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MRI substrates of sustained attention system and cognitive impairment in pediatric MS patients
Ermelinda De Meo1, Lucia Moiola1, Angelo Ghezzi1
1From the Neuroimaging Research Unit (E.D.M., E.P., M.F., M.A.R.) and Department of Neurology (E.D.M., L.M., A. Fiorino, G.C., M.F., M.A.R.), Institute of Experimental Neurology, Division of Neuroscience, and Department of Neuroradiology (A. Falini), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Multiple Sclerosis Center (A.G., L.P.), Ospedale di Gallarate; Department of Child Neurology and Psychiatry (P.V., M.C.P.), C. Mondino National Neurological Institute, Brain and Behaviour Department, University of Pavia; Multiple Sclerosis Center (R.C.), Spedali Civili of Brescia; and Department NEUROFARBA (M.P.A.), Section Neurosciences, University of Florence, Italy.
Objective:
To explore the structural and functional integrity of the sustained attention system in patients with pediatric multiple sclerosis (MS) and its effect on cognitive impairment.
Methods:
We enrolled 57 patients with pediatric MS and 14 age- and sex-matched healthy controls (HCs). Patients with >3 abnormal tests at neuropsychological evaluation were classified as cognitively impaired (CI). Sustained attention system activity was studied with fMRI during the Conners Continuous Performance Test (CCPT). Structural integrity of attention network connections was quantified with diffusion tensor (DT) MRI.
Results:
Within-group analysis showed similar patterns of recruitment of the attention network in HCs and patients with pediatric MS. Diffuse network DT MRI structural abnormalities were found in patients with MS. During CCPT, with increasing task demand, patients with pediatric MS showed increased activation of the left thalamus, anterior insula, and anterior cingulate cortex (ACC) and decreased recruitment of the right precuneus compared to HCs. Thirteen patients (23%) were classified as CI. Compared to cognitively preserved patients, CI patients with pediatric MS had decreased recruitment of several areas located mainly in parietal and occipital lobes and cerebellum and increased deactivation of the ACC, combined with more severe structural damage of white matter tracts connecting these regions.
Conclusions:
Our results suggest that the age-expected level of sustained attention system functional competence is achieved in patients with pediatric MS. Inefficient regulation of the functional interaction between different areas of this system, due to abnormal white matter integrity, may result in global cognitive impairment in these patients.
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