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Proton MRS (\n 1<\/jats:sup>\n H\u2010MRS) enables in vivo measurement of small molecules implicated in multiple sclerosis, but its application to key metabolites glutamate, \u03b3\u2010aminobutyric acid (GABA), and glutathione has been sparse. We employed, at 7 T, a previously validated\n 1<\/jats:sup>\n H\u2010MRS protocol to measure glutamate, GABA, and glutathione, as well as glutamine,\n N<\/jats:italic>\n \u2010acetyl aspartate, choline, and myoinositol, in the frontal cortex of individuals with relapsing\u2010remitting (\n N<\/jats:italic>\n \u2009=\u200926) or progressive (\n N<\/jats:italic>\n \u2009=\u200921) multiple sclerosis or healthy control adults (\n N<\/jats:italic>\n \u2009=\u200925) in a cross\u2010sectional analysis. Only individuals with progressive multiple sclerosis demonstrated reduced glutamate (\n F<\/jats:italic>\n 2,65<\/jats:sub>\n \u2009=\u20093.424,\n p<\/jats:italic>\n \u2009=\u20090.04; 12.40\u2009\u00b1\u20090.62\u2009mM versus control 13.17\u2009\u00b1\u20090.95\u2009mM,\n p<\/jats:italic>\n \u2009=\u20090.03) but not glutamine (\n F<\/jats:italic>\n 2,65<\/jats:sub>\n \u2009=\u20090.352,\n p<\/jats:italic>\n \u2009=\u20090.7; 4.71\u2009\u00b1\u20090.35\u2009mM versus control 4.84\u2009\u00b1\u20090.42\u2009mM), reduced GABA (\n F<\/jats:italic>\n 2,65<\/jats:sub>\n \u2009=\u20093.89,\n p<\/jats:italic>\n \u2009=\u20090.03; 1.29\u2009\u00b1\u20090.23\u2009mM versus control 1.47\u2009\u00b1\u20090.25\u2009mM,\n p<\/jats:italic>\n \u2009=\u20090.05), and possibly reduced glutathione (\n F<\/jats:italic>\n 2,65<\/jats:sub>\n \u2009=\u20090.352,\n p<\/jats:italic>\n \u2009=\u20090.056; 2.23\u2009\u00b1\u20090.46\u2009mM versus control 2.51\u2009\u00b1\u20090.48\u2009mM,\n p<\/jats:italic>\n \u2009<\u20090.1). As a group, multiple sclerosis patients demonstrated significant negative correlations between disease duration and glutamate or GABA (\n \u03c1<\/jats:italic>\n \u00a0\n =\u2009\u2212<\/jats:bold>\n 0.4,\n p<\/jats:italic>\n \u2009=\u20090.02) but not glutamine or glutathione. Alone, only relapsing\u2010remitting multiple sclerosis patients exhibited a significant negative correlation between disease duration and GABA (\n \u03c1<\/jats:italic>\n \u2009=\u2009\u22120.5,\n p<\/jats:italic>\n \u2009=\u20090.03). Taken together, these results indicate that frontal cortex metabolism is differentially disturbed in progressive and relapsing\u2010remitting multiple sclerosis.\n <\/jats:p>","DOI":"10.1002\/nbm.4590","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T07:15:34Z","timestamp":1627456534000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["In vivo evidence of differential frontal cortex metabolic abnormalities in progressive and relapsing\u2010remitting multiple sclerosis"],"prefix":"10.1002","volume":"34","author":[{"given":"Kelley M.","family":"Swanberg","sequence":"first","affiliation":[{"name":"Department of Radiology and Biomedical Imaging Yale University School of Medicine New Haven Connecticut"},{"name":"Department of Biomedical Engineering Columbia University School of Engineering and Applied Science New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hetty","family":"Prinsen","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"DeStefano","sequence":"additional","affiliation":[{"name":"Department of Neurology Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Neurology Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhinav V.","family":"Kurada","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Columbia University School of Engineering and Applied Science New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Pitt","sequence":"additional","affiliation":[{"name":"Department of Neurology Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert K.","family":"Fulbright","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Juchem","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging Yale University School of Medicine New Haven Connecticut"},{"name":"Department of Biomedical Engineering Columbia University School of Engineering and Applied Science New York New York"},{"name":"Department of Neurology Yale University School of Medicine New Haven Connecticut"},{"name":"Department of Radiology Columbia University Medical Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70305-9"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000768"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70101-2"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13835"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.198"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO;2-Q"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh641"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31320-4"},{"key":"e_1_2_10_10_1","first-page":"932351","article-title":"Heterogeneity in multiple sclerosis: scratching the surface of a complex disease","volume":"2011","author":"Disanto G","year":"2010","journal-title":"Autoimmune Dis"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1552-6569.2007.00134.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/71555"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/nen.0b013e31812571b0"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2015.04.013"},{"key":"e_1_2_10_15_1","first-page":"440","article-title":"Improvement of experimental allergic encephalomyelitis (EAE) by thymoquinone; 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