Ramping activity is a cortical mechanism of temporal control of action

Highlights

• Timing involves frontal areas of the cerebral cortex.

• Neurons in the frontal cortex ramp, or increase or decrease activity during temporal intervals.

• These neurons are necessary and may be sufficient for temporal control of action.

• These insights may be relevant for diseases with impaired timing.

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.

Introduction

Finding food and evading threats is critical for mammalian behavior and requires the ability to guide movements in time. For humans, the temporal control of action is central to complex activities such as cooking and driving. In this review, I argue that ramping activity in the prefrontal cortex critically regulates how movements are guided in time to achieve behavioral goals. I focus on epochs of several seconds, as temporal processing at shorter or longer scales can involve distinct neural systems [1, 2].

Timing has been extensively addressed by theoreticians for decades [3]. Much of this work concerns the perception of time by the brain. Perceptual timing consistently recruits subcortical networks in the cerebellum, striatum, and brainstem [4]. In the last decade, evidence has accumulated that frontal and visual cortical areas are also required for temporal control of action. Posterior cortical areas are discussed in a companion review by Shuler et al., in this issue. Here, I focus on the frontal cortex, which is chiefly concerned with motor control.

Neurophysiology facilitates investigation into how neural networks instantiate timing processes that allow movements to be coordinated in time. Most neurophysiological tasks involve some amount of temporal expectation, or the anticipation of when events or movements will occur in time. Temporal expectation can be captured mathematically via a ‘hazard’ function [5]. For instance, when an event is likely to occur within a given amount of time, if the event fails to occur at time x, then the probability that it will occur at time x + 1 will increase. Organisms capitalize upon temporal information when preparing movements, as certainty regarding when events will occur will progressively increase as time unfolds. For instance, sprinters might respond to the starting gun fastest after waiting a long time, because after a long delay they are fully prepared to respond [6]. Temporal preparation can be ‘embodied’ in movements [7]. In this sense, temporal control of action is a subset of motor control. Furthermore, temporal control demands executive resources such as working memory and attention [8, 9] albeit at an elementary level [10, 11]. That is, loading executive functions such as working memory or attention can interfere with guiding movements in time [8]. These data indicate that timing shares resources with classical executive processes such as working memory, attention, and reasoning [8, 10].