In vivo measurements of limbic glutamate and GABA concentrations in epileptic patients during affective and cognitive tasks: A microdialysis study

Limbic system structures such as the amygdala (AMG) and the hippocampus (HIPP) are involved in affective and cognitive processing. However, because of the limitations in noninvasive technology, absolute concentrations of the neurotransmitters underlying limbic system engagement are not known. Here, we report changes in the concentrations of the neurotransmitters glutamate (Glu) and gamma-aminobutyric acid (GABA) in the HIPP and the AMG of patients with nonlesional temporal lobe epilepsy undergoing surgery for intracranial subdural and depth electrode implantation. We utilized an in-vivo microdialysis technique while subjects were engaged in cognitive tasks with or without emotional content. The performance of an emotion learning task (EmoLearn) was associated with a significant increase in the concentration of glutamate in the HIPP when images with high valence content were processed, as compared to its concentration while processing images with low valence. In addition, significantly decreased levels of glutamate were found in the AMG when images with predominantly low valence content were processed, as compared to its concentration at baseline. The processing of face stimuli with anger/fear content (FaceMatch task) was accompanied with significantly decreased concentrations of GABA in the AMG and HIPP compared to its levels at the baseline. The processing of shapes on the other hand was accompanied with a significantly decreased concentration of the glutamate in the AMG as well as in the HIPP compared to the baseline. Finally, the performance of a nondeclarative memory task (weather prediction task-WPT) was associated with relatively large and opposite changes in the GABA levels compared to the baseline in the AMG (decrease) and the HIPP (increase). These data are relevant for showing an involvement of the amygdala and the hippocampus in emotional processing and provide additional neurochemical clues towards a more refined model of the functional circuitry of the human limbic system.