A normalization circuit of attention in primate lateral prefrontal cortex

The way in which visual neurons encode information pertaining to a cluttered scene with multiple stimuli, and subsequently filter behaviorally relevant information using attention remains poorly understood. Neurons of area 8a in the macaque lateral prefrontal cortex have been shown to encode visual and attentional signals. We trained two macaque monkeys in a visuospatial attention task and performed neurophysiological recordings to test how neurons in this area encode multiply presented stimuli and attentionally filter target stimuli from distractors. We found area 8a neuronal responses to several concurrently presented stimuli to resemble the average of individual responses to those stimuli when presented alone; this nonlinear response is characteristic of divisive normalization, a canonical brain computation seen to operate in various neural systems. Interestingly, the strength of normalization was dependent on visuospatial tuning, with neurons tuned for the ipsilateral visual hemifield displaying stronger normalized responses than those tuned for the contralateral hemifield. Furthermore, when presented with multiple stimuli and attending toward a target stimulus lying in the receptive field, contralateral-tuned neural activity increased and resembled that of when the target was presented alone (i.e. Winner-take-all response), whereas ipsilateral-tuned neurons were less modulated by attention and remained best-described by an average response. Taken together, our findings suggest a normalization circuit underlying attention in the primate lateral prefrontal cortex

State Dependence of Stimulus-Induced Variability Tuning in Macaque MT

Behavioral states marked by varying levels of arousal and attention modulate some properties of cortical responses (e.g. average firing rates or pairwise correlations), yet it is not fully understood what drives these response changes and how they might affect downstream stimulus decoding. Here we show that changes in state modulate the tuning of response variance-to-mean ratios (Fano factors) in a fashion that is neither predicted by a Poisson spiking model nor changes in the mean firing rate, with a substantial effect on stimulus discriminability. We recorded motion-sensitive neurons in middle temporal cortex (MT) in two states: alert fixation and light, opioid anesthesia. Anesthesia tended to lower average spike counts, without decreasing trial-to-trial variability compared to the alert state. Under anesthesia, within-trial fluctuations in excitability were correlated over longer time scales compared to the alert state, creating supra-Poisson Fano factors. In contrast, alert-state MT neurons have higher mean firing rates and largely sub-Poisson variability that is stimulus-dependent and cannot be explained by firing rate differences alone. The absence of such stimulus-induced variability tuning in the anesthetized state suggests different sources of variability between states. A simple model explains state-dependent shifts in the distribution of observed Fano factors via a suppression in the variance of gain fluctuations in the alert state. A population model with stimulus-induced variability tuning and behaviorally constrained information-limiting correlations explores the potential enhancement in stimulus discriminability by the cortical population in the alert state.Comment: 36 pages, 18 figure

Neural representation of complex motion in the primate cortex

This dissertation is concerned with how information about the environment is represented by neural activity in the primate brain. More specifically, it contains several studies that explore the representation of visual motion in the brains of humans and nonhuman primates through behavioral and physiological measures. The majority of this work is focused on the activity of individual neurons in the medial superior temporal area (MST) – a high-level, extrastriate area of the primate visual cortex. The first two studies provide an extensive review of the scientific literature on area MST. The area’s prominent role at the intersection of low-level, bottom-up, sensory processing and high-level, top-down mechanisms is highlighted. Furthermore, a specific article on how information about self-motion and object motion can be decoded from a population of MSTd neurons is reviewed in more detail. The third study describes a published and annotated dataset of MST neurons’ responses to a series of different motion stimuli. This dataset is analyzed using a variety of different analysis approaches in the fifth study. Classical tuning curve approaches confirm that MST neurons have large, but well-defined spatial receptive fields and are independently tuned for linear and spiral motion, as well as speed. We also confirm that the tuning for spiral motion is position invariant in a majority of MST neurons. A bias-free characterization of receptive field profiles based on a new stimulus that generates smooth, complex motion patterns turned out to be predictive of some of the tuning properties of MST neurons, but was generally less informative than similar approaches have been in earlier visual areas. The fifth study introduces a new motion stimulus that consists of hexgonal segments and presents an optimization algorithm for an adaptive online analysis of neurophysiological recordings. Preliminary physiological data and simulations show these tools to have a strong potential in characterizing the response functions of MST neurons. The final study describes a behavioral experiment with human subjects that explores how different stimulus features, such as size and contrast, affect motion perception and discusses what conclusions can be drawn from that about the representation of visual motion in the human brain. Together these studies highlight the visual motion processing pathway of the primate brain as an excellent model system for studying more complex relations of neural activity and external stimuli. Area MST in particular emerges as a gateway between perception, cognition, and action planning.2021-11-1

