Task interference as a neuronal basis for the cost of cognitive flexibility.

Humans and animals have an impressive ability to juggle multiple tasks in a constantly changing environment. This flexibility, however, leads to decreased performance under uncertain task conditions. Here, we combined monkey electrophysiology, human psychophysics, and artificial neural network modeling to investigate the neuronal mechanisms of this performance cost. We developed a behavioural paradigm to measure and influence participants' decision-making and perception in two distinct perceptual tasks. Our data revealed that both humans and monkeys, unlike an artificial neural network trained for the same tasks, make less accurate perceptual decisions when the task is uncertain. We generated a mechanistic hypothesis by comparing this neural network trained to produce correct choices with another network trained to replicate the participants' choices. We hypothesized, and confirmed with further behavioural, physiological, and causal experiments, that the cost of task flexibility comes from what we term task interference. Under uncertain conditions, interference between different tasks causes errors because it results in a stronger representation of irrelevant task features and entangled neuronal representations of different features. Our results suggest a tantalizing, general hypothesis: that cognitive capacity limitations, both in health and disease, stem from interference between neural representations of different stimuli, tasks, or memories.

Orthogonal neural representations support perceptual judgements of natural stimuli.

In natural behavior, observers must separate relevant information from a barrage of irrelevant information. Many studies have investigated the neural underpinnings of this ability using artificial stimuli presented on simple backgrounds. Natural viewing, however, carries a set of challenges that are inaccessible using artificial stimuli, including neural responses to background objects that are task-irrelevant. An emerging body of evidence suggests that the visual abilities of humans and animals can be modeled through the linear decoding of task-relevant information from visual cortex. This idea suggests the hypothesis that irrelevant features of a natural scene should impair performance on a visual task only if their neural representations intrude on the linear readout of the task relevant feature, as would occur if the representations of task-relevant and irrelevant features are not orthogonal in the underlying neural population. We tested this hypothesis using human psychophysics and monkey neurophysiology, in response to parametrically variable naturalistic stimuli. We demonstrate that 1) the neural representation of one feature (the position of a central object) in visual area V4 is orthogonal to those of several background features, 2) the ability of human observers to precisely judge object position was largely unaffected by task-irrelevant variation in those background features, and 3) many features of the object and the background are orthogonally represented by V4 neural responses. Our observations are consistent with the hypothesis that orthogonal neural representations support stable perception of objects and features despite the tremendous richness of natural visual scenes.

Targeted V1 comodulation supports task-adaptive sensory decisions.

Sensory-guided behavior requires reliable encoding of stimulus information in neural populations, and flexible, task-specific readout. The former has been studied extensively, but the latter remains poorly understood. We introduce a theory for adaptive sensory processing based on functionally-targeted stochastic modulation. We show that responses of neurons in area V1 of monkeys performing a visual discrimination task exhibit low-dimensional, rapidly fluctuating gain modulation, which is stronger in task-informative neurons and can be used to decode from neural activity after few training trials, consistent with observed behavior. In a simulated hierarchical neural network model, such labels are learned quickly and can be used to adapt downstream readout, even after several intervening processing stages. Consistently, we find the modulatory signal estimated in V1 is also present in the activity of simultaneously recorded MT units, and is again strongest in task-informative neurons. These results support the idea that co-modulation facilitates task-adaptive hierarchical information routing.

Contributions of early and mid-level visual cortex to high-level object categorization.

The complexity of visual features for which neurons are tuned increases from early to late stages of the ventral visual stream. Thus, the standard hypothesis is that high-level functions like object categorization are primarily mediated by higher visual areas because they require more complex image formats that are not evident in early visual processing stages. However, human observers can categorize images as objects or animals or as big or small even when the images preserve only some low- and mid-level features but are rendered unidentifiable ('texforms', Long et al., 2018). This observation suggests that even the early visual cortex, in which neurons respond to simple stimulus features, may already encode signals about these more abstract high-level categorical distinctions. We tested this hypothesis by recording from populations of neurons in early and mid-level visual cortical areas while rhesus monkeys viewed texforms and their unaltered source stimuli (simultaneous recordings from areas V1 and V4 in one animal and separate recordings from V1 and V4 in two others). Using recordings from a few dozen neurons, we could decode the real-world size and animacy of both unaltered images and texforms. Furthermore, this neural decoding accuracy across stimuli was related to the ability of human observers to categorize texforms by real-world size and animacy. Our results demonstrate that neuronal populations early in the visual hierarchy contain signals useful for higher-level object perception and suggest that the responses of early visual areas to simple stimulus features display preliminary untangling of higher-level distinctions.

