Research Article

Neuroscience

Electric field causes volumetric changes in the human brain

The Zucker Hillside Hospital, United States
Center for Neuroscience, Feinstein Institute for Medical Research, United States
Zucker School of Medicine, United States
University of Bergen, Norway
Haukeland University Hospital, Mohn Medical Imaging and Visualization Centre, Norway
National Institute of Mental Health, United States
University of California, Los Angeles, United States
The City College of the City University of New York, United States
University of California, San Diego, United States
Bellvitge University Hospital-IDIBELL, Spain
CIBERSAM, Carlos III Health Institute, Spain
University of Muenster, Germany
Amsterdam UMC, location VUmc, GGZinGeest, Old Age Psychiatry, Amsterdam Neuroscience, Netherlands
Haukeland University Hospital, University of Bergen, Norway
Keio University School of Medicine, Japan
Center for Psychiatry and Behavioral Science, Komagino Hospital, Japan
KU Leuven, Belgium
Hospital del Mar, Spain
Radboud University Medical Center, Netherlands
Donders Institute for Brain Cognition and Behavior, Centre for Cognitive Neuroimaging, Netherlands
University of Duisburg-Essen, Germany
University of New Mexico School of Medicine, United States

Oct 23, 2019

https://doi.org/10.7554/eLife.49115

Open access
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Figures
Tables
Additional files

6 figures, 2 tables and 8 additional files

Figures

Figure 1

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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 1—source data 1 Mean electric field and volume change in 85 brain regions.: https://cdn.elifesciences.org/articles/49115/elife-49115-fig1-data1-v2.csv
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Figure 2

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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 2—source data 1 Mean electric field and volume change asymteries in corresponding 42 brain regions.: https://cdn.elifesciences.org/articles/49115/elife-49115-fig2-data1-v2.csv
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Figure 3 with 1 supplement

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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—source data 1 Left and right hippocampal EF and volume change in 151 individual.: https://cdn.elifesciences.org/articles/49115/elife-49115-fig3-data1-v2.csv
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Figure 3—figure supplement 1

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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 3—figure supplement 1—source data 1 Hippocampal EF and volume change: permutation values.: https://cdn.elifesciences.org/articles/49115/elife-49115-fig3-figsupp1-data1-v2.csv
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Figure 4 with 1 supplement

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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—source data 1 Left and right amygdala EF and volume change in 151 individual.: https://cdn.elifesciences.org/articles/49115/elife-49115-fig4-data1-v2.csv
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Figure 4—figure supplement 1

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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 4—figure supplement 1—source data 1 Amygdala EF and volume change: permutation values.: https://cdn.elifesciences.org/articles/49115/elife-49115-fig4-figsupp1-data1-v2.csv
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Figure 5

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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

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Tables

Table 1

The relationship between volume changes and EF across individuals (Δ Vol ~ EF + Age + ECTnum).

