The primary outcome of the sham-controlled trial was fatigue, but the findings presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) focused on a secondary cognitive measure, called the Brief International Cognitive Assessment for MS (BICAMS).
The intervention may still be a work in progress as far as a treatment technique “but the more important point is that there is a path to remote cognitive rehab interventions which, as a concept, is important,” said Mark Gudesblatt, MD, medical director at South Shore Neurologic Associates in Patchogue, N.Y., who was asked to comment on the study.
Adaptive mechanisms
The study grew out of work done with BrainHQ, which is a brain-training program available commercially through Posit Science. It employs an algorithm to recommend and tailor exercises for participants and to adjust the difficulty of the exercises in order to maintain engagement. “We believe the key ingredient is really the adaptive mechanisms that adjust to users in real time, for instance slowing down when the user slows down or speeding up to drive the learning to maintain a level of engagement. The games are designed to target processing speed that then has a transfer effect to other aspects of cognitive function,” Leigh Charvet, PhD, said during her presentation of the study results. Dr. Charvet is director of MS research and a professor of neurology at New York University.
The researchers previously conducted a large trial in patients with MS and showed that the adaptive mechanism, used for 60 hours over 12 weeks, could improve cognitive functioning. “We had two learnings from that trial: One that the brain training in at least a very intense dose was beneficial for cognitive functioning, and the second was that at-home treatments are very popular,” said Dr. Charvet.
In the most recent trial, the researchers turned to tDCS in an effort to boost the effect of brain training. “The idea is that if you can stimulate the region of the brain that is engaged with the training activity, you can boost or potentiate the outcomes of the training,” said Dr. Charvet. The tDCS treatment applies 1.0-4.0 mA current to the scalp, where it can be placed to specifically affect a brain region of interest. The study targeted the dorsolateral prefrontal cortex, which is a key region for executive function and cognitive flexibility.
The team developed a protocol that would allow the intervention to be conducted at home, with live supervision via HIPAA-compliant teleconferencing and technology that was designed for ease of use. The tDCS devices were preprogrammed and operated on an unlock code, which initiated active or sham tDCS. “We replicated onsite lab standards, but delivered it to people at home,” said Dr. Charvet.
In the new study, 106 patients with MS who had fatigue, but not depression, underwent 30 20-minute training sessions over a 6-week period, with active or sham tDCS. The participants were tested before and after treatment using the BICAMS. The sham group had a mean change of –0.17 in the BICAMS z score, compared with a mean of +0.05 in the tDCS group (P = .027).
One of the tests that make up the BICAMS battery, the single digit modalities test (SDMT), showed a trend toward improvement in the tDCS group (z sore, +0.09 versus –0.19; P = .058). There was no significant difference between the groups In the Rey’s Auditory Verbal Learning Test or the Brief Visuospatial Memory Test–Revised.
What about fatigue?
The emphasis on a secondary outcome drew some criticism. “It’s odd, because the primary outcome was fatigue. They didn’t report the primary outcome, they focused on a secondary outcome of cognitive measure,” said Patricia Coyle, MD, who was asked to comment on the study.
“I think the most important finding in this study was that they were able to deliver the transcranial direct current stimulation at home, via computer. They were able to do this study by computer with their patients at home, and it was a fairly large number. You could consider it broadly as a proof of principle that this can be done,” said Dr. Coyle, professor of neurology and director of Stony Brook MS Comprehensive Care Center.
The study was funded by the National MS Society. Dr. Gudesblatt has no relevant financial disclosures. Dr. Coyle has consulted or received speaker fees from Accord-ant, Alexion, Biogen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Dr. Coyle has received research funding from Actelion, Alker-mes, Celgene, CorEvitas LLC, Genentech/Roche, MedDay, Novartis, and Sanofi Genzyme.