Advertisement

Glutamatergic response to a low load working memory paradigm in the left dorsolateral prefrontal cortex in patients with mild cognitive impairment: a functional magnetic resonance spectroscopy study

  • Anupa A. Vijayakumari
  • Ramshekhar N. Menon
  • Bejoy Thomas
  • Thumboli Muyyayil Arun
  • Mohanan Nandini
  • Chandrasekharan KesavadasEmail author
ORIGINAL RESEARCH
  • 21 Downloads

Abstract

Working memory deficits have been widely reported in mild cognitive impairment (MCI). However, the neural mechanisms of working memory dysfunction in MCI have not been clearly understood. In this study, we used proton functional magnetic resonance spectroscopy (1H-fMRS) and functional magnetic resonance imaging (fMRI) to understand the underlying neurobiology of working memory deficits in patients with MCI. We aimed at detecting the changes in the concentration of glutamate and blood oxygen level dependent (BOLD) activity using 1H-fMRS and fMRI respectively during a low load verbal (0 back and 1 back) working memory in the left dorsolateral prefrontal cortex (DLPFC) between patients with MCI and healthy controls. Fifteen patients with amnestic MCI and twenty two age, gender and education matched healthy controls underwent a low load verbal working memory 1H-fMRS and fMRI. We observed significant increase in glutamate during working memory task (both 0 back and 1 back) in healthy controls and such changes were absent in patients with MCI. However, percent signal changes representing BOLD activity during both 0 back and 1 back was not significantly different between two groups. Our findings suggest that 1H-fMRS complements fMRI in understanding the working memory mechanism in the left DLPFC.

Keywords

Working memory Functional magnetic resonance spectroscopy Functional magnetic resonance imaging Glutamate neurotransmission Mild cognitive impairment 

Notes

Acknowledgements

The study was financially supported by the Science and Engineering Research Board, Department of Science and Technology, India (Grant no. PDF/2016/000494 dated 28 November 2016 to Dr. Anupa A Vijayakumari). The authors express their deep sense of gratitude to all the research participants who graciously took part in this project, as well as the staff of the Department of Imaging Sciences and Technology at SCTIMST. In addition, we specifically thank Mr. Jithin B and Ms. Anusree TV for their technical assistance

