Frontal lobe abnormalities on MRS correlate with poor letter fluency in ALS

Abstract

Objective: To examine whether frontal lobe abnormalities on magnetic resonance spectroscopy (MRS) in amyotrophic lateral sclerosis (ALS) correlate with poor letter fluency (LF).

Methods: Twenty-five patients with ALS (20 with definite, probable, or possible ALS and 5 with progressive muscular atrophy) performed an LF task, involving F word generation in 1 minute, and underwent MRS. Comparisons were made between patients with ALS with impaired LF and unimpaired LF based on an empirically derived cutoff score. A Spearman correlation was performed between the patient's N-acetyl acetate/creatinine-phosphocreatinine ratio (NAA/Cr) and the number of F words generated.

Results: LF was impaired in 50% of patients with ALS. Patients with impaired LF had reduced NAA/Cr in the DLPFC compared with those with unimpaired LF (p = 0.007). There was a significant correlation between LF and NAA/Cr in the DLPFC (r = 0.51, p = 0.0009). The ALS Functional Rating Scale score, clinical region of motor onset, and disease category had no effect on LF or NAA/Cr in the DLPFC.

Conclusions: A reduced NAA/Cr in the DLPFC of patients with ALS is a marker of neuronal dysfunction and correlates with impaired performance on a clinical measure of executive function.

Figure 1. MRI images demonstrating the region of interest and representative spectrogram

(A) Axial T1 image (left) used as reference for selection of region of interest in echo-planar spectroscopic imaging (EPSI) (right). Ten voxels were selected from the right and left dorsolateral prefrontal cortex (shown here) and from the right and left occipital cortex. (B) A representative spectrograph demonstrating the separate peaks of N-acetyl aspartate (NAA) and creatinine-phosphocreatine (Cr).

Figure 2. Correlation of letter fluency with an average of the left and right N-acetyl aspartate/ creatinine-phosphocreatine ratio (NA/Cr) ratio in the dorsolateral prefrontal cortex (PF) and occipital cortex

(A) The average (AVG) of right and left NA/Cr in the dorsolateral prefrontal cortex correlated with letter fluency, i.e., the number of F words generated in 1 minute (* = statistical significance). (B) The average of right and left NA/Cr in the occipital cortex did not correlate with letter fluency.