Attention and processing speed performance in multiple sclerosis is mostly related to thalamic volume
- 281 Downloads
Cognitive impairment (CI), mainly involving attention and processing speed (A-PS), is a common and disabling symptom in multiple sclerosis (MS). Symbol Digit Modalities Test (SDMT) is one of the more sensitive and reliable tests to assess A-PS deficits in MS. Structural MRI correlates of A-PS in MS still need to be clarified. This study aimed to investigate, in a large group of MS patients, the relationship between regional gray matter (GM) atrophy and SDMT performance. 125 relapsing remitting MS patients and 52 healthy controls (HC) underwent a 3 T–MRI protocol including high-resolution 3D–T1 imaging. All subjects underwent a neurological evaluation and SDMT. A Voxel Based Morphometry analysis was performed to assess: 1) correlations between regional GM volume and SDMT performance in MS patients; 2) regional differences in GM volume between MS patients and HC. Thalamic, putamen and cerebellar volumes were also calculated using FIRST tool from the FMRIB Software Library. A linear regression analysis was performed to assess the contribution of each one of these structures to A-PS performance. A significant negative correlation was found between regional GM volume and SDMT score at the level of the thalamus, cerebellum, putamen, and occipital cortex in MS patients. Thalamus, cerebellum and putamen also showed significant GM atrophy in MS patients compared to HC. Thalamic atrophy is also an independent and additional contributor to A-PS deficits in MS patients. These findings support the role of thalamus as the most relevant GM structure subtending A-PS performance in MS, as measured by SDMT.
KeywordsMultiple sclerosis Attention Processing speed Gray matter Magnetic resonance imaging Thalamus
The authors thank all subjects, especially the patients with MS for the time and effort devoted to this study; Antonella Paccone, MRI Center “SUN-FISM,” University of Campania “Luigi Vanvitelli” and Institute of Diagnosis and Care “Hermitage-Capodimonte,” Naples, Italy for technical support; Mattia Siciliano, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania “Luigi Vanvitelli”, Italy for contributing to statistical analysis.
Compliance with ethical standards
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of interest
Alvino Bisecco, Svetlana Stamenova, Giuseppina Caiazzo, Alessandro d’Ambrosio, Rosaria Sacco, Renato Docimo, Sabrina Esposito, Mario Cirillo and Fabrizio Esposito have no disclosures. Simona Bonavita received speakers’ honoraria from Biogen Idec, Novartis, and Merck-Serono. Gioacchino Tedeschi has received compensation for consulting services and/or speaking activities from Bayer Schering Pharma, Biogen Idec, Merck Serono, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck Serono, and Fondazione Italiana Sclerosi Multipla. Antonio Gallo received honoraria for speaking and travel grants from Biogen, Sanofi-Aventis, Merck Serono, Genzyme, Teva, Bayer-Schering and Novartis.
This study was approved by the by the local Ethic Committee. All procedures performed in this study involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- Amato, M. P., Portaccio, E., Goretti, B., Zipoli, V., Ricchiuti, L., De Caro, M. F., et al. (2006). The Rao's brief repeatable battery and Stroop test: normative values with age, education and gender corrections in an Italian population. Multiple Sclerosis, 12(6), 787–793.CrossRefPubMedGoogle Scholar
- Batista, S., Zivadinov, R., Hoogs, M., Bergsland, N., Heininen-Brown, M., Dwyer, M. G., et al. (2012). Basal ganglia, thalamus and neocortical atrophy predicting slowed cognitive processing in multiple sclerosis. Journal of Neurology, 259(1), 139–146. doi: 10.1007/s00415-011-6147-1.CrossRefPubMedGoogle Scholar
- Benedict, R. H., Duquin, J. A., Jurgensen, S., Rudick, R. A., Feitcher, J., Munschauer, F. E., et al. (2008). Repeated assessment of neuropsychological deficits in multiple sclerosis using the symbol digit modalities test and the MS neuropsychological screening questionnaire. Multiple Sclerosis, 14(7), 940–946. doi: 10.1177/1352458508090923.CrossRefPubMedGoogle Scholar
