Multiple Sclerosis: Clinical Features and MRI Changes of Decision-Making Difficulties

Dr Nils Muhlert Wellcome Trust ISSF Research Fellow School of Psychology Cardiff Interview with:
Dr Nils Muhlert
Wellcome Trust ISSF Research Fellow
School of Psychology
Cardiff University

Medical Research: What are the main findings of the study?

Dr. Muhlert: Decision making impairments are known to occur in people with multiple sclerosis (MS), and are important, given they can contribute to employment status, treatment compliance and function in everyday life. Studies by Kleeberg, Simioni and others have demonstrated that decision-making impairments can occur early in the course of multiple sclerosis and get worse as the disease progresses. Questions however remain over whether these impairments are linked to more general cognitive difficulties, differences between multiple sclerosis subtypes, and their relationship with MRI changes.

We assessed decision-making and examined MRI changes in a relatively large sample of people with multiple sclerosis (N = 105) and healthy controls (N = 43). All participants performed the Cambridge Gambling Task, which independently measures risk-taking, impulsivity, deliberation and risk adjustment, and underwent an MRI scan including T1-weighted and diffusion MRI sequences.

We demonstrate that people with multiple sclerosis experience difficulties with risk adjustment (gauging risk and adapting accordingly) and in the speed of making decisions but not in impulsivity. These problems were seen in those classified as having cognitive impairment and those not (i.e. cognitively unimpaired). We found that decision-making impairments were twice as common in people with relapsing-remitting and primary progressive MS than healthy controls, and almost four times as common in people with secondary progressive multiple sclerosis. In addition, decision making impairments in multiple sclerosis were linked to MRI changes in regions previously linked to decision-making in other conditions, including fronto-striatal and hippocampal regions. These findings offer insight into the precise decision-making difficulties experienced by people with multiple sclerosis, the relative prevalences in different subtypes of the disease and the pathological processes that may underlie them.

Medical Research: Were any of the findings unexpected?

Dr. Muhlert: To examine diffusion changes on MRI we used a novel technique, called diffusion orientational complexity (DOC). This examines the number of different orientations in which water molecules diffuse within each voxel. In white matter tracts, where there is often one dominant diffusion direction, DOC is low. In cortical grey matter, diffusion is likely to be multi-directional due to the presence of neurons and neurites, and so DOC is higher. The direction of DOC changes in people with multiple sclerosis differed between regions – being significantly decreased in cortical grey matter but significantly increased in the hippocampus, relative to healthy controls. This is plausible given histopathology, in which reduced cortical diffusion may be caused by processes including cortical demyelination, neurite transection and neuronal loss in the normally complex and multi-layered architecture of cortical grey matter. In contrast, increased hippocampal DOC in multiple sclerosis may result from a reduction in the dominance of diffusion along its axis. However a combined MRI-histopathology study is required to elucidate the relationship of pathological processes in multiple sclerosis grey matter with changes in DOC.

Medical Research: What should clinicians and patients take away from your report?

Dr. Muhlert: Greater awareness of decision-making difficulties in people with MS may be prudent given its implications for employment, social situations and quality of life. Understanding how these impairments relate to clinical features or MRI changes may help to improve our knowledge of why such difficulties develop and what may be done to reduce them.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Muhlert: Future longitudinal studies can examine whether it is possible to predict whether certain people with multiple sclerosis are more likely to develop decision-making impairments. Understanding of the clinical or MRI features that may predict these problems could lead to earlier interventions to minimise or even prevent the establishment of decision-making impairments in people with MS.


The grey matter correlates of impaired decision-making in multiple sclerosis

Nils Muhlert, Varun Sethi, Lisa Cipolotti, Hamied Haroon, Geoff J M Parker, Tarek Yousry, Claudia Wheeler-Kingshott,

David Miller, Maria Ron, Declan Chard

J Neurol Neurosurg Psychiatry jnnp-2014-308169Published Online First: 8 July 2014 doi:10.1136/jnnp-2014-308169



Last Updated on July 14, 2014 by Marie Benz MD FAAD