Topological insights into the neural basis of flexible behavior.

It is widely accepted that there is an inextricable link between neural computations, biological mechanisms, and behavior, but it is challenging to simultaneously relate all three. Here, we show that topological data analysis (TDA) provides an important bridge between these approaches to studying how brains mediate behavior. We demonstrate that cognitive processes change the topological description of the shared activity of populations of visual neurons. These topological changes constrain and distinguish between competing mechanistic models, are connected to subjects' performance on a visual change detection task, and, via a link with network control theory, reveal a tradeoff between improving sensitivity to subtle visual stimulus changes and increasing the chance that the subject will stray off task. These connections provide a blueprint for using TDA to uncover the biological and computational mechanisms by which cognition affects behavior in health and disease.

Coordinated multiplexing of information about separate objects in visual cortex.

Sensory receptive fields are large enough that they can contain more than one perceptible stimulus. How, then, can the brain encode information about each of the stimuli that may be present at a given moment? We recently showed that when more than one stimulus is present, single neurons can fluctuate between coding one vs. the other(s) across some time period, suggesting a form of neural multiplexing of different stimuli (Caruso et al., 2018). Here, we investigate (a) whether such coding fluctuations occur in early visual cortical areas; (b) how coding fluctuations are coordinated across the neural population; and (c) how coordinated coding fluctuations depend on the parsing of stimuli into separate vs. fused objects. We found coding fluctuations do occur in macaque V1 but only when the two stimuli form separate objects. Such separate objects evoked a novel pattern of V1 spike count ('noise') correlations involving distinct distributions of positive and negative values. This bimodal correlation pattern was most pronounced among pairs of neurons showing the strongest evidence for coding fluctuations or multiplexing. Whether a given pair of neurons exhibited positive or negative correlations depended on whether the two neurons both responded better to the same object or had different object preferences. Distinct distributions of spike count correlations based on stimulus preferences were also seen in V4 for separate objects but not when two stimuli fused to form one object. These findings suggest multiple objects evoke different response dynamics than those evoked by single stimuli, lending support to the multiplexing hypothesis and suggesting a means by which information about multiple objects can be preserved despite the apparent coarseness of sensory coding.

Dynamic task-belief is an integral part of decision-making.

Natural decisions involve two seemingly separable processes: inferring the relevant task (task-belief) and performing the believed-relevant task. The assumed separability has led to the traditional practice of studying task-switching and perceptual decision-making individually. Here, we used a novel paradigm to manipulate and measure macaque monkeys' task-belief and demonstrated inextricable neuronal links between flexible task-belief and perceptual decision-making. We showed that in animals, but not in artificial networks that performed as well or better than the animals, stronger task-belief is associated with better perception. Correspondingly, recordings from neuronal populations in cortical areas 7a and V1 revealed that stronger task-belief is associated with better discriminability of the believed-relevant, but not the believed-irrelevant, feature. Perception also impacts belief updating; noise fluctuations in V1 help explain how task-belief is updated. Our results demonstrate that complex tasks and multi-area recordings can reveal fundamentally new principles of how biology affects behavior in health and disease.

A general decoding strategy explains the relationship between behavior and correlated variability.

Improvements in perception are frequently accompanied by decreases in correlated variability in sensory cortex. This relationship is puzzling because overall changes in correlated variability should minimally affect optimal information coding. We hypothesize that this relationship arises because instead of using optimal strategies for decoding the specific stimuli at hand, observers prioritize generality: a single set of neuronal weights to decode any stimuli. We tested this using a combination of multineuron recordings in the visual cortex of behaving rhesus monkeys and a cortical circuit model. We found that general decoders optimized for broad rather than narrow sets of visual stimuli better matched the animals' decoding strategy, and that their performance was more related to the magnitude of correlated variability. In conclusion, the inverse relationship between perceptual performance and correlated variability can be explained by observers using a general decoding strategy, capable of decoding neuronal responses to the variety of stimuli encountered in natural vision.

Methylphenidate as a causal test of translational and basic neural coding hypotheses.

