Bidirectional signaling between neocortex and limbic cortex has been hypothesized to contribute to the retrieval of long-term memory. We tested this hypothesis by comparing the time courses of perceptual and memory-retrieval signals in two neighboring areas in temporal cortex, area TE (TE) and perirhinal cortex (PRh), while monkeys were performing a visual pair-association task. Perceptual signal reached TE before PRh, confirming its forward propagation. In contrast, memory-retrieval signal appeared earlier in PRh, and TE neurons were then gradually recruited to represent the sought target. A reasonable interpretation of this finding is that the rich backward fiber projections from PRh to TE may underlie the activation of TE neurons that represent a visual object retrieved from long-term memory.

Microsaccades exhibit systematic oscillations in direction after spatial cueing, and these oscillations correlate with facilitatory and inhibitory changes in behavioral performance in the same tasks. However, independent of cueing, facilitatory and inhibitory changes in visual sensitivity also arise pre-microsaccadically. Given such pre-microsaccadic modulation, an imperative question to ask becomes: how much of task performance in spatial cueing may be attributable to these peri-movement changes in visual sensitivity? To investigate this question, we adopted a theoretical approach. We developed a minimalist model in which: (1) microsaccades are repetitively generated using a rise-to-threshold mechanism, and (2) pre-microsaccadic target onset is associated with direction-dependent modulation of visual sensitivity, as found experimentally. We asked whether such a model alone is sufficient to account for performance dynamics in spatial cueing. Our model not only explained fine-scale microsaccade frequency and direction modulations after spatial cueing, but it also generated classic facilitatory (i.e., attentional capture) and inhibitory [i.e., inhibition of return (IOR)] effects of the cue on behavioral performance. According to the model, cues reflexively reset the oculomotor system, which unmasks oscillatory processes underlying microsaccade generation; once these oscillatory processes are unmasked, “attentional capture” and “IOR” become direct outcomes of pre-microsaccadic enhancement or suppression, respectively. Interestingly, our model predicted that facilitatory and inhibitory effects on behavior should appear as a function of target onset relative to microsaccades even without prior cues. We experimentally validated this prediction for both saccadic and manual responses. We also established a potential causal mechanism for the microsaccadic oscillatory processes hypothesized by our model. We used retinal-image stabilization to experimentally control instantaneous foveal motor error during the presentation of peripheral cues, and we found that post-cue microsaccadic oscillations were severely disrupted. This suggests that microsaccades in spatial cueing tasks reflect active oculomotor correction of foveal motor error, rather than presumed oscillatory covert attentional processes. Taken together, our results demonstrate that peri-microsaccadic changes in vision can go a long way in accounting for some classic behavioral phenomena.

The macaque inferotemporal (IT) cortex, which serves as the storehouse of visual long-term memory, consists of two distinct but mutually interconnected areas: area TE (TE) and area 36 (A36). In the present study, we tested whether memory encoding is put forward at this stage, i.e., whether association between the representations of different but semantically linked objects proceeds forward from TE to A36. To address this question, we trained monkeys in a pair-association (PA) memory task, after which single-unit activities were recorded from TE and A36 during PA trials. Neurons in both areas showed stimulus-selective cue responses (347 in TE, 76 in A36; "cue-selective neurons") that provided, at the population level, mnemonic linkage between the paired associates. The percentage of neurons in which responses to the paired associates were significantly (p < 0.01) correlated at the single-neuron level ("pair-coding neuron") dramatically increased from TE (4.9% of the cue-selective neurons) to A36 (33%). The pair-coding neurons in A36 were further separable into Type1 (68%) and Type2 (32%) on the basis of their initial transient responses after cue stimulus presentation. Type1 neurons, but not Type2 neurons, began to encode association between paired stimuli as soon as they exhibited stimulus selectivity. Thus, the representation of long-term memory encoded by Type1 neurons in A36 is likely substantiated without feedback input from other higher centers. Therefore, we conclude that association between the representations of the paired associates proceeds forward at this critical step within IT cortex, suggesting selective convergence onto a single A36 neuron from two TE neurons that encode separate visual objects.

Inherent in visual scene analysis is a bottleneck associated with the need to sequentially sample locations with foveating eye movements. The concept of a ‘saliency map’ topographically encoding stimulus conspicuity over the visual scene has proven to be an efficient predictor of eye movements. Our work reviews insights into the neurobiological implementation of visual salience computation. We start by summarizing the role that different visual brain areas play in salience computation, whether at the level of feature analysis for bottom-up salience or at the level of goal-directed priority maps for output behaviour. We then delve into how a subcortical structure, the superior colliculus (SC), participates in salience computation. The SC represents a visual saliency map via a centre-surround inhibition mechanism in the superficial layers, which feeds into priority selection mechanisms in the deeper layers, thereby affecting saccadic and microsaccadic eye movements. Lateral interactions in the local SC circuit are particularly important for controlling active populations of neurons. This, in turn, might help explain long-range effects, such as those of peripheral cues on tiny microsaccades. Finally, we show how a combination of in vitro neurophysiology and large-scale computational modelling is able to clarify how salience computation is implemented in the local circuit of the SC.This article is part of the themed issue ‘Auditory and visual scene analysis’.

