Cortical Thickness in the Right Anterior Cingulate Cortex Relates to Clinical Response to Left Prefrontal Accelerated Intermittent Theta Burst Stimulation: An Exploratory Study

Abstract

Objectives: Accelerated intermittent theta burst stimulation (aiTBS) is a promising treatment option for depressed patients. However, there is a large interindividual variability in clinical effectiveness and individual biomarkers to guide treatment outcome are needed.

Materials and methods: Here, the relation between cortical thickness and clinical response (17-item Hamilton Depression Rating Scale) was studied using anatomical MRI data of 50 depressed patients who were included in a randomized, sham-controlled, double-blinded, cross-over aiTBS design (NCT01832805).

Results: Baseline cortical thickness in the right caudal part of the anterior cingulate cortex (cACC) was significantly correlated with direct clinical responses in the subgroup who received active aiTBS during the first stimulation week. No correlations were found between baseline cortical thickness and delayed clinical effectiveness. In this particular region, longitudinal changes in cortical thickness were significantly correlated with clinical effectiveness. Furthermore, direct changes in cortical thickness in the right cACC showed predictive potential of delayed clinical responses.

Conclusion: Cortical thickness within the right cACC might be an important biomarker to predict clinical responses to aiTBS. Additional studies are warranted to substantiate the specific biomarker potential of these parts of the ACC.

Keywords: Brain stimulation/TMS/DBS/VNS; biological markers; depression; neuroimaging; neurostimulation.

Figure 1

Overall design of this randomized, sham‐controlled, double‐blinded, cross‐over trial. Adapted from Duprat et al. (7).

Figure 2

Correlations between baseline cortical thickness (CT) and direct changes in HDRS. Significant correlations between the baseline (T1) cortical thickness and ΔHDRS_dir. Figure a includes all subjects (n = 46, order corrected, dof = 40), whereas in figure b and c, results are split for the subjects receiving active aiTBS (n = 21, dof = 18) or sham aiTBS (n = 25, dof = 22), respectively. Note the different statistical thresholds to compensate for the loss of power when studying the subgroups. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Overview of the baseline (T1) cortical thickness vs. ΔHDRS_dir in the ROI in the left superior prefrontal cortex. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 4

Significant ROI in the left dorsolateral prefrontal cortex vs. individual stimulation positions. (a) Shows the position of the significant ROI in the left superior prefrontal cortex (green) with respect to the individual stimulation sites (red, mean shown in yellow). The TMS‐induced electric field distribution is shown (coil placement at the mean coil position) to provide additional insight in the spread of the TMS effects. In (b), there is no significant correlation between the baseline cortical thickness in the individual stimulation site and the direct clinical response to aiTBS. Note that because information on the individual coil positioning was not available for all subjects, this analysis was performed on a subset of 41 patients. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 5

Significant ROIs when splitting the analysis in subgroups who received active (n = 21) or sham (n = 25) aiTBS during the first stimulation week. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 6

Significant correlations between ΔCT and ΔHDRS_dir. Figure a includes all subjects (n = 45, order corrected, dof = 39) whereas in b and c, results are split for the subjects receiving active aiTBS (n = 21, dof = 18) or sham aiTBS (n = 24, dof = 21), respectively. Note the different statistical thresholds. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 7

Overview of ΔCT vs. ΔHDRS_dir in the ROI in the right isthmus part of the cingulate cortex (CC). [Color figure can be viewed at wileyonlinelibrary.com]

Figure 8

Relation between ΔCT and ΔHDRS_dir for the two ROIs that showed significant (p < 0.01) correlations: right caudal part of the ACC and the right precuneus. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 9

ROC curve of the predictive value of the direct changes in cortical thickness in the right caudal part of the cingulate cortex for the delayed clinical responders. The figure is based on the subgroup of patients who received active aiTBS during the first week of stimulation (n = 21, of which eight responded at T4).