Associate Professor Virginia Tech Carilion School of Medicine Roanoke, Virginia, United States
Disclosure(s):
Mark Witcher, MD PhD: No financial relationships to disclose
Introduction: Neuromodulatory systems, such as the dopamine, serotonin, and norepinephrine systems, are critical for physical and mental health. These systems have been implicated in a range of clinical conditions, including movement disorders, neuropathic pain, depression, anxiety, post-traumatic stress disorder, and schizophrenia. Yet, our understanding of the role of these systems in health and disease has been impeded by an inability to measure neurotransmitter release in the human brain, as well as an inability to contextualize these neural signals with human cognition and behavior.
Methods: Here, we solve this problem, by extending electrochemistry to sEEG depth electrodes implanted in the human amygdala for epilepsy monitoring. Electrodes were implanted into 2 patients undergoing intracranial monitoring for seizure localization. Each patient participated in standardized, emotionally evocative visual tasks while an implanted contact was used for voltammetric recordings. Post-explant, voltammetric models were validated in an in-vitro setting for each electrode. The prediction model was then applied to the voltammetric recordings from each patient’s brain to generate in-vivo neuromodulator estimates.
Results: We demonstrate (1) that our approach can detect and separate dopamine, serotonin, and norepinephrine in an experimentally controlled in-vitro setting and (2) that measurement can be combined with behavioral tasks during inpatient epilepsy monitoring to obtain in-vivo estimates of neurotransmitter release with sub-second temporal resolution. As proof of concept, we obtained sub-second estimates of norepinephrine in the human amygdala correlated with the performance of a visual attention task involving standardized emotionally evocative images.
Conclusion : We show that the release of norepinephrine in the human amygdala reflects emotional modulation of visual attention – a result which fits with the hypothesized roles of the norepinephrine system and the amygdala in emotional processing. The capacity to perform real-time, behaviorally-correlated neurotransmitter measurements in the EMU opens the door to a deeper understanding of the neuromodulatory basis of human health and disease.
