Heart-Brain Coupling Factor as a Correlate of iTBS Target Engagement, Clinical Effectiveness, and Cortical Excitability

COEX 

Introduction:
Interoception refers to both the processing by the brain of afferent signals arising from bodily organs, as well as to the efferent signals the brain sends to modify their function. The interaction between the brain and heart, via the vagus nerve, is especially dynamic. We used the heart-brain coupling (HBC) factor, a measure of heart rate entrainment induced by repetitive transcranial magnetic stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (L-DLPFC). It can be derived using Neuro-Cardiac-Guided (NCG) TMS-2.0, and reflects the spectral density of the 0.1 Hz frequency. This entrainment occurs during conventional rTMS, and also during intermittent theta burst stimulation (iTBS), which is used in Stanford Neuromodulation Therapy (SNT). In this talk, we discuss the use of HBC factor to as a measure of target engagement, clinical effectiveness, and cortical excitability.

Methods:
15 participants were included in this study, 8 in the active and 7 in the sham condition, with participants and treaters blinded. There were 7 women and 8 men in the study, with 3 women in the sham and 4 women in the active condition. The mean age 50.1 yrs. Each participant underwent 10 iTBS sessions a day for 5 days, in accordance with SNT procedures. During treatment sessions, electrocardiogram (ECG) recordings were collected (NCG-ENGAGE, Neurocare). Recordings were visually inspected and artifact free sections of 300 seconds identified for analysis. These were then processed using a modified version of the script described in Dijkstra et al., 2023 in order to generate the HBC factor values. These were then analyzed using SPSS version 29. The resulting values were also categorized as being above or below a threshold of 2, a practice which had proven accurate in a prior study for categorizing recordings as coming from an active or sham condition.

Target engagement & clinical effectiveness

Results:
A linear mixed effects model was constructed with HBC factor as the dependent variable in which the model included Day, Session, and Active/Sham as fixed effects, while participants were included as a random effect. Age and sex were included as covariates. Only Active/Sham was significant (F=9.356, df=1,484, p<.01). Looking across participants, on each day, HBC factor for the active condition was numerically greater than HBC factor for the sham condition (although not significant). Negative Pearson’s correlations were found between the mean percent of HBC factors above 2 for each participant and the percent reduction from baseline in MADRS score at week 2 (r(12) = -.638, p = .025), week 4 (r(14) = -.670, p = .009), and week 5 (r(14) = -.577, p = .031) following SAINT treatment.

Discussion:
The HBC factor appears to have associations with meaningful clinical outcomes. More data is still needed to determine if it can function as a predictor of treatment outcome. It may have quantifiable relationships with cortical excitability.

Cortical excitability

Preliminary findings from a pilot study of HBC factor as a measure of cortical excitability will be discussed, as well as their relevance for thresholding during SAINT and other TMS applications.