Neural Network Dynamics of Visual Processing in the Higher-Order Visual System

Vision is one of the most important human senses that facilitate rich interaction with the external environment. For example, optimal spatial localization and subsequent motor contact with a specific physical object amongst others requires a combination of visual attention, discrimination, and sensory-motor coordination. The mammalian brain has evolved to elegantly solve this problem of transforming visual input into an efficient motor output to interact with an object of interest. The frontal and parietal cortices are two higher-order (i.e. processes information beyond simple sensory transformations) brain areas that are intimately involved in assessing how an animal’s internal state or prior experiences should influence cognitive-behavioral output. It is well known that activity within each region and functional interactions between both regions are correlated with visual attention, decision-making, and memory performance. Therefore, it is not surprising that impairment in the fronto-parietal circuit is often observed in many psychiatric disorders. Network- and circuit-level fronto-parietal involvement in sensory-based behavior is well studied; however, comparatively less is known about how single neuron activity in each of these areas can give rise to such macroscopic activity. The goal of the studies in this dissertation is to address this gap in knowledge through simultaneous recordings of cellular and population activity during sensory processing and behavioral paradigms. Together, the combined narrative builds on several themes in neuroscience: variability of single cell function, population-level encoding of stimulus properties, and state and context-dependent neural dynamics.Doctor of Philosoph

Perceptual learning of contrast discrimination and its neural correlates in macaque V4 and V1

PhD ThesisWe make frequent evaluations of subtle contrast differences in our visual environment, and often under challenging illumination conditions, whether photopic, scotopic or mesopic. Our contrast discrimination abilities are rigorously honed from an early age, and we continue to carry out these fine perceptual judgments throughout our lifetimes. Thus, the issue of whether substantial improvement in contrast discrimination is possible during later periods in life, such as during adulthood- and the circumstances that allow this- has sometimes come under discussion. Our adult macaque subjects underwent extensive training on a contrast discrimination task, in which stimuli were positioned at a variety of peripheral and parafoveal locations. We present clear evidence of contrast perceptual learning at the behavioural level and show that these changes have neuronal correlates primarily in V4, rather than in V1. Learning was specific to stimulus location and spatial frequency, but was transferable across orientations; it took place to a limited degree under stimulus roving conditions, and could be either facilitated or impeded by the addition of flanker stimuli, depending on the subject. Upon removal of flankers, levels of psychometric and neurometric performance returned to their pre-flanker state. In V4, learning-induced changes encompassed a shift in the point of neurometric equality and the semi-saturation constant (C50) towards the trained contrast; a decrease in noise correlations across channels; and an increase in choice probability. In V1, enhancements in performance were characterised by an increase in spike discriminability; a shift in the point of neurometric equality and the C50 towards the trained contrast(s); and a widening in the range and a steepening of the contrast response function, during the early phase of training. Deteriorations in performance were accompanied by the reverse effects on V1 activity; furthermore, a general decrease in V1 firing rates occurred when training was carried out over an extended period of time, after performance had reached its peak.The Medical Research Council, UK

Pulvinar modulates contrast response function of neurons in the primary visual cortex