Most systems neuroscience studies fall into one of two categories: basic science work aimed at understanding the relationship between neurons and behavior, or translational work aimed at developing treatments for neuropsychiatric disorders. Here we use these two approaches to inform and enhance each other. Our study both tests hypotheses about basic science neural coding principles and elucidates the neuronal mechanisms underlying clinically relevant behavioral effects of systemically administered methylphenidate (Ritalin). We discovered that orally administered methylphenidate, used clinically to treat attention deficit hyperactivity disorder (ADHD) and generally to enhance cognition, increases spatially selective visual attention, enhancing visual performance at only the attended location. Further, we found that this causal manipulation enhances vision in rhesus macaques specifically when it decreases the mean correlated variability of neurons in visual area V4. Our findings demonstrate that the visual system is a platform for understanding the neural underpinnings of both complex cognitive processes (basic science) and neuropsychiatric disorders (translation). Addressing basic science hypotheses, our results are consistent with a scenario in which methylphenidate has cognitively specific effects by working through naturally selective cognitive mechanisms. Clinically, our findings suggest that the often staggeringly specific symptoms of neuropsychiatric disorders may be caused and treated by leveraging general mechanisms.

Priority coding in the visual system.

Although we are continuously bombarded with visual input, only a fraction of incoming visual events is perceived, remembered or acted on. The neural underpinnings of various forms of visual priority coding, including perceptual expertise, goal-directed attention, visual salience, image memorability and preferential looking, have been studied. Here, we synthesize information from these different examples to review recent developments in our understanding of visual priority coding and its neural correlates, with a focus on the role of behaviour to evaluate candidate correlates. We propose that the brain combines different types of priority into a unified priority signal while also retaining the ability to differentiate between them, and that this happens by leveraging partially overlapping low-dimensional neural subspaces for each type of priority that are shared with the downstream neural populations involved in decision-making. Finally, we describe the gulfs in understanding that have resulted from different research approaches, and we point towards future directions that will lead to fundamental insights about neural coding and how prioritization influences visually guided behaviours.

Attention improves information flow between neuronal populations without changing the communication subspace.

Visual attention allows observers to change the influence of different parts of a visual scene on their behavior, suggesting that information can be flexibly shared between visual cortex and neurons involved in decision making. We investigated the neural substrate of flexible information routing by analyzing the activity of populations of visual neurons in the medial temporal area (MT) and oculo-motor neurons in the superior colliculus (SC) while rhesus monkeys switched spatial attention. We demonstrated that attention increases the efficacy of visuomotor communication: trial-to-trial variability in SC population activity could be better predicted by the activity of the MT population (and vice versa) when attention was directed toward their joint receptive fields. Surprisingly, this improvement in prediction was not explained by changes in the dimensionality of the shared subspace or in the magnitude of local or shared pairwise noise correlations. These results lay a foundation for future theoretical and experimental studies into how visual attention can flexibly change information flow between sensory and decision neurons.

Low rank mechanisms underlying flexible visual representations.

Neuronal population responses to sensory stimuli are remarkably flexible. The responses of neurons in visual cortex have heterogeneous dependence on stimulus properties (e.g., contrast), processes that affect all stages of visual processing (e.g., adaptation), and cognitive processes (e.g., attention or task switching). Understanding whether these processes affect similar neuronal populations and whether they have similar effects on entire populations can provide insight into whether they utilize analogous mechanisms. In particular, it has recently been demonstrated that attention has low rank effects on the covariability of populations of visual neurons, which impacts perception and strongly constrains mechanistic models. We hypothesized that measuring changes in population covariability associated with other sensory and cognitive processes could clarify whether they utilize similar mechanisms or computations. Our experimental design included measurements in multiple visual areas using four distinct sensory and cognitive processes. We found that contrast, adaptation, attention, and task switching affect the variability of responses of populations of neurons in primate visual cortex in a similarly low rank way. These results suggest that a given circuit may use similar mechanisms to perform many forms of modulation and likely reflects a general principle that applies to a wide range of brain areas and sensory, cognitive, and motor processes.

Simultaneous multi-area recordings suggest that attention improves performance by reshaping stimulus representations.

Visual attention dramatically improves individuals' ability to see and modulates the responses of neurons in every known visual and oculomotor area, but whether such modulations can account for perceptual improvements is unclear. We measured the relationship between populations of visual neurons, oculomotor neurons and behavior during detection and discrimination tasks. We found that neither of the two prominent hypothesized neuronal mechanisms underlying attention (which concern changes in information coding and the way sensory information is read out) provide a satisfying account of the observed behavioral improvements. Instead, our results are more consistent with the hypothesis that attention reshapes the representation of attended stimuli to more effectively influence behavior. Our results suggest a path toward understanding the neural underpinnings of perception and cognition in health and disease by analyzing neuronal responses in ways that are constrained by behavior and interactions between brain areas.

Circuit Models of Low-Dimensional Shared Variability in Cortical Networks.

