A Spiking Neural Integrator Model of the Adaptive Control of Action by the Medial Prefrontal Cortex

Bekolay, Trevor; Laubach, Mark; Eliasmith, Chris

doi:10.1523/jneurosci.2421-13.2014

Cited by 32 publications

(40 citation statements)

References 45 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the MFC, PCA identified three prominent patterns of neuronal activity. As in previous studies, the first principal component (PC1) was a ‘ramp’—a monotonic linear change in neuronal activity over time (Figure 3D)[13,28–30]. Ramping activity, or PC1, explained 51% of neuronal variance.…”

Section: Resultssupporting

confidence: 63%

Optogenetic Stimulation of Frontal D1 Neurons Compensates for Impaired Temporal Control of Action in Dopamine-Depleted Mice

et al. 2017

View full text Add to dashboard Cite

Summary Disrupted mesocortical dopamine contributes to cognitive symptoms of Parkinson’s disease (PD). Past work has implicated medial frontal neurons expressing D1 dopamine receptors (D1DRs) in temporal processing. Here, we investigate if these neurons can compensate for behavioral deficits resulting from midbrain dopamine dysfunction. We report three main results. First, both PD patients and mice with ventral tegmental area (VTA) dopamine depletion had attenuated delta activity (1–4 Hz) in the medial frontal cortex (MFC) during interval timing. Second, we found that optogenetically stimulating MFC D1DR neurons could increase ramping activity among MFC neurons. Finally, stimulating MFC D1DR neurons specifically at delta frequencies (2 Hz) compensated for deficits in temporal control of action caused by VTA dopamine depletion. Our results suggest that cortical networks can be targeted by frequency-specific brain stimulation to improve dopamine-dependent cognitive processing.

show abstract

Section: Resultssupporting

confidence: 63%

Optogenetic Stimulation of Frontal D1 Neurons Compensates for Impaired Temporal Control of Action in Dopamine-Depleted Mice

et al. 2017

View full text Add to dashboard Cite

show abstract

“…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%

“…Our data do not indicate that these signals are directly predictive of timing behavior. Rather, they are present at the time of cue, altered in humans and rodents with dysfunctional medial frontal dopamine, and can be coherent with medial frontal neurons that encode temporal signals (Bekolay et al 2014;Durstewitz 2003;Matell and Meck 2004;Niki and Watanabe 1979). This paper and prior work indicate that delta/theta oscillations could be involved in synchronizing neurons involved in temporal processing at the time of cue (Parker et al 2014).…”

Section: Discussionmentioning

confidence: 63%

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

177

View full text Add to dashboard Cite

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...

show abstract

“…Many cells with persistent activity can have ramping features [21]. Moreover, ramping is the integral or cumulative sum of persistent activity, indicating that ramping could encode cognitive variables in addition to timing, such as error signals or working memory [13]…”

Section: Ramping Activitymentioning

confidence: 99%

Ramping activity is a cortical mechanism of temporal control of action

Narayanan

2016

Current Opinion in Behavioral Sciences

View full text Add to dashboard Cite

A fundamental feature of the mammalian cortex is to guide movements in time. One common pattern of neural activity observed across cortical regions during temporal control of action is ramping activity. Ramping activity can be defined as consistent increases or decreases in neuronal firing rate across behaviorally relevant epochs of time. Prefrontal brain regions, including medial frontal and lateral prefrontal cortex, are critical for temporal control of action. Ramping is among the most common pattern of neural activity in these prefrontal areas during behavioral tasks. Finally, stimulating prefrontal neurons in medial frontal cortex can influence the timing of movement. These data can be helpful in approaching human diseases with impaired temporal of action, such as Parkinson's disease and schizophrenia. Cortical ramping activity might contribute to new diagnostic and therapeutic strategies for these and other debilitating human diseases.

show abstract

A Spiking Neural Integrator Model of the Adaptive Control of Action by the Medial Prefrontal Cortex

Cited by 32 publications

References 45 publications

Optogenetic Stimulation of Frontal D1 Neurons Compensates for Impaired Temporal Control of Action in Dopamine-Depleted Mice

Optogenetic Stimulation of Frontal D1 Neurons Compensates for Impaired Temporal Control of Action in Dopamine-Depleted Mice

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

Ramping activity is a cortical mechanism of temporal control of action

Contact Info

Product

Resources

About