Prefrontal dopamine signaling and cognitive symptoms of Parkinson’s disease

Narayanan, Nandakumar S.; Rodnitzky, Robert L.; Uç, Ergun Y.

doi:10.1515/revneuro-2013-0004

Cited by 156 publications

(141 citation statements)

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“…Recent work has implicated decreased theta in addition to alpha and beta frequencies in diagnosis of PD, in distinct brain regions (Benz et al 2014;Gu et al 2014Han et al 2013Praamstra and Pope 2007). Our work extends this line of research by focusing on MFC and linking spectral activity in PD patients with mechanistic theories (Cavanagh and Frank 2014) and single neuron activity that is consistently involved in temporal processing (Bekolay et al 2014;Kim et al 2013;Matell and Meck 2004;Narayanan and Laubach 2009;Niki and Watanabe 1979;Parker et al 2014;Xu et al 2014).…”

Section: Discussionmentioning

confidence: 56%

“…The findings reported here suggest that cortical dopamine is a significant contributor to temporal processing by medial frontal brain networks (Narayanan et al 2013b). In MFC, cortical dopamine appears to act via D1 dopamine receptors to achieve temporal control.…”

Section: Discussionmentioning

confidence: 59%

“…Blocking D1-type dopamine receptors impairs both interval timing performance and neural activity correlated with temporal control (Narayanan et al 2012;Parker et al 2014). Sustained activity of single MFC neurons appears to be involved in temporal processing across species, including humans, primates, and rodents (Kim et al 2013;Narayanan and Laubach 2009;Niki and Watanabe 1979;Sheth et al 2012;). These single MFC neurons are strongly functionally coupled with delta (1-4 Hz) and theta (4 -8 Hz) rhythms, which can be attenuated by focal D1 dopamine blockade in the MFC (Parker et al 2014).…”

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confidence: 99%

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Medial frontal ∼4-Hz activity in humans and rodents is attenuated in PD patients and in rodents with cortical dopamine depletion

Parker

Chen

Kingyon

et al. 2015

Journal of Neurophysiology

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Parker KL, Chen KH, Kingyon JR, Cavanagh JF, Narayanan NS. Medial frontal ϳ4-Hz activity in humans and rodents is attenuated in PD patients and in rodents with cortical dopamine depletion. J Neurophysiol 114: 1310 -1320, 2015. First published July 1, 2015; doi:10.1152/jn.00412.2015.-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. medial frontal cortex; dopamine; Parkinson's disease; interval timing TEMPORAL CONTROL OF action, or guiding movements in time to achieve behavioral goals, is a crucial function of mammalian nervous systems. This process depends on the integrated activity of corticostriatal systems (Buhusi and Meck 2005;Jahanshahi et al. 2010;Matell et al. 2003) and requires intact dopaminergic signaling (Drew et al. 2003). Patients with Parkinson's disease (PD) with depleted dopamine have dramatically impaired temporal control (Malapani et al. 1998). Despite these data, the neural circuitry influenced by dopamine during temporal computations is not understood.Here we study this issue in PD patients and in animal models by investigating the neural basis of an elementary cognitive task: interval timing. In this task, participants estimate an interval of several seconds as instructed by a cue. In the range of seconds, interval timing requires executive resources, such as working memory and attention to time (Brown 2006;Parker et al. 2013), and is consistently impaired in patients with PD (Buhusi and Meck 2005;Malapani et al. 1998;Merchant et al. 2008). Because this task is highly conserved across mammalian species (Buhusi and Meck 2005;Merchant et al. 2013), it can be rapidly trained in rodent models, facilitating mechanistic hypothesis testing (Drew et al. 2003;Narayanan et al. 2012).Controlling the timing of action requires the integrated activity of corticostriatal circuits (Hinton and Meck 2004;Matell and Meck 2004) that are dysfunctional in PD patients (Jahanshahi et al. 2010). Recent work...

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 59%

mentioning

confidence: 99%

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Medial frontal ∼4-Hz activity in humans and rodents is attenuated in PD patients and in rodents with cortical dopamine depletion

Parker

Chen

Kingyon

et al. 2015

Journal of Neurophysiology

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177

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“…Although the motor deficits arising from striatal DA depletion are the most pronounced symptoms of Parkinson's disease, there is also loss of DA in the PFC, and deficits in PFC cognition are common albeit complex (Owen et al, 1992;Narayanan et al, 2013;Robbins and Cools, 2014). Treatment of such cognitive deficits can be challenging, because the doses of DA medications that normalize striatal function are often too high for optimal PFC function (Gotham et al, 1988).…”

Section: Relevance To Human Disordersmentioning

confidence: 99%

Dopamine’s Actions in Primate Prefrontal Cortex: Challenges for Treating Cognitive Disorders

2015

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“…Disturbances of prefrontal functions are involved in a multitude of neuropsychiatric diseases, including depression, schizophrenia, addiction, dementia, and Parkinson´s disease [7][8][9][10][11] . Thus understanding the complexity of prefrontal physiology is of crucial importance to understand human experience and behavior in health and disease.…”

Section: Introductionmentioning

confidence: 99%

Exploring prefrontal cortex functions in healthy humans by transcranial electrical stimulation

Kuo

Nitsche²

2015

Neurosci. Bull.

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The prefrontal cortex is involved in a multitude of cognitive, emotional, motivational, and social processes, so exploring its specifi c functions is crucial for understanding human experience and behavior. Functional imaging approaches have largely contributed to the enhancement of our understanding, but might have limitations in establishing causal relationships between physiology and the related psychological and behavioral processes. Non-invasive electrical stimulation with direct or alternating currents can help to enhance our understanding with regard to specific processes, and might provide future protocols able to improve them in case of malfunctions. We review the current state of the fi eld, and provide an outlook for future developments.

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Prefrontal dopamine signaling and cognitive symptoms of Parkinson’s disease

Cited by 156 publications

References 147 publications

Medial frontal ∼4-Hz activity in humans and rodents is attenuated in PD patients and in rodents with cortical dopamine depletion

Medial frontal ∼4-Hz activity in humans and rodents is attenuated in PD patients and in rodents with cortical dopamine depletion

Dopamine’s Actions in Primate Prefrontal Cortex: Challenges for Treating Cognitive Disorders

Exploring prefrontal cortex functions in healthy humans by transcranial electrical stimulation

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