Trial-to-trial variability is a reflection of the circuitry and cellular physiology that make up a neuronal network. A pervasive yet puzzling feature of cortical circuits is that despite their complex wiring, population-wide shared spiking variability is low dimensional. Previous model cortical networks cannot explain this global variability, and rather assume it is from external sources. We show that if the spatial and temporal scales of inhibitory coupling match known physiology, networks of model spiking neurons internally generate low-dimensional shared variability that captures population activity recorded in vivo. Shifting spatial attention into the receptive field of visual neurons has been shown to differentially modulate shared variability within and between brain areas. A top-down modulation of inhibitory neurons in our network provides a parsimonious mechanism for this attentional modulation. Our work provides a critical link between observed cortical circuit structure and realistic shared neuronal variability and its modulation.

Neuronal population mechanisms of lightness perception.

The way that humans and animals perceive the lightness of an object depends on its physical luminance as well as its surrounding context. While neuronal responses throughout the visual pathway are modulated by context, the relationship between neuronal responses and lightness perception is poorly understood. We searched for a neuronal mechanism of lightness by recording responses of neuronal populations in monkey primary visual cortex (V1) and area V4 to stimuli that produce a lightness illusion in humans, in which the lightness of a disk depends on the context in which it is embedded. We found that the way individual units encode the luminance (or equivalently for our stimuli, contrast) of the disk and its context is extremely heterogeneous. This motivated us to ask whether the population representation in either V1 or V4 satisfies three criteria: 1) disk luminance is represented with high fidelity, 2) the context surrounding the disk is also represented, and 3) the representations of disk luminance and context interact to create a representation of lightness that depends on these factors in a manner consistent with human psychophysical judgments of disk lightness. We found that populations of units in both V1 and V4 fulfill the first two criteria but that we cannot conclude that the two types of information in either area interact in a manner that clearly predicts human psychophysical measurements: the interpretation of our population measurements depends on how subsequent areas read out lightness from the population responses. NEW & NOTEWORTHY A core question in visual neuroscience is how the brain extracts stable representations of object properties from the retinal image. We searched for a neuronal mechanism of lightness perception by determining whether the responses of neuronal populations in primary visual cortex and area V4 could account for a lightness illusion measured using human psychophysics. Our results suggest that comparing psychophysics with population recordings will yield insight into neuronal mechanisms underlying a variety of perceptual phenomena.

Cognition as a Window into Neuronal Population Space.

Understanding how cognitive processes affect the responses of sensory neurons may clarify the relationship between neuronal population activity and behavior. However, tools for analyzing neuronal activity have not kept up with technological advances in recording from large neuronal populations. Here, we describe prevalent hypotheses of how cognitive processes affect sensory neurons, driven largely by a model based on the activity of single neurons or pools of neurons as the units of computation. We then use simple simulations to expand this model to a new conceptual framework that focuses on subspaces of population activity as the relevant units of computation, uses comparisons between brain areas or to behavior to guide analyses of these subspaces, and suggests that population activity is optimized to decode the large variety of stimuli and tasks that animals encounter in natural behavior. This framework provides new ways of understanding the ever-growing quantity of recorded population activity data.

Attentional modulation of neuronal variability in circuit models of cortex.

The circuit mechanisms behind shared neural variability (noise correlation) and its dependence on neural state are poorly understood. Visual attention is well-suited to constrain cortical models of response variability because attention both increases firing rates and their stimulus sensitivity, as well as decreases noise correlations. We provide a novel analysis of population recordings in rhesus primate visual area V4 showing that a single biophysical mechanism may underlie these diverse neural correlates of attention. We explore model cortical networks where top-down mediated increases in excitability, distributed across excitatory and inhibitory targets, capture the key neuronal correlates of attention. Our models predict that top-down signals primarily affect inhibitory neurons, whereas excitatory neurons are more sensitive to stimulus specific bottom-up inputs. Accounting for trial variability in models of state dependent modulation of neuronal activity is a critical step in building a mechanistic theory of neuronal cognition.

A normalization model suggests that attention changes the weighting of inputs between visual areas.

