal rhythms (i.e., 2.5 (red line), 5 (green line) and 10 Hz (blue line)) with 1/f noise. Sample entropy values were calculated up to 100 scale factors.

Fig. 2

Multiscale entropy (MSE) analysis of 22 pre-treatment schizophrenia (red line), 15 post-treatment schizophrenia (green line) and 24 healthy control subjects (blue line). Each panel presents the average of the intermediate, left and right hemisphere MSE values. (a) Comparisons between healthy control and pre-treatment schizophrenia subjects. (b) Comparisons between healthy control and post-treatment schizophrenia subjects. (c) Comparisons between pre-treatment schizophrenia and post-treatment schizophrenia subjects. (d) Summary of MSE profiles for healthy controls and pre- and post-treatment schizophrenia. Post-hoc comparisons between groups: P < 0.01 (light blue shaded areas) and P < 0.001 (dark blue shaded areas).

Fig. 2

Multiscale entropy (MSE) analysis of 22 pre-treatment schizophrenia (red line), 15 post-treatment schizophrenia (green line) and 24 healthy control subjects (blue line). Each panel presents the average of the intermediate, left and right hemisphere MSE values. (a) Comparisons between healthy control and pre-treatment schizophrenia subjects. (b) Comparisons between healthy control and post-treatment schizophrenia subjects. (c) Comparisons between pre-treatment schizophrenia and post-treatment schizophrenia subjects. (d) Summary of MSE profiles for healthy controls and pre- and post-treatment schizophrenia. Post-hoc comparisons between groups: P < 0.01 (light blue shaded areas) and P < 0.001 (dark blue shaded areas).

Fig. 2

Multiscale entropy (MSE) analysis of 22 pre-treatment schizophrenia (red line), 15 post-treatment schizophrenia (green line) and 24 healthy control subjects (blue line). Each panel presents the average of the intermediate, left and right hemisphere MSE values. (a) Comparisons between healthy control and pre-treatment schizophrenia subjects. (b) Comparisons between healthy control and post-treatment schizophrenia subjects. (c) Comparisons between pre-treatment schizophrenia and post-treatment schizophrenia subjects. (d) Summary of MSE profiles for healthy controls and pre- and post-treatment schizophrenia. Post-hoc comparisons between groups: P < 0.01 (light blue shaded areas) and P < 0.001 (dark blue shaded areas).

Fig. 2

Multiscale entropy (MSE) analysis of 22 pre-treatment schizophrenia (red line), 15 post-treatment schizophrenia (green line) and 24 healthy control subjects (blue line). Each panel presents the average of the intermediate, left and right hemisphere MSE values. (a) Comparisons between healthy control and pre-treatment schizophrenia subjects. (b) Comparisons between healthy control and post-treatment schizophrenia subjects. (c) Comparisons between pre-treatment schizophrenia and post-treatment schizophrenia subjects. (d) Summary of MSE profiles for healthy controls and pre- and post-treatment schizophrenia. Post-hoc comparisons between groups: P < 0.01 (light blue shaded areas) and P < 0.001 (dark blue shaded areas).

Fig. 3

Relative power analysis of 22 pre-treatment schizophrenia (red line), 15 post-treatment schizophrenia (green line) and 24 healthy control subjects (blue line). Each panel presents the average of the intermediate, left and right hemisphere relative power values. Post-hoc comparisons between groups: *P < 0.01 (healthy control vs. pre-treatment schizophrenia subjects) and ^†P < 0.001 (healthy control vs. post-treatment schizophrenia subjects).