On the perception of probable things: neural substrates of associative memory, imagery, and perception

Perception is influenced both by the immediate pattern of sensory inputs and by memories acquired through prior experiences with the world. Throughout much of its illustrious history, however, study of the cellular basis of perception has focused on neuronal structures and events that underlie the detection and discrimination of sensory stimuli. Relatively little attention has been paid to the means by which memories interact with incoming sensory signals. Building upon recent neurophysiological/behavioral studies of the cortical substrates of visual associative memory, I propose a specific functional process by which stored information about the world supplements sensory inputs to yield neuronal signals that can account for visual perceptual experience. This perspective represents a significant shift in the way we think about the cellular bases of perception.     

Attentional modulations related to spatial gating but not to allocation of limited resources in primate V1

Attention can modulate neural responses in sensory cortical areas and improve behavioral performance in perceptual tasks. However, the nature and purpose of these modulations remain under debate. Here we?used voltage-sensitive dye imaging (VSDI) to measure V1 population responses while monkeys performed a difficult detection task under focal or distributed attention. We found that V1 responses at attended locations are significantly elevated relative to actively ignored or irrelevant locations, consistent with the hypothesis that an important goal of attention in V1 is to highlight task-relevant information. Surprisingly, these modulations were indistinguishable under focal and distributed attention, suggesting a minor or no role for attention as a mechanism for allocating limited representational resources in V1. The response elevation at attended locations is additive, is widespread, and starts shortly before stimulus onset. This elevation could contribute to spatial gating by biasing competition in subsequent processing stages in favor of attended stimuli.     

Integrating information from different senses in the auditory cortex

Multisensory integration was once thought to be the domain of brain areas high in the cortical hierarchy, with early sensory cortical fields devoted to unisensory processing of inputs from their given set of sensory receptors. More recently, a wealth of evidence documenting visual and somatosensory responses in auditory cortex, even as early as the primary fields, has changed this view of cortical processing. These multisensory inputs may serve to enhance responses to sounds that are accompanied by other sensory cues, effectively making them easier to hear, but may also act more selectively to shape the receptive field properties of auditory cortical neurons to the location or identity of these events. We discuss the new, converging evidence that multiplexing of neural signals may play a key role in informatively encoding and integrating signals in auditory cortex across multiple sensory modalities. We highlight some of the many open research questions that exist about the neural mechanisms that give rise to multisensory integration in auditory cortex, which should be addressed in future experimental and theoretical studies.     

Electrophysiological evidence for spatiotemporal flexibility in the ventrolateral attention network

Successful completion of many everyday tasks depends on interactions between voluntary attention, which acts to maintain current goals, and reflexive attention, which enables responding to unexpected events by interrupting the current focus of attention. Past studies, which have mostly examined each attentional mechanism in isolation, indicate that volitional and reflexive orienting depend on two functionally specialized cortical networks in the human brain. Here we investigated how the interplay between these two cortical networks affects sensory processing and the resulting overt behavior. By combining measurements of human performance and electrocortical recordings with a novel analytical technique for estimating spatiotemporal activity in the human cortex, we found that the subregions that comprise the reflexive ventrolateral attention network dissociate both spatially and temporally as a function of the nature of the sensory information and current task demands. Moreover, we found that together with the magnitude of the early sensory gain, the spatiotemporal neural dynamics accounted for the high amount of the variance in the behavioral data. Collectively these data support the conclusion that the ventrolateral attention network is recruited flexibly to support complex behaviors.     

The Primary Visual Cortex Is Differentially Modulated by Stimulus-Driven and Top-Down Attention

Selective attention can be focused either volitionally, by top-down signals derived from task demands, or automatically, by bottom-up signals from salient stimuli. Because the brain mechanisms that underlie these two attention processes are poorly understood, we recorded local field potentials (LFPs) from primary visual cortical areas of cats as they performed stimulus-driven and anticipatory discrimination tasks. Consistent with our previous observations, in both tasks, we found enhanced beta activity, which we have postulated may serve as an attention carrier. We characterized the functional organization of task-related beta activity by (i) cortical responses (EPs) evoked by electrical stimulation of the optic chiasm and (ii) intracortical LFP correlations. During the anticipatory task, peripheral stimulation that was preceded by high-amplitude beta oscillations evoked large-amplitude EPs compared with EPs that followed low-amplitude beta. In contrast, during the stimulus-driven task, cortical EPs preceded by high-amplitude beta oscillations were, on average, smaller than those preceded by low-amplitude beta. Analysis of the correlations between the different recording sites revealed that beta activation maps were heterogeneous during the bottom-up task and homogeneous for the top-down task. We conclude that bottom-up attention activates cortical visual areas in a mosaic-like pattern, whereas top-down attentional modulation results in spatially homogeneous excitation.     

