Objective: To obtain quantitative neurometabolite measurements, specifically myoinositol (mI) and glutamate plus glutamine (Glx), markers of glial and neuronal excitation, in deep gray matter structures after mild traumatic brain injury (mTBI) using proton magnetic resonance spectroscopy ( 1 H-MRS) and to compare these measurements against normal healthy control subjects.Methods: This study approved by the institutional review board is Health Insurance Portability and Accountability Act compliant. T1-weighted MRI and multi-voxel 1 H-MRS imaging were acquired at 3 tesla from 26 patients with mTBI an average of 22 days postinjury and from 13 age-matched healthy controls. Two-way analysis of variance was used to compare patients and controls for mean N-acetylaspartate, choline, creatine (Cr), Glx, and mI levels as well as the respective ratios to Cr within the caudate, globus pallidus, putamen, and thalamus.Results: Quantitative putaminal mI was higher in patients with mTBI compared with controls (p 5 0.02).Quantitative neurometabolite ratios of putaminal mI and Glx relative to Cr, mI/Cr, and Glx/Cr were also higher among patients with mTBI compared with controls (p 5 0.01 and 0.02, respectively). No other differences in neurometabolite levels or ratios were observed in any other brain region evaluated.Conclusion: Increased putaminal mI, mI/Cr, and Glx/Cr in patients after mTBI compared with control subjects supports the notion of a complex glial and excitatory response to injury without concomitant neuronal loss, evidenced by preserved N-acetylaspartate levels in this region. Neurology ® 2014;82:521-528 GLOSSARY ANCOVA 5 analysis of covariance; Cho 5 choline; Cr 5 creatine; FLAIR 5 fluid-attenuated inversion recovery; FOV 5 field of view; GCS 5 Glasgow Coma Scale; Glx 5 glutamate plus glutamine; 1 H-MRS 5 proton magnetic resonance spectroscopy; IS 5 inferior-superior; mI 5 myoinositol; MP-RAGE 5 magnetization-prepared rapid-acquisition gradient echo; mTBI 5 mild traumatic brain injury; NAA 5 N-acetylaspartate; ROI 5 region of interest; TBI 5 traumatic brain injury; TE 5 echo time; TR 5 repetition time; VOI 5 volume of interest. Traumatic brain injury (TBI) is a major cause of morbidity and mortality, with a US annual incidence of approximately 1.7 million.1 Mild TBI (mTBI) accounts for 75% of these injuries. 1 Although focal injuries occur frequently after moderate and severe head injury, conventional imaging evaluation of the brain after mTBI detects abnormalities in only a small minority of patients.2 Nevertheless, cognitive, neurologic, and psychological problems persist in 10% to 55%, 3 suggesting that mTBI may have greater consequences than formerly assumed. 4 Previous studies have documented deep gray matter injury, believed to contribute to complex neurocognitive and psychological dysfunction after injury. 5,6 The thalami and the nuclei of the basal ganglia form a series of centrally located relay stations for information transmitted throughout the brain and to the brainstem and spinal cord and, ...