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MRS reveals motor cortex basal GABA levels are correlated with handedness
Yasmin Geiger1 and Assaf Tal1

1Chemical and Biological Physics, Weizmann Institute of Science, Rehovot, Israel

Synopsis

Motor skills acquisition can manifest in changes in basal levels of metabolites in the motor cortex. We aim to study difference in metabolites basal levels in the ipsilateral and contralateral motor cortex using single voxel MRS. Our study showed significant difference only in basal GABA levels and the basal GABA/Glx ratio. This result should be kept in mind when interpreting or designing experiments studying the metabolic correlates of motor function.

Introduction

Motor learning is the acquisition of motor skills through practice, experience and interaction with the environment1,2. Previous 1H-MRS studies have shown that motor learning leads to short term GABA decreases in the primary (M1) and supplementary (SMA) motor areas3,4. The long term dynamics of GABA remains unstudied. A phenomenon which leads to the asymmetric acquisition of motor skill across a person’s lifetime is handedness; this model can be used to correlate spectroscopic findings with the long-term effects of skill acquisition. In this work, we scanned the contra and ipsi-lateral primary motor areas in a cohort of healthy volunteers using MEGA-PRESS5 to assess whether they exhibit any metabolic differences.

Methods

Cohort: This study was conducted on 36 healthy female adults (aged 25±3, mean±standard deviation) with no motor disability or neurological disorder, who gave informed consent. Dominant hand was determined with Edinburgh Handedness Inventory test6. Exclusion criteria included current or chronic use of medication, any known learning disabilities, attention deficit or sleep disorders, more than 2 years of formal music training and professional typists.

MRS: All scans were carried out on Siemens 3-T Tim Trio (Siemens-Healthineers, Erlangen, Germany) using a 32-channel receive array coil. Structural images were acquired using a sagittal magnetization prepared rapid gradient echo (MPRAGE) three-dimensional T1-weighted sequence. 1H‑MRS spectra were acquired from single 18.75 mL voxel, placed once at the ipsilateral and once at the contralateral motor cortex according to anatomical landmarks7. The spectra were acquired using MEGA-PRESS5, with TR/TE = 3000/68 ms and 14 ms sinc-Gaussian editing pulses applied interleaved at 4.1 ppm (“OFF”) and 1.9 ppm (“ON”), symmetrically about creatine. 192 interleaved scans were collected from (a total of 96 scans) with TA≈10 min for each voxel.

Post-processing: GABA concentrations were extracted by integrating the difference spectrum between 2.9 and 3.1 ppm. GABA measurements contain contributions from co-edited macromolecules. Metabolites concentrations for all other metabolites were extracted from the “Off” spectra using LCModel v6.3, using an appropriately simulated basis set. containing: NAA, NAAG, Cr., glutamate, glutamine, GABA, lactate, alanine, aspartate, myo-Inisotol, scyllo-inositol, glutathione, glycerophosphocholine and Tau. All concentrations were normalized to water.

Results

An example of “Off” and difference spectra from a single volunteer can be seen in Fig. 1. T-tests were performed to compare basal metabolite concentrations between hemispheres. Statistical significance was observed only for GABA (p= 0.02) and the ratio GABA/Glx (p = 0.007) (Fig.2). This difference in baseline may indicate a connection between GABAs’ baseline level and long-term learning and skill acquisition.

Discussion & Conclusion

Our preliminary results have revealed GABA is significantly elevated in the contralateral motor cortex. GABA is thought to modulate long term potentiation and skill acquisition8. Prior studies have shown short-term decreases in GABA following motor learning3,4; however, it is unclear what is the long term dynamics of these short term changes. Furthermore, elevated GABA levels in the sensorimotor region were shown to correlate with higher performance in discrimination task9 and with smaller subliminal motor activation effect10. Such studies may indicate GABA as a marker for adjusting the sensorimotor cortex to allow greater discrimination of stimuli and improved performances. In line with these studies our results may reveal higher “tuning” of the contralateral motor cortex to allow for better discrimination and more controlled responses. Our results might also contain additional confounding factors, such as metabolic imbalances which originate from the same genetic mechanisms which lead to the phenomenon of handedness itself.

Regardless, our findings of a lateral metabolic imbalance should be kept in mind when interpreting the results of experiments studying the correlation of MRS and motor learning, as well as when selecting a study’s cohort.

Acknowledgements

Assaf Tal acknowledges the support of the Monroy‐Marks Career Development Fund, the Minerva Foundation, the Carolito Stiftung Fund, the Leona M. and Harry B.Helmsley Charitable Trust and the historic generosity of the Harold Perlman Family.

References

  1. Brem, A.-k., K. Ran, and A. Pascual-leone, Chapter 55 - Learning and memory, in Handbook of Clinical Neurology, M.L. Andres and H. Mark, Editors. 2013, Elsevier. p. 693-737.
  2. Adams, J.A., Historical Review and Appraisal of Research on the Learning, Retention, and Transfer of Human Motor-Skills. Psychological Bulletin, 1987. 101(1): p. 41-74.
  3. Floyer-Lea, A., et al., Rapid modulation of GABA concentration in human sensorimotor cortex during motor learning. Journal of neurophysiology, 2006. 95(3): p. 1639-1644.
  4. Kolasinski, J., et al., The dynamics of cortical GABA in human motor learning. bioRxiv, 2018: p. 341503.
  5. Mullins, P.G., et al., Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA. Neuroimage, 2014. 86: p. 43-52.
  6. Oldfield, R.C., The Assessment and Analysis of Handedness: The Edinburgh Inventory. Neuropsychologia, 1971. 9(1): p. 97-113.
  7. Yousry, T., et al., Localization of the motor hand area to a knob on the precentral gyrus. A new landmark. Brain: a journal of neurology, 1997. 120(1): p. 141-157.
  8. Cohen Kadosh, K., et al., Linking GABA and glutamate levels to cognitive skill acquisition during development. Hum Brain Mapp, 2015. 36(11): p. 4334-45.
  9. Puts, N.A., et al., Regionally specific human GABA concentration correlates with tactile discrimination thresholds. Journal of Neuroscience, 2011. 31(46): p. 16556-16560.
  10. Boy, F., et al., Individual Differences in Subconscious Motor Control Predicted by GABA Concentration in SMA. Current Biology, 2010. 20(19): p. 1779-1785.

Figures

Figure 1. (a) voxels placement. (b) LCModel fit (red) for “off” spectrum taken from contralateral motor cortex of a single volunteer. NAA, Cr, Glx and GPC were countrified with SD of less than 10%. (c) Difference spectrum taken from contralateral motor cortex of a single volunteer. GABA signal is isolated from other signals, enabling to sum the signal between 2.9 and 3.2 ppm to calculate GABA concentration.

Figure 2. Cr., NAA, Glx and GABA difference (%) between contralateral and ipsilateral motor cortex at rest in healthy volunteers. Cr., NAA and Glx concentrations were deduced from “off” MEGA-PRESS spectra using LCModel. GABA concentrations were deduced from integration on the difference MEPG-PRESS (“on”-off”) spectra between 2.9 and 3.2 ppm. All metabolites are normalized to water.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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