Background: Lesion dissemination in time and space represents a key feature and diagnostic marker of multiple sclerosis (MS). The correlation between magnetic resonance imaging (MRI) lesion load and ...disability is only modest, however. Strategic lesion location might at least partially account for this ‘clinico-radiologic paradox’.
Objectives: Here we used a non-parametric permutation-based approach to map lesion location probability based on MS lesions identified on T2-weighted MRI. We studied 121 patients with clinically isolated syndrome, relapsing–remitting or secondary progressive MS and correlated these maps to assessments of neurologic and cognitive functions.
Results: The Expanded Disability Status Scale correlated with bilateral periventricular lesion location (LL), and sensory and coordination functional system deficits correlated with lesion accumulation in distinct anatomically plausible regions, i.e. thalamus and middle cerebellar peduncule. Regarding cognitive performance, decreased verbal fluency correlated with left parietal LL comprising the putative superior longitudinal fascicle. Delayed spatial recall correlated with _amygdalar, _left frontal and parietal LL. Delayed selective reminding correlated with bilateral frontal and temporal LL. However, only part of the spectrum of cognitive and neurological problems encountered in our cohort could be explained by specific lesion location.
Conclusions: Lesion probability mapping supports the association of specific lesion locations with symptom development in MS, but only to limited extent.
Cognitive dysfunction (CD) is frequent in multiple sclerosis (MS) and can occur at early stages. Whereas functional reorganization with disease progression has been described for the motor system in ...MS using fMRI, no such studies exist for cognition. We attempted to assess the concept of functional reorganization concerning cognition using a simple "Go/No-go" fMRI paradigm.
Patients with a clinically isolated syndrome (CIS, n = 10), relapsing-remitting MS (RRMS) (n = 10), or secondary progressive MS (SPMS) (n = 10), and 28 healthy controls (HC), underwent a comprehensive neuropsychological test battery, clinical examination, structural imaging, and an fMRI Go/No-go discrimination task at 3 T.
Patients performed worse than HC regarding memory, sustained attention and concentration, and information processing. These differences were driven by patients with SPMS. The fMRI task elicited activation in a widespread network including bilateral mesial and dorsolateral frontal, parietal, insular, basal ganglia, and cerebellar regions. Task performance was similar between phenotypes, but deviation from the activation pattern observed in HC and patients with CIS increased with disease progression. Patients with RRMS showed increased brain activation in the precuneus, both superior parietal lobes, and the right fusiform gyrus, and recruited the hippocampus with increasing demands. Patients with SPMS demonstrated the most abnormal network function, including recruitment of pre-SMA, bilateral superior and inferior parietal, dorsolateral prefrontal, right precentral, bilateral postcentral, and right temporal brain areas.
Using a cognitive fMRI paradigm, we were able to confirm adaptive changes of neuronal activation with progressing MS and to provide strong evidence for their compensatory nature, at least partially.
Background: Cognitive dysfunction in multiple sclerosis (MS) can occur even in the earliest disease stages and its prevalence increases with disease duration. Whether and how the neural correlates ...change in parallel is incompletely understood. Objective: We therefore created a functional magnetic resonance imaging (fMRI) paradigm with applicability across a large clinical spectrum of MS aiming to elicit activation in a widespread cognitive network. Methods: We investigated 40 MS patients n=10 clinically isolated syndrome (Expanded Disability Status Scale(EDSS) score 0-2, age 23-50), n=10 relapsing-remitting MS (0-3.5, 24-49), n=10; secondary progressive MS (3.5-7.5, 25-57), n=10; long-term low disability MS (0-3.5, 33-58) and 21 healthy age-matched controls using a 3T scanner and a `Go/No Go' paradigm. Participants also underwent extensive behavioral and neuropsychological testing (including the Brief Repeatable Battery for Neuropsychological Tests, the Wisconsin Card Sorting Test, the `Zahlen-Verbindungstest', the Nine-Hole Peg Test and the Maximal Finger Tapping Rate). Results: Behaviorally, reaction times and the number of correct responses were lower in patients than controls. This was mostly attributable to a worse performance of secondary progressive MS patients. On fMRI, both patients and controls demonstrated robust activation of a frontoparietal cerebral network. Depending on task difficulty, differential recruitment of network components became evident. Also, brain activity increased with increasing cognitive demand in the pre- and supplementary motor area (SMA) in both groups. However, in contrast with healthy controls, MS patients showed additional activity in posterior parietal areas with the most difficult task. Differences in activation were more pronounced in patients with longstanding disease. Conclusions: Our results confirm previous studies on the role of pre-SMA/SMA in response inhibition. They also support the concept of increasing cortical recruitment with increasing cognitive demands which is supported by cortical reorganization in longstanding MS.