The rat postsubiculum has head direction cells that fire persistently when the rat's head is oriented in particular directions. This persistent firing is maintained even if the rat is motionless, when spatial cues are removed from the environment and in the dark, but the mechanism that supports persistent firing of the head direction cells is still unclear. Here, using in vitro whole-cell patch recording, we found that a short-triggering stimulus (as few as five induced spikes) can initiate persistent firing in cells of the postsubiculum. Pharmacological results indicated that this persistent firing is driven by a calcium-sensitive nonselective cation current. The distribution of cells with persistent firing in superficial and deep layers in the postsubiculum was similar to that of head direction cells. These results suggest that persistent firing of head direction cells in the postsubiculum could be supported by an intrinsic mechanism.

Persistent firing is believed to be a crucial mechanism for memory function including working memory. Recent in vivo and in vitro findings suggest an involvement of metabotropic glutamate receptors (mGluRs) in persistent firing. Using whole-cell patch recording techniques in a rat entorhinal cortex (EC) slice preparation, we tested if EC layer III neurons display persistent firing due to mGluR-activation, independently from cholinergic activation. Stimulation of the angular bundle drove persistent firing in 90% of the cells in the absence of cholinergic agonist. The persistent firing was typically stable for more than 4.5 min at which point persistent firing was terminated by the experimenter. The average frequency of the persistent firing was 2.1 Hz, ranging from 0.4 to 5.5 Hz. This persistent firing was observed even in the presence of atropine (2 μM), suggesting that the persistent firing can occur independent of cholinergic activation. Furthermore, ionotropic glutamate and GABAergic synaptic blockers (2 mM kynurenic acid, 100 μM picrotoxin and 1 μM CGP55845) did not block the persistent firing. On the other hand, blockers of group I mGluRs (100 μM LY367385 and 20 μM MPEP) completely blocked or suppressed the persistent firing. An agonist of group I mGluRs (20 μM DHPG) greatly enhanced the persistent firing induced by current injection. These results indicate that persistent firing can be driven through group I mGluRs in entorhinal layer III neurons suggesting that glutamatergic synaptic input alone could enable post-synaptic neurons to hold input signals in the form of persistent firing.

Monkeys with unilateral lesions of the primary visual cortex (V1) can make saccades to visual stimuli in their contralateral ("affected") hemifield, but their sensitivity to luminance contrast is reduced. We examined whether the effects of V1 lesions were restricted to vision or included later stages of visual-oculomotor processing. Monkeys with unilateral V1 lesions were tested with a visually guided saccade task with stimuli in various spatial positions and of various luminance contrasts. Saccades to the stimuli in the affected hemifield were compared with those to the near-threshold stimuli in the normal hemifield so that the performances of localization were similar. Scatter in the end points of saccades to the affected hemifield was much larger than that of saccades to the near-threshold stimuli in the normal hemifield. Additional analysis revealed that this was because the initial directional error was not as sufficiently compensated as it was in the normal hemifield. The distribution of saccadic reaction times in the affected hemifield tended to be narrow. We modeled the distribution of saccadic reaction times by a modified diffusion model and obtained evidence that the decision threshold for initiation of saccades to the affected hemifield was lower than that for saccades to the normal hemifield. These results suggest that the geniculostriate pathway is crucial for on-line compensatory mechanisms of saccadic control and for decision processes. We propose that these results reflect deficits in deliberate control of visual-oculomotor processing after V1 lesions, which may parallel loss of visual awareness in human blindsight patients.

Microsaccades are systematically modulated by peripheral spatial cues, and these eye movements have been implicated in perceptual and motor performance changes in cueing tasks. However, an additional oculomotor factor that may also influence performance in these tasks, fixational eye position itself, has been largely neglected so far. Using precise eye tracking and real-time retinal-image stabilization, we carefully analyzed fixational eye position dynamics and related them to microsaccade generation during spatial cueing. As expected, during baseline fixation, microsaccades corrected for a foveal motor error away from the preferred retinal locus of fixation (the so-called ocular position "set point" of the oculomotor system). However, we found that this relationship was violated during a short period immediately after cue onset; a subset of cue-directed "express microsaccades" that were highly precise in time and direction, and that were larger than regular microsaccades, occurred. These movements, having <100-ms latencies from cue onset, were triggered when fixational eye position was already at the oculomotor set point when the cue appeared; they were thus error-increasing rather than error-decreasing. Critically, even when no microsaccades occurred, fixational eye position itself was systematically deviated toward the cue, again with ~100-ms latency, suggesting that the oculomotor system establishes a new set point at different postcue times. This new set point later switched to being away from the cue after ~200-300 ms. Because eye position alters the location of retinal images, our results suggest that both eye position and microsaccades can be associated with performance changes in spatial cueing tasks. NEW & NOTEWORTHY Covert spatial cueing tasks are a workhorse for studying cognitive processing in humans and monkeys, but gaze is not perfectly stable during these tasks. We found that minute fixational eye position changes, independent of the more studied microsaccades, are not random in cueing tasks and are thus not "averaged out" in analyses. These changes can additionally dictate microsaccade times. Thus, in addition to microsaccadic influences, retinal image changes associated with fixational eye position are relevant for performance in cueing tasks.