Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, UK; NeuroImaging Center (NIC), Johannes Gutenberg University Medical Center, Germany.
Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark.
Brain Stimul. 2022 Sep-Oct;15(5):1153-1162. doi: 10.1016/j.brs.2022.07.049. Epub 2022 Aug 18.
Transcranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the electric field (E-field) induced in the cortex. Here, we tested whether the variability in the E-field in the stimulated cortex during anodal tDCS, estimated using computational simulations, explains the variability in tDCS induced changes in GABA, a neurophysiological marker of stimulation effect.
Data from five previously conducted MRS studies were combined. The anode was placed over the left primary motor cortex (M1, 3 studies, N = 24) or right temporal cortex (2 studies, N = 32), with the cathode over the contralateral supraorbital ridge. Single voxel spectroscopy was performed in a 2x2x2cm voxel under the anode in all cases. MRS data were acquired before and either during or after 1 mA tDCS using either a sLASER sequence (7T) or a MEGA-PRESS sequence (3T). sLASER MRS data were analysed using LCModel, and MEGA-PRESS using FID-A and Gannet. E-fields were simulated in a finite element model of the head, based on individual structural MR images, using SimNIBS. Separate linear mixed effects models were run for each E-field variable (mean and 95th percentile; magnitude, and components normal and tangential to grey matter surface, within the MRS voxel). The model included effects of time (pre or post tDCS), E-field, grey matter volume in the MRS voxel, and a 3-way interaction between time, E-field and grey matter volume. Additionally, we ran a permutation analysis using PALM to determine whether E-field anywhere in the brain, not just in the MRS voxel, correlated with GABA change.
In M1, higher mean E-field magnitude was associated with greater anodal tDCS-induced decreases in GABA (t(24) = 3.24, p = 0.003). Further, the association between mean E-field magnitude and GABA change was moderated by the grey matter volume in the MRS voxel (t(24) = -3.55, p = 0.002). These relationships were consistent across all E-field variables except the mean of the normal component. No significant relationship was found between tDCS-induced GABA decrease and E-field in the temporal voxel. No significant clusters were found in the whole brain analysis.
Our data suggest that the electric field induced by tDCS within the brain is variable, and is significantly related to anodal tDCS-induced decrease in GABA, a key neurophysiological marker of stimulation. These findings strongly support individualised dosing of tDCS, at least in M1. Further studies examining E-fields in relation to other outcome measures, including behaviour, will help determine the optimal E-fields required for any desired effects.
经颅直流电刺激（tDCS）在神经行为和生理研究以及神经康复中有着广泛的应用。然而，目前它受到了来自于个体间差异的限制，这种差异导致了在大脑皮层中诱导的电场（E-field）的变化。在这里，我们通过计算模拟来测试在阳极 tDCS 期间刺激皮层中的 E-field 的可变性是否可以解释 tDCS 诱导的 GABA 变化的可变性，GABA 是刺激效果的神经生理标志物。
合并了五项之前进行的 MRS 研究的数据。阳极放置在左侧初级运动皮层（M1，3 项研究，N=24）或右侧颞叶皮层（2 项研究，N=32），阴极放置在对侧眶上嵴上。在所有情况下，在阳极下都进行了 2x2x2cm 体素的单体素波谱。在使用 sLASER 序列（7T）或 MEGA-PRESS 序列（3T）进行 1mA tDCS 期间或之后，采集 MRS 数据。使用 LCModel 分析 sLASER MRS 数据，使用 FID-A 和 Gannet 分析 MEGA-PRESS 数据。基于个体结构磁共振成像，在头部的有限元模型中模拟 E-field，使用 SimNIBS。对于每个 E-field 变量（平均值和 95%分位数；幅度，以及在 MRS 体素内垂直和切向于灰质表面的分量），分别运行线性混合效应模型。该模型包括时间（tDCS 前后）、E-field、MRS 体素中的灰质体积以及时间、E-field 和灰质体积之间的三向相互作用的影响。此外，我们使用 PALM 进行了置换分析，以确定大脑中任何位置的 E-field（不仅在 MRS 体素内）是否与 GABA 变化相关。
在 M1 中，更高的平均 E-field 幅度与阳极 tDCS 诱导的 GABA 减少呈正相关（t(24)=3.24，p=0.003）。进一步的，平均 E-field 幅度与 GABA 变化之间的关系受到 MRS 体素中灰质体积的调节（t(24)=-3.55，p=0.002）。除了正常分量的平均值之外，这些关系在所有 E-field 变量中都是一致的。在颞叶体素中未发现 tDCS 诱导的 GABA 减少与 E-field 之间存在显著关系。在全脑分析中未发现显著的聚类。
我们的数据表明，tDCS 在大脑中诱导的电场是可变的，并且与阳极 tDCS 诱导的 GABA 减少显著相关，GABA 是刺激的关键神经生理标志物。这些发现强烈支持 tDCS 的个体化剂量，至少在 M1 中是如此。进一步研究 E-field 与其他结果测量（包括行为）之间的关系，将有助于确定任何预期效果所需的最佳 E-field。