	roi	t_EF	p_EF	t_Age	t_ECTnum	BH^EF_FDR
1	Δ VOL_{Left.Cerebellum.Cortex}	−0.3668	0.7143	−0.1150	1.9368	0.8205
2	Δ VOL_{Left.Thalamus.Proper}	0.0244	0.9805	−0.4046	2.8696	0.9952
3	Δ VOL_Left.Caudate	0.6555	0.5132	−0.8301	2.6428	0.6924
4	Δ VOL_Left.Putamen	0.5737	0.5671	−0.5992	1.3203	0.7212
5	Δ VOL_{Left.Pallidum}	0.0060	0.9952	0.1026	1.2295	0.9952
6	Δ VOL_Brain.Stem	1.2114	0.2278	0.8536	1.2309	0.4466
7	Δ VOL_{Left.Hippocampus}	4.5102	0.0000	−2.6814	3.3221	0.0012
8	Δ VOL_{Left.Amygdala}	3.9069	0.0001	−1.0572	2.1018	0.0061
9	Δ VOL_{Left.Accumbens.area}	2.0238	0.0449	−3.4456	1.7246	0.1737
10	Δ VOL_{Left.VentralDC}	0.1740	0.8621	0.0605	2.2614	0.9395
11	Δ VOL_{Right.Cerebellum.Cortex}	−0.5564	0.5788	0.0677	1.3212	0.7235
12	Δ VOL_{Right.Thalamus.Proper}	0.4582	0.6475	0.3541	4.0787	0.7712
13	Δ VOL_{Right.Caudate}	1.2293	0.2210	1.0254	1.5097	0.4466
14	Δ VOL_{Right.Putamen}	1.0724	0.2854	−0.5112	1.4987	0.4756
15	Δ VOL_{Right.Pallidum}	0.6045	0.5465	0.8016	2.9589	0.7181
16	Δ VOL_{Right.Hippocampus}	1.5090	0.1336	−1.2924	3.2473	0.3441
17	Δ VOL_{Right.Amygdala}	2.9945	0.0032	−0.6087	4.2603	0.0344
18	Δ VOL_{Right.Accumbens.area}	1.9563	0.0524	−0.8782	3.5228	0.1937
19	Δ VOL_{Right.VentralDC}	0.3488	0.7278	0.5197	0.7438	0.8248
20	Δ VOL_{ctx.lh.bankssts}	1.1757	0.2417	−0.4102	2.5801	0.4466
21	Δ VOL_{ctx.lh.caudalanteriorcingulate}	1.3404	0.1823	−1.2881	2.2330	0.4254
22	Δ VOL_{ctx.lh.caudalmiddlefrontal}	−1.8989	0.0596	−0.3804	2.0087	0.2112
23	Δ VOL_{ctx.lh.cuneus}	0.9827	0.3274	0.1037	2.0348	0.5352
24	Δ VOL_{ctx.lh.entorhinal}	3.2229	0.0016	−1.2447	1.6659	0.0335
25	Δ VOL_{ctx.lh.fusiform}	3.0717	0.0026	−0.1806	2.1319	0.0344
26	Δ VOL_{ctx.lh.inferiorparietal}	1.5131	0.1325	0.8515	2.3077	0.3441
27	Δ VOL_{ctx.lh.inferiortemporal}	2.6985	0.0078	0.6415	1.9131	0.0577
28	Δ VOL_{ctx.lh.isthmuscingulate}	−0.3275	0.7438	−0.4344	2.9060	0.8319
29	Δ VOL_{ctx.lh.lateraloccipital}	1.1916	0.2354	0.3669	1.2752	0.4466
30	Δ VOL_{ctx.lh.lateralorbitofrontal}	1.4274	0.1557	−0.0081	1.5758	0.3780
31	Δ VOL_{ctx.lh.lingual}	0.1391	0.8896	0.3506	2.4745	0.9572
32	Δ VOL_{ctx.lh.medialorbitofrontal}	1.0744	0.2845	−0.1246	1.1852	0.4756
33	Δ VOL_{ctx.lh.middletemporal}	2.0679	0.0405	−0.3780	2.2600	0.1720
34	Δ VOL_{ctx.lh.parahippocampal}	1.2683	0.2068	−0.2446	2.8373	0.4466
35	Δ VOL_{ctx.lh.paracentral}	−2.0829	0.0391	0.2511	4.0937	0.1720
36	Δ VOL_{ctx.lh.parsopercularis}	−0.6949	0.4883	−0.7822	1.8435	0.6694
37	Δ VOL_{ctx.lh.parsorbitalis}	0.8057	0.4218	−1.0427	0.9524	0.6289
38	Δ VOL_{ctx.lh.parstriangularis}	0.8228	0.4120	−1.2157	2.7977	0.6254
39	Δ VOL_{ctx.lh.pericalcarine}	0.4426	0.6587	−0.0479	1.8463	0.7712
40	Δ VOL_{ctx.lh.postcentral}	0.8692	0.3862	−1.7655	2.5145	0.5969
41	Δ VOL_{ctx.lh.posteriorcingulate}	−0.8698	0.3859	−0.6961	3.3193	0.5969
42	Δ VOL_{ctx.lh.precentral}	−0.7279	0.4679	−1.2884	2.4234	0.6682
43	Δ VOL_{ctx.lh.precuneus}	−1.5879	0.1145	−0.4353	3.6729	0.3441
