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Previous studies have evaluated motor and extramotor cerebral cortical regions in patients with amyotrophic lateral sclerosis (ALS) using (1) H MRS, but none have evaluated the thalamus or basal ganglia. The objective of this exploratory study was to evaluate the subclinical involvement of the basal ganglia and thalamus in patients with ALS using (1) H MRS. Fourteen patients (52±7 years) with sporadic definite ALS and 17 age-matched controls were studied using volumetric MRSI on a 3-T scanner. The concentration of the metabolites N-acetylaspartate (NAA), choline (Cho) and their ratio (NAA/Cho) were obtained bilaterally from the basal ganglia (lentiform nucleus, caudate) and thalamus. The maximum rates of finger and foot tap and lip and tongue movements were obtained to assess extrapyramidal and pyramidal tract function. In patients with ALS, relative to controls, the NAA concentration was significantly lower (p<0.02) in the basal ganglia and thalamus, and the Cho concentration was higher (p<0.01) in these structures, except in the caudate (p=0.04). Correspondingly, the NAA/Cho ratio was significantly lower (p<0.01) in these structures, except in the caudate (p=0.03), in patients than in controls. There were mild to strong correlations (r=0.4-0.7) between the metabolites of the basal ganglia and finger tap, foot tap and lip and tongue movement rates. In conclusion, decreased NAA in the basal ganglia and thalamus and increased Cho and decreased NAA/Cho in the lentiform nucleus and thalamus are indicative of neuronal loss or dysfunction and alterations in choline-containing membranes in these structures.