Ramping activity is a cortical mechanism of temporal control of action

Abstract

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.

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

“…We noticed that stimulation of MFC D1DR neurons in the same MFC network could increase ramping activity of untagged MFC neurons (Figure 4C–F). As above, ramping activity can be represented by PC1 in PCA[13,17,18]; and we found that MFC D1DR delta stimulation markedly affected PCA resulting in significant differences for PC1 among untagged MFC neurons (Figure 4G–H; PC1: paired t (233) =2.1, p<0.04). PC3 also increased with MFC D1DR delta stimulation (paired t (233) =3.9, PC3: p<0.0001; no difference was found for PC2).…”

“…Ramping activity, or PC1, explained 51% of neuronal variance. Of note, our past work indicates that ramping activity can be coherent with delta oscillations and can predict when animals respond during the interval-timing task[9,10,13,17]. PC2 showed modulation during the interval and explained 27% of variance.…”

“…Blocking D1- but not D2-type dopamine receptors impairs temporal processing and neuronal activity correlated with temporal control in rodents[11,13,14], paralleling work in primates and humans implicating frontal D1-dopamine receptors (D1DRs) in cognitive processing[15,16]. During interval timing, MFC neurons that ‘ramp’ – or monotonically increase/decrease their activity in time – are involved in temporal processing[17]. Ramping neurons can be strongly functionally coupled with delta rhythms (1–4 Hz), which are influenced by focal MFC D1DR agonists and antagonists[13,18].…”

Clock Speed as a Window into Dopaminergic Control of Emotion and Time Perception

“…Neuroimaging studies have repeatedly implicated medial frontal regions in timing tasks, in addition to cerebellar and basal ganglia networks (e.g., Coull et al, 2011;Merchant et al, 2013a;Spencer, 2015;Teki et al, 2012). Notably, medial frontal regions in humans and rodents can have similar patterns of neuronal activity (Narayanan, 2016;Narayanan et al, 2013;Parker et al, 2015a), facilitating mechanistic investigation of temporal processing in rodents. Disrupting rodent medial frontal cortex impairs performance of operant tasks requiring temporal control of action (e.g., Kim et al, 2009;Laubach et al, 2015;Narayanan & Laubach 2006;Narayanan et al, 2012;Xu et al, 2014).…”

“…Specifically, medial frontal neurons appear to 'ramp', or have linear changes in firing rate with time (e.g., Kim et al, 2013;Parker et al, 2014). This pattern of activity has been shown to encode temporal processing by other brain areas and modeling studies have demonstrated that ramping activity can be key for integration of temporal information (e.g., Hass & Durstewitz, 2014;Narayanan, 2016;Reutimann et al, 2004;Simen et al, 2011).…”