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. 2019 Oct 23:8:e49115.
doi: 10.7554/eLife.49115.

Electric field causes volumetric changes in the human brain

Miklos Argyelan  1   2   3 , Leif Oltedal  4   5 , Zhi-De Deng  6 , Benjamin Wade  7 , Marom Bikson  8 , Andrea Joanlanne  1 , Sohag Sanghani  1 , Hauke Bartsch  5   9 , Marta Cano  10   11 , Anders M Dale  9   12   13 , Udo Dannlowski  14 , Annemiek Dols  15 , Verena Enneking  14 , Randall Espinoza  16   17 , Ute Kessler  4   18 , Katherine L Narr  16   17 , Ketil J Oedegaard  4   18 , Mardien L Oudega  15 , Ronny Redlich  14 , Max L Stek  15 , Akihiro Takamiya  19   20 , Louise Emsell  21 , Filip Bouckaert  21   22 , Pascal Sienaert  22 , Jesus Pujol  11   23 , Indira Tendolkar  24   25   26 , Philip van Eijndhoven  24   25 , Georgios Petrides  1   2   3 , Anil K Malhotra  1   2   3 , Christopher Abbott  27
Affiliations

Electric field causes volumetric changes in the human brain

Miklos Argyelan et al. Elife. .

Abstract

Recent longitudinal neuroimaging studies in patients with electroconvulsive therapy (ECT) suggest local effects of electric stimulation (lateralized) occur in tandem with global seizure activity (generalized). We used electric field (EF) modeling in 151 ECT treated patients with depression to determine the regional relationships between EF, unbiased longitudinal volume change, and antidepressant response across 85 brain regions. The majority of regional volumes increased significantly, and volumetric changes correlated with regional electric field (t = 3.77, df = 83, r = 0.38, p=0.0003). After controlling for nuisance variables (age, treatment number, and study site), we identified two regions (left amygdala and left hippocampus) with a strong relationship between EF and volume change (FDR corrected p<0.01). However, neither structural volume changes nor electric field was associated with antidepressant response. In summary, we showed that high electrical fields are strongly associated with robust volume changes in a dose-dependent fashion.

Keywords: ECT; depression; electric field modeling; human; human biology; medicine; neuroimaging; volume change.

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Conflict of interest statement

MA, LO, ZD, BW, AJ, SS, HB, MC, UD, AD, VE, RE, UK, KN, KO, MO, RR, MS, AT, LE, FB, PS, JP, IT, Pv, GP, AM, CA No competing interests declared, MB reports that The City University of New York (CUNY) has intellectual property (IP) on neuro-stimulation system and methods with MB as inventor; serves on the scientific advisory boards of Boston Scientific and GSK; has equity in Soterix Medical, AD reports that he is a Founder of and holds equity in CorTechs Labs, Inc, and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc and receives funding through research agreements with General Electric Healthcare and Medtronic, Inc

Figures

Figure 1.
Figure 1.. Electric Field (EF) and volume change across 85 brain regions.
Upper panel first row: Mean EF across 85 brain regions; second row: the effect size of volume changes between baseline and at the end of the course of ECT across 85 regions. Lower panel, left: Effect sizes of right unilateral stimulations were consistently higher on the right side than on the left side. Lower panel, right: Scatter plot of regional EF versus regional volume change (r = 0.38; p <0.001; df = 83; t = 3.77). (d) = Cohen’s d effect size..
Figure 2.
Figure 2.. Laterality differences in EF and ∆vol (upper panel) as well as the relationship between laterality between EF/∆vol (lower panel).
Regression line indicates the correlation between laterality indices of EF and volume change (r = 0.32; p<0.05; df = 40; t = 2.13).
Figure 3.
Figure 3.. Individual specific relationship between EF and volume change in the hippocampus.
Left: Scatterplot of EF versus volume change in the hippocampus (t = 5.97, df = 300, r = 0.33, p < 0.0001, left and right side together). There is a significant relationship on the left side (orange dots; t = 4.53, df = 149, r = 0.35, p < 0.0001), but not on the right side (probably due to ceiling effect) (t = 1.59, df = 149, r = 0.13, p = 0.11). Right: The difference in right and left hippocampal volume changes is significant (t = 7.76, df = 150, mean difference = 0.011, p < 0.0001).
Figure 3—figure supplement 1.
Figure 3—figure supplement 1.. Hippocampal EF and volume change.
To test the specificity of our measures in the left hippocampus (FDR corrected finding) we permutated the labels across the 85 ROIs, both for the volume changes (left) and for the EF values (right) and calculated correlations between the EF and volume change of these regions, respectively. This way we received 85 different values, where one of them was the ‘correct’ correlation, indicated with red dots. The ‘correct’ correlations between the EF and corresponding volume outperformed the other correlations (were in the top five percentile) from non-matching pairs, indicating that our findings were not merely a general correlation with some average values across regions, further strengthening the casual link between EF and volume change.
Figure 4.
Figure 4.. Individual specific relationship between EF and volume change in the amygdala.
Left: Scatterplot of EF versus volume change in the amygdala (t = 11.35, df = 300, r = 0.55, p<0.0001; left and right side together). Both the left (orange dots) and right (blue dots) hemisphere shows highly significant relationships (t = 4.01, df = 149, r = 0.31, p=0.0001; and t = 4.02, df = 149, r = 0.31, p=0.0001). Right: The difference in right and left amygdala volume changes is significant (t = 13.58, df = 150, mean difference = 0.029, p<0.0001).
Figure 4—figure supplement 1.
Figure 4—figure supplement 1.. Amygdala EF and volume change.
To test the specificity of our measures in the left amygdala (FDR corrected finding) we permutated the labels across the 85 ROIs, both for the volume changes (left) and for the EF values (right) and calculated correlations between the EF and volume change of these regions, respectively. This way we received 85 different values, where one of them was the ‘correct’ correlation, indicated with red dots. The ‘correct’ correlations between the EF and corresponding volume outperformed the other correlations (were in the top five percentile) from non-matching pairs, indicating that our findings were not merely a general correlation with some average values across regions, further strengthening the casual link between EF and volume change.
Figure 5.
Figure 5.. Illustration of the methods.
We analyzed longitudinal structural MRI data from 151 individuals. We calculated the volume change and the magnitude of electrical field in 85 regions across the human cortex and subcortical structures.
Author response image 1.
Author response image 1.
See this image and copyright information in PMC

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References

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