Advancing Innovative Brain Imaging to Detect Altered Glutamate Modulation and Network Dynamics in Schizophrenia

The understanding of the neural basis of learning and memory with respect to the NMDA-mediated modulation of hippocampal glutamate is poorly understood.  In a recent study, compelling results provided the first ever evidence of biochemical dynamics of the in vivo glutamate in the hippocampus during associative learning using ¹H functional MRS (fMRS). Heightened glutamate was observed in the initial encoding epochs, which is consistent with the increased hippocampal activity necessary for memory formation in this hippocampal-demanding task. Additionally, learning proficiency was highly predictive of glutamate modulation and its dynamics, which highlights the innovative values of ¹H fMRS in assessing in vivo brain (dys)function.

This approach is currently being applied to two studies: 1) to gain a greater understanding of the relationship between brain plasticity, function and network dynamics related to learning and memory in schizophrenia using ¹H fMRS; and 2) To gain a greater understanding of the contribution of the glutamatergic system underlying age-related cognitive deficits in learning and memory using ¹H fMRS. Both studies have the potential of providing an effective framework to test better-targeted therapies to mitigate impending cognitive decline.

  1. Stanley JA, Burgess A, Khatib D, Ramaseshan K, Arshad M, Wu H, Diwadkar VA. Functional dynamics of hippocampal glutamate during associative learning assessed with in vivo 1H functional magnetic resonance spectroscopy. Neuroimage. 2017; 153: 189–197.