Glutamate, and its relationship to task-induced functional connectivity in the human brain: A focus on schizophrenia
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Brain Imaging Research Division
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Glutamate is the brain’s major excitatory neurotransmitter mediating both neuroplasticity and network function (Zhou & Danbolt, 2014). Basal glutamate (Glu) measured using proton magnetic resonance spectroscopy (1H-MRS) provides insight into a region’s density of neuropil related to the glutamatergic system. Moreover, given the role of glutamate in mediating brain network function, Glu levels may play a role in the brain’s functional connectivity (FC), which is typically estimated from functional magnetic resonance imaging (fMRI) time series data. These questions converge when considering the clinical syndrome of schizophrenia (SCZ). Patients with SCZ show abnormalities in basal Glu in the hippocampus and prefrontal cortex (Tebartz et al., 2013). They also show functional dys-connectivity across brain networks induced by tasks of learning (Baajour et al., 2020). Yet, no investigations have systematically assessed relationships between basal Glu and task-induced FC in healthy controls (HC), and possibly altered relationships in SCZ. Here, we will explore relationships between Glu (hippocampus and prefrontal cortex) and whole-brain functional connectivity derived from fMRI data acquired using a specifically tailored learning task (Ravishankar et al., 2019). Data was acquired in a single session in 72 participants (36 SCZ and 36 HC). From Glu quantitated in the hippocampus and the prefrontal cortex (LC Model, Woodcock et al., 2018), we will explore statistical relationships to FC estimated across a 90-node brain network, using a combination of clustering and graph theoretic methods, and address whether these relationships differ between HC and SCZ.
Behavioral Neurobiology | Behavior and Behavior Mechanisms | Medicine and Health Sciences | Neuroscience and Neurobiology | Psychiatry and Psychology
Young, Kathleen Liu; Kopchick, John; Stanley, Jeffrey; and Diwadkar, Vaibhav, "Glutamate, and its relationship to task-induced functional connectivity in the human brain: A focus on schizophrenia" (2023). Medical Student Research Symposium. 233.
Baajour, S. J., Chowdury, A., Thomas, P., Rajan, U., Khatib, D., Zajac‐Benitez, C., Falco, D., Haddad, L., Amirsadri, A., Bressler, S., Stanley, J. A., & Diwadkar, V. A. (2020). Disordered directional brain network interactions during learning dynamics in schizophrenia revealed by multivariate autoregressive models. Human Brain Mapping, 41(13), 3594–3607. https://doi.org/10.1002/hbm.25032
Ravishankar, M., Morris, A., Burgess, A., Khatib, D., Stanley, J. A., & Diwadkar, V. A. (2019). Cortical-hippocampal functional connectivity during covert consolidation sub-serves associative learning: Evidence for an active “rest” state. Brain and Cognition, 131, 45–55. https://doi.org/10.1016/j.bandc.2017.10.003
Tebartz van Elst, L., Valerius, G., Büchert, M., Thiel, T., Rüsch, N., Bubl, E., Hennig, J., Ebert, D., & Olbrich, H. M. (2005). Increased prefrontal and hippocampal glutamate concentration in schizophrenia: Evidence from a magnetic resonance spectroscopy study. Biological Psychiatry, 58(9), 724–730. https://doi.org/10.1016/j.biopsych.2005.04.041
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 1H fmrs. Frontiers in Psychiatry, 9. https://doi.org/10.3389/fpsyt.2018.00066
Zhou, Y., & Danbolt, N. C. (2014, August). Glutamate as a neurotransmitter in the healthy brain. Journal of neural transmission (Vienna, Austria : 1996). Retrieved December 9, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133642/