Models of divisive normalization can explain the trial-averaged responses of neurons in sensory, association, and motor areas under a wide range of conditions, including how visual attention changes the gains of neurons in visual cortex. Attention, like other modulatory processes, is also associated with changes in the extent to which pairs of neurons share trial-to-trial variability. We showed recently that in addition to decreasing correlations between similarly tuned neurons within the same visual area, attention increases correlations between neurons in primary visual cortex (V1) and the middle temporal area (MT) and that an extension of a classic normalization model can account for this correlation increase. One of the benefits of having a descriptive model that can account for many physiological observations is that it can be used to probe the mechanisms underlying processes such as attention. Here, we use electrical microstimulation in V1 paired with recording in MT to provide causal evidence that the relationship between V1 and MT activity is nonlinear and is well described by divisive normalization. We then use the normalization model and recording and microstimulation experiments to show that the attention dependence of V1-MT correlations is better explained by a mechanism in which attention changes the weights of connections between V1 and MT than by a mechanism that modulates responses in either area. Our study shows that normalization can explain interactions between neurons in different areas and provides a framework for using multiarea recording and stimulation to probe the neural mechanisms underlying neuronal computations.

Attention Increases Spike Count Correlations between Visual Cortical Areas.

UNLABELLED: Visual attention, which improves perception of attended locations or objects, has long been known to affect many aspects of the responses of neuronal populations in visual cortex. There are two nonmutually exclusive hypotheses concerning the neuronal mechanisms that underlie these perceptual improvements. The first hypothesis, that attention improves the information encoded by a population of neurons in a particular cortical area, has considerable physiological support. The second hypothesis is that attention improves perception by selectively communicating relevant visual information. This idea has been tested primarily by measuring interactions between neurons on very short timescales, which are mathematically nearly independent of neuronal interactions on longer timescales. We tested the hypothesis that attention changes the way visual information is communicated between cortical areas on longer timescales by recording simultaneously from neurons in primary visual cortex (V1) and the middle temporal area (MT) in rhesus monkeys. We used two independent and complementary approaches. Our correlative experiment showed that attention increases the trial-to-trial response variability that is shared between the two areas. In our causal experiment, we electrically microstimulated V1 and found that attention increased the effect of stimulation on MT responses. Together, our results suggest that attention affects both the way visual stimuli are encoded within a cortical area and the extent to which visual information is communicated between areas on behaviorally relevant timescales. SIGNIFICANCE STATEMENT: Visual attention dramatically improves the perception of attended stimuli. Attention has long been thought to act by selecting relevant visual information for further processing. It has been hypothesized that this selection is accomplished by increasing communication between neurons that encode attended information in different cortical areas. We recorded simultaneously from neurons in primary visual cortex and the middle temporal area while rhesus monkeys performed an attention task. We found that attention increased shared variability between neurons in the two areas and that attention increased the effect of microstimulation in V1 on the firing rates of MT neurons. Our results provide support for the hypothesis that attention increases communication between neurons in different brain areas on behaviorally relevant timescales.

Stimulus Dependence of Correlated Variability across Cortical Areas.

UNLABELLED: The way that correlated trial-to-trial variability between pairs of neurons in the same brain area (termed spike count or noise correlation, rSC) depends on stimulus or task conditions can constrain models of cortical circuits and of the computations performed by networks of neurons (Cohen and Kohn, 2011). In visual cortex, rSC tends not to depend on stimulus properties (Kohn and Smith, 2005; Huang and Lisberger, 2009) but does depend on cognitive factors like visual attention (Cohen and Maunsell, 2009; Mitchell et al., 2009). However, neurons across visual areas respond to any visual stimulus or contribute to any perceptual decision, and the way that information from multiple areas is combined to guide perception is unknown. To gain insight into these issues, we recorded simultaneously from neurons in two areas of visual cortex (primary visual cortex, V1, and the middle temporal area, MT) while rhesus monkeys viewed different visual stimuli in different attention conditions. We found that correlations between neurons in different areas depend on stimulus and attention conditions in very different ways than do correlations within an area. Correlations across, but not within, areas depend on stimulus direction and the presence of a second stimulus, and attention has opposite effects on correlations within and across areas. This observed pattern of cross-area correlations is predicted by a normalization model where MT units sum V1 inputs that are passed through a divisive nonlinearity. Together, our results provide insight into how neurons in different areas interact and constrain models of the neural computations performed across cortical areas. SIGNIFICANCE STATEMENT: Correlations in the responses of pairs of neurons within the same cortical area have been a subject of growing interest in systems neuroscience. However, correlated variability between different cortical areas is likely just as important. We recorded simultaneously from neurons in primary visual cortex and the middle temporal area while rhesus monkeys viewed different visual stimuli in different attention conditions. We found that correlations between neurons in different areas depend on stimulus and attention conditions in very different ways than do correlations within an area. The observed pattern of cross-area correlations was predicted by a simple normalization model. Our results provide insight into how neurons in different areas interact and constrain models of the neural computations performed across cortical areas.