Motor Cortex Metabolic Profile is Sensitive to Pathology: Evidence from Mr Spectroscopy Studies of Subcortical Stroke and Cervical Myelopathy

Hand motor impairments due to corticospinal tract insult diminish the ability to perform activities of daily living. Primary motor cortex (M1) remodeling plays a major role in the recovery of such impairments. Understanding of the mechanisms underlying M1 remodeling will aid the development of new rehabilitative therapies. We used magnetic resonance spectroscopy (MRS) to unravel in-vivo metabolic bases of M1 remodeling in two neurological conditions insulting M1 output. We also tested the sensitivity of M1 metabolic profiles to pathology.Eighteen survivors of a subcortical stroke (mean ± standard deviation, 60.2 ± 9.5 years old, 39% female, 11.7 ± 10.4 months after diagnosis) and eight preoperative patients with cervical myelopathy (CM, 61.9 ± 8.2 years old, 38% female, with MRI spinal/spinal cord changes, 10.7 ± 4.5 months) experiencing unilateral hand/arm motor impairment (assessed by Fugl-Meyer Upper Extremity and 9-Hole Peg Test respectively) made up the study cohort. Point-resolved spectroscopy was used to quantify the metabolic profile (consisting of biomarkers of neuronal integrity - N-acetyl aspartate or NAA, glia function and number - myoinositol or mI, cell membrane formation and degradation - choline or Cho, and cortical excitability - glutamate-glutamine complex or Glx) of M1 controlling the impaired hand. Metabolite (or marker) levels and correlational patterns were calculated for each condition and compared to those from matched controls (n = 18 for stroke and 8 for CM).Relative to M1 metabolic pattern in controls, stroke survivors showed significantly altered levels of the metabolites related to neuronal-glial interactions and cortical excitability (lower NAA, p < 0.001; higher mI, 0.04; lower Glx, 0.005) and altered correlational pattern (lower correlation coefficients, ranged from 0.12 to 0.62 compared to 0.91 to 0.95 in controls, and lower number of correlations found statistically significant, NAA-Glx, 0.007, and mI-Cho, 0.02, compared to all six pairs in controls, all < 0.001). The metabolic profile found in CM patients showed altered levels of the metabolite related to cell membrane formation and degradation (higher Cho, 0.01) and altered metabolic correlational pattern (lower correlation coefficients, ranging from -0.06 to 0.75, with only one pair of metabolites reaching significance, NAA-Cho, 0.03).These preliminary findings suggest the sensitivity of the M1 MRS-detected metabolic profile to the underlying pathology. Establishing sensitive neurobiomarkers is essential to identify targets and determine the proper timing for altering neuroplasticity to promote neurological recovery.