Poster M3 - Spectral Changes due to rTMS in Major Depressive Disorder

Introduction: According to a report by the World Health Organization, in 2017 an estimated 322 million people globally were affected by major depressive disorder (MDD) [1]. The number of adults in the U.S. with MDD increased by 12.9%, from 15.5 to 17.5 million, between 2010 and 2018, whereas the proportion of adults with MDD aged 18–34 years increased from 34.6 to 47.5% [2 ].
MDD interferes and limits major life activities and is characterized by a long period of depression, loss of pleasure, or lack of interest in activities. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive procedure based on the resonances of magnetic fields to stimulate nerve cells in the brain, was approved by the FDA to treat medically refractory MDD in 2008.
The subjectivity of patient responses to psychological evaluation questionnaires and the lack of established biomarkers makes it difficult to diagnose MDD accurately or to precisely tailor therapy. Studies have revealed that rTMS can potentially improve MDD symptoms and may restore brain activity to resemble that of people without MDD. The long-term goal of our work is to develop more precisely targeted rTMS to deliver more reliable outcomes based on quantitative biomarkers from surface electroencephalography (sEEG). Our objective in this work is to determine changes in spectral band power as well as coherence changes after 7 weeks of rTMS and how these changes correlate with assessments on a standardized scale of depression and anxiety.

Materials and

Methods: Data was collected from six patients clinically diagnosed with MDD and who completed rTMS treatment at Brainstim Center (BSC), TMS clinics. The target brain region (Left, Right or Left and Right dorsolateral prefrontal cortex, or DLPFC) for the stimulation and stimulus parameters are set according to the given clinical indication, in this case MDD, but can be adjusted for each patient. The subject demographics and customized stimulation settings are listed in Table I.
Surface EEG, and scores on two standard questionnaires (Montgomery–Åsberg Depression Rating Scale, or MADRS, and the Generalized Anxiety Disorder-7, or GAD-7) were obtained pre- and post-rTMS treatment. All methods used in this study were determined exempt from review by Cal State LA’s Institutional Review Board (Ref. # 23-116X).
Power spectral density (PSD) was computed using MATLAB’s (Mathworks, Inc. Natick, MA) built-in pwelch command using 1.28-s windows with 50% overlap and a frequency resolution of 0.098Hz. Band power was estimated by using the trapezoid method to numerically integrate spectral power density within the defined bands: Gamma (γ) < 35 Hz; Beta (β) 12–35 Hz; Alpha (α) 8–12 Hz; Theta (θ) 4–8 Hz; and Delta (δ) 0.5–4 Hz. Coherence was computed using MATLAB’s built-in mscohere function and the same parameters used to compute the PSD.
Correlation between changes in spectral band power and coherence with clinical outcome were quantified with Pear-son’s correlation coefficient (r) which was computed using the built-in function corrcoef.

Results, Conclusions, and Discussions: Results :
Results indicate alpha and beta power were positively correlated with MADRS and GAD-7, while the alpha:beta ratio was positively correlated only in the ipsilateral temporal, central, and parietal regions; indicating that increases in this ratio were associated with improvements in MDD symptoms. Finally, there was a strong negative correlation between the changes in MADRS scores and changes in coherence for the Fp1-Fp3 and Fp2-Fz indicating that these areas were mainly associated with improvements in depression. A more complete analysis after more MDD patients complete their course of rTMS therapy is expected to confirm that rTMS could be strengthening prefrontal-frontal connections, as indicated by increases in coherence, and thereby improving MDD symptoms.

Conclusions :
In this study, we have analyzed the spectral characteristics of six patients who received their full course of rTMS treatment for MDD. All six subjects’ MADRS and GAD-7 scores decreased, indicating improvement in MDD and anxiety symptoms post-treatment. At the frontal electrodes, expected to be most associated with ACC activity), MADRS and GAD-7 scores were positively correlated with alpha and beta power across brain regions, while they were negatively correlated with delta power, and with theta power in the parietal and occipital regions. Correlation with the alpha:beta ratio was much more dependent on location. Consistent with the literature, decreases in alpha:beta power were associated with decreases in MADRS and GAD-7 scores, indicating improvements in MDD [3].

Discussions :
These preliminary results are contributing to a growing body of work aimed at quantitatively characterizing clinical manifestations of MDD, which in turn would allow for more precisely targeted therapies and treatment of MDD.

Acknowledgements (Optional): [1] Geneva: World Health Organization. (2017). Depression and Other Common Mental Disorders: Global Health Estimates.
[2] Greenberg, P. E. (2021). The Economic Burden of Adults with Major Depressive Disorder in the United States (2010 and 2018). PharmacoEconomics, 653–665. doi:10.1007/s40273-021-01019-4
[3] Chang, J., & Choi, Y. (2023). Depression diagnosis based on electroencephalography power ratios. Brain and Behavior, 13(8). doi:10.1002/brb3.3173