Susan Jeffrey

September 16, 2014

BOSTON — A new study shows that cognitive training using a commercially available game led to clinical improvements in patients with multiple sclerosis (MS), improvements that correlated with changes in connectivity seen on resting-state functional MRI (fMRI).

"After an 8-week home-based rehabilitation program, we showed increased thalamic connectivity in cortical areas that partially overlapped the posterior component of default mode-network," Laura De Giglio, MD, PhD, Sapiena University of Rome, Italy, concluded.

The increased connectivity positively correlated with improvement of cognitive performance, suggesting a compensatory role, she said. "So, we can suggest that these changes in thalamic functional connectivity induced by cognitive rehabilitation may represent a functional substrate underlying clinical recovery."

Their findings were presented here at MS Boston 2014, the 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS) meeting.

Common Complaint

Cognitive symptoms are common in MS, Dr. De Giglio noted, with a prevalence estimated between 35% and 60% of patients. Most commonly affected are processing speed, visual learning, and memory, resulting in deleterious effects on social interaction, occupation, and overall quality of life that are independent of physical functioning in the disease.

Dr. Laura De Giglio

No pharmacologic treatments are effective for cognitive issues in this setting, but the researchers' group has a study in press looking at cognitive computer-assisted, home-based rehabilitation as a means to address these problems. "To improve the treatment of cognitive deficit in MS, we have to understand mechanism," she noted, so they have used neuroimaging studies to look at this.

A study published in June 2014 in Radiology by their group showed that the thalamic resting-state network is disrupted in patients with MS, and the decreased performance in cognitive testing is associated with increased thalamo-cortical functional connectivity. "Our interpretation of this is that there are some neuroplastic changes in the thalamic resting state network in MS that are unable to fully compensate for tissue damage to prevent cognitive dysfunction," Dr. De Giglio said.

The aim of the current study was to see whether thalamic connectivity on fMRI can be modified by a home-based cognitive rehabilitation program. Patients with MS from the authors' center with failure on at least 1 of 3 tests — the Stroop Test (ST), Paced Auditory Serial Addition Test (PASAT), and Symbol Digit Modalities Test — took part in an 8-week home-based cognitive rehabilitation program using a commercially available cognitive training game (Dr. Kawashima's Brain Training, Nintendo DS) aimed at improving measures of attention, information processing, and executive function.

A total of 24 patients were asked to use the system at home for 30 minutes per day, 5 days per week, for 8 consecutive weeks. Adherence to the intervention could be ascertained from log-in information on the game console. Control patients were assigned to a waitlist for the rehabilitation intervention and were told they would receive their console at a later time. Patients with dementia or pathologic depression or anxiety were excluded, and 1 patient in each group was excluded because the data were not suitable for analysis.

All patients underwent clinical evaluation and 3T resting-state fMRI at baseline and after the 8-week intervention. The fMRI data were analyzed by using a seed-based method, with an a priori choice of the region of interest, to assess the functional connectivity of the thalamus with other brain areas, and identifying the thalamic resting-state network.

No difference was found in baseline clinical characteristics or thalamic connectivity between groups, and no clinical relapses or clinical disability worsening was seen during the study.

"With regard to clinical findings, we confirm our previous reports and show an increase in all the 3 cognitive tests, which reached significance for PASAT (P = .018) and the Stroop Test (P = .030)," Dr. De Giglio noted. "This is a little different from our previous work, in which we showed significant differences for all 3 tests," possibly because of the smaller sample size and patients with less impairment.

After intervention, thalamo-cortical functional connectivity showed significantly different patterns in the intervention group when compared with controls. "Moreover, we observed that an improvement in PASAT and ST scores after intervention was related with an increased thalamic functional connectivity in specific brain areas," the authors note.

Brenda L. Banwell, MD, chief of neurology at The Children's Hospital of Philadelphia, Pennsylvania, who comoderated the Young Investigators session where these results were presented, asked if the researchers planned to look at whether these benefits are maintained after the intervention period or whether continued practice would be necessary.

Dr. De Giglio noted some data in the literature suggest that benefits of cognitive training are maintained for 6 months or more, "so it would be very interesting to look at this." In these studies, the benefit was maintained without further intervention, she added, "but we can suppose that like for physical rehabilitation," it would eventually be lost without some further work.

Promising Area

This paper was selected as a conference highlight at the end of the meeting in a wrap-up talk on Clinical Research Highlights given by Ellen Mowry, MD, Johns Hopkins University, Baltimore, Maryland.

"This was a small study, but essentially patients received a Nintendo game called the Dr. Kawashima Brain Training Program, and some were randomized to receive the game and some were randomized to a waitlist," Dr. Mowry said.

"They were able to demonstrate that those who used this particular program for just 8 weeks had improvements in their PASAT scores and Stroop Test performance compared to those randomized to the wait list. There were corresponding changes in thalamic connectivity as well," she noted, "suggesting this is a very promising area in the future."

Dr. De Giglio has disclosed no relevant financial relationships.

MS Boston 2014, the 2014 Joint Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS/ECTRIMS) meeting: Abstract YI1.7. Presented September 10, 2014.

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