The impact of large structural brain changes in chronic stroke patients on the electric field caused by transcranial brain stimulation

Abstract

Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) are two types of non-invasive transcranial brain stimulation (TBS). They are useful tools for stroke research and may be potential adjunct therapies for functional recovery. However, stroke often causes large cerebral lesions, which are commonly accompanied by a secondary enlargement of the ventricles and atrophy. These structural alterations substantially change the conductivity distribution inside the head, which may have potentially important consequences for both brain stimulation methods. We therefore aimed to characterize the impact of these changes on the spatial distribution of the electric field generated by both TBS methods. In addition to confirming the safety of TBS in the presence of large stroke-related structural changes, our aim was to clarify whether targeted stimulation is still possible. Realistic head models containing large cortical and subcortical stroke lesions in the right parietal cortex were created using MR images of two patients. For TMS, the electric field of a double coil was simulated using the finite-element method. Systematic variations of the coil position relative to the lesion were tested. For TDCS, the finite-element method was used to simulate a standard approach with two electrode pads, and the position of one electrode was systematically varied. For both TMS and TDCS, the lesion caused electric field "hot spots" in the cortex. However, these maxima were not substantially stronger than those seen in a healthy control. The electric field pattern induced by TMS was not substantially changed by the lesions. However, the average field strength generated by TDCS was substantially decreased. This effect occurred for both head models and even when both electrodes were distant to the lesion, caused by increased current shunting through the lesion and enlarged ventricles. Judging from the similar peak field strengths compared to the healthy control, both TBS methods are safe in patients with large brain lesions (in practice, however, additional factors such as potentially lowered thresholds for seizure-induction have to be considered). Focused stimulation by TMS seems to be possible, but standard tDCS protocols appear to be less efficient than they are in healthy subjects, strongly suggesting that tDCS studies in this population might benefit from individualized treatment planning based on realistic field calculations.

Keywords: Brain lesions; Chronic stroke; Field simulations; Finite element method; Transcranial direct current stimulation; Transcranial magnetic stimulation.

Fig. 1

A) Coronal view of patient P01 with a cortical lesion in the right hemisphere. The top shows the T1-weighted MR image and the bottom the reconstructed head mesh. The view was chosen to include the lesion centre. The lesion is marked by red dashed circles. B) Corresponding view of patient P02 with a large subcortical lesion at a similar location in the right hemisphere. C) Corresponding view of the data set of the healthy control. D) The coil and electrode positions were systematically moved along two directions that were approximately perpendicular to each other. Five positions were manually placed every 2 cm in posterior – anterior direction symmetrically around the centre of the cortical lesion. The same was repeated along the lateral – medial direction. Both lines share the same centre position above the lesion, resulting in 9 positions in total. E) At each position, two coil orientations were tested which resulted in a current flow underneath the coil centre from anterior to posterior (top) and from lateral to medial, respectively (bottom). F) For each position of the yellow “stimulating” electrode, two positions of the blue return electrode were tested. First, the contralateral equivalent of the electrode position above the centre of the cortical lesion was used (top). In addition, a position on the contralateral forehead was tested (bottom).

Fig. 2

TMS simulations. A) Decay of the field strength underneath the coil centre with increasing stimulation depth. The results for patient P01 are compared with those of the healthy control. Mean curves averaged across both coil orientations and for groups of positions with similar distances to the lesion centre are shown. Top left: Results for the position directly above the lesion centre (indicated in green on the head model). Top right: Average of all positions directly neighbouring the lesion site (light blue spheres on the head model). Bottom left: Average of all positions distant to the lesion site (dark blue spheres on the head model). The vertical lines indicate the standard deviation. For none of the distances, a systematic difference between the results obtained for patient P01 and the healthy control is seen. B) Decay of the field strength with depth for patient P02, averaged across all nine positions and both coil orientations. The results are very similar to those of the healthy control. C) Sagittal cut through the head model of patient P01. The coil was positioned above the lesion centre (the green dots indicate a line perpendicular to the coil plane and starting at the coil centre) and the current orientation was anterior-posterior. The position at the lesion boundary highlighted by the red arrow experiences high field strengths, despite being distant to the coil centre. This effect is caused by the anterior-posterior currents induced in the lesion cavity which hit the gyrus approximately perpendicularly. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

