High-resolution modeling assisted design of customized and individualized transcranial direct current stimulation protocols

Abstract

Objectives: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity currents facilitating or inhibiting spontaneous neuronal activity. tDCS is attractive since dose is readily adjustable by simply changing electrode number, position, size, shape, and current. In the recent past, computational models have been developed with increased precision with the goal to help customize tDCS dose. The aim of this review is to discuss the incorporation of high-resolution patient-specific computer modeling to guide and optimize tDCS.

Methods: In this review, we discuss the following topics: 1) The clinical motivation and rationale for models of transcranial stimulation is considered pivotal in order to leverage the flexibility of neuromodulation; 2) the protocols and the workflow for developing high-resolution models; 3) the technical challenges and limitations of interpreting modeling predictions; and 4) real cases merging modeling and clinical data illustrating the impact of computational models on the rational design of rehabilitative electrotherapy.

Conclusions: Though modeling for noninvasive brain stimulation is still in its development phase, it is predicted that with increased validation, dissemination, simplification, and democratization of modeling tools, computational forward models of neuromodulation will become useful tools to guide the optimization of clinical electrotherapy.

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Role of computational models in rational electrotherapy: (left) Neuromodulation is a promising therapeutic modality as it allows affecting the brain in a way not possible with other techniques and a high degree of individualized optimization. The goal of computational models is to assist clinicians in leveraging the power and flexibility of neuromodulation. (right) Computational forward models are used to predict brain current flow during transcranial stimulation to guide clinical practice. As with pharmacotherapy, electrotherapy dose is controlled by the operator and leads a complex pattern of internal current flow that is described by the model. In this way, clinicians can apply computational models to determine with dose will activate (or avoid) brain regions of interest.

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Imaging and computational work-flow for the generation of high-resolution individualized models: Though the specific processes and software packages will vary across technical groups and applications, in each case high-resolution modeling initiated with precise anatomical scans that allow demarcation of key tissues. Tissues with distinct resistivity are used to form “masks”. These masks along with the representation of the physical electrodes are “meshed” to allow FEM calculations. The boundary conditions (generally simply reflecting how the electrodes are energized) and the governing equations (related to ohms law) are well established. The reproduction of the stimulation dose and the underlying anatomy thus allow for the prediction of resulting brain current. These current flow patterns are represented in false-color map and analyzed through various post-processing tools.

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Computational model of current flow in subjects with skull defects/plates. A defect in skull tissue which is the most resistive tissue in the head would hypothetically effect current flow in the underlying brain regions. Furthermore, the exact location of the defect (under/between the stimulation pads) in combination with the 'material' filling up the defect with the stimulation montage employed will influence induced current flow. Sample segmentation masks are shown on the left. A small defect under the anode pad (top right) leads to current flow in the cortex restricted to directly under the defect (avoiding the intermediate regions). A similar sized defect placed between the pads (bottom right) does not significantly alter current flow patterns in comparison with a healthy head with no defects.

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Computational models predict current flow during tDCS in subjects with lesions. Brain lesions, as occur during stroke, are considered to be largely cannibalized and replaced by CSF, which is significantly more conductive than brain. For this reason, brain current flow during tDCS is expected to be altered. A) Patient-specific left hemisphere stroke model. Two stimulation montages are illustrated, a conventional sponge montage (top right) and a high-definition montage (bottom right). B) Patient-specific visual stroke model. Segmentation masks (left) and induced current flow using the experimental montage (right).

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Individualized head model of a 12 yr old: Segmentation masks and induced current flow for motor cortex tDCS.