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Introduction: Bidirectional effects between cognition and pain have been extensively reported. Although brain regions involved in cognitive and pain processing seem to partly overlap, it is unknown what specific brain regions are involved in the interaction between pain and cognition. Furthermore, the role of gonadal hormones on these interacting effects has not been examined. This study investigated brain activation patterns of the interaction between pain and cognition over different phases of the naturally occurring menstrual cycle., Methods: Fifteen healthy normally cycling females were examined over the course of 4 different cycle phases. Sensory stimulation was applied using electrical pulses and cognitive performance was assessed using the Multi-Source Interference Task. Brain imaging consisted of functional magnetic resonance imaging using a repeated measures ANOVA group analysis approach., Results: Sensory stimulation was found to interact with task performance in the left precuneus, left posterior cingulate cortex and right inferior parietal lobule. No effects of cycle phase were observed to interact with main effects of stimulation, task or interaction effects between task performance and sensory stimulation., Conclusion: Potential neural correlates of shared resources between pain and cognition were demonstrated providing further insights into the potential mechanisms behind cognitive performance difficulties in pain patients and opening avenues for new treatment options including targeting specific cognitive factors in pain treatment such as cognitive interference., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Summary: N-acetylaspartate (NAA) is an intermediary metabolite that is found in relatively high concentrations in the human brain. More specifically, NAA is so concentrated in the neurons that it generates one of the most visible peaks in nuclear magnetic resonance (NMR) spectra, thus allowing NAA to serve as “a neuronal marker”. However, to date there is no generally accepted physiological (primary) role for NAA. Another molecule that is found at similar concentrations in the brain is glutamate. Glutamate is an amino acid and neurotransmitter with numerous functions in the brain. We propose that NAA, a six-carbon amino acid derivative, is converted to glutamate (five carbons) in an energetically favorable set of reactions. This set of reactions starts when aspartoacylase converts the six carbons of NAA to aspartate and acetate, which are subsequently converted to oxaloacetate and acetyl CoA, respectively. Aspartylacylase is found in astrocytes and oligodendrocytes. In the mitochondria, oxaloacetate and acetyl CoA are combined to form citrate. Requiring two steps, the citrate is oxidized in the Kreb’s cycle to α-ketoglutarate, producing NADH. Finally, α-ketoglutarate is readily converted to glutamate by transaminating the α-keto to an amine. The resulting glutamate can be used by multiple cells types to provide optimal brain functional and structural needs. Thus, the abundant NAA in neuronal tissue can serve as a large reservoir for replenishing glutamate in times of rapid or dynamic signaling demands and stress. This is beneficial in that proper levels of glutamate serve critical functions for neurons, astrocytes, and oligodendrocytes including their survival. In conclusion, we hypothesize that NAA conversion to glutamate is a logical and favorable use of this highly concentrated metabolite. It is important for normal brain function because of the brain’s relatively unique metabolic demands and metabolite fluxes. Knowing that NAA is converted to glutamate will be important for better understanding myriad neurodegenerative diseases such as Canavan’s Disease and Multiple Sclerosis, to name a few. Future studies to demonstrate the chemical, metabolic and pathological links between NAA and glutamate will support this hypothesis. [Copyright &y& Elsevier]