References

  1. Apsvalka, D., Gadie, A., Clemence, M., & Mullins, P. G. (2015). Event-related dynamics of glutamate and BOLD effects measured using functional magnetic resonance spectroscopy (fMRS) at 3T in a repetition suppression paradigm. Neuroimage, 118, 292–300.  https://doi.org/10.1016/j.neuroimage.2015.06.015.CrossRefGoogle Scholar
  2. Bednarik, P., Tkac, I., Giove, F., DiNuzzo, M., Deelchand, D. K., Emir, U. E., Eberly, L. E., & Mangia, S. (2015). Neurochemical and BOLD responses during neuronal activation measured in the human visual cortex at 7 tesla. Journal of Cerebral Blood Flow and Metabolism, 35(4), 601–610.  https://doi.org/10.1038/jcbfm.2014.233.CrossRefGoogle Scholar
  3. Bokde, A. L., Karmann, M., Born, C., Teipel, S. J., Omerovic, M., Ewers, M., Frodl, T., Meisenzahl, E., Reiser, M., Moller, H. J., & Hampel, H. (2010). Altered brain activation during a verbal working memory task in subjects with amnestic mild cognitive impairment. Journal of Alzheimer's Disease, 21(1), 103–118.  https://doi.org/10.3233/JAD-2010-091054.CrossRefGoogle Scholar
  4. Braver, T. S., Cohen, J. D., Nystrom, L. E., Jonides, J., Smith, E. E., & Noll, D. C. (1997). A parametric study of prefrontal cortex involvement in human working memory. Neuroimage, 5(1), 49–62.  https://doi.org/10.1006/nimg.1996.0247.CrossRefGoogle Scholar
  5. Brett Matthew, A. J.-L., Romain, V., & Jean-Baptiste, P. (2002). Region of interest analysis using an SPM toolbox. Paper presented at the 8th international conference on functional mapping of the human brain (pp. 2–6). Sendai: June.Google Scholar
  6. Curtis, C. E., & D'Esposito, M. (2003). Persistent activity in the prefrontal cortex during working memory. Trends in Cognitive Sciences, 7(9), 415–423.CrossRefGoogle Scholar
  7. Dohnel, K., Sommer, M., Ibach, B., Rothmayr, C., Meinhardt, J., & Hajak, G. (2008). Neural correlates of emotional working memory in patients with mild cognitive impairment. Neuropsychologia, 46(1), 37–48.  https://doi.org/10.1016/j.neuropsychologia.2007.08.012.CrossRefGoogle Scholar
  8. Hertz, L., & Rodrigues, T. B. (2014). Astrocytic-neuronal-astrocytic pathway selection for formation and degradation of glutamate/GABA. Front Endocrinol (Lausanne), 5, 42.  https://doi.org/10.3389/fendo.2014.00042.CrossRefGoogle Scholar
  9. Huang, Z., Davis, H. I., Yue, Q., Wiebking, C., Duncan, N. W., Zhang, J., Wagner, N. F., Wolff, A., & Northoff, G. (2015). Increase in glutamate/glutamine concentration in the medial prefrontal cortex during mental imagery: A combined functional mrs and fMRI study. Human Brain Mapping, 36(8), 3204–3212.  https://doi.org/10.1002/hbm.22841.CrossRefGoogle Scholar
  10. Jacola, L. M., Willard, V. W., Ashford, J. M., Ogg, R. J., Scoggins, M. A., Jones, M. M., Wu, S., & Conklin, H. M. (2014). Clinical utility of the N-back task in functional neuroimaging studies of working memory. Journal of Clinical and Experimental Neuropsychology, 36(8), 875–886.  https://doi.org/10.1080/13803395.2014.953039.CrossRefGoogle Scholar
  11. Kessels, R. P., Molleman, P. W., & Oosterman, J. M. (2011). Assessment of working-memory deficits in patients with mild cognitive impairment and Alzheimer's dementia using Wechsler's working memory index. Aging Clinical and Experimental Research, 23(5–6), 487–490.CrossRefGoogle Scholar
  12. Kuhn, S., Schubert, F., Mekle, R., Wenger, E., Ittermann, B., Lindenberger, U., & Gallinat, J. (2016). Neurotransmitter changes during interference task in anterior cingulate cortex: Evidence from fMRI-guided functional MRS at 3 T. Brain Structure & Function, 221(5), 2541–2551.  https://doi.org/10.1007/s00429-015-1057-0.CrossRefGoogle Scholar
  13. Logothetis, N. K., Pauls, J., Augath, M., Trinath, T., & Oeltermann, A. (2001). Neurophysiological investigation of the basis of the fMRI signal. Nature, 412(6843), 150–157.  https://doi.org/10.1038/35084005.CrossRefGoogle Scholar
  14. Mathuranath, P. S., Cherian, J. P., Mathew, R., George, A., Alexander, A., & Sarma, S. P. (2007). Mini mental state examination and the Addenbrooke's cognitive examination: Effect of education and norms for a multicultural population. Neurology India, 55(2), 106–110.CrossRefGoogle Scholar
  15. Menon, R., Lekha, V., Justus, S., Sarma, P. S., & Mathuranath, P. (2014). A pilot study on utility of Malayalam version of Addenbrooke's cognitive examination in detection of amnestic mild cognitive impairment: A critical insight into utility of learning and recall measures. Annals of Indian Academy of Neurology, 17(4), 420–425.  https://doi.org/10.4103/0972-2327.144018.CrossRefGoogle Scholar
  16. Michels, L., Martin, E., Klaver, P., Edden, R., Zelaya, F., Lythgoe, D. J., Luchinger, R., Brandeis, D., & O'Gorman, R. L. (2012). Frontal GABA levels change during working memory. PLoS One, 7(4), e31933.  https://doi.org/10.1371/journal.pone.0031933.CrossRefGoogle Scholar
  17. Migo, E. M., Mitterschiffthaler, M., O'Daly, O., Dawson, G. R., Dourish, C. T., Craig, K. J., Simmons, A., Wilcock, G. K., McCulloch, E., Jackson, S. H., Kopelman, M. D., Williams, S. C., & Morris, R. G. (2015). Alterations in working memory networks in amnestic mild cognitive impairment. Neuropsychology, Development, and Cognition. Section B, Aging, Neuropsychology and Cognition, 22(1), 106–127.  https://doi.org/10.1080/13825585.2014.894958.CrossRefGoogle Scholar
  18. Nagel, B. J., Herting, M. M., Maxwell, E. C., Bruno, R., & Fair, D. (2013). Hemispheric lateralization of verbal and spatial working memory during adolescence. Brain and Cognition, 82(1), 58–68.  https://doi.org/10.1016/j.bandc.2013.02.007.CrossRefGoogle Scholar
