Table 2: Summary of Status, Issues, and Solution for tDCS Studies.
| Current Status | Key Issues | Potential Solutions | |
|---|---|---|---|
| Interhemispheric imbalance model | - Lesioned hemisphere shows lower excitability while the contralesional hemisphere shows normal or increased excitability. | - Model is simplified and does not generalize to all strokes - Stimulation location (lesional vs contralesional cortex) and timeline to stimulate (acute vs. chronic stage) will need to be determined |
- Dedicated clinical trials to evaluate the effects of anodal/cathodal stimulation at lesional/contralesional cortices at sub-acute or chronic stages of stroke. - further validate the model or develop a better model |
| Stimulation montages | - Anodal stimulation on lesioned hemisphere; cathodal stimulation on contralesional hemisphere; or simultaneous bihemispheric stimulation were all tested; - Meta-analysis shows bihemispheric stimulation is likely advantageous |
- Studies comparing efficacy among all three montages are lacking, and the effect size is unknown. | - Proof of concept study to examine electric field distribution across different montages; - Four-arm clinical trial comparing anodal, cathodal, bihemispheric and sham tDCS intervention are needed. |
| tDCS response variability and modeling | - High inter-subject variability noted possibly due to factors like scalp fat, head size, anisotropy, montage, lesion size, time since stroke (chronic vs. acute), small vessel lesion load, membrane around a cystic lesion, etc. | - Lack of experimental validation of simulation models; - No imaging or behavioral marker for patient selection. |
- Experimental measurement of intracranial electric fields in human subjects and use of this information to validate/refine existing simulation models; - Investigate whether behavioral, imaging or neurophysiology tool or combination can be used to predict therapeutic response. - Consider personalized/biomarker approach in tDCS research |
| Optimal stimulation dose and safety concerns | - Dose-response relationship is observed in current density, charge density, but not conventional current level in meta-analysis; - At least 2 orders of magnitude higher dose were safely administered in animal models. |
- Only up to 2 mA current with different pad sizes are tested, i.e., dose-response relationship was only observed in the range of 0.03–0.09 mA/cm²; - Safety, especially long-term safety, beyond 2 mA is unknown in humans. |
- Dedicated phase I dosage escalation and safety study; - Phase II equivalent dose-response study to find the most efficacious dosage; - Proof-of-concept study towards “individualized” dosage towards achieving comparable “targeted” dose. |
| Subject selection | - Effect size is not well defined in tDCS trial yet. - Patient selection was an issue in the past studies. |
- Lack of appropriate patient selection can likely lead to failure or small effect size of the study. | - Use of behavioral assessment, imaging marker and/or TMS as tools for patient selection. |
| Choice of Peripheral Therapy | - Various peripheral therapy options were used, including robotic, virtual reality, regular occupational therapy. | - Lack of standardization, quantification of these therapy protocol - Therapy dose may not be equal between active and sham group |
- Control therapy dose between groups - Choose peripheral therapy that can be standardized, such as. CIMT therapy |
| Outcome measures | - Majority of proof-concept of trials did not incorporate comprehensive hierarchy outcome measures; - the group difference was assessed for statistical significance only; - various outcomes were used. |
- Statistical significance may not be clinically meaningful; - Not all outcome measure used in the literature have been well validated |
- Only include outcomes with well-defined psychometric property and MCID. - Addressed outcomes in three aspects: motor impairment, functional improvement, and quality of life |