Quaddles: A multidimensional 3-D object set with parametrically controlled and customizable features.

Many studies of vision and cognition require novel three-dimensional object sets defined by a parametric feature space. Creating such sets and verifying that they are suitable for a given task, however, can be time-consuming and effortful. Here we present a new set of multidimensional objects, Quaddles, designed for studies of feature-based learning and attention, but adaptable for many research purposes. Quaddles have features that are all equally visible from any angle around the vertical axis and can be designed to be equally discriminable along feature dimensions; these objects do not show strong or consistent response biases, with a small number of quantified exceptions. They are available as two-dimensional images, rotating videos, and FBX object files suitable for use with any modern video game engine. We also provide scripts that can be used to generate hundreds of thousands of further Quaddles, as well as examples and tutorials for modifying Quaddles or creating completely new object sets from scratch, with the aim to speed up the development time of future novel-object studies.

Theta-gamma coordination between anterior cingulate and prefrontal cortex indexes correct attention shifts.

Anterior cingulate and lateral prefrontal cortex (ACC/PFC) are believed to coordinate activity to flexibly prioritize the processing of goal-relevant over irrelevant information. This between-area coordination may be realized by common low-frequency excitability changes synchronizing segregated high-frequency activations. We tested this coordination hypothesis by recording in macaque ACC/PFC during the covert utilization of attention cues. We found robust increases of 5-10 Hz (theta) to 35-55 Hz (gamma) phase-amplitude correlation between ACC and PFC during successful attention shifts but not before errors. Cortical sites providing theta phases (i) showed a prominent cue-induced phase reset, (ii) were more likely in ACC than PFC, and (iii) hosted neurons with burst firing events that synchronized to distant gamma activity. These findings suggest that interareal theta-gamma correlations could follow mechanistically from a cue-triggered reactivation of rule memory that synchronizes theta across ACC/PFC.

Neural timescales reflect behavioral demands in freely moving rhesus macaques.

Previous work demonstrated a highly reproducible cortical hierarchy of neural timescales at rest, with sensory areas displaying fast, and higher-order association areas displaying slower timescales. The question arises how such stable hierarchies give rise to adaptive behavior that requires flexible adjustment of temporal coding and integration demands. Potentially, this lack of variability in the hierarchical organization of neural timescales could reflect the structure of the laboratory contexts. We posit that unconstrained paradigms are ideal to test whether the dynamics of neural timescales reflect behavioral demands. Here we measured timescales of local field potential activity while male rhesus macaques foraged in an open space. We found a hierarchy of neural timescales that differs from previous work. Importantly, although the magnitude of neural timescales expanded with task engagement, the brain areas' relative position in the hierarchy was stable. Next, we demonstrated that the change in neural timescales is dynamic and contains functionally-relevant information, differentiating between similar events in terms of motor demands and associated reward. Finally, we demonstrated that brain areas are differentially affected by these behavioral demands. These results demonstrate that while the space of neural timescales is anatomically constrained, the observed hierarchical organization and magnitude is dependent on behavioral demands.

Hierarchical action encoding in prefrontal cortex of freely moving macaques.

Our natural behavioral repertoires include coordinated actions of characteristic types. To better understand how neural activity relates to the expression of actions and action switches, we studied macaques performing a freely moving foraging task in an open environment. We developed a novel analysis pipeline that can identify meaningful units of behavior, corresponding to recognizable actions such as sitting, walking, jumping, and climbing. On the basis of transition probabilities between these actions, we found that behavior is organized in a modular and hierarchical fashion. We found that, after regressing out many potential confounders, actions are associated with specific patterns of firing in each of six prefrontal brain regions and that, overall, encoding of action category is progressively stronger in more dorsal and more caudal prefrontal regions. Together, these results establish a link between selection of units of primate behavior on one hand and neuronal activity in prefrontal regions on the other.

Hierarchical organization of rhesus macaque behavior.

Primatologists, psychologists and neuroscientists have long hypothesized that primate behavior is highly structured. However, delineating that structure has been impossible due to the difficulties of precision behavioral tracking. Here we analyzed a dataset consisting of continuous measures of the 3D position of two male rhesus macaques (Macaca mulatta) performing three different tasks in a large unrestrained environment over several hours. Using an unsupervised embedding approach on the tracked joints, we identified commonly repeated pose patterns, which we call postures. We found that macaques' behavior is characterized by 49 distinct postures, lasting an average of 0.6 seconds. We found evidence that behavior is hierarchically organized, in that transitions between poses tend to occur within larger modules, which correspond to identifiable actions; these actions are further organized hierarchically. Our behavioral decomposition allows us to identify universal (cross-individual and cross-task) and unique (specific to each individual and task) principles of behavior. These results demonstrate the hierarchical nature of primate behavior, provide a method for the automated ethogramming of primate behavior, and provide important constraints on neural models of pose generation.

Widespread coding of navigational variables in prefrontal cortex.

To navigate effectively, we must represent information about our location in the environment. Traditional research highlights the role of the hippocampal complex in this process. Spurred by recent research highlighting the widespread cortical encoding of cognitive and motor variables previously thought to have localized function, we hypothesized that navigational variables would be likewise encoded widely, especially in the prefrontal cortex, which is associated with volitional behavior. We recorded neural activity from six prefrontal regions while macaques performed a foraging task in an open enclosure. In all regions, we found strong encoding of allocentric position, allocentric head direction, boundary distance, and linear and angular velocity. These encodings were not accounted for by distance, time to reward, or motor factors. The strength of coding of all variables increased along a ventral-to-dorsal gradient. Together, these results argue that encoding of navigational variables is not localized to the hippocampus and support the hypothesis that navigation is continuous with other forms of flexible cognition in the service of action.