  19. Niu, H. J., Li, X., Chen, Y. J., Ma, C., Zhang, J. Y., & Zhang, Z. J. (2013). Reduced frontal activation during a working memory task in mild cognitive impairment: A non-invasive near-infrared spectroscopy study. CNS Neuroscience & Therapeutics, 19(2), 125–131.  https://doi.org/10.1111/cns.12046.CrossRefGoogle Scholar
  20. Ogawa, S., Lee, T. M., Kay, A. R., & Tank, D. W. (1990). Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proceedings of the National Academy of Sciences of the United States of America, 87(24), 9868–9872.CrossRefGoogle Scholar
  21. Opitz, B., Mecklinger, A., & Friederici, A. D. (2000). Functional asymmetry of human prefrontal cortex: Encoding and retrieval of verbally and nonverbally coded information. Learning & Memory, 7(2), 85–96.CrossRefGoogle Scholar
  22. Parasuraman, R. (1998). The attentive brain. Cambridge: MIT Press.Google Scholar
  23. Petersen, R. C. (2004). Mild cognitive impairment as a diagnostic entity. Journal of Internal Medicine, 256(3), 183–194.  https://doi.org/10.1111/j.1365-2796.2004.01388.x.CrossRefGoogle Scholar
  24. Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999). Mild cognitive impairment: Clinical characterization and outcome. Archives of Neurology, 56(3), 303–308.CrossRefGoogle Scholar
  25. Petrides, M. (2005). Lateral prefrontal cortex: Architectonic and functional organization. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 360(1456), 781–795.  https://doi.org/10.1098/rstb.2005.1631.CrossRefGoogle Scholar
  26. Ross, B. D. (1991). Biochemical considerations in 1H spectroscopy. Glutamate and glutamine; myo-inositol and related metabolites. NMR in Biomedicine, 4(2), 59–63.CrossRefGoogle Scholar
  27. Rothman, D. L., Sibson, N. R., Hyder, F., Shen, J., Behar, K. L., & Shulman, R. G. (1999). In vivo nuclear magnetic resonance spectroscopy studies of the relationship between the glutamate-glutamine neurotransmitter cycle and functional neuroenergetics. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 354(1387), 1165–1177.  https://doi.org/10.1098/rstb.1999.0472.CrossRefGoogle Scholar
  28. Saunders, N. L., & Summers, M. J. (2010). Attention and working memory deficits in mild cognitive impairment. Journal of Clinical and Experimental Neuropsychology, 32(4), 350–357.  https://doi.org/10.1080/13803390903042379.CrossRefGoogle Scholar
  29. Saykin, A. J., Wishart, H. A., Rabin, L. A., Flashman, L. A., McHugh, T. L., Mamourian, A. C., & Santulli, R. B. (2004). Cholinergic enhancement of frontal lobe activity in mild cognitive impairment. Brain, 127 (Pt 7, 1574–1583.  https://doi.org/10.1093/brain/awh177.CrossRefGoogle Scholar
  30. Sibson, N. R., Dhankhar, A., Mason, G. F., Rothman, D. L., Behar, K. L., & Shulman, R. G. (1998). Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. Proceedings of the National Academy of Sciences of the United States of America, 95(1), 316–321.CrossRefGoogle Scholar
  31. Stanley, J. A., & Raz, N. (2018). Functional magnetic resonance spectroscopy: The "new" MRS for cognitive neuroscience and psychiatry research. Frontiers in Psychiatry, 9, 76.  https://doi.org/10.3389/fpsyt.2018.00076.CrossRefGoogle Scholar
  32. Szatkowski, M., & Attwell, D. (1994). Triggering and execution of neuronal death in brain ischaemia: Two phases of glutamate release by different mechanisms. Trends in Neurosciences, 17(9), 359–365.CrossRefGoogle Scholar
  33. Taylor, R., Neufeld, R. W., Schaefer, B., Densmore, M., Rajakumar, N., Osuch, E. A., Williamson, P. C., & Theberge, J. (2015). Functional magnetic resonance spectroscopy of glutamate in schizophrenia and major depressive disorder: Anterior cingulate activity during a color-word Stroop task. NPJ Schizophrenia, 1, 15028.  https://doi.org/10.1038/npjschz.2015.28.CrossRefGoogle Scholar
  34. Thomason, M. E., Race, E., Burrows, B., Whitfield-Gabrieli, S., Glover, G. H., & Gabrieli, J. D. (2009). Development of spatial and verbal working memory capacity in the human brain. Journal of Cognitive Neuroscience, 21(2), 316–332.  https://doi.org/10.1162/jocn.2008.21028.CrossRefGoogle Scholar
  35. Vijayakumari, A. A., Thomas, B., Menon, R. N., & Kesavadas, C. (2018a). Association between glutamate/glutamine and blood oxygen level dependent signal in the left dorsolateral prefrontal region during verbal working memory. Neuroreport, 29(6), 478–482.  https://doi.org/10.1097/WNR.0000000000001000.CrossRefGoogle Scholar
  36. Vijayakumari, A. A., Thomas, B., Menon, R. N., & Kesavadas, C. (2018b). Task-based metabolic changes in the left dorsolateral prefrontal region during the letter N-back working memory task using proton magnetic resonance spectroscopy. Neuroreport, 29(2), 147–152.  https://doi.org/10.1097/WNR.0000000000000943.CrossRefGoogle Scholar
  37. Woodcock, E. A., Anand, C., Khatib, D., Diwadkar, V. A., & Stanley, J. A. (2018). Working memory modulates glutamate levels in the dorsolateral prefrontal cortex during (1)H fMRS. Frontiers in Psychiatry, 9, 66.  https://doi.org/10.3389/fpsyt.2018.00066.CrossRefGoogle Scholar
  38. Yetkin, F. Z., Rosenberg, R. N., Weiner, M. F., Purdy, P. D., & Cullum, C. M. (2006). FMRI of working memory in patients with mild cognitive impairment and probable Alzheimer's disease. European Radiology, 16(1), 193–206.  https://doi.org/10.1007/s00330-005-2794-x.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Medical Image Processing Laboratory, Department of Imaging Sciences and Interventional Radiology (IS & IR)Sree Chitra Tirunal Institute for Medical Sciences and TechnologyTrivandrumIndia
  2. 2.Department of NeurologySree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST)TrivandrumIndia

Personalised recommendations