Transcranial Direct Current Stimulation in Neurodegenerative Disease

• ¹ Johns Hopkins University School of Medicine, Neurology, United States

We review rationale, challenges, study designs, reported results, and future directions in the use of transcranial direct cranial stimulation (tDCS) in neurodegenerative disease, focusing on treatment of spelling in primary progressive aphasia (PPA). Rationale Evidence from both animal studies and human studies indicates that anodal and cathodal tDCS over the brain result in a temporary change in membrane potentials, reducing the threshold for long-term potentiation of neurons in the affected area. This may allow unaffected brain regions to assume functions of diseased regions. Challenges Special challenges in treating individuals with progressive conditions include altered goals of treatment and the possibility that participants may accumulate new deficits over the course of the treatment program that interfere with their ability to understand, retain, or cooperate with aspects of the program. The most serious challenge – particularly for single case designs - is that there may be no stable baseline against which to measure change with treatment. Thus, it is essential to demonstrate that treatment results in a statistically significant change in the slope of decline or improvement. Therefore, demonstration of a significant difference between tDCS and control (sham) requires either a large number of participants or a large effect size. Designs The choice of a treatment design reflects these limitations. Group studies with a randomized, double-blind, sham control trial design (without cross-over) provide the greatest power to detect a difference between intervention and control conditions, with the fewest participants. A cross-over design, in which all participants (from 1 to many) receive both active and sham conditions, in randomized order, requires a larger effect size for the active condition relative to the control condition (or little to no maintenance of treatment gains or carry-over effect) to show significant differences between treatment and control conditions. Stimulation site The stimulation site may be chosen on the basis of the most atrophied area (e.g. homologous to that area) or an area of activation based on fMRI. Alternatively, one can select the site on the basis of the language process to be treated, or select from a set of sites on the basis of the language process to be treated, and exclude sites where there is significant atrophy. Observations to Date While several studies have incorporated tDCS in treatment of recognition memory and in Alzheimer’s disease, effective use of tDCS to treat language in neurodegenenerative disease has primarily been in primary progressive aphasia (PPA). We will illustrate its use in aphasia by reporting results of a series of single case cross-over studies of spelling therapy plus left inferior frontal anodal tDCS versus spelling therapy plus sham. Results indicate that both conditions result in temporary improvement of spelling, but significantly greater maintenance of treatment gains and generalization to untrained stimuli and tasks after tDCS condition relative to sham. Future Directions Future studies must determine the most effective way to improve maintenance of treatment results and determine the mechanisms by which tDCS augments language therapy.