Cognitive functions in multiple sclerosis: impact of gray matter integrity

Objectives: Our aim was to investigate the impact of gray matter (GM) integrity on cognitive performance in multiple sclerosis (MS), and its relationship with white matter (WM) integrity and presence of lesions. Methods: Sixty-seven patients with MS and 26 healthy controls underwent voxel-based analysis of diffusion tensor images (DTI) in GM and tract-based spatial statistics (TBSS) from WM to identify the regional correlations between cognitive functions and integrity. Lesion probability mapping (LPM) was generated for correlation analysis with cognition. Multiple linear regression analyses were used to identify the imaging measures associated with cognitive scores. Results: Compared with controls, patients showed abnormal DTI indices in several GM regions and in most WM tracts. Impairment in DTI indices in specific GM regions was associated with worse performance of distinct cognitive functions. Those regions showed anatomical correspondence with cognitively relevant tracts in TBSS and LPM. The combination of regional GM and WM DTI and lesion volume accounted for 36–51% of the variance of memory and attention scores. Regional GM DTI explained less than 5% of that variance. Conclusion: GM and WM integrity of specific networks influences cognitive performance in MS. However, GM damage assessed by DTI only adds a small increment to the explained variance by WM in predicting cognitive functioning.

[1]  R Bakshi,et al.  The Impact of Lesion In-Painting and Registration Methods on Voxel-Based Morphometry in Detecting Regional Cerebral Gray Matter Atrophy in Multiple Sclerosis , 2012, American Journal of Neuroradiology.

[2]  L. Squire.  Memory systems of the brain: A brief history and current perspective , 2004, Neurobiology of Learning and Memory.

[3]  Pablo Villoslada,et al.  Mapping the brain pathways of declarative verbal memory: Evidence from white matter lesions in the living human brain , 2008, NeuroImage.

[4]  Bradford C. Dickerson,et al.  Fractionating verbal episodic memory in Alzheimer's disease , 2011, NeuroImage.

[5]  Dieter Vaitl,et al.  Evidence for a direct association between cortical atrophy and cognitive impairment in relapsing–remitting MS , 2006, NeuroImage.

[6]  M. Sdika,et al.  Nonrigid registration of multiple sclerosis brain images using lesion inpainting for morphometry or lesion mapping , 2009, Human brain mapping.

[7]  John Ashburner,et al.  A fast diffeomorphic image registration algorithm , 2007, NeuroImage.

[8]  S Ropele,et al.  Lesion probability mapping to explain clinical deficits and cognitive performance in multiple sclerosis , 2011, Multiple sclerosis.

[9]  J. Kurtzke.  Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[10]  Frederik Barkhof,et al.  Regional DTI differences in multiple sclerosis patients , 2009, NeuroImage.

[11]  Vicente Belloch,et al.  Anatomical and functional differences between the Paced Auditory Serial Addition Test and the Symbol Digit Modalities Test , 2011, Journal of clinical and experimental neuropsychology.

[12]  Gareth J. Barker,et al.  Diffusion tensor imaging of post mortem multiple sclerosis brain , 2007, NeuroImage.

[13]  Shu-Wei Sun,et al.  Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia , 2003, NeuroImage.

[14]  Evan Fletcher,et al.  Episodic memory function is associated with multiple measures of white matter integrity in cognitive aging , 2011, Front. Hum. Neurosci..

[15]  F. Barkhof,et al.  Cognitive impairment in MS , 2013, Neurology.

[16]  Michael Montag,et al.  Corpus callosal diffusivity predicts motor impairment in relapsing–remitting multiple sclerosis: A TBSS and tractography study , 2011, NeuroImage.

[17]  S. Rombouts,et al.  The contribution of MRI in assessing cognitive impairment in multiple sclerosis , 2010, Neurology.

[18]  M. Rovaris,et al.  Cognitive dysfunction in patients with mildly disabling relapsing–remitting multiple sclerosis: an exploratory study with diffusion tensor MR imaging , 2002, Journal of the Neurological Sciences.

[19]  Hui Jing Yu,et al.  Multiple white matter tract abnormalities underlie cognitive impairment in RRMS , 2012, NeuroImage.

[20]  Daniel Rueckert,et al.  Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data , 2006, NeuroImage.

[21]  Olga Ciccarelli,et al.  Diffusion tensor imaging in early relapsing-remitting multiple sclerosis , 2001, Multiple sclerosis.

[22]  Chiara Romualdi,et al.  The changing clinical course of multiple sclerosis: A matter of gray matter , 2013, Annals of neurology.

[23]  Emily Snook,et al.  Cognitive impairments in relapsing-remitting multiple sclerosis: a meta-analysis , 2008, Multiple Sclerosis.

[24]  Stephen M. Rao,et al.  Cognitive dysfunction in multiple sclerosis. , 1991, Neurology.

[25]  D. Auer,et al.  Disconnection as a mechanism for cognitive dysfunction in multiple sclerosis. , 2009, Brain : a journal of neurology.

[26]  Massimo Filippi,et al.  Association between pathological and MRI findings in multiple sclerosis , 2012, The Lancet Neurology.

[27]  N. De Stefano,et al.  Neocortical volume decrease in relapsing–remitting MS patients with mild cognitive impairment , 2004, Neurology.

[28]  Stephen M. Smith,et al.  Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference , 2009, NeuroImage.

[29]  Robert Zivadinov,et al.  Clinical significance of atrophy and white matter mean diffusivity within the thalamus of multiple sclerosis patients , 2013, Multiple sclerosis.

[30]  N. Bargalló,et al.  Influence of Corpus Callosum Damage on Cognition and Physical Disability in Multiple Sclerosis: A Multimodal Study , 2012, PloS one.

[31]  J. DeLuca,et al.  Cognitive impairment in multiple sclerosis , 2008, The Lancet Neurology.

[32]  M. Horsfield,et al.  Microstructural magnetic resonance imaging of cortical lesions in multiple sclerosis , 2013, Multiple sclerosis.

[33]  O Garcea,et al.  Cognitive impairment in patients with multiple sclerosis using the Brief Repeatable Battery-Neuropsychology test , 2006, Multiple sclerosis.

[34]  Heidi Johansen-Berg,et al.  A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology , 2012, Brain : a journal of neurology.