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To produce goal-directed eye movements known as saccades, we must channel sensory input from our environment through a process known as sensorimotor transformation. The behavioral output of this phenomenon (an accurate eye movement) is straightforward, but the coordinated activity of neurons underlying its dynamics is not well understood. We searched for a neural correlate of sensorimotor transformation in the activity patterns of simultaneously recorded neurons in the superior colliculus (SC) of three male rhesus monkeys performing a visually guided, delayed saccade task. Neurons in the intermediate layers produce a burst of spikes both following the appearance of a visual (sensory) stimulus and preceding an eye movement command, but many also exhibit a sustained activity level during the intervening time ("delay period"). This sustained activity could be representative of visual processing or motor preparation, along with countless cognitive processes. Using a novel measure we call the Visuomotor Proximity Index (VMPI), we pitted visual and motor signals against each other by measuring the degree to which each session's population activity (as summarized in a low-dimensional framework) could be considered more visual-like or more motor-like. The analysis highlighted two salient features of sensorimotor transformation. One, population activity on average drifted systematically toward a motor-like representation and intermittently reverted to a visual-like representation following a microsaccade. Two, activity patterns that drift to a stronger motor-like representation by the end of the delay period may enable a more rapid initiation of a saccade, substantiating the idea that this movement initiation mechanism is conserved across motor systems.

Brain computation depends on intricately connected yet highly distributed neural networks. Due to the absence of the requisite technologies, causally testing fundamental hypotheses on the nature of inter-areal processing have remained largely out-of-each. Here we developed the first two photon holographic mesoscope, a system capable of simultaneously reading and writing neural activity patterns with single cell resolution across large regions of the brain. We demonstrate the precise photo-activation of spatial and temporal sequences of neurons in one brain area while reading out the downstream effect in several other regions. Investigators can use this new platform to understand feed-forward and feed-back processing in distributed neural circuits with single cell precision for the first time.

The biophysical properties of existing optogenetic tools constrain the scale, speed, and fidelity of precise optogenetic control. Here, we use structure-guided mutagenesis to engineer opsins that exhibit very high potency while retaining fast kinetics. These new opsins enable large-scale, temporally and spatially precise control of population neural activity. We extensively benchmark these new opsins against existing optogenetic tools and provide a detailed biophysical characterization of a diverse family of opsins under two-photon illumination. This establishes a resource for matching the optimal opsin to the goals and constraints of patterned optogenetics experiments. Finally, by combining these new opsins with optimized procedures for holographic photostimulation, we demonstrate the simultaneous coactivation of several hundred spatially defined neurons with a single hologram and nearly double that number by temporally interleaving holograms at fast rates. These newly engineered opsins substantially extend the capabilities of patterned illumination optogenetic paradigms for addressing neural circuits and behavior., Competing Interests: Declaration of interests H. Adesnik has a patent related to this work: 3D Sparse Holographic Temporal focusing, 2016, L. Waller, N. Pegard, and H. Adesnik, Provisional Patent Application #62-429,017., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Sensorimotor transformations are mediated by premotor brain networks where individual neurons represent sensory, cognitive, and movement-related information. Such multiplexing poses a conundrum-how does a decoder know precisely when to initiate a movement if its inputs are active at times when a movement is not desired (e.g., in response to sensory stimulation)? Here, we propose a novel hypothesis: movement is triggered not only by an increase in firing rate but, critically, also by a reliable temporal pattern in the population response. Laminar recordings in the macaque superior colliculus (SC), a midbrain hub of orienting control, and pseudo-population analyses in SC and cortical frontal eye fields (FEFs) corroborated this hypothesis. Specifically, using a measure that captures the fidelity of the population code-here called temporal stability-we show that the temporal structure fluctuates during the visual response but becomes increasingly stable during the movement command. Importantly, we used spatiotemporally patterned microstimulation to causally test the contribution of population temporal stability in gating movement initiation and found that stable stimulation patterns were more likely to evoke a movement. Finally, a spiking neuron model was able to discriminate between stable and unstable input patterns, providing a putative biophysical mechanism for decoding temporal structure. These findings offer new insights into the long-standing debate on motor preparation and generation by situating the movement gating signal in temporal features of activity in shared neural substrates, and they highlight the importance of short-term population history in neuronal communication and behavior., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The superior colliculus (SC) is an excellent substrate to study sensorimotor transformations. To date, the spatial and temporal properties of population activity along its dorsoventral axis have been inferred from single electrode studies. Here, we recorded SC population activity in non-human primates using a linear multi-contact array during delayed saccade tasks. We show that during the visual epoch, information appeared first in dorsal layers and systematically later in ventral layers. During the delay period, the laminar organization of low-spiking rate activity matched that of the visual epoch. During the pre-saccadic epoch, spiking activity emerged first in a more ventral layer, ~ 100 ms before saccade onset. This buildup of activity appeared later on nearby neurons situated both dorsally and ventrally, culminating in a synchronous burst across the dorsoventral axis, ~ 28 ms before saccade onset. Collectively, these results reveal a principled spatiotemporal organization of SC population activity underlying sensorimotor transformation for the control of gaze., Competing Interests: Competing interestsThe authors declare no competing interests.

