Ultra-fast Monitoring of Neurotransmitter Micro-fluctuations During Choice and Subjective Experience in Humans  Kenneth Kishida (Department of Physiology and Pharmacology and Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, NC )   C19

The ascending neuromodulatory systems that release the neurotransmitters dopamine, serotonin, and norepinephrine are critical for human brain function. Until recently, it was not possible to monitor the release of these neurotransmitters in the human brain with the temporal resolution necessary to investigate their role in encoding real-time changes in human behavior and conscious experience. We sought to develop an approach to directly monitor dopamine, serotonin, and norepinephrine with sub-second temporal resolution in the human brain. We have developed a novel approach, which we call 'elastic net electrochemistry', that permits continuous sub-second (10Hz) measurements of dopamine, serotonin, and norepinephrine (as well as other neurochemicals of interest). These first-of-their-kind recordings require electrodes implanted in the brain, thus we have deployed our approach in humans undergoing deep brain stimulation electrode implantation surgery and, more recently, in patients undergoing stereo-EEG monitoring. We have paired these novel measurements with tasks designed to investigate the computational underpinnings of human choice behavior and associated moment-to-moment changes in subjective experience. We show that simultaneously recorded dopamine and serotonin micro-fluctuations in the striatum encode computational signals critical for learning and ongoing adaptations in human behavior. These neurochemically encoded signals correlate with moment-to-moment changes in behavior that are consistent with reactions to reward and punishment, but also the subjective experiences of 'regret' and 'relief'. Direct, ultra-fast, intracranial monitoring of dopamine, serotonin and norepinephrine in consciously behaving humans is now possible. Going forward, such work may provide unprecedented insight into how these neuromodulatory systems contribute to changes in willful behavior and associated representations of subjective phenomenal experience.