Direct contribution of the sensory cortex to the judgment of stimulus duration.

Decision making frequently depends on monitoring the duration of sensory events. To determine whether, and how, the perception of elapsed time derives from the neuronal representation of the stimulus itself, we recorded and optogenetically modulated vibrissal somatosensory cortical activity as male rats judged vibration duration. Perceived duration was dilated by optogenetic excitation. A second set of rats judged vibration intensity; here, optogenetic excitation amplified the intensity percept, demonstrating sensory cortex to be the common gateway both to time and to stimulus feature processing. A model beginning with the membrane currents evoked by vibrissal and optogenetic drive and culminating in the representation of perceived time successfully replicated rats' choices. Time perception is thus as deeply intermeshed within the sensory processing pathway as is the sense of touch itself, suggesting that the experience of time may be further investigated with the toolbox of sensory coding.

Time coding in rat dorsolateral striatum.

To assess the role of dorsolateral striatum (DLS) in time coding, we recorded neuronal activity in rats tasked with comparing the durations of two sequential vibrations. Bayesian decoding of population activity revealed a representation of the unfolding of the trial across time. However, further analyses demonstrated a distinction between the encoding of trial time and perceived time. First, DLS did not show a privileged representation of the stimulus durations compared with other time spans. Second, higher intensity vibrations were perceived as longer; however, time decoded from DLS was unaffected by vibration intensity. Third, DLS did not encode stimulus duration differently on correct versus incorrect trials. Finally, in rats trained to compare the intensities of two sequential vibrations, stimulus duration was encoded even though it was a perceptually irrelevant feature. These findings lead us to posit that temporal information is inherent to DLS activity irrespective of the rat's ongoing percept.

A sensory integration account for time perception.

The connection between stimulus perception and time perception remains unknown. The present study combines human and rat psychophysics with sensory cortical neuronal firing to construct a computational model for the percept of elapsed time embedded within sense of touch. When subjects judged the duration of a vibration applied to the fingertip (human) or whiskers (rat), increasing stimulus intensity led to increasing perceived duration. Symmetrically, increasing vibration duration led to increasing perceived intensity. We modeled real spike trains recorded from vibrissal somatosensory cortex as input to dual leaky integrators-an intensity integrator with short time constant and a duration integrator with long time constant-generating neurometric functions that replicated the actual psychophysical functions of rats. Returning to human psychophysics, we then confirmed specific predictions of the dual leaky integrator model. This study offers a framework, based on sensory coding and subsequent accumulation of sensory drive, to account for how a feeling of the passage of time accompanies the tactile sensory experience.

A Fluorescent Dye Method Suitable for Visualization of One or More Rat Whiskers.

Visualization and tracking of the facial whiskers is critical to many studies of rodent behavior. High-speed videography is the most robust methodology for characterizing whisker kinematics, but whisker visualization is challenging due to the low contrast of the whisker against its background. Recently, we showed that fluorescent dye(s) can be applied to enhance visualization and tracking of whisker(s) ( Rigosa et al., 2017 ), and this protocol provides additional details on the technique.

Dye-enhanced visualization of rat whiskers for behavioral studies.

Visualization and tracking of the facial whiskers is required in an increasing number of rodent studies. Although many approaches have been employed, only high-speed videography has proven adequate for measuring whisker motion and deformation during interaction with an object. However, whisker visualization and tracking is challenging for multiple reasons, primary among them the low contrast of the whisker against its background. Here, we demonstrate a fluorescent dye method suitable for visualization of one or more rat whiskers. The process makes the dyed whisker(s) easily visible against a dark background. The coloring does not influence the behavioral performance of rats trained on a vibrissal vibrotactile discrimination task, nor does it affect the whiskers' mechanical properties.

Transformation of Perception from Sensory to Motor Cortex.

To better understand how a stream of sensory data is transformed into a percept, we examined neuronal activity in vibrissal sensory cortex, vS1, together with vibrissal motor cortex, vM1 (a frontal cortex target of vS1), while rats compared the intensity of two vibrations separated by an interstimulus delay. Vibrations were "noisy," constructed by stringing together over time a sequence of velocity values sampled from a normal distribution; each vibration's mean speed was proportional to the width of the normal distribution. Durations of both stimulus 1 and stimulus 2 could vary from 100 to 600 ms. Psychometric curves reveal that rats overestimated the longer-duration stimulus-thus, perceived intensity of a vibration grew over the course of hundreds of milliseconds even while the sensory input remained, on average, stationary. Human subjects demonstrated the identical perceptual phenomenon, indicating that the underlying mechanisms of temporal integration generalize across species. The time dependence of the percept allowed us to ask to what extent neurons encoded the ongoing stimulus stream versus the animal's percept. We demonstrate that vS1 firing correlated with the local features of the vibration, whereas vM1 firing correlated with the percept: the final vM1 population state varied, as did the rat's behavior, according to both stimulus speed and stimulus duration. Moreover, vM1 populations appeared to participate in the trace of the percept of stimulus 1 as the rat awaited stimulus 2. In conclusion, the transformation of sensory data into the percept appears to involve the integration and storage of vS1 signals by vM1.

Effect of spinal transcutaneous direct current stimulation on somatosensory evoked potentials in humans.

OBJECTIVE: Invasive stimulation of the spinal cord is used to treat a number of pathological conditions. Aiming to modulate human spinal cord function non-invasively, we evaluated whether transcutaneous direct current (DC) stimulation induces long-lasting changes in conduction along the sensory spinal pathways. METHODS: Somatosensory evoked potentials (SEPs) by posterior tibial nerve and by median nerve stimulation were recorded, before, at current offset and at 20 min after transcutaneous anodal or cathodal DC stimulation over the thoracic spinal cord (2.5 mA, 15 min) in a group of 12 healthy subjects. RESULTS: Whereas both polarities left the spinal (N22) and the cortical potentials (P39) unchanged, anodal transcutaneous spinal DC stimulation decreased significantly by about 25% the amplitude of the cervico-medullary component of posterior tibial nerve SEPs (P30) for at least 20 min. Thoracic transcutaneous spinal cord stimulation left median nerve SEPs unchanged. CONCLUSIONS: Transcutaneous DC stimulation over the thoracic spinal cord induces changes in conduction along human lemniscal pathway that persist after stimulation ends. SIGNIFICANCE: Our results support the use of transcutaneous DC stimulation as a novel tool for non-invasive spinal neuromodulation. Because the method is non-expensive and simple, it can be tested in patients with disorders presently treated with invasive procedures.