Neurophysiological markers of response to theta burst stimulation in youth depression

Abstract

Background: Theta burst stimulation (TBS) has recently been proposed as a novel treatment for youth depression. However, the impact of TBS on the youth brain and neurophysiological predictors of response to TBS in this population have not been investigated.

Methods: Cortical reactivity was assessed at baseline and following 2 weeks of bilateral dorsolateral prefrontal cortex (DLPFC) TBS treatment in 16 youth with depression (aged 16-24 years old). In 16 age-matched health youths, cortical reactivity was assessed twice, 2 weeks apart. Transcranial magnetic stimulation (TMS) combined with electroencephalography was used to assess TMS-evoked potentials in bilateral DLPFC, motor cortices, and intraparietal lobules (IPL). Resting-state functional magnetic resonance imaging (fMRI) data was also collected at baseline.

Results: Left DLPFC pretreatment cortical reactivity, specifically the negativity at 45 ms (i.e., N45), which is related to GABAA neurotransmission, was associated with changes in depressive symptoms. Furthermore, TBS treatment was found to alter the N45 in the right IPL, a site distal to the treatment sites. The magnitude of the right IPL N45 modulation was correlated with the baseline fMRI connectivity between the right IPL and right DLPFC.

Conclusions: TMS-probed cortical inhibition at the site of TBS application may have potential as a predictor of treatment response in youth depression. Furthermore, pre-treatment functional connectivity may predict the impact of TBS on the neurophysiology of regions distal to the stimulation site. Collectively, these results offer novel neurophysiological insights into the application of TBS for youth depression, which may facilitate its wider use in the youth population.

Trial registration: ClinicalTrials.gov NCT02472470.

Keywords: depression; electrophysiology; theta burst stimulation; transcranial magnetic stimulation; youth.

Conflict of interest statement

CONFLICT OF INTERESTS

Dr. Croarkin has received research support from the Brain and Behavior Research Foundation, National Institute of Mental Health, Neuronetics, NeoSync, and Pfizer. He has received material support from and provided consultation to Myriad Genetics. He has consulted for Procter & Gamble Company.The remaining authors declare that there are no conflict of interests.

© 2020 Wiley Periodicals LLC.

Figures

FIGURE 1

TEPs following stimulation of each of the six cortical sites of interest. Illustrated are the TEPs from electrode FCz for each group at each time point following stimulation of the bilateral DLPFC, motor cortex (MC), and IPL. DLPFC, dorsolateral prefrontal cortex; IPL, intraparietal lobules; TEPs, transcranial magnetic stimulation-evoked potentials.

FIGURE 2

Right IPL N45 interaction effect. (a) Mean N45 (30–50 ms) topoplots for each group by time factor. (b) Topoplots displaying electrodes (with asteriks) that belonged to a significant interaction cluster between group and time. (c) Topoplots displaying electrodes (with asteriks) that belonged to a significant cluster for the simple effect contrast of pre-treatment versus post-treatment right IPL N45 in the youth MDD group. Cold colour areas represent where and when the absolute magnitude of the N45 became smaller following TBS treatment. All other simple effects were found to be nonsignificant. (d) A TEP plot demonstrating the reduction (i.e., becoming less negative) of the right IPL N45 in the youth MDD group following TBS treatment. (e) Cortical maps illustrate areas of significant difference (based on t-values derived from dependent samples t-test, projected on an ICBM152 cortex template) within the youth MDD group for the right IPL N45 (uncorrected threshold at p < .05). IPL, intraparietal lobules; MDD, major depressive disorder; TBS, theta burst stimulation; TEP, transcranial magnetic stimulation-evoked potential.

FIGURE 3

Significant correlation results. Topoplots displaying electrodes (with asteriks) that belonged to a significant positive or negative correlation cluster at the latency provided above each topoplot. (a) Correlation between baseline left DLPFC N45 and change in depressive symptoms in youth MDD. (b) Correlation between baseline right DLPFC and right IPL functional connectivity and changes in the right IPL N45 in youth MDD. (c) Correlation between changes in left DLPFC N100 and the left DLPFC's baseline functional connectivity with the right DLPFC. (d) Correlation between changes in right DLPFC P200 and the right DLPFC's baseline functional connectivity with the left DLPFC. DLPFC, dorsolateral prefrontal cortex; IPL, intraparietal lobules; MDD, major depressive disorder