Estimating Time and Rhythm by Predicting External Stimuli.

In this chapter, we present recent findings from our group showing that elapsed time, interval timing, and rhythm maintenance might be achieved by the well-known ability of the brain to predict the future states of the world. The difference between predictions and actual sensory evidence is used to generate perceptual and behavioral adjustments that help subjects achieve desired behavioral goals. Concretely, we show that (1) accumulating prediction errors is a plausible strategy humans could use to determine whether a train of consecutive stimuli arrives at regular or irregular intervals.

A Second Introduction to the Neurobiology of Interval Timing.

Time is a critical variable that organisms must be able to measure in order to survive in a constantly changing environment. Initially, this paper describes the myriad of contexts where time is estimated or predicted and suggests that timing is not a single process and probably depends on a set of different neural mechanisms. Consistent with this hypothesis, the explosion of neurophysiological and imaging studies in the last 10 years suggests that different brain circuits and neural mechanisms are involved in the ability to tell and use time to control behavior across contexts.

Keeping time and rhythm by internal simulation of sensory stimuli and behavioral actions.

Effective behavior often requires synchronizing our actions with changes in the environment. Rhythmic changes in the environment are easy to predict, and we can readily time our actions to them. Yet, how the brain encodes and maintains rhythms is not known.

Motor cortex projections to red and pontine nuclei have distinct roles during movement in the mouse.

Motor control largely depends on the deep layer 5 (L5) pyramidal neurons that project to subcortical structures. However, it is largely unknown if these neurons are functionally segregated with distinct roles in movement performance. Here, we analyzed mouse motor cortex L5 pyramidal neurons projecting to the red and pontine nuclei during movement preparation and execution.

Different subtypes of motor cortex pyramidal tract neurons projects to red and pontine nuclei.

Introduction: Pyramidal tract neurons (PTNs) are fundamental elements for motor control. However, it is largely unknown if PTNs are segregated into different subtypes with distinct characteristics.

Methods: Using anatomical and electrophysiological tools, we analyzed in mice motor cortex PTNs projecting to red and pontine midbrain nuclei, which are important hubs connecting cerebral cortex and cerebellum playing a critical role in the regulation of movement.

An abstract categorical decision code in dorsal premotor cortex.

The dorsal premotor cortex (DPC) has classically been associated with a role in preparing and executing the physical motor variables during cognitive tasks. While recent work has provided nuanced insights into this role, here we propose that DPC also participates more actively in decision-making. We recorded neuronal activity in DPC while two trained monkeys performed a vibrotactile categorization task, utilizing two partially overlapping ranges of stimulus values that varied on two physical attributes: vibrotactile frequency and amplitude.

Discrimination of Regular and Irregular Rhythms Explained by a Time Difference Accumulation Model.

Perceiving the temporal regularity in a sequence of repetitive sensory events facilitates the preparation and execution of relevant behaviors with tight temporal constraints. How we estimate temporal regularity from repeating patterns of sensory stimuli is not completely understood. We developed a decision-making task in which participants had to decide whether a train of visual, auditory, or tactile pulses, had a regular or an irregular temporal pattern.

Sucrose intensity coding and decision-making in rat gustatory cortices.

Sucrose's sweet intensity is one attribute contributing to the overconsumption of high-energy palatable foods. However, it is not known how sucrose intensity is encoded and used to make perceptual decisions by neurons in taste-sensitive cortices. We trained rats in a sucrose intensity discrimination task and found that sucrose evoked a widespread response in neurons recorded in posterior-Insula (pIC), anterior-Insula (aIC), and Orbitofrontal cortex (OFC).

Entrainment and maintenance of an internal metronome in supplementary motor area.

To prepare timely motor actions, we constantly predict future events. Regularly repeating events are often perceived as a rhythm to which we can readily synchronize our movements, just as in dancing to music. However, the neuronal mechanisms underlying the capacity to encode and maintain rhythms are not understood.

Regaining the senses of touch and movement.

Artificially activating neurons in the cortex can make a tetraplegic patient feel naturalistic sensations of skin pressure and arm movement.

Dopamine reward prediction error signal codes the temporal evaluation of a perceptual decision report.

Learning to associate unambiguous sensory cues with rewarded choices is known to be mediated by dopamine (DA) neurons. However, little is known about how these neurons behave when choices rely on uncertain reward-predicting stimuli. To study this issue we reanalyzed DA recordings from monkeys engaged in the detection of weak tactile stimuli delivered at random times and formulated a reinforcement learning model based on belief states.

Tactile object categories can be decoded from the parietal and lateral-occipital cortices.

The visual system classifies objects into categories, and distinct populations of neurons within the temporal lobe respond preferentially to objects of a given perceptual category. We can also classify the objects we recognize with the sense of touch, but less is known about the neuronal correlates underlying this cognitive function. To address this question, we performed a multivariate pattern analysis (MVPA) of functional magnetic resonance imagining (fMRI) activity to identify the cortical areas that can be used to decode the category of objects explored with the hand.

Monkeys Share the Human Ability to Internally Maintain a Temporal Rhythm.

Timing is a fundamental variable for behavior. However, the mechanisms allowing human and non-human primates to synchronize their actions with periodic events are not yet completely understood. Here we characterize the ability of rhesus monkeys and humans to perceive and maintain rhythms of different paces in the absence of sensory cues or motor actions.

Comment on "Single-trial spike trains in parietal cortex reveal discrete steps during decision-making".

Latimeret al (Reports, 10 July 2015, p. 184) claim that during perceptual decision formation, parietal neurons undergo one-time, discrete steps in firing rate instead of gradual changes that represent the accumulation of evidence. However, that conclusion rests on unsubstantiated assumptions about the time window of evidence accumulation, and their stepping model cannot explain existing data as effectively as evidence-accumulation models.

Dynamic Control of Response Criterion in Premotor Cortex during Perceptual Detection under Temporal Uncertainty.

Under uncertainty, the brain uses previous knowledge to transform sensory inputs into the percepts on which decisions are based. When the uncertainty lies in the timing of sensory evidence, however, the mechanism underlying the use of previously acquired temporal information remains unknown. We study this issue in monkeys performing a detection task with variable stimulation times.

Representation of accumulating evidence for a decision in two parietal areas.

Decisions are often made by accumulating evidence for and against the alternatives. The momentary evidence represented by sensory neurons is accumulated by downstream structures to form a decision variable, linking the evolving decision to the formation of a motor plan. When decisions are communicated by eye movements, neurons in the lateral intraparietal area (LIP) represent the accumulation of evidence bearing on the potential targets for saccades.

Introduction to the neurobiology of interval timing.

Time is a fundamental variable that organisms must quantify in order to survive. In humans, for example, the gradual development of the sense of duration and rhythm is an essential skill in many facets of social behavior such as speaking, dancing to-, listening to- or playing music, performing a wide variety of sports, and driving a car (Merchant H, Harrington DL, Meck WH. Annu Rev Neurosci.

How confident do you feel?

In this issue of Neuron, Fetsch et al. (2014) show that microstimulation of motion-sensitive neurons in the visual cortex (MT/MST) of primates mimics the addition of sensory information for which the stimulated neurons are selective. Such microstimulation increases the confidence that monkeys have in their decisions about motion direction.