title: Features and timing of the response of single neurons to novelty in the substantia nigra.
abstract: Substantia nigra neurons are known to play a key role in normal cognitive processes and disease states. While animal models and neuroimaging studies link dopamine neurons to novelty detection, this has not been demonstrated electrophysiologically in humans. We used single neuron extracellular recordings in awake human subjects undergoing surgery for Parkinson disease to characterize the features and timing of this response in the substantia nigra. We recorded 49 neurons in the substantia nigra. Using an auditory oddball task, we showed that they fired more rapidly following novel sounds than repetitive tones. The response was biphasic with peaks at approximately 250 ms, comparable to that described in primate studies, and a second peak at 500 ms. This response was primarily driven by slower firing neurons as firing rate was inversely correlated to novelty response. Our data provide human validation of the purported role of dopamine neurons in novelty detection and suggest modifications to proposed models of novelty detection circuitry.
authors.affiliation: Columbia University Medical Center, Department of Neurological Surgery, 710W 168th Street, New York, NY 10032, United States. Electronic address: cbm2104@columbia.edu.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Mikell
authors.affiliation: Barrow Neurological Institute, 350 West Thomas Road, Phoenix, AZ 85013, United States.
authors.forename: John P
authors.initials: JP
authors.lastname: Sheehy
authors.affiliation: Columbia University Medical Center, Department of Neurological Surgery, 710W 168th Street, New York, NY 10032, United States.
authors.forename: Brett E
authors.initials: BE
authors.lastname: Youngerman
authors.affiliation: Columbia University Medical Center, Department of Neurological Surgery, 710W 168th Street, New York, NY 10032, United States.
authors.forename: Robert A
authors.initials: RA
authors.lastname: McGovern
authors.affiliation: Columbia University Medical Center, Department of Neurological Surgery, 710W 168th Street, New York, NY 10032, United States.
authors.forename: Teresa J
authors.initials: TJ
authors.lastname: Wojtasiewicz
authors.affiliation: Columbia University Medical Center, Department of Neurological Surgery, 710W 168th Street, New York, NY 10032, United States.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Chan
authors.affiliation: Columbia University, Department of Neurology, 710W 168th Street, New York, NY 10032, United States.
authors.forename: Seth L
authors.initials: SL
authors.lastname: Pullman
authors.affiliation: Columbia University, Department of Neurology, 710W 168th Street, New York, NY 10032, United States.
authors.forename: Qiping
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, St. Luke's-Roosevelt and Beth Israel Hospitals, 1000 10th Ave, New York, NY 10019, United States.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Goodman
authors.affiliation: Columbia University, Department of Neurology, 710W 168th Street, New York, NY 10032, United States.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Schevon
authors.affiliation: Columbia University Medical Center, Department of Neurological Surgery, 710W 168th Street, New York, NY 10032, United States.
authors.forename: Guy M
authors.initials: GM
authors.lastname: McKhann
mesh_terms: D000161:Acoustic Stimulation; D000200:Action Potentials / Q000502:physiology*; D000368:Aged; D004594:Electrophysiology; D006801:Humans; D008875:Middle Aged; D009474:Neurons / Q000502:physiology*; D010300:Parkinson Disease / Q000473:pathology; D025341:Principal Component Analysis; D013378:Substantia Nigra / Q000473:pathology*; D013997:Time Factors; D013998:Time Perception / Q000502:physiology*; D014851:Wakefulness
keywords: Deep brain stimulation; Dopamine neurons; Human substantia nigra; Neurophysiology; Novelty