If tDCS continues to be revealed as a viable option for treatment in chronic stroke, the consideration of tDCS-generated current flow through the brain is of fundamental importance for the identification of candidates, optimization of electrotherapies for specific brain targets, and interpretation of patient-specific results - thus the ability to individualize tDCS therapy must be leveraged. Whereas, tDCS electrode montages are commonly designed using “gross” intuitive rules (e.g., anode positioned “over” the target region), our results reinforce the complexity of current flow, including the critical importance of “return” electrode positioning (19
), and thus the value of applying predictive modeling as one tool in the rational design of safe and effective electrotherapies. Moreover, our results support the value of individualized models and therapy design because of the profound effect of cortical damage on overall current flow.
Our high-resolution individualized tDCS model predicts current flow (electric field) through each brain region. Though it is rational to speculate that those regions with higher electric fields will be more likely candidates for brain modulation - and thus electrode montages should be selected to maximize currents in “target” regions – there remain fundamental unknowns about both the neurophysiology of prolonged weak DC stimulation and the processes of stroke recovery. There are indeed competing or complementary views of optimal brain activation/de-activation to facilitate stroke recovery. Regardless of the conceptual treatment strategy, it is critical to know the resulting brain current flow for a given montage – and because of this complexity, requires individualized high-resolution modeling, as shown here. Indeed, these models thus provide a needed substrate to distinguish between therapeutic hypotheses precisely because simplistic and non-individualized conceptions about brain current flow are insufficient.
Specifically, without models such as the one presented here, it will be difficult to understand the importance of electrode placement upon tDCS treatment outcome. For example, we have shown before that aphasia treatment success in stroke patients is supported by left-hemisphere brain plasticity (13
). If tDCS can be used to enhance brain plasticity in the left hemisphere, then it will be crucial to ensure that greatest stimulation occurs in left hemisphere regions. It is noteworthy that Montage A which produced significant benefit for the case-study subject also produced maximal stimulation of the posterior peri-lesional cortex, which was precisely the region of interest identified through fMRI analysis prior to therapy. Naturally, future research will have to adjudicate whether detailed, patient-specific electrode placement is crucial for tDCS benefit or if the same electrode placement can be applied to all patients, regardless of lesion location. We are currently working to solve this issue.
The tools developed for this case-report represent an important advancement in high-resolution individualized modeling. The high spatial resolution makes it possible to resolve/segment thin structures more accurately which in turn leads to more precise/accurate - and hence individualized - 3D rendering. An accurate 3D model allows for the precise computation of current flow and evaluation of individual factors, especially defects (11
) and lesions. Preservation of 1 mm resolution in our models, led to several features being accurately captured (for example: true lesion borders, cortical folds, zygomatic arch/process, foramen magnum, contiguous CSF layer and ventricular architecture, etc.). For example, the general position of the lesion resulted in distinct brain-wide current flow distortion for each montage. On a still finer level, the precise representation of the peri-lesional region revealed detailed, but pronounced, differences across montages.
Continued technical improvements are indicated. Namely, further automation of the modeling process (critical for economical and broad dissemination) and additional sophistication in the imaging and modeling tissue properties around lesions is needed. Ultimately neural activation is predicted by directly coupling field data to multi-compartment biophysical models of individual neurons (20
). However it becomes unfeasible to incorporate neuron models of the entire cortex (with multiple different classes of neurons) in a macroscopic model presented here. Conversely, even as we demonstrate the value of precise and individualized anatomical representation, the use of generic and simplified geometries in a) spheres (14
) and b) idealized lesions/defects (7
) will continue to inform overall approaches to montage design.
In closing, the accuracy of predictions using forward models is limited by the precise representation of anatomy. Our development of high-resolution individualized models is thus an important advancement towards the use of computer models to retrospectively analyze results and prospectively design optimal electrotherapies.