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. 2021 Jul;42(10):3119-3130.
doi: 10.1002/hbm.25421. Epub 2021 May 3.

Cortical N-acetylaspartate concentrations are impacted in chronic stroke but do not relate to motor impairment: A magnetic resonance spectroscopy study

Jennifer K Ferris  1 , Jason L Neva  2   3 , Irene M Vavasour  4 , Kaitlin J Attard  1 , Brian Greeley  1 , Kathryn S Hayward  5 , Katie P Wadden  6 , Alex L MacKay  4 , Lara A Boyd  1
Affiliations

Cortical N-acetylaspartate concentrations are impacted in chronic stroke but do not relate to motor impairment: A magnetic resonance spectroscopy study

Jennifer K Ferris et al. Hum Brain Mapp. 2021 Jul.

Abstract

Magnetic resonance spectroscopy (MRS) measures cerebral metabolite concentrations, which can inform our understanding of the neurobiological processes associated with stroke recovery. Here, we investigated whether metabolite concentrations in primary motor and somatosensory cortices (sensorimotor cortex) are impacted by stroke and relate to upper-extremity motor impairment in 45 individuals with chronic stroke. Cerebral metabolite estimates were adjusted for cerebrospinal fluid and brain tissue composition in the MRS voxel. Upper-extremity motor impairment was indexed with the Fugl-Meyer (FM) scale. N-acetylaspartate (NAA) concentration was reduced bilaterally in stroke participants with right hemisphere lesions (n = 23), relative to right-handed healthy older adults (n = 15; p = .006). Within the entire stroke sample (n = 45) NAA and glutamate/glutamine (GLX) were lower in the ipsilesional sensorimotor cortex, relative to the contralesional cortex (NAA: p < .001; GLX: p = .003). Lower ipsilesional NAA was related to greater extent of corticospinal tract (CST) injury, quantified by a weighted CST lesion load (p = .006). Cortical NAA and GLX concentrations did not relate to the severity of chronic upper-extremity impairment (p > .05), including after a sensitivity analysis imputing missing metabolite data for individuals with large cortical lesions (n = 5). Our results suggest that NAA, a marker of neuronal integrity, is sensitive to stroke-related cortical damage and may provide mechanistic insights into cellular processes of cortical adaptation to stroke. However, cortical MRS metabolites may have limited clinical utility as prospective biomarkers of upper-extremity outcomes in chronic stroke.

Keywords: hemiparesis; magnetic resonance spectroscopy; motor cortex; movement; somatosensory cortex; stroke; upper extremity.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
(a,b) MRS voxel placement for a participant with chronic stroke, over (a) T1 and (b) T2 scans. (c) Visualization of 1H‐MRS spectra for a representative participant. Cho, choline; Cre, creatine; GLX, glutamate/glutamine; mI, myo‐inositol; NAA, N‐acetylaspartate
FIGURE 2
FIGURE 2
Lesion overlap for 45 individuals with chronic stroke, overlaid onto the MNI T1 template brain in MNI152 space. Symptomatic stroke lesions were flipped to the left hemisphere for visualization. Color scale indicates the number of participants with a stroke involving this voxel
FIGURE 3
FIGURE 3
Boxplots illustrating hemispheric differences in cerebral metabolite concentrations after adjustment for tissue composition in the MRS voxel. Hemispheric differences were assessed with paired samplet tests. Notched line within the boxplot represents median metabolite concentrations. Boxes and lines represent the interquartile range of the data, with outliers represented by solid black circles. (a) Choline concentration; (b) Creatine concentration; (c) myo‐inositol (mI) concentration; (d) N‐acetylaspartate (NAA) concentration; (e) Glutamate + glutamine (GLX) concentration. *p < .01; **p < .001
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