The cortical signature of amyotrophic lateral sclerosis

Abstract

The aim of this study was to explore the pattern of regional cortical thickness in patients with non-familial amyotrophic lateral sclerosis (ALS) and to investigate whether cortical thinning is associated with disease progression rate. Cortical thickness analysis was performed in 44 ALS patients and 26 healthy controls. Group differences in cortical thickness and the age-by-group effects were assessed using vertex-by-vertex and multivariate linear models. The discriminatory ability of MRI variables in distinguishing patients from controls was estimated using the Concordance Statistics (C-statistic) within logistic regression analyses. Correlations between cortical thickness measures and disease progression rate were tested using the Pearson coefficient. Relative to controls, ALS patients showed a bilateral cortical thinning of the primary motor, prefrontal and ventral frontal cortices, cingulate gyrus, insula, superior and inferior temporal and parietal regions, and medial and lateral occipital areas. There was a significant age-by-group effect in the sensorimotor cortices bilaterally, suggesting a stronger association between age and cortical thinning in ALS patients compared to controls. The mean cortical thickness of the sensorimotor cortices distinguished patients with ALS from controls (C-statistic ≥ 0.74). Cortical thinning of the left sensorimotor cortices was related to a faster clinical progression (r = -0.33, p = 0.03). Cortical thickness measurements allowed the detection and quantification of motor and extramotor involvement in patients with ALS. Cortical thinning of the precentral gyrus might offer a marker of upper motor neuron involvement and disease progression.

Figure 1. Vertex-by-vertex analysis: regions of significantly thinner cortex in patients with amyotrophic lateral sclerosis compared with healthy controls represented on an averaged brain map.

Color bar represents t values (p<0.05, uncorrected for multiple comparisons).

Figure 2. Cortical regions showing a significant cortical thinning in patients with amyotrophic lateral sclerosis compared with healthy controls overlaid on the lateral (top row) and medial (bottom row) views of the left and right hemispheres.

Regions are color-coded according to the percent difference of cortical thickness between the two groups.

Figure 3. Relationship between cortical thickness and age.

Top: vertex-by-vertex analysis; regions of significant age-by-group interaction with cortical thickness. Color bar represents t values (p<0.05). Bottom: scatterplots of the correlations between the cortical thickness measures and subject age in patients with amyotrophic lateral sclerosis (blue circles) and healthy controls (red squares).