BRAIN BIOCHEMISTRY IN WILLIAMS-SYNDROME - EVIDENCE FOR A ROLE OF THE CEREBELLUM IN COGNITION

Objective: To determine what biochemical changes may occur in the brai n in Williams syndrome (WS) and whether these changes may be related t o the cognitive deficits. Background: WS is a rare, congenital disorde r with a characteristic physical, linguistic, and behavioral phenotype with known cognitive deficits. Methods: We obtained P-31 magnetic res onance spectra (MRS) from a region consisting of mostly frontal and pa rietal lobe of 14 patients with WS (age, 8 to 37 years) and 48 similar ly-aged controls. H-1 MRS (27 cm(3)) localized to the left cerebellum obtained from the WS cohort were compared with those from 16 chronolog ical age- and sex-matched normal controls. A battery of cognitive test s were administered to all subjects undergoing H-1 MRS. Results: WS br ains exhibited significant biochemical abnormalities. Al P-31 MRS rati os containing the phosphomonoester (PME) peak were significantly alter ed in WS, suggesting that PME is significantly decreased. Ratios of ch oline-containing compounds and creatine-containing compounds to N-acet ylaspartate (Cho/NA and Cre/NA) were significantly elevated in the cer ebellum in WS cf. controls, whereas the ratio of Cho/Cre was not alter ed. This suggests a decrease in the neuronal marker N-acetylaspartate in the cerebellum. Significant correlations were found between the cer ebellar ratios Cho/NA and Cre/NA and the ability of all subjects at va rious neuropsychological tests, including Verbal and Performance IQ, B ritish Picture Vocabulary Scale, Ravens Progressive Matrices, and Insp ection Time. Conclusions: The correlations can be interpreted in two w ays: 1) Our sampling of cerebellar biochemistry reflects a measure of ''global'' cerebral biochemistry and is unrelated to cerebellar functi on, or 2) The relations indicate that cerebellar neuronal integrity is a requirement ton a developmental time scale or in real-time) for abi lity on a variety of cognitive tests.