A pilot study of changes in functional brain activity during a working memory task after mSMT treatment: The MEMREHAB trial

Abstract

Background Working memory deficits are common in multiple sclerosis (MS). The modified Story Memory Technique (mSMT) has been shown to improve new learning and memory in MS, but its effects on working memory (WM) are currently unknown. Objective The present study presents a secondary analysis of data from a larger double-blind, placebo-controlled, randomized clinical trial and examines changes in cerebral activation on a WM task following mSMT treatment. Methods Sixteen participants with clinically definite MS were randomly assigned to treatment (n = 7) or placebo-control groups (n = 9) matched for gender, age and education. Baseline and immediate follow-up functional Magnetic Resonance Imaging (fMRI) was obtained for all subjects. During fMRI participants completed an N-back task, consisting of 0-, 1- and 2-back conditions. Results Significant increases in cerebral activation were noted in the dorsolateral prefrontal cortex, supplementary motor area and inferior parietal lobule at follow-up in the treatment group. No significant changes were noted in the placebo control group. Conclusion Due to the small sample size, results of the current study should be interpreted as preliminary. However, the observed pattern of activation of the frontoparietal network involved in WM found in the treatment group, suggests that mSMT training increases recruitment of attention- and WM-related neural networks. We conclude that mSMT treatment leads to changes in WM-related cerebral activation.

Beyond clinical changes: Rehabilitation-induced neuroplasticity in MS

“…Studies on the imagery- and context-based memory retraining program based on the modified Story Memory Technique showed an increased task-related activation of various associative areas of frontal, parietal, temporal, and occipital cortices 52,53,65 and cerebellum. 52,53 Increased RS-fMRI connectivity of hippocampus with insula, parietal cortex, and cerebellum as well as increased RS-fMRI connectivity of posterior cingulum and thalami were also reported.…”

“…10, Structural plasticity was investigated more often than functional plasticity following motor rehabilitation (nine articles) [36][37][38]40,41,[43][44][45]47 than following cognitive rehabilitation (four articles), 56,62,64,67 especially by means of DTI techniques. Functional plasticity was investigated in nine articles on motor rehabilitation 10,35,39,40,42,[45][46][47][48] and always following cognitive rehabilitation, [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] with both task-related fMRI and RS-fMRI in most articles. The effect of motor and cognitive rehabilitation on regional brain volumes was investigated in five articles; 41,44,45,56,67 just one article used a MTR-based technique.…”

“…Studies on cognitive rehabilitation, [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67] most of which were focussed on computer-assisted training of attention or working memory, provided findings that, to some extent, can be considered similar despite the heterogeneity in the adopted fMRI tasks and RS-fMRI analyses. Most of the articles provide indeed evidence of increased activation in rehabilitation-targeted areas at task-related fMRI and increased connectivity or reorganization of targeted brain networks at RS-fMRI (Table 3).…”

“…We identified 15 articles regarding motor rehabilitation and 19 articles on cognitive rehabilitation. 10,35–67 Structural plasticity was investigated more often than functional plasticity following motor rehabilitation (nine articles) 36–38,40,41,43–45,47 than following cognitive rehabilitation (four articles), 56,62,64,67 especially by means of DTI techniques. Functional plasticity was investigated in nine articles on motor rehabilitation 10,35,39,40,42,45–48 and always following cognitive rehabilitation, 49…”

The Role of Advanced Magnetic Resonance Imaging Techniques in Multiple Sclerosis Clinical Trials

“…Many multicenter studies have been performed by the MRI in MS group, demonstrating their feasibility [85]. A few small trials have investigated connectivity changes with task-related fMRI for cognitive rehabilitation with transcranial magnetic stimulation [86], with rs-fMRI for Nintendo® [87], and memory retraining (modified Story Memory Technique) [88]. Given these findings and small studies suggesting the between-scanner and between-subject reproducibility of rs-fMRI [89,90] and task-related fMRI [91] measures, there exists a significant potential for their use as key secondary outcomes in cognitive rehabilitation trials.…”