Basal ganglia, thalamus and neocortical atrophy predicting slowed cognitive processing in multiple sclerosis

Abstract

Information-processing speed (IPS) slowing is a primary cognitive deficit in multiple sclerosis (MS). Basal ganglia, thalamus and neocortex are thought to have a key role for efficient information-processing, yet the specific relative contribution of these structures for MS-related IPS impairment is poorly understood. To determine if basal ganglia and thalamus atrophy independently contribute to visual and auditory IPS impairment in MS, after controlling for the influence of neocortical volume, we enrolled 86 consecutive MS patients and 25 normal controls undergoing 3T brain MRI and neuropsychological testing. Using Sienax and FIRST software, neocortical and deep gray matter (DGM) volumes were calculated. Neuropsychological testing contributed measures of auditory and visual IPS using the Paced Auditory Serial Addition Test (PASAT) and the Symbol Digit Modalities Test (SDMT), respectively. MS patients exhibited significantly slower IPS relative to controls and showed reduction in neocortex, caudate, putamen, globus pallidus, thalamus and nucleus accumbens volume. SDMT and PASAT were significantly correlated with all DGM regions. These effects were mitigated by controlling for the effects of neocortical volume, but all DGM volumes remained significantly correlated with SDMT, putamen (r = 0.409, p < 0.001) and thalamus (r = 0.362, p < 0.001) having the strongest effects, whereas for PASAT, the correlation was significant for putamen (r = 0.313, p < 0.01) but not for thalamus. We confirm the significant role of thalamus atrophy in MS-related IPS slowing and find that putamen atrophy is also a significant contributor to this disorder. These DGM structures have independent, significant roles, after controlling for the influence of neocortex atrophy.

Subcortical and Cortical Gray Matter Atrophy in a Large Sample of Patients with Clinically Isolated Syndrome and Early Relapsing-Remitting Multiple Sclerosis

“…28 Normalized SDGM volumes were thus obtained by multiplying the estimated volumes from FIRST by the volumetric scaling factor from SIENAX. 29 Reproducibility of FIRST was previously reported.…”

Cognitive Deficits and Neuropsychological Assessment in Multiple Sclerosis

“…The range of specific cognitive deficits, such as memory disorders, reduced processing speed, and attention disorders, can be better explained by the cortical gray matter lesions (lesions and atrophy) than subcortical white matter lesions [25]. It has been shown that neocortical atrophy is associated with impaired verbal memory, visual episodic and working memory, verbal fluency, attention/concentration, and processing speed [26]. It is also possible that the neocortical atrophy is further responsible for slight personality changes, such as euphoria, that are seen in MS patients [27].…”

Subcortical Atrophy Is Associated with Cognitive Impairment in Mild Parkinson Disease: A Combined Investigation of Volumetric Changes, Cortical Thickness, and Vertex-Based Shape Analysis

“…23 The reproducibility of FIRST has been previously reported. 37 Examples of subcortical segmentation of a subject classified as having PD-MCI and of a subject classified as having PD-NCI are presented in Fig 1. In subsequent volumetric analyses, the normalization factor from SIENAX was included to reduce the effects of interindividual variability due to head size. 34 Vertex Analysis for Assessment of SDGM Shape Alterations.…”