Sensory gain control (amplification) as a mechanism of selective attention: electrophysiological and neuroimaging evidence.

Both physiological and behavioral studies have suggested that stimulus-driven neural activity in the sensory pathways can be modulated in amplitude during selective attention. Recordings of event-related brain potentials indicate that such sensory gain control or amplification processes play an important role in visual-spatial attention. Combined event-related brain potential and neuroimaging experiments provide strong evidence that attentional gain control operates at an early stage of visual processing in extrastriate cortical areas. These data support early selection theories of attention and provide a basis for distinguishing between separate mechanisms of attentional suppression (of unattended inputs) and attentional facilitation (of attended inputs).     

Timing actions to avoid refractoriness: a simple solution for streaming sensory signals

Segmenting self- from allo-generated signals is crucial for active sensory processing. We report a dynamic filter used by South American pulse electric fish to distinguish active electro-sensory signals carried by their own electric discharges from other concomitant electrical stimuli (i.e. communication signals). The filter has a sensory component, consisting of an onset type central electro-sensory neuron, and a motor component, consisting of a change in the fish's discharge rate when allo-generated electrical events occur in temporal proximity to the fish's own discharge. We investigated the sensory component of the filter by in vitro mimicking synaptic inputs occurring during behavioral responses to allo-generated interfering signals. We found that active control of the discharge enhances self-generated over allo-generated responses by forcing allo-generated signals into a central refractory period. This hypothesis was confirmed by field potential recordings in freely discharging fish. Similar sensory-motor mechanisms may also contribute to signal segmentation in other sensory systems.     

Habitat-specific sensory-exploitative signals in birds: propensity of dipteran prey to cause evolution of plumage variation in flush-pursuit insectivores

Sensory exploitation occurs when signals trigger behavioral reactions that diminish the receiver's fitness. Research in this area focuses on the match between the signal's form and the receiver's sensitivity, but the effect of habitat on interspecific sensory exploitation is rarely addressed. Myioborus redstarts use conspicuous wing and tail displays of contrasting black-and-white plumage patches to flush dipteran insects, which are then pursued and captured in flight. Previous studies have shown that by increasing the distance at which insects perform an escape response, conspicuous visual displays improve the birds' foraging performance. We tested the hypothesis that selection for a visual signal that maximizes prey escape distance under local habitat conditions can lead to the evolution of geographic variation in plumage pattern among Myioborus redstarts. Using models of foraging birds, we recorded the escape responses of Dipterous insects to a range of plumage patterns and background tones (from light to dark) to determine whether the plumage pattern that maximizes prey flushing is dependent upon that habitat (background) against which birds are viewed by their prey. Our results indicate that the effectiveness of a particular plumage pattern in flushing dipteran prey depends strongly on the background against which that plumage pattern is displayed, and darker habitat (background) conditions generally favor plumages with more extensive patches of white in the tail. However, the addition of white wing patches that imitate the plumage of the painted redstart (Myioborus pictus) generally increases insect escape responses but reduces the effect that tail pattern variation and background tone have on escape behavior. These experiments support the hypothesis that habitat-specific natural selection to enhance sensory exploitation of prey escape responses could produce geographic variation in plumage patterns of flush-pursuers.     

Cross-modal deactivations during modality-specific selective attention

Background  

Processing stimuli in one sensory modality is known to result in suppression of other sensory-specific cortices. Additionally, behavioral experiments suggest that the primary consequence of paying attention to a specific sensory modality is poorer task performance in the unattended sensory modality. This study was designed to determine how focusing attention on the auditory or visual modality impacts neural activity in cortical regions responsible for processing stimuli in the unattended modality.     

Sound-driven synaptic inhibition in primary visual cortex

Multimodal objects and events activate many sensory cortical areas simultaneously. This is possibly reflected in reciprocal modulations of neuronal activity, even at the level of primary cortical areas. However, the synaptic character of these interareal interactions, and their impact on synaptic and behavioral sensory responses are unclear. Here, we found that activation of auditory cortex by a noise burst drove local GABAergic inhibition on supragranular pyramids of the mouse primary visual cortex, via cortico-cortical connections. This inhibition was generated by sound-driven excitation of a limited number of cells in infragranular visual cortical neurons. Consequently, visually driven synaptic and spike responses were reduced upon bimodal stimulation. Also, acoustic stimulation suppressed conditioned behavioral responses to a dim flash, an effect that was prevented by acute blockade of GABAergic transmission in visual cortex. Thus, auditory cortex activation by salient stimuli degrades potentially distracting sensory processing in visual cortex by recruiting local, translaminar, inhibitory circuits.     

