Non-linear processing and reinforcement learning to predict rTMS treatment response in depression

Forecasting the efficacy of repetitive transcranial magnetic stimulation (rTMS) therapy can lead to substantial time and cost savings by preventing futile treatments. To achieve this objective, we've formulated a machine learning approach aimed at categorizing patients with major depressive disorder (MDD) into two groups: individuals who respond (R) positively to rTMS treatment and those who do not respond (NR).

Preceding the commencement of treatment, we obtained resting-state EEG data from 106 patients diagnosed with MDD, employing 32 electrodes for data collection. These patients then underwent a 7-week course of rTMS therapy, and 54 of them exhibited positive responses to the treatment. Employing Independent Component Analysis (ICA) on the EEG data, we successfully pinpointed relevant brain sources that could potentially serve as markers of neural activity within the dorsolateral prefrontal cortex (DLPFC). These identified sources were further scrutinized to estimate the sources of activity within the sensor domain. Then, we integrated supplementary physiological data and implemented specific criteria to yield more realistic estimations when compared to conventional EEG analysis. In the end, we selected components corresponding to the DLPFC region within the sensor domain. Features were derived from the time-series data of these relevant independent components. To identify the most significant features, we used Reinforcement Learning (RL). In categorizing patients into two groups - R and NR to rTMS treatment - we utilized three distinct classification algorithms including K-Nearest Neighbor (KNN), Support Vector Machine (SVM), and Multilayer Perceptron (MLP). We assessed the performance of these classifiers through a ten-fold cross-validation method. Additionally, we conducted a statistical test to evaluate the discriminative capacity of these features between responders and non-responders, opening the door for further exploration in this field.

We identified EEG features that can anticipate the response to rTMS treatment. The most robust discriminators included EEG beta power, the sum of bispectrum diagonal elements in the delta and beta frequency bands. When these features were combined into a single vector, the classification of responders and non-responders achieved impressive performance, with an accuracy of 95.28 %, specificity at 94.23 %, sensitivity reaching 96.29 %, and precision standing at 94.54 %, all achieved using SVM.

The results of this study suggest that the proposed approach, utilizing power, non-linear, and bispectral features extracted from relevant independent component time-series, has the capability to forecast the treatment outcome of rTMS for MDD patients based solely on a single pre-treatment EEG recording session. The achieved findings demonstrate the superior performance of our method compared to previous techniques.