Oscillations as a window into neuronal mechanisms underlying dorsal anterior cingulate cortex function.

The function of dorsal Anterior Cingulate Cortex (dACC) remains poorly understood. While many methods, spanning bottom-up and top-down approaches, have been deployed, the view they offer is often conflicting. Integrating bottom-up and top-down approaches requires an intermediary with sufficient explanatory power, theoretical development, and empirical support. Oscillations in the local field potential (LFP) provide such a link. LFP oscillations arise from empirically well-characterized neuronal circuit motifs. Synchronizing the firing of individual units has appealing properties to bind disparate brain regions and propagate information, including gating, routing, and coding. Moreover, the LFP, rather than single unit activity, more closely relates to macro-scale recordings, such as the electroencephalogram and functional magnetic resonance imaging. Thus, LFP oscillations are a critical link that allow for the inference of neuronal micro-circuitry underlying macroscopic brain recordings.

Phase of firing coding of learning variables across the fronto-striatal network during feature-based learning.

The prefrontal cortex and striatum form a recurrent network whose spiking activity encodes multiple types of learning-relevant information. This spike-encoded information is evident in average firing rates, but finer temporal coding might allow multiplexing and enhanced readout across the connected network. We tested this hypothesis in the fronto-striatal network of nonhuman primates during reversal learning of feature values. We found that populations of neurons encoding choice outcomes, outcome prediction errors, and outcome history in their firing rates also carry significant information in their phase-of-firing at a 10-25 Hz band-limited beta frequency at which they synchronize across lateral prefrontal cortex, anterior cingulate cortex and anterior striatum when outcomes were processed. The phase-of-firing code exceeds information that can be obtained from firing rates alone and is evident for inter-areal connections between anterior cingulate cortex, lateral prefrontal cortex and anterior striatum. For the majority of connections, the phase-of-firing information gain is maximal at phases of the beta cycle that were offset from the preferred spiking phase of neurons. Taken together, these findings document enhanced information of three important learning variables at specific phases of firing in the beta cycle at an inter-areally shared beta oscillation frequency during goal-directed behavior.

MAD saccade: statistically robust saccade threshold estimation via the median absolute deviation.

Saccade detection is a critical step in the analysis of gaze data. A common method for saccade detection is to use a simple threshold for velocity or acceleration values, which can be estimated from the data using the mean and standard deviation. However, this method has the downside of being influenced by the very signal it is trying to detect, the outlying velocities or accelerations that occur during saccades. We propose instead to use the median absolute deviation (MAD), a robust estimator of dispersion that is not influenced by outliers. We modify an algorithm proposed by Nyström and colleagues, and quantify saccade detection performance in both simulated and human data. Our modified algorithm shows a significant and marked improvement in saccade detection - showing both more true positives and less false negatives - especially under higher noise levels. We conclude that robust estimators can be widely adopted in other common, automatic gaze classification algorithms due to their ease of implementation.

USE: An integrative suite for temporally-precise psychophysical experiments in virtual environments for human, nonhuman, and artificially intelligent agents.

BACKGROUND: There is a growing interest in complex, active, and immersive behavioral neuroscience tasks. However, the development and control of such tasks present unique challenges. NEW METHOD: The Unified Suite for Experiments (USE) is an integrated set of hardware and software tools for the design and control of behavioral neuroscience experiments. The software, developed using the Unity video game engine, supports both active tasks in immersive 3D environments and static 2D tasks used in more traditional visual experiments. The custom USE SyncBox hardware, based around an Arduino Mega2560 board, integrates and synchronizes multiple data streams from different pieces of experimental hardware. The suite addresses three key issues with developing cognitive neuroscience experiments in Unity: tight experimental control, accurate sub-ms timing, and accurate gaze target identification. RESULTS: USE is a flexible framework to realize experiments, enabling (i) nested control over complex tasks, (ii) flexible use of 3D or 2D scenes and objects, (iii) touchscreen-, button-, joystick- and gaze-based interaction, and (v) complete offline reconstruction of experiments for post-processing and temporal alignment of data streams. COMPARISON WITH EXISTING METHODS: Most existing experiment-creation tools are not designed to support the development of video-game-like tasks. Those that do use older or less popular video game engines as their base, and are not as feature-rich or enable as precise control over timing as USE. CONCLUSIONS: USE provides an integrated, open source framework for a wide variety of active behavioral neuroscience experiments using human and nonhuman participants, and artificially-intelligent agents.

A Role of Phase-Resetting in Coordinating Large Scale Neural Networks During Attention and Goal-Directed Behavior.

Short periods of oscillatory activation are ubiquitous signatures of neural circuits. A broad range of studies documents not only their circuit origins, but also a fundamental role for oscillatory activity in coordinating information transfer during goal directed behavior. Recent studies suggest that resetting the phase of ongoing oscillatory activity to endogenous or exogenous cues facilitates coordinated information transfer within circuits and between distributed brain areas. Here, we review evidence that pinpoints phase resetting as a critical marker of dynamic state changes of functional networks. Phase resets: (1) set a "neural context" in terms of narrow band frequencies that uniquely characterizes the activated circuits; (2) impose coherent low frequency phases to which high frequency activations can synchronize, identifiable as cross-frequency correlations across large anatomical distances; (3) are critical for neural coding models that depend on phase, increasing the informational content of neural representations; and (4) likely originate from the dynamics of canonical E-I circuits that are anatomically ubiquitous. These multiple signatures of phase resets are directly linked to enhanced information transfer and behavioral success. We survey how phase resets re-organize oscillations in diverse task contexts, including sensory perception, attentional stimulus selection, cross-modal integration, Pavlovian conditioning, and spatial navigation. The evidence we consider suggests that phase-resets can drive changes in neural excitability, ensemble organization, functional networks, and ultimately, overt behavior.