Reproducibility of Resting State Connectivity in Patients with Stable Multiple Sclerosis.

Given increasing efforts to use resting-state fMRI (rfMRI) as a biomarker of disease progression in multiple sclerosis (MS) we here explored the reproducibility of longitudinal rfMRI over three months in patients with clinically and radiologically stable MS. To pursue this aim, two approaches were applied in nine rfMRI networks: First, the intraclass correlation coefficient (ICC 3,1) was assessed for the mean functional connectivity maps across the entire network and a region of interest (ROI). Second, the ratio of overlap between Z-thresholded connectivity maps for each network was assessed. We quantified between-session functional reproducibility of rfMRI for 20 patients with stable MS and 14 healthy controls (HC). Nine rfMRI networks (RSNs) were examined at baseline and after 3 months of follow-up: three visual RSNs, the default-mode network, sensorimotor-, auditory-, executive control, and the left and right fronto-parietal RSN. ROI analyses were constrained to thresholded overlap masks for each individual (Z>0) at baseline and follow-up.In both stable MS and HC mean functional connectivity across the entire network did not reach acceptable ICCs for several networks (ICC<0.40) but we found a high reproducibility of ROI ICCs and of the ratio of overlap. ROI ICCs of all nine networks were between 0.98 and 0.99 for HC and ranged from 0.88 to 0.99 in patients with MS, respectively. The ratio of overlap for all networks was similar for both groups, ranging from 0.60 to 0.75.Our findings attest to a high reproducibility of rfMRI networks not only in HC but also in patients with stable MS when applying ROI analysis. This supports the utility of rfMRI to monitor functional changes related to disease progression or therapeutic interventions in MS.

An exploratory intervention study suggests clinical benefits of training in chronic stroke to be paralleled by changes in brain activity using repeated fMRI.

PURPOSE: Previous studies demonstrated changes in sensorimotor network activation over time after stroke that have been interpreted as partly compensatory. Locomotor and balance trainings may improve both mobility and cognition even in chronic stroke and thereby impact on cerebral activation patterns. We here aimed at testing these assumptions in an exploratory study to inform subsequent larger intervention studies. PATIENTS AND METHODS: Eight patients (73.3±4.4 years) with a chronic lacunar stroke (mean interval 3.7 years after the acute event with a range from 2 to 4 years) and residual leg paresis leading to gait disturbance received a guided 5-week training focusing on mobility, endurance, and coordination. Before and afterward, they underwent clinical, neuropsychological, and gait assessments and brain MRI at 3 T including a functional ankle movement paradigm. Sixteen healthy controls (HCs; 68.8±5.4 years) followed the same protocol without intervention. RESULTS: After training, patients had improved in mobility, memory, and delayed recall of memory. While cerebral activations in HC remained completely unaltered, patients showed increased activations in the right precentral gyrus, the right and left superior frontal gyri, and the right frontal lobe, with bipedal ankle movements after training. CONCLUSION: In this exploratory study of chronic stroke, we found not only significant effects of physical training on mobility but also distinct aspects of cognition already with a small number of highly selected patients. These improvements were paralleled by alterations in cerebral activity possibly reflecting neuronal plasticity. Larger studies including randomization are needed.

Training of verbal creativity modulates brain activity in regions associated with language- and memory-related demands.

This functional magnetic resonance (fMRI) study was designed to investigate changes in functional patterns of brain activity during creative ideation as a result of a computerized, 3-week verbal creativity training. The training was composed of various verbal divergent thinking exercises requiring participants to train approximately 20 min per day. Fifty-three participants were tested three times (psychometric tests and fMRI assessment) with an intertest-interval of 4 weeks each. Participants were randomly assigned to two different training groups, which received the training time-delayed: The first training group was trained between the first and the second test, while the second group accomplished the training between the second and the third test session. At the behavioral level, only one training group showed improvements in different facets of verbal creativity right after the training. Yet, functional patterns of brain activity during creative ideation were strikingly similar across both training groups. Whole-brain voxel-wise analyses (along with supplementary region of interest analyses) revealed that the training was associated with activity changes in well-known creativity-related brain regions such as the left inferior parietal cortex and the left middle temporal gyrus, which have been shown as being particularly sensitive to the originality facet of creativity in previous research. Taken together, this study demonstrates that continuous engagement in a specific complex cognitive task like divergent thinking is associated with reliable changes of activity patterns in relevant brain areas, suggesting more effective search, retrieval, and integration from internal memory representations as a result of the training.