44	Δ VOL_{ctx.lh.rostralanteriorcingulate}	1.3315	0.1852	−0.4449	0.5630	0.4254
45	Δ VOL_{ctx.lh.rostralmiddlefrontal}	−0.7192	0.4732	−1.6205	1.1936	0.6682
46	Δ VOL_{ctx.lh.superiorfrontal}	−1.2073	0.2293	−0.5851	2.1065	0.4466
47	Δ VOL_{ctx.lh.superiorparietal}	−1.7423	0.0836	0.6952	3.3288	0.2734
48	Δ VOL_{ctx.lh.superiortemporal}	2.2820	0.0240	−2.0868	1.6393	0.1199
49	Δ VOL_{ctx.lh.supramarginal}	0.5717	0.5685	−0.2467	2.1282	0.7212
50	Δ VOL_{ctx.lh.frontalpole}	−0.2029	0.8395	−0.2904	0.4776	0.9267
51	Δ VOL_{ctx.lh.temporalpole}	2.5288	0.0125	−0.0731	1.3167	0.0762
52	Δ VOL_{ctx.lh.transversetemporal}	0.4387	0.6616	−0.4617	2.1817	0.7712
53	Δ VOL_{ctx.rh.bankssts}	0.1121	0.9109	2.0777	2.9991	0.9678
54	Δ VOL_{ctx.rh.caudalanteriorcingulate}	−1.4295	0.1551	1.2935	2.4016	0.3780
55	Δ VOL_{ctx.rh.caudalmiddlefrontal}	−2.9569	0.0036	1.6943	2.6065	0.0344
56	Δ VOL_{ctx.rh.cuneus}	−0.0087	0.9930	−1.1806	2.4017	0.9952
57	Δ VOL_{ctx.rh.entorhinal}	1.2514	0.2129	0.7897	2.4722	0.4466
58	Δ VOL_{ctx.rh.fusiform}	1.5380	0.1263	0.7997	4.7854	0.3441
59	Δ VOL_{ctx.rh.inferiorparietal}	−2.9902	0.0033	1.6520	0.7114	0.0344
60	Δ VOL_{ctx.rh.inferiortemporal}	0.9300	0.3540	1.9310	3.3455	0.5677
61	Δ VOL_{ctx.rh.isthmuscingulate}	0.0325	0.9741	0.4230	1.1493	0.9952
62	Δ VOL_{ctx.rh.lateraloccipital}	1.1796	0.2401	0.6095	1.5161	0.4466
63	Δ VOL_{ctx.rh.lateralorbitofrontal}	0.5347	0.5937	0.3393	2.9240	0.7314
64	Δ VOL_{ctx.rh.lingual}	−0.0753	0.9401	−1.9555	3.5258	0.9865
65	Δ VOL_{ctx.rh.medialorbitofrontal}	0.7090	0.4795	1.5479	2.3419	0.6682
66	Δ VOL_{ctx.rh.middletemporal}	−0.6005	0.5492	2.1275	3.6781	0.7181
67	Δ VOL_{ctx.rh.parahippocampal}	1.5217	0.1303	0.5057	3.1874	0.3441
68	Δ VOL_{ctx.rh.paracentral}	−3.5101	0.0006	2.1809	2.2718	0.0170
69	Δ VOL_{ctx.rh.parsopercularis}	−2.5585	0.0116	2.8854	2.9459	0.0756
70	Δ VOL_{ctx.rh.parsorbitalis}	1.0872	0.2788	−0.5812	2.3737	0.4756
71	Δ VOL_{ctx.rh.parstriangularis}	−1.2468	0.2146	1.0686	2.6086	0.4466
72	Δ VOL_{ctx.rh.pericalcarine}	1.5878	0.1146	−0.0096	2.2815	0.3441
73	Δ VOL_{ctx.rh.postcentral}	−1.7565	0.0812	1.2943	3.0605	0.2734
74	Δ VOL_{ctx.rh.posteriorcingulate}	−1.5171	0.1315	2.0716	1.4731	0.3441
75	Δ VOL_{ctx.rh.precentral}	−2.4918	0.0139	0.9967	3.7013	0.0762
76	Δ VOL_{ctx.rh.precuneus}	−2.0231	0.0450	−0.1921	2.5419	0.1737
77	Δ VOL_{ctx.rh.rostralanteriorcingulate}	2.2083	0.0288	1.3734	2.3606	0.1362
78	Δ VOL_{ctx.rh.rostralmiddlefrontal}	−2.6842	0.0081	0.5804	2.2235	0.0577
79	Δ VOL_{ctx.rh.superiorfrontal}	−3.0013	0.0032	1.1011	3.2699	0.0344
80	Δ VOL_{ctx.rh.superiorparietal}	−2.7495	0.0067	0.9014	2.0779	0.0574
81	Δ VOL_{ctx.rh.superiortemporal}	0.4377	0.6623	1.2455	4.4002	0.7712
82	Δ VOL_{ctx.rh.supramarginal}	−2.4794	0.0143	2.7408	3.0429	0.0762
83	Δ VOL_{ctx.rh.frontalpole}	1.1256	0.2623	−0.1784	1.9185	0.4644
84	Δ VOL_{ctx.rh.temporalpole}	0.7274	0.4682	0.5099	3.7696	0.6682
85	Δ VOL_{ctx.rh.transversetemporal}	1.1426	0.2551	0.6448	3.2405	0.4614

