REVIEW Proton Magnetic Resonance Spectroscopy: Relevance of Glutamate and GABA to Neuropsychology Gabriele Ende 1 Received: 9 April 2015 /Accepted: 29 July 2015 # Springer Science+Business Media New York 2015 Abstract Proton Magnetic Resonance Spectroscopy (MRS) has been widely used to study the healthy and diseased brain in vivo. The availability of whole body MR scanners with a field strength of 3 Tesla and above permit the quantification of many metabolites including the neurotransmitters glutamate (Glu) and γ-aminobutyric acid (GABA). The potential link between neurometabolites identified by MRS and cognition and behavior has been explored in numerous studies both in healthy subjects and in patient populations. Preliminary find- ings suggest direct or opposite associations between GABA or Glu with impulsivity, anxiety, and dexterity. This chapter is intended to provide an overview of basic principles of MRS and the literature reporting correlations between GABA or Glu and results of neuropsychological assessments. Keywords Magnetic resonance spectroscopy . Glutamate . GABA . N-acetylaspartate . N-acetylaspartylglutamate . Neuropsychological assessment Introduction This review will describe how proton Magnetic Resonance Spectroscopy (MRS) measures that reflect brain tissue quality might be associated with behavior and cognition as deter- mined by neuropsychological assessments. The chapter starts with a basic introduction to the principles of in vivo MRS followed by an overview of the literature regarding associa- tions between MRS measures of γ-aminobutyric acid (GABA) and glutamate (Glu) and results of neuropsycholog- ical assessments. Finally, the chapter provides potential future MRS research directions. A review of the entire literature on MRS and neuropsychology is beyond the scope of this chapter because of the variety of possible keywords and combinations of key words on this topic is large and results are very hetero- geneous e.g., the query B(neuropsychological OR neuropsy- chology) AND (magnetic resonance spectroscopy OR mag- netic resonance spectroscopic imaging)^ returns at least 650 hits in pubmed. This review only scratches the surface of reported relations between MR-detectable neurometabolites and neuropsychological performance parameters. Neverthe- less, it provides insight into the current status of the literature and offers directions regarding the future of MRS studies in combination with neuropsychological assessment. Magnetic Resonance Spectroscopy: Basics A comprehensive essay of in vivo MRS is provided by (de Graaf 1998). Included here is a basic introduction to the prin- ciples of MRS. NMR spectroscopy is the predecessor of MR Imaging (MRI) as it is used in clinical and research applica- tions today. The methodological advancement of NMR for MRS applications at whole body clinical MR scanners and potential applications in neuroscience research goes back to the 1980s. MRS is a unique method to non-invasively inves- tigate molecules in vivo by means of their resonance frequen- cy and spectral patterns. The hydrogen nucleus (proton, 1 H) holds an exceptional position in in vivo MR applications since it has by far the largest abundance in living tissue as well as the highest MR sensitivity. The hydrogen nuclei can be thought of as tiny * Gabriele Ende gabi.ende@zi-mannheim.de 1 Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim / Heidelberg University, J5, D-68159 Mannheim, Germany Neuropsychol Rev DOI 10.1007/s11065-015-9295-8