Evoked response potential markers for anesthetic and behavioral states

The rodent whisker sensory system is a commonly used model of cortical processing; however, anesthetics cause profound differences in the shape and timing of evoked responses. Evoked response studies, especially those that use spatial mapping techniques, such as fMRI or optical imaging, will thus show significantly different results depending on the anesthesia used. To describe the effect of behavioral states and commonly used anesthetics, we characterized the early surface-evoked response potentials (ERPs) components (first ERP peak: gamma band 25-45 Hz; fast oscillation: 200-400 Hz; and very fast oscillation: 400-600 Hz) using a 25-channel electrode array on the somatosensory cortex during whisker stimulation. We found significant differences in the ERP shape when ketamine/xylazine, urethane, propofol, isoflurane, and pentobarbital sodium were administered and during sleep and wake states. The highest ERP amplitudes were observed under propofol anesthesia and during quiet sleep. Under isoflurane, the ERP was nearly absent, except for a very late component, which was concombinant with burst synchronization. The slowest responses were seen under urethane and propofol anesthesia. Spatial mapping experiments that use electrical, NMR, or optical techniques must consider the anesthetic dependency of these signals, especially when stimulation protocols or electrical and metabolic responses are compared.     

Brain states: top-down influences in sensory processing

All cortical and thalamic levels of sensory processing are subject to powerful top-down influences, the shaping of lower-level processes by more complex information. New findings on the diversity of top-down interactions show that cortical areas function as adaptive processors, being subject to attention, expectation, and perceptual task. Brain states are determined by the interactions between multiple cortical areas and the modulation of intrinsic circuits by feedback connections. In perceptual learning, both the encoding and recall of learned information involves a selection of the appropriate inputs that convey information about the stimulus being discriminated. Disruption of this interaction may lead to behavioral disorders, including schizophrenia.     

Experience-dependent adult cortical plasticity requires cognitive association between sensation and reward

We tested the involvement of cognition in adult experience-dependent neuroplasticity using primate cortical implants. In a prior study, learning an operant sensory discrimination increased cortical excitability and target selectivity. Here, the prior task was separated into three behavioral phases. First, naive animals were exposed to stimulus-reward pairings from the prior study. These yoked animals did not have to discriminate to be rewarded and did not learn the discrimination. The plasticity observed in the prior study did not occur. Second, the animals were classically conditioned to discriminate the same stimuli in a simplified format. Learning was accompanied by increased sensory response strength and an increased range of sensory inputs eliciting responses. The third study recreated the original operant discrimination, and selectivity for task targets increased. These studies demonstrate that cognitive association between sensory stimuli and reinforcers accompanies adult experience-dependent cortical plasticity and suggest that selectivity in representation and action are linked.     

A Normalization Model of Attentional Modulation of Single Unit Responses

Although many studies have shown that attention to a stimulus can enhance the responses of individual cortical sensory neurons, little is known about how attention accomplishes this change in response. Here, we propose that attention-based changes in neuronal responses depend on the same response normalization mechanism that adjusts sensory responses whenever multiple stimuli are present. We have implemented a model of attention that assumes that attention works only through this normalization mechanism, and show that it can replicate key effects of attention. The model successfully explains how attention changes the gain of responses to individual stimuli and also why modulation by attention is more robust and not a simple gain change when multiple stimuli are present inside a neuron''s receptive field. Additionally, the model accounts well for physiological data that measure separately attentional modulation and sensory normalization of the responses of individual neurons in area MT in visual cortex. The proposal that attention works through a normalization mechanism sheds new light a broad range of observations on how attention alters the representation of sensory information in cerebral cortex.     

Reshaping sensory representations by task-specific brain states: Toward cortical circuit mechanisms

Perception is internally constructed by integrating brain states with external sensory inputs, a process depending on the topdown modulation of sensory representations. A wealth of earlier studies described task-dependent modulations of sensory cortex corroborating perceptual and behavioral phenomena. But only with recent technological advancements, the underlying circuit-level mechanisms began to be unveiled. We review recent progress along this line of research. It begins to be appreciated that topdown signals can encode various types of task-related information, ranging from task engagement, and category knowledge to decision execution; these signals are transferred via feedback pathways originating from distinct association cortices and interact with sensory cortical circuits. These plausible mechanisms support a broad range of computations from predictive coding to inference making, ultimately form dynamic percepts and endow behavioral flexibility.     

