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. Here, we trained primates to internally maintain rhythms of different tempos and performed large-scale recordings of neuronal activity across the sensory-motor hierarchy. Results show that maintaining rhythms engages multiple brain areas, including visual, parietal, premotor, prefrontal, and hippocampal regions. Each recorded area displayed oscillations in firing rates and oscillations in broadband local field potential power that reflected the temporal and spatial characteristics of an internal metronome, which flexibly encoded fast, medium, and slow tempos. The presence of widespread metronome-related activity, in the absence of stimuli and motor activity, suggests that internal simulation of stimuli and actions underlies timekeeping and rhythm maintenance.

A chinrest-based approach to measure eye movements and experimental task engagement in macaques with minimal restraint.

BACKGROUND: The use of Rhesus macaques in vision research is crucial due to their visual system's similarity to humans. While invasive techniques have been the norm, there has been a shift towards non-invasive methods, such as facemasks and head molds, to enhance animal welfare and address ethical concerns. NEW METHOD: We present a non-invasive, 3D-printed chinrest with infrared sensors, adapted from canine research, allowing for accurate eye movement measurements and voluntary animal participation in experiments. RESULTS: The chinrest method showed a 16% and 28% increase in average trial numbers for Monkey 1 and Monkey 2, respectively, compared to the traditional headpost method. The engagement was high, with monkeys performing over 500 trials per session and initiating a new trial after an average intertrial interval of approximately 1 second. The hit rate improved by about 10% for Monkey 1 in the chinrest condition, and the fixation precision, measured by the standard deviation of gaze positions, was significantly better in the chinrest condition, with Monkey 1 showing a reduction in fixation imprecision from 0.26° to 0.17° in the X-axis. COMPARISON WITH EXISTING METHODS: The chinrest approach showed significant improvements in trial engagement and reduction in aborted trials due to fixation breaks, indicating less stress and potentially improved data quality compared to previous non-invasive methods. CONCLUSIONS: The chinrest method offers a significant advancement in primate cognitive testing by allowing for precise data collection while addressing animal welfare concerns, possibly leading to better scientific outcomes and a paradigm shift in primate research methodologies.

Optogenetic stimulation of the primary visual cortex drives activity in the visual association cortex.

Developing optogenetic methods for research in non-human primates (NHP) is important for translational neuroscience and for delineating brain function with unprecedented specificity. Here we assess, in macaque monkeys, the selectivity by which optogenetic stimulation of the primary visual cortex (V1) drives the local laminar and widespread cortical connectivity related to visual perception. Towards this end, we transfected neurons with light-sensitive channelrhodopsin in dorsal V1. fMRI revealed that optogenetic stimulation of V1 using blue light at 40 Hz increased functional activity in the visual association cortex, including areas V2/V3, V4, motion-sensitive area MT and frontal eye fields, although nonspecific heating and eye movement contributions to this effect could not be ruled out. Neurophysiology and immunohistochemistry analyses confirmed optogenetic modulation of spiking activity and opsin expression with the strongest expression in layer 4-B in V1. Stimulating this pathway during a perceptual decision task effectively elicited a phosphene percept in the receptive field of the stimulated neurons in one monkey. Taken together, our findings demonstrate the great potential of optogenetic methods to drive the large-scale cortical circuits of the primate brain with high functional and spatial specificity.

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. We trained nonhuman primates to maintain the rhythm of a visual metronome of diverse tempos and recorded neural activity in the supplementary motor area (SMA). SMA exhibited rhythmic bursts of gamma band (30-40 Hz) reflecting an internal tempo that matched the extinguished visual metronome. Moreover, gamma amplitude increased throughout the trial, providing an estimate of total elapsed time. Notably, the timing of gamma bursts and firing rate modulations allowed predicting whether monkeys were ahead or behind the correct tempo. Our results indicate that SMA uses dynamic motor plans to encode a metronome for rhythms and a stopwatch for total elapsed time.

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. In our rhythm task subjects had to observe and then internally follow a visual stimulus that periodically changed its location along a circular perimeter. Crucially, they had to maintain this visuospatial tempo in the absence of movements. Our results show that the probability of remaining in synchrony with the rhythm decreased, and the variability in the timing estimates increased, as a function of elapsed time, and these trends were well described by the generalized law of Weber. Additionally, the pattern of errors shows that human subjects tended to lag behind fast rhythms and to get ahead of slow ones, suggesting that a mean tempo might be incorporated as prior information. Overall, our results demonstrate that rhythm perception and maintenance are cognitive abilities that we share with rhesus monkeys, and these abilities do not depend on overt motor commands.

Involvement of the AATn polymorphism of the CNR1 gene in the efficiency of procedural learning in humans.

Procedural learning refers to the acquisition of motor skills and the practice that refines their performance. The striatum participates in this learning through a function regulated by endocannabinoid signaling and other systems. This study relates the efficiency in learning a procedural task with the AATn polymorphism of the CNR1 gene, which encodes for the CB1 receptor. The mirror-drawing star task was solved by 99 healthy young subjects in three trials. The sample was divided into high- and low-performance groups based on performance efficiency. AAT12/14 carriers were more frequent in the former group, while there were more AAT12/13 carriers in the latter, which also made more errors/min. Therefore, we characterized two efficiency phenotypes: high- vs. low-performers associated with the two AATn genotypes, AAT12/14 vs. AAT12/13. The findings suggest that AATn polymorphism modifies CNR1 translation, indicating a different modulation of CB1.