Over the past decade or so much interest has emerged in proton Magnetic Resonance Spectroscopy (1H-MRS) investigations of the human brain. This largely reflects exciting findings from two major lines of research regarding N-acetyl-aspartate (NAA), the most prominent neurometabolite resolved in vivo. First, NAA concentrations appear to be reduced in diverse brain diseases, including both neurodevelopmental disorders and frank trauma [1]. Second, and the focus of this chapter, NAA concentrations have frequently been found to predict individual variation in higher cognitive function. Indeed, many studies have now identified rather impressive correlations between NAA and standard measures of cognitive function [2]. These relationships may eventually prove clinically useful, as for example in predicting long-term outcome from traumatic brain injury or the rate of progression to dementia in degenerative diseases. But they also raise compelling and important questions about the nature of the neurometabolic underpinnings of individual variation in cognition, and the specific ways in which NAA might be important for human brain function.

The central limitation of human studies linking NAA to cognition is readily apparent: we are permitted only investigations that are fundamentally correlational in nature. Progress in understanding the role of NAA in human cognition will clearly require studies of nonhuman animals, particularly nonhuman primates. Nonetheless, analyses of human studies may help generate research hypotheses, provide specificity and boundary conditions regarding NAA-cognition relationships, and suggest important

Department of Neurology University of New Mexico, Albuquerque, NM 87131 [email protected].; William M. Brooks, Hogland Brain Imaging Center, The University of Kansas Medical Center [email protected].; Rex E. Jung, Department of Neurology, University of New Mexico School of Medicine, Albuquerque, NM 87131, [email protected]; author for correspondence: Ronald A. Yeo.

clinical applications. In this chapter we will review two major domains of 1H-MRS research suggesting a NAA-cognition link: studies of traumatic brain injury (TBI) and studies of normal controls. We will focus on spectroscopic investigations of cortical gray matter and underlying white matter tissue. First, though, we briefly review what 1H-MRS may reveal about neurochemistry and salient issues in neurometabolite quantitation.

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