title: Medial frontal ∼4-Hz activity in humans and rodents is attenuated in PD patients and in rodents with cortical dopamine depletion.
abstract: The temporal control of action is a highly conserved and critical mammalian behavior. Here, we investigate the neuronal basis of this process using an interval timing task. In rats and humans, instructional timing cues triggered spectral power across delta and theta bands (2-6 Hz) from the medial frontal cortex (MFC). Humans and rodents with dysfunctional dopamine have impaired interval timing, and we found that both humans with Parkinson's disease (PD) and rodents with local MFC dopamine depletion had attenuated delta and theta activity. In rodents, spectral activity in this range could functionally couple single MFC neurons involved in temporal processing. Without MFC dopamine, these neurons had less functional coupling with delta/theta activity and less temporal processing. Finally, in humans this 2- to 6-Hz activity was correlated with executive function in matched controls but not in PD patients. Collectively, these findings suggest that cue-evoked low-frequency rhythms could be a clinically important biomarker of PD that is translatable to rodent models, facilitating mechanistic inquiry and the development of neurophysiological biomarkers for human disease.
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa;
authors.forename: Krystal L
authors.initials: KL
authors.lastname: Parker
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa;
authors.forename: Kuan-Hua
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa;
authors.forename: Johnathan R
authors.initials: JR
authors.lastname: Kingyon
authors.affiliation: Department of Psychology, University of New Mexico, Albuquerque, New Mexico.
authors.forename: James F
authors.initials: JF
authors.lastname: Cavanagh
authors.affiliation: Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa; Aging Mind and Brain Initiative, Carver College of Medicine, University of Iowa, Iowa City, Iowa; and Nandakumar-narayanan@uiowa.edu.
authors.forename: Nandakumar S
authors.initials: NS
authors.lastname: Narayanan
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D003216:Conditioning, Operant / Q000502:physiology; D003700:Delta Rhythm / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D004569:Electroencephalography; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000502:physiology; D009483:Neuropsychological Tests; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology*; D020318:Rats, Long-Evans; D013826:Theta Rhythm / Q000502:physiology*; D013998:Time Perception / Q000502:physiology*
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D016627:Oxidopamine; D004298:Dopamine
keywords: Parkinson's disease; dopamine; interval timing; medial frontal cortex