TMS simulations. Grey matter volumes in [mm³] in which the field strength exceeds a threshold of 1.3 V/m. The results for patient P01 are shown as green bars, those for patient P02 are marked in blue and the data of the healthy control is coded in red. Overall, the volumes vary in a similar range across positions and orientations in the patient head models compared to the healthy control. A) Average plots over coil positions grouped according to their distance to the lesion centre (indicated on the head model shown in Fig. 2A). While a two-way ANOVA indicated differences between the head models (factor “subject” was significant at p = 0.01), pairwise comparisons of the volumes for the two patient heads with those of the healthy control were not significant (tested at p = 0.05 using post-hoc t-tests, corrected via Tukey's HSD). Factor “position” of the ANOVA was significant at p = 0.0066, the interaction between “subject” and “position” was not significant (p = 0.43). No statistical testing was performed for the positions above the lesion due to the low number of data points (one position with two coil orientations per head model). B) Detailed results for variation of the coil positions from posterior to anterior, with the coil orientation from anterior to posterior. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

TMS simulations. Anatomical features, which likely contribute to the variability in the stimulated grey matter volume. A) Electric field distribution for the most anterior coil position for the healthy control with the coil orientation from anterior-posterior. For this position, the grey matter volume above threshold was comparatively high (rightmost red bar in Fig. 3B). This is likely caused by a rather flat brain surface underneath the coil centre, as indicated by the red line. B) Electric field distribution for the most posterior coil position for the healthy control with the same coil orientation as in A. The grey matter volume above threshold is lower in this case (leftmost red bar in Fig. 3B), likely caused by the higher local curvature of the brain surface (as indicated by the red line). C) Electric field distribution on the grey matter surface of the healthy control for the most medial coil position with the current flow in anterior-posterior direction. D) Field distribution for the same coil position as used in C, but for patient P01. The gyri underneath the coil centre seem to be less densely packed compared to the healthy control, resulting in a smaller grey matter volume above threshold (leftmost red and green bars in Fig. 3C). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 5

TDCS simulations. A) Average depth profiles for TDCS applied to the head model of patient P01 (green). The profiles were assessed underneath the stimulation electrode above the right hemisphere, averaged across all nine tested electrode positions. The vertical lines indicate the standard deviation. The results obtained for the healthy control are shown for comparison (red). Left: Return electrode above the contralateral forehead. Right: Return electrode above the contralateral parietal cortex, created by mirroring the electrode position directly above the lesion. Except for the very superficial cortex, the field strength in the head model with the cortical lesion is consistently lower than seen in the healthy control. B) Average field profiles for patient P02, averaged across all nine positions. The results are very similar to those obtained for the model of the cortical lesion. The position of the return electrode is above the left forehead (left) and the parietal cortex (right). C) Detailed results for patient P01 (return on the left forehead, variation of electrode position from lateral to medial). At some positions, an increase in the field strength close to the brain surface is clearly visible. Similarly, a slight increase in the field strength rather deep in the brain (~ 45 mm) is observed for some positions. Both effects are highlighted by red arrows. They are further investigated in Fig. 7 and the corresponding parts of the Results section. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 6

TDCS simulations. Grey matter volumes in which the field strength is above 0.15 V/m (green: P01; blue: P02; red: healthy control). The most striking observation are the much lower volumes, which are affected in the lesion models compared to the healthy control. A) Average plots over electrode positions grouped according to their distance to the lesion centre (indicated on the head model shown in Fig. 2A). For the two patient head models, significant differences to the healthy control are marked by the asterisk (p < 0.05; post-hoc pairwise t-tests, corrected via Tukey's HSD). Factor “subject” of the underlying two-way ANOVA was highly significant (p = 1.4e−23), while factor “position” was not (p = 0.63). The interaction was not significant (p = 0.61). No statistical testing was performed for the positions above the lesion due to the low number of data points (one position with two positions of the return electrode per head model). B) Detailed results for variation of the electrode positions from lateral to medial with the return electrode over the left parietal cortex. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 7

TDCS simulations. Selected examples depicting the occurrence of localized “hot spots” of the electric field distribution in case of TDCS stimulation. A) Patient P01: Coronal cut through grey matter when placing the stimulation electrode just lateral to the lesion and the return electrode above the left forehead (corresponding to the orange line in Fig. 5C). There are several grey matter structures, which experienced high field strength. The hot spot directly underneath the stimulation electrode (indicated by the red arrow) is caused by the currents passing from superficial CSF to the CSF in the lesion. B) Patient P02: Coronal cut through grey matter with the stimulation electrode placed at the medial position and the return electrode above the left parietal cortex. Surprisingly, a small hot spot distant to the electrodes occurs in the right hemisphere (indicated by the red arrow). This is caused by a current pathway through CSF, as favoured by its comparatively good conductivity. Starting in superficial CSF, it goes further into the lesion cavity (thereby causing the hotspot in GM), the ventricles and back into superficial CSF. C) Coronal cut through the head model of patient P01. The return electrode is placed on the left forehead and three positions of the stimulation electrode are shown (most posterior, centrally above the lesion and most anterior). The transition area between lesion and the ventricle continuously experiences high field strength. This results again from currents, which flow predominantly within CSF. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)