The ability to interact with our environment requires the brain to transform spatially represented sensory signals into temporally encoded motor commands for appropriate control of the relevant effectors. For visually guided eye movements, or saccades, the superior colliculus (SC) is assumed to be the final stage of spatial representation, and instantaneous control of the movement is achieved through a rate code representation in the lower brain stem. We investigated whether SC activity in nonhuman primates (Macaca mulatta, 2 male and 1 female) also uses a dynamic rate code, in addition to the spatial representation. Noting that the kinematics of amplitude-matched movements exhibit trial-to-trial variability, we regressed instantaneous SC activity with instantaneous eye velocity and found a robust correlation throughout saccade duration. Peak correlation was tightly linked to time of peak velocity, the optimal efferent delay between SC activity and eye velocity was constant at ∼12 ms both at onset and during the saccade, and SC neurons with higher firing rates exhibited stronger correlations. Moreover, the strong correlative relationship and constant efferent delay observation were preserved when eye movement profiles were substantially altered by a blink-induced perturbation. These results indicate that the rate code of individual SC neurons can control instantaneous eye velocity and argue against a serial process of spatial-to-temporal transformation. They also motivated us to consider a new framework of saccade control that does not incorporate traditionally accepted elements, such as the comparator and resettable integrator, whose neural correlates have remained elusive. SIGNIFICANCE STATEMENT All movements exhibit time-varying features that are under instantaneous control of the innervating neural command. At what stage in the brain is dynamical control present? It is well known that, in the skeletomotor system, neurons in the motor cortex use dynamical control. In the oculomotor system, in contrast, instantaneous velocity control of saccadic eye movements is not thought to be enforced until the lower brainstem. Using correlations between residual signals across trials, we show that instantaneous control of saccade velocity is present earlier in the visuo-oculomotor neuraxis, at the level of superior colliculus. The results require us to consider alternate frameworks of the neural control of saccades., (Copyright © 2018 the authors 0270-6474/18/3810156-12$15.00/0.)

The motor system prepares for movements well in advance of their execution. In the gaze control system, the dynamics of preparatory neural activity have been well described by stochastic accumulation-to-threshold models. However, it is unclear whether this activity has features indicative of a hidden movement command. We explicitly tested whether preparatory neural activity in premotor neurons of the primate superior colliculus has 'motor potential'. We removed downstream inhibition on the saccadic system using the trigeminal blink reflex, triggering saccades at earlier-than-normal latencies. Accumulating low-frequency activity was predictive of eye movement dynamics tens of milliseconds in advance of the actual saccade, indicating the presence of a latent movement command. We also show that reaching a fixed threshold level is not a necessary condition for movement initiation. The results bring into question extant models of saccade generation and support the possibility of a concurrent representation for movement preparation and generation.

Unlabelled: Executive control of voluntary movements is a hallmark of the mammalian brain. In the gaze-control network, this function is thought to be mediated by a critical balance between neurons responsible for generating movements and those responsible for fixating or suppressing movements, but the nature of this balance between the relevant elements-saccade-generating and fixation-related neurons-remains unclear. Specifically, it has been debated whether the two functions are necessarily coupled (i.e., push-and-pull) or independently controlled. Here we show that behavioral perturbation of ongoing fixation with the trigeminal blink reflex in monkeys (Macaca mulatta) alters the effective balance between fixation and saccade-generating neurons in the superior colliculus (SC) and can lead to premature gaze shifts reminiscent of compromised inhibitory control. The shift in balance is primarily driven by an increase in the activity of visuomovement neurons in the caudal SC, and the extent to which fixation-related neurons in the rostral SC play a role seems to be linked to the animal's propensity to make microsaccades. The perturbation also reveals a hitherto unknown feature of sensorimotor integration: the presence of a hidden visual response in canonical movement neurons. These findings offer new insights into the latent functional interactions, or lack thereof, between components of the gaze-control network, suggesting that the perturbation technique used here may prove to be a useful tool for probing the neural mechanisms of movement generation in executive function and dysfunction., Significance Statement: Eye movements are an integral part of how we explore the environment. Although we know a great deal about where sensorimotor transformations leading to saccadic eye movements are implemented in the brain, less is known about the functional interactions between neurons that maintain gaze fixation and neurons that program saccades. In this study, we used a novel approach to study these interactions. By transient disruption of fixation, we found that activity of saccade-generating neurons can increase independently of modulation in fixation-related neurons, which may occasionally lead to premature movements mimicking lack of impulse control. Our findings support the notion of a common pathway for sensory and movement processing and suggest that impulsive movements arise when sensory processes become "motorized.", (Copyright © 2016 the authors 0270-6474/16/366129-12$15.00/0.)

Computational models of semantic memory exploit information about cooccurrences of words in naturally-occurring text to extract information about the meaning of the words that are present in the language. Such models implicitly specify a representation of temporal context. Depending on the model, words are said to have occurred in the same context if they are presented within a moving window, within the same sentence or within the same document. The temporal context model (TCM), a specific quantitative specification of temporal context has proved useful in the study of episodic memory. The predictive temporal context model (pTCM) uses the same definition of temporal context to generate semantic memory representations. Taken together pTCM and TCM may prove to be part of a general model of declarative memory.