Heartbeat-Evoked Potential in Major Depressive Disorder: A Biomarker for Differential Treatment Prediction between Venlafaxine and rTMS?

Abstract

<b><i>Introduction:</i></b> Currently, major depressive disorder (MDD) treatment plans are based on trial-and-error, and remission rates remain low. A strategy to replace trial-and-error and increase remission rates could be treatment stratification. We explored the heartbeat-evoked potential (HEP) as a biomarker for treatment stratification to either antidepressant medication or rTMS treatment. <b><i>Methods:</i></b> Two datasets were analyzed: (1) the International Study to Predict Optimized Treatment in Depression (iSPOT-D; <i>n</i> = 1,008 MDD patients, randomized to escitalopram, sertraline, or venlafaxine, and <i>n</i> = 336 healthy controls) and (2) a multi-site, open-label rTMS study (<i>n</i> = 196). The primary outcome measure was remission. Cardiac field artifacts were removed from the baseline EEG using independent component analysis (ICA). The HEP-peak was detected in a bandwidth of 20 ms around 8 ms and 270 ms (N8, N270) after the R-peak of the electrocardiogram signal. Differences between remitters and non-remitters were statistically assessed by repeated-measures ANOVAs for electrodes Fp1, Cz, and Oz. <b><i>Results:</i></b> In the venlafaxine subgroup, remitters showed a lower HEP around the N8 peak than non-remitters on electrode site Cz (<i>p</i> = 0.004; <i>d</i> = 0.497). The rTMS group showed a non-significant difference in the opposite direction (<i>d</i> = −0.051). Retrospective stratification to one of the treatments based on the HEP resulted in enhanced treatment outcome prediction for venlafaxine (+22.98%) and rTMS (+10.66%). <b><i>Conclusion:</i></b> These data suggest that the HEP could be used as a stratification biomarker between venlafaxine and rTMS; however, future out-of-sample replication is warranted.

Neural Interoceptive Processing is Modulated by Deep Brain Stimulation for Treatment Resistant Depression

“…HEP amplitude was greater after 24 weeks of treatment ( t (7)=-4.40, p =.003, g= -1.38, 95% Cl [-2.3, -0.42]), and this change was inversely correlated with latency of treatment response (rho = -0.75, 95% Cl [-0.95, -0.11], p= .03). An acute effect of DBS was also observed, but as a decrease in HEP amplitude ( t (6) =6.66, p <.001, g= 2.19, 95% Cl [0.81, 3.54]). HEP differences were most pronounced over left posterior sensors from 405-425 ms post-stimulus.…”

“…There was a significant difference in the HEP amplitude between Baseline and WK24 DBS Off, showing a more positive HEP amplitude for the WK24 DBS Off condition than Baseline (cluster electrodes, t (7)=-4.40, p =.003, g= -1.38, 95% Cl [-2.3, -0.42]). Additionally, there was a significant difference in the HEP amplitude between WK4 DBS On and WK4 DBS Off, showing a more negative HEP amplitude for the WK4 DBS On condition than WK4 DBS Off (cluster electrodes, t (6) =6.66, p <.001, g= 2.19, 95% Cl [0.81, 3.54]). WK24 DBS On vs. WK24 DBS Off revealed no significant effect of acute DBS ( p= > .…”

“…States of depression appear to modulate an electrocortical measure of interoceptive processing, the heartbeat evoked potential (HEP) (5,6). However, neural evidence of an interoceptive contribution to successful treatment for depression is lacking.…”

BrainBeats, an Open-Source EEGLAB Plugin to Jointly Analyze EEG and Cardiovascular Signals

“…This approach examines how the brain processes cardiovascular activity with millisecond accuracy and requires that both time series are time-locked, the heartbeats be marked with events in the EEG signals, and the heart signal removed. This approach is the most popular [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] .…”

Brain State Relays Self-Processing and Heartbeat-Evoked Cortical Responses

“…The attentional state can manifest in measures such as reaction time [36][37][38][39][40], accuracy [40], recall percentage [41], and N2 posterior-contralateral component, which serves as a neural marker of spatial selective attention [42]. Mood states can be gauged in a self-reported way [43][44][45][46][47][48][49][50][51][52][53][54][55][56] or by physiological indices such as blood pressure [57] and cortisol levels [58].…”