Table 2

Clinical and demographics summary.

Table 2A Overall Summary
Site	N		Age (sd)	Medications (med. free, SSRI/SNRI, TCA, AP*)	Average number of ECT	Baseline MADRS	Δ MADRS (%)
All	151		57.5 (17.1)	69,65,10,62	10.6	33.9	61.3
Female	92		56.4 (18.4)	42,36,8,42	10.4	34.4	63.4
Male	59		59.3 (14.7)	27,29,2,20	10.9	33.3	58.1
Table 2B Site Summary
Site	N	Age (mean)	Age (sd)			Baseline MADRS	Δ MADRS (%)
1	30	39.87	12.68			40.73	45.12
2	33	64.48	8.93			31.36	69.48
3	16	73.62	12.45			29.56	77.24
4	23	46.87	9.19			29.96	43.18
5	2	62.50	0.71			36.75	32.03
6	18	48.50	16.77			33.83	57.12
7	29	72.66	7.57			35.07	79.13

^*med. free: medication free, SSRI: selective serotonin reuptake inhibitor, SNRI: serotonin and norepinephrine reuptake inhibitors, TCA: tricyclic antidepressants, AP: antipsychotic medications, there were not patients on MAO inhibitors.

Additional files

Source code 1 Once EF and ΔVol were collected across 85 ROI in 151 subjects, all the rest of the calculations were carried out in R environment. This file is the source code of these calculations organized in org-mode (https://orgmode.org/) for reproducibility.: https://cdn.elifesciences.org/articles/49115/elife-49115-code1-v2.org
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Supplementary file 1 Volume changes following electroconvulsive treatment (ECT). One sample t-test in each ROIs. The table indicates t, uncorrected p, Cohen’s d effect size, and FDR corrected p values. This sample is a sub-cohort of a recent publication of 331 subjects (Ousdal et al., 2019). In contrast with that publication we included patients with RUL only electrode placement.: https://cdn.elifesciences.org/articles/49115/elife-49115-supp1-v2.docx
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Supplementary file 2 The laterality of volume changes after RUL ECT. The table contains the results of 42 pairwise t-tests between the volume changes of the right and the left side of the corresponding regions. The table indicates t, uncorrected p, mean, Cohen’s d effect size and FDR corrected p values.: https://cdn.elifesciences.org/articles/49115/elife-49115-supp2-v2.docx
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Supplementary file 3 The relationship between clinical response and volume change across individuals. The table indicates the t values of the corresponding clinical covariates modeled as fixed effects: volume change, age, and number of ECT.: https://cdn.elifesciences.org/articles/49115/elife-49115-supp3-v2.docx
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Supplementary file 4 The relationship between clinical response and electric field across individuals. The table indicates the t values of the corresponding clinical covariates modeled as fixed effects: electric field, age, and number of ECT.: https://cdn.elifesciences.org/articles/49115/elife-49115-supp4-v2.docx
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Supplementary file 5 The relationship between the baseline volume and age across 85 ROIs.: https://cdn.elifesciences.org/articles/49115/elife-49115-supp5-v2.docx
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Supplementary file 6 MRI summary. The table indicates the parameters of the structural image acquisition across sites.: https://cdn.elifesciences.org/articles/49115/elife-49115-supp6-v2.docx
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Transparent reporting form: https://cdn.elifesciences.org/articles/49115/elife-49115-transrepform-v2.pdf
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