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Establishing Neuropsychological Measures to Test Corpus Callosum Integrity in Patients with Multiple Sclerosis

Breonna Mabry Photo

Hampshire College (Massachusetts)

Breonna Mabry, Emily Wood, Brandon Loughridge, Irene Cortese, & Daniel S. Reich 

Multiple sclerosis (MS) is an immune-mediated, demyelinating disease of the central nervous system of unknown origin and highly variable course. Common complaints from sufferers of the disease include cognitive decline such as impairment of attention, executive functions, and bimanual coordination. Literature suggests that diminished white matter integrity in callosal pathways is, in part, responsible for the inter-individual variations of these cognitive and coordination deficits. Current neuroimaging techniques, which are sensitive to alterations in white matter microstructure, have demonstrated correlations between corpus callosum (CC) damage and decreased performance on some tests of neuropsychological performance and coordination. Diffusion tensor imaging (DTI) provides information about microscopic structural features of anisotropic tissues such as white matter tracts. In particular, fractional anisotropy (FA), a measure procured from DTI that reflects axonal fiber directionality and integrity, is decreased in MS in association with lower cognitive and coordination performance. However, the pathological sensitivity of DTI is limited because the signal is derived from water protons, which are found in all tissue types (including inflammatory cells, myelin, and neurons). Our lab is developing a novel MRI technique, diffusion weighted spectroscopy (DWS), which combines features of DTI with compartmentally specific MR spectroscopy. In order to test the specificity of DWS for axonal integrity in MS, we require neuropsychological measures that are sensitive to disruption of the midline corpus callosum.

Breonna Mabry Figure

This study aims to establish a battery of neuropsychological tests sensitive to damage in the strongly coherent, parallel projection fibers of the anterior CC in a heterogeneous population of MS patients. In addition to tests of frontal lobe functions (attention and executive capacity), bilateral coordination should be a particularly sensitive measure of anterior CC projection fiber integrity, as these movements require synchronized processing by right and left brain hemispheres. We examined both patient and healthy volunteer performance in the Symbol Digit Modalities Test (SDMT), the Paced Auditory Symbols Audition Test (PASAT), the Cross Lateralization of Fingertips Test, the Trail Making Test, a bimanual synchronous finger tapping task, a verbal fluency task, a Stroop task, and a word recognition task. Importantly, in order to be able to better assess patients with low disability, we designed and implemented a dual task by combining bimanual synchronous finger tapping with applicable measures such as the verbal fluency task, the Stroop task, and the word recognition task. Finger tapping data was processed with in-house MATLAB scripts. We found that dual tasking resulted in asynchronous tapping as measured by mean inter-hand interval between synchronous taps (see figure), increased error rates and reaction time contingent on the difficulty of the tasks presented. Findings suggest that dual tasking challenges bimanual coordination such that it should be considered an alternative measure of increased difficulty for less impaired sufferers of MS. Overall, we established a neuropsychological testing protocol and analysis scheme for application to our ongoing study of novel MRI measures in multiple sclerosis.

Acknowledgements: the NINDS Intramural Research Program, the Summer Internship Program (Rita Devine and Tony Casco), George Dold, and Govind Nair

Last Modified November 27, 2013