Predicting Intermittent TBS Treatment Response in Patients With Major Depressive Disorder Using Concurrent TBS/Fnirs and Machine Learning

Background The instantaneous prefrontal activation during and immediately after theta burst stimulation (TBS) may serve as biomarker for TBS treatment response. Aims & Objectives The first objective of this study was to assess TBS-induced prefrontal cortical excitability in individuals with major depressive disorder (MDD) and healthy controls (HCs) by applying TBS to the dorsolateral prefrontal cortex (DLPFC). The second objective was to identify novel predictive biomarkers as indicated by localized prefrontal activation for the antidepressant response to four weeks TBS treatment. Method All participants (including MDD and HC) underwent concurrent TBS/functional near-infrared spectroscopy (fNIRS) measurement, followed by four weeks (20 sessions) of standard iTBS treatment over the left DLPFC for MDD patients. One-way repeated measures ANOVA and independent t-tests were performed to examine the changes in prefrontal hemoglobin levels during and after TBS and to compare the prefrontal hemoglobin concentration changes between individuals with MDD and HCs. The most relevant features were selected by the Least Absolute Shrink and Selection Operator (LASSO). Supervised machine learning using the 5-fold cross-validation method was applied to assess the clinical utility of these biomarkers for the classification of TBS response. Results Significant increases in deoxyhemoglobin (∆HbR) but not oxyhemoglobin (∆HbO) were observed during and after TBS. However, there were no significant differences in TBS-induced hemoglobin changes between the MDD and HCs groups. Two imaging features, along with two clinical features demonstrated good classification into responders and non-responders to four weeks of antidepressant TBS treatment (accuracy: 82.9%, AUC: 0.902) using support-vector machine. Discussion & Conclusions The results demonstrated significant prefrontal activation during and after TBS. Although TBS-induced hemoglobin changes were unable to differentiate between MDD and HCs, the findings suggest that these changes can provide valuable information about the response to four weeks of TBS treatment.