The pulvinar, which is located in the posterior thalamus, establishes reciprocal connections with nearly all of the visual cortical areas and is consequently in a strategic position to influence their stimulus decoding processes. Projections from the pulvinar to the primary visual cortex (V1) are thought to be modulatory, altering the response of neurons without changing their basic receptive field properties. Here, we investigate this issue by studying V1 single unit responses to sine wave gratings during the reversible inactivation of the lateral posterior nucleus (LP) - pulvinar complex in the cat. We also studied the contrast response function of V1 neurons, before and during the inactivation of the LP-pulvinar complex. No change in the preferred orientation or direction selectivity of V1 neurons was observed during pulvinar inactivation. However, for the majority of the cells tested the response amplitude to the optimal stimulus was reduced. The contrast response function of neurons was fitted with the Naka-Rushton function and analysis of the effects of pulvinar deactivation revealed a diverse set of modulations: 35% of cells had a decrease in their peak response, 11% had an increase in their C50, 6% showed modulations of the slope factor and 22% exhibited changes in more than one parameter. Our results suggest that the pulvinar modulates activity of V1 neurons in a contrast dependent manner and provides gain control at lower levels of the visual cortical hierarchy.Le pulvinar, localisé dans le thalamus postérieur, établit des connections réciproques avec la vaste majorité des aires visuelles corticales et il est ainsi dans une position stratégique afin d’influencer les processus de décodage de celles-ci. Les projections du pulvinar au cortex visuel primaire (V1) sont considérées comme étant des projections modulatrices, qui modifieraient les réponses neuronales sans toutefois changer les propriétés de base des champs récepteurs. Dans la présente étude, nous avons étudié les réponses des neurones de V1 suite à l’inactivation réversible du complexe noyau latéral postérieur (LP)-pulvinar chez le chat. Des courbes de réponse au contraste ont été générées par la présentation de réseaux ayant plusieurs niveaux de contraste pendant l’inactivation du LP-pulvinar. Aucun changement n’a été observé concernant l’orientation préférée ou la sélectivité à la direction des neurones de V1 lors de l’inactivation du pulvinar. Néanmoins, pour la majorité des cellules testées, l’amplitude de la réponse aux stimuli optimaux a été réduite. La fonction de Naka-Rushton a été appliquée aux courbes de réponse au contraste et l’analyse des effets de l’inactivation du pulvinar a montré une panoplie d’effets modulateurs : 35% des cellules ont présenté une réduction de leur réponse maximale, 11% ont eu une augmentation de leur C50, 6% ont montré une modulation de la pente et 22% des neurones ont présenté des changements dans plus d’un paramètre. Nos résultats suggèrent que le pulvinar module l’activité des neurones de V1 d’une façon dépendante du contraste et qu’il contrôle le gain des réponses des neurones des aires primaires du cortex visuel

Contextual signals in visual cortex:How sounds, state, and task setting shape how we see

What we see is not always what we get. Even though the light that hits the retina might convey the same images, how visual information is processed and what we eventually do with it depend on many contextual factors. In this thesis, we show in a series of experiments how the sensory processing of the same visual input in the visual cortex of mice is affected by our internal state, movements, other senses and any task we are performing. We found that recurrent activity originating within higher visual areas modulates activity in the primary visual cortex (V1) and selectivity amplifies weak compared to strong sensory-evoked responses. Second, visual stimuli evoked similar early activity in V1, but later activity strongly depended on whether mice were trained to report the visual stimuli, and on the specific task. Specifically, adding a second modality to the task demands extended the temporal window during which V1 was causally involved in visual perception. Third, we report that not only visual stimuli but also sounds led to strong responses in V1, composed of distinct auditory-related and motor-related activity. Finally, we studied the role of Posterior Parietal Cortex in an audiovisual change detection task. Despite extensive single-neuron and population-level encoding of task-relevant visual and auditory stimuli, as well as upcoming behavioral responses, optogenetic inactivation did not affect task performance. Whereas these contextual factors have previously been studied in isolation, we obtain a more integrated understanding of how factors beyond visual information determine what we actually see