Abstract
Proton magnetic resonance spectroscopy (1H MRS) is a well-established technique for quantifying the brain regional biochemistry in vivo. In most studies, however, the 1H MRS is acquired during rest with little to no constraint on behavior. Measured metabolite levels, therefore, reflect steady-state concentrations whose associations with behavior and cognition are unclear. With the recent advances in MR technology—higher-field MR systems, robust acquisition techniques and sophisticated quantification methods—1H MRS is now experiencing a resurgence. It is sensitive to task-related and pathology-relevant regional dynamic changes in neurotransmitters, including the most ubiquitous among them, glutamate. Moreover, high temporal resolution approaches allow tracking glutamate modulations at a time scale of under a minute during perceptual, motor, and cognitive tasks. The observed task-related changes in brain glutamate are consistent with new metabolic steady states reflecting the neural output driven by shifts in the local excitatory and inhibitory balance on local circuits. Unlike blood oxygen level differences-base functional MRI, this form of in vivo MRS, also known as functional MRS (1H fMRS), yields a more direct measure of behaviorally relevant neural activity and is considerably less sensitive to vascular changes. 1H fMRS enables noninvasive investigations of task-related glutamate changes that are relevant to normal and impaired cognitive performance, and psychiatric disorders. By targeting brain glutamate, this approach taps into putative neural correlates of synaptic plasticity. This review provides a concise survey of recent technological advancements that lay the foundation for the successful use of 1H fMRS in cognitive neuroscience and neuropsychiatry, including a review of seminal 1H fMRS studies, and the discussion of biological significance of task-related changes in glutamate modulation. We conclude with a discussion of the promises, limitations, and outstanding challenges of this new tool in the armamentarium of cognitive neuroscience and psychiatry research.
Highlights
Understanding of human behavior and cognition as products of their neural substrates depends on elucidation of the neural foundations of information processing
Because of strong evidence implicating the glutamatergic and GABAergic neurotransmission in psychiatric disorders [8,9,10], and cognitive aging [11], it is plausible that a dysfunction in the ability to modulate excitatory and inhibitory (E/I) equilibrium of local circuits would affect function within broader networks in which complex cognition is implemented
We focus on 1H magnetic resonance spectroscopy (MRS) findings pertaining to changes in glutamate with task in the context of 1H fMRS [for a review on 1H fMRS of glutamate and γ-aminobutyric acid (GABA), see Duncan et al [16]]
Summary
Understanding of human behavior and cognition as products of their neural substrates depends on elucidation of the neural foundations of information processing. Sensitivity of glutamate levels to stimulus characteristics was illustrated by a 1H fMRS study that found an almost 12% increase within the left occipital cortex during passive viewing of novel pictures compared to a (pseudo-) rest control condition, but no change during repeated picture presentation [45].
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