- Benedict, R. H., Hulst, H. E., Bergsland, N., Schoonheim, M. M., Dwyer, M. G., Weinstock-Guttman, B., et al. (2013). Clinical significance of atrophy and white matter mean diffusivity within the thalamus of multiple sclerosis patients. Multiple Sclerosis, 19(11), 1478–1484. doi: 10.1177/1352458513478675.CrossRefPubMedGoogle Scholar
- Ceccarelli, A., Jackson, J. S., Tauhid, S., Arora, A., Gorky, J., Dell'Oglio, E., et al. (2012). The impact of lesion in-painting and registration methods on voxel-based morphometry in detecting regional cerebral gray matter atrophy in multiple sclerosis. AJNR. American Journal of Neuroradiology, 33(8), 1579–1585. doi: 10.3174/ajnr.A3083.CrossRefPubMedPubMedCentralGoogle Scholar
- Cerasa, A., Valentino, P., Chiriaco, C., Pirritano, D., Nistico, R., Gioia, C. M., et al. (2013). MR imaging and cognitive correlates of relapsing-remitting multiple sclerosis patients with cerebellar symptoms. Journal of Neurology, 260(5), 1358–1366. doi: 10.1007/s00415-012-6805-y.CrossRefPubMedGoogle Scholar
- Drake, A. S., Weinstock-Guttman, B., Morrow, S. A., Hojnacki, D., Munschauer, F. E., & Benedict, R. H. (2010). Psychometrics and normative data for the multiple sclerosis functional composite: replacing the PASAT with the symbol digit modalities test. Multiple Sclerosis, 16(2), 228–237. doi: 10.1177/1352458509354552.CrossRefPubMedGoogle Scholar
- Genova, H. M., Hillary, F. G., Wylie, G., Rypma, B., & Deluca, J. (2009). Examination of processing speed deficits in multiple sclerosis using functional magnetic resonance imaging. Journal of the International Neuropsychological Society, 15(3), 383–393. doi: 10.1017/S1355617709090535.CrossRefPubMedGoogle Scholar
- Lansley, J., Mataix-Cols, D., Grau, M., Radua, J., & Sastre-Garriga, J. (2013). Localized grey matter atrophy in multiple sclerosis: a meta-analysis of voxel-based morphometry studies and associations with functional disability. Neuroscience and Biobehavioral Reviews, 37(5), 819–830. doi: 10.1016/j.neubiorev.2013.03.006.CrossRefPubMedGoogle Scholar
- Lopez-Gongora, M., Querol, L., & Escartin, A. (2015). A one-year follow-up study of the symbol digit modalities test (SDMT) and the paced auditory serial addition test (PASAT) in relapsing-remitting multiple sclerosis: an appraisal of comparative longitudinal sensitivity. BMC Neurology, 15, 40. doi: 10.1186/s12883-015-0296-2.CrossRefPubMedPubMedCentralGoogle Scholar
- Minagar, A., Barnett, M. H., Benedict, R. H., Pelletier, D., Pirko, I., Sahraian, M. A., et al. (2013). The thalamus and multiple sclerosis: modern views on pathologic, imaging, and clinical aspects. Neurology, 80(2), 210–219. doi: 10.1212/WNL.0b013e31827b910b.CrossRefPubMedPubMedCentralGoogle Scholar
- Morrow, S. A., Drake, A., Zivadinov, R., Munschauer, F., Weinstock-Guttman, B., & Benedict, R. H. (2010). Predicting loss of employment over three years in multiple sclerosis: clinically meaningful cognitive decline. The Clinical Neuropsychologist, 24(7), 1131–1145. doi: 10.1080/13854046.2010.511272.CrossRefPubMedGoogle Scholar
- Nocentini, U., Bozzali, M., Spano, B., Cercignani, M., Serra, L., Basile, B., et al. (2014). Exploration of the relationships between regional grey matter atrophy and cognition in multiple sclerosis. Brain Imaging and Behavior, 8(3), 378–386. doi: 10.1007/s11682-012-9170-7.CrossRefPubMedGoogle Scholar
- Sastre-Garriga, J., Arevalo, M. J., Renom, M., Alonso, J., Gonzalez, I., Galan, I., et al. (2009). Brain volumetry counterparts of cognitive impairment in patients with multiple sclerosis. Journal of the Neurological Sciences, 282(1–2), 120–124. doi: 10.1016/j.jns.2008.12.019.CrossRefPubMedGoogle Scholar
- Sastre-Garriga, J., Alonso, J., Renom, M., Arevalo, M. J., Gonzalez, I., Galan, I., et al. (2011). A functional magnetic resonance proof of concept pilot trial of cognitive rehabilitation in multiple sclerosis. Multiple Sclerosis, 17(4), 457–467. doi: 10.1177/1352458510389219.CrossRefPubMedGoogle Scholar
- Smith, A. (1982). Symbol digits modalities test: Manual. Los Angeles: Western Psychological Services.Google Scholar