Attention control in the primate brain

Attention is fundamental to all cognition. In the primate brain, it is implemented by a large-scale network that consists of areas spanning across all major lobes, also including subcortical regions. Classical attention accounts assume that control over the selection process in this network is exerted by ‘top-down’ mechanisms in the fronto-parietal cortex that influence sensory representations via feedback signals. More recent studies have expanded this view of attentional control. In this review, we will start from a traditional top-down account of attention control, and then discuss more recent findings on feature-based attention, thalamic influences, temporal network dynamics, and behavioral dynamics that collectively lead to substantial modifications. We outline how the different emerging accounts can be reconciled and integrated into a unified theory.     

Gamma oscillations of spiking neural populations enhance signal discrimination

Selective attention is an important filter for complex environments where distractions compete with signals. Attention increases both the gamma-band power of cortical local field potentials and the spike-field coherence within the receptive field of an attended object. However, the mechanisms by which gamma-band activity enhances, if at all, the encoding of input signals are not well understood. We propose that gamma oscillations induce binomial-like spike-count statistics across noisy neural populations. Using simplified models of spiking neurons, we show how the discrimination of static signals based on the population spike-count response is improved with gamma induced binomial statistics. These results give an important mechanistic link between the neural correlates of attention and the discrimination tasks where attention is known to enhance performance. Further, they show how a rhythmicity of spike responses can enhance coding schemes that are not temporally sensitive.     

Reduced variability of ongoing and evoked cortical activity leads to improved behavioral performance

Sensory responses of the brain are known to be highly variable, but the origin and functional relevance of this variability have long remained enigmatic. Using the variable foreperiod of a visual discrimination task to assess variability in the primate cerebral cortex, we report that visual evoked response variability is not only tied to variability in ongoing cortical activity, but also predicts mean response time. We used cortical local field potentials, simultaneously recorded from widespread cortical areas, to gauge both ongoing and visually evoked activity. Trial-to-trial variability of sensory evoked responses was strongly modulated by foreperiod duration and correlated both with the cortical variability before stimulus onset as well as with response times. In a separate set of experiments we probed the relation between small saccadic eye movements, foreperiod duration and manual response times. The rate of eye movements was modulated by foreperiod duration and eye position variability was positively correlated with response times. Our results indicate that when the time of a sensory stimulus is predictable, reduction in cortical variability before the stimulus can improve normal behavioral function that depends on the stimulus.     

Reticular activation and the dynamics of neuronal networks

It is postulated that during arousal the cortical system is driven by a spatially and temporally noisy signal arising from non-specific reticulo-cortical pathways. An elementary unit of cortical neuroanatomy is assumed, which permits non-linear dynamics to be represented by stochastic linear equations. Under these assumptions the resonant modes of the system of cortical dendrites approach thermodynamic equilibrium. Specific sensory signals perturb the dendritic system about equilibrium, generate low frequency, linear, non-dispersive waves corresponding to the EEG, which in turn regulate action potential sequences, and instantiate internal inputs to the dendritic field. A large and distributed memory capacity in axo-synaptic couplings, resistance to interference between functionally separate logical operations, and a very large next-state function set emerge as properties of the network. The model is able to explain the close association of the EEG with cognition, the channel of low capacity corresponding to the field of immediate attention, the low overall correlation of action potentials with EEG, and specificity of action potentials in some neurons during particular cognitive activity. Predictions made from hypothesis include features of thermal equilibrium in EEG (determinable by autoregression) and expectation that the cortical evoked response can be accounted for as the response to a sensory impulse of specific time characteristics.     

Intracellular and computational evidence for a dominant role of internal network activity in cortical computations

The mammalian cerebral cortex is characterized by intense spontaneous activity, depending on brain region, age, and behavioral state. Classically, the cortex is considered as being driven by the senses, a paradigm which corresponds well to experiments in quiescent or deeply anesthetized states. In awake animals, however, the spontaneous activity cannot be considered as 'background noise', but is of comparable-or even higher-amplitude than evoked sensory responses. Recent evidence suggests that this internal activity is not only dominant, but also it shares many properties with the responses to natural sensory inputs, suggesting that the spontaneous activity is not independent of the sensory input. Such evidence is reviewed here, with an emphasis on intracellular and computational aspects. Statistical measures, such as the spike-triggered average of synaptic conductances, show that the impact of internal network state on spiking activity is major in awake animals. Thus, cortical activity cannot be considered as being driven by the senses, but sensory inputs rather seem to modulate and modify the internal dynamics of cerebral cortex. This view offers an attractive interpretation not only of dreaming activity (absence of sensory input), but also of several mental disorders.