Katherine M. Armstrong

Selective gating of visual signals by microstimulation of frontal cortex

Several decades of psychophysical and neurophysiological studies have established that visual signals are enhanced at the locus of attention. What remains a mystery is the mechanism that initiates biases in the strength of visual representations. Recent evidence argues that, during spatial attention, these biases reflect nascent saccadic eye movement commands. We examined the functional interaction of saccade preparation and visual coding by electrically stimulating sites within the frontal eye fields (FEF) and measuring its effect on the activity of neurons in extrastriate visual cortex. Here we show that visual responses in area V4 could be enhanced after brief stimulation of retinotopically corresponding sites within the FEF using currents below that needed to evoke saccades. The magnitude of the enhancement depended on the effectiveness of receptive field stimuli as well as on the presence of competing stimuli outside the receptive field. Stimulation of non-corresponding FEF representations could suppress V4 responses. The results suggest that the gain of visual signals is modified according to the strength of spatially corresponding eye movement commands.

Stimulus onset quenches neural variability: a widespread cortical phenomenon

Neural responses are typically characterized by computing the mean firing rate, but response variability can exist across trials. Many studies have examined the effect of a stimulus on the mean response, but few have examined the effect on response variability. We measured neural variability in 13 extracellularly recorded datasets and one intracellularly recorded dataset from seven areas spanning the four cortical lobes in monkeys and cats. In every case, stimulus onset caused a decline in neural variability. This occurred even when the stimulus produced little change in mean firing rate. The variability decline was observed in membrane potential recordings, in the spiking of individual neurons and in correlated spiking variability measured with implanted 96-electrode arrays. The variability decline was observed for all stimuli tested, regardless of whether the animal was awake, behaving or anaesthetized. This widespread variability decline suggests a rather general property of cortex, that its state is stabilized by an input.

Visuomotor Origins of Covert Spatial Attention

Covert spatial attention produces biases in perceptual performance and neural processing of behaviorally relevant stimuli in the absence of overt orienting movements. The neural mechanism that gives rise to these effects is poorly understood. This paper surveys past evidence of a relationship between oculomotor control and visual spatial attention and more recent evidence of a causal link between the control of saccadic eye movements by frontal cortex and covert visual selection. Both suggest that the mechanism of covert spatial attention emerges as a consequence of the reciprocal interactions between neural circuits primarily involved in specifying the visual properties of potential targets and those involved in specifying the movements needed to fixate them.

Visual and oculomotor selection: links, causes and implications for spatial attention

Natural scenes contain far more information than can be processed simultaneously. Thus, our visually guided behavior depends crucially on the capacity to attend to relevant stimuli. Past studies have provided compelling evidence of functional overlap of the neural mechanisms that control spatial attention and saccadic eye movements. Recent neurophysiological work demonstrates that the neural circuits involved in the preparation of saccades also play a causal role in directing covert spatial attention. At the same time, other studies have identified separable neural populations that contribute uniquely to visual and oculomotor selection. Taken together, all of the recent work suggests how visual and oculomotor signals are integrated to simultaneously select the visual attributes of targets and the saccades needed to fixate them.

Changes in Visual Receptive Fields with Microstimulation of Frontal Cortex

The influence of attention on visual cortical neurons has been described in terms of its effect on the structure of receptive fields (RFs), where multiple stimuli compete to drive neural responses and ultimately behavior. We stimulated the frontal eye field (FEF) of passively fixating monkeys and produced changes in V4 responses similar to known effects of voluntary attention. Subthreshold FEF stimulation enhanced visual responses at particular locations within the RF and altered the interaction between pairs of RF stimuli to favor those aligned with the activated FEF site. Thus, we could influence which stimulus drove the responses of individual V4 neurons. These results suggest that spatial signals involved in saccade preparation are used to covertly select among multiple stimuli appearing within the RFs of visual cortical neurons.

Rapid enhancement of visual cortical response discriminability by microstimulation of the frontal eye field

Visual attention provides a means of selecting among the barrage of information reaching the retina and of enhancing the perceptual discriminability of relevant stimuli. Neurophysiological studies in monkeys and functional imaging studies in humans have demonstrated neural correlates of these perceptual improvements in visual cortex during attention. Importantly, voluntary attention improves the discriminability of visual cortical responses to relevant stimuli. Recent work aimed at identifying sources of attentional modulation has implicated the frontal eye field (FEF) in driving spatial attention. Subthreshold microstimulation of the FEF enhances the responses of area V4 neurons to spatially corresponding stimuli. However, it is not known whether these enhancements include improved visual-response discriminability, a hallmark of voluntary attention. We used receiver-operator characteristic analysis to quantify how well V4 responses discriminated visual stimuli and examined how discriminability was affected by FEF microstimulation. Discriminability of responses to stable visual stimuli decayed over time but was transiently restored after microstimulation of the FEF. As observed during voluntary attention, the enhancement resulted only from changes in the magnitude of V4 responses and not in the relationship between response magnitude and variance. Enhanced response discriminability was apparent immediately after microstimulation and was reliable within 40 ms of microstimulation onset, indicating a direct influence of FEF stimulation on visual representations. These results contribute to the mounting evidence that saccade-related signals are a source of spatial attentive selection.

Selection and Maintenance of Spatial Information by Frontal Eye Field Neurons

Voluntary attention is often allocated according to internally maintained goals. Recent evidence indicates that the frontal eye field (FEF) participates in the deployment of spatial attention, even in the absence of saccadic eye movements. In addition, many FEF neurons maintain persistent representations of impending saccades. However, the role of persistent activity in the general maintenance of spatial information, and its relationship to spatial attention, has not been explored. We recorded the responses of single FEF neurons in monkeys trained to remember cued locations in order to detect changes in targets embedded among distracters in a task that did not involve saccades. We found that FEF neurons persistently encoded the cued location throughout the trial during the delay period, when no visual stimuli were present, and during visual discrimination. Furthermore, FEF activity reliably predicted whether monkeys would detect the target change. Population analyses revealed that FEF neurons with persistent activity were more effective at selecting the target from among distracters than neurons lacking persistent activity. These results demonstrate that FEF neurons maintain spatial information in the absence of saccade preparation and suggest that this maintenance contributes to the selection of relevant visual stimuli.

Probing neural circuitry and function with electrical microstimulation

Since the discovery of the nervous systems electrical excitability more than 200 years ago, neuroscientists have used electrical stimulation to manipulate brain activity in order to study its function. Microstimulation has been a valuable technique for probing neural circuitry and identifying networks of neurons that underlie perception, movement and cognition. In this review, we focus on the use of stimulation in behaving primates, an experimental system that permits causal inferences to be made about the effect of stimulation-induced activity on the resulting behaviour or neural signals elsewhere in the brain.

Dissociation of Response Variability from Firing Rate Effects in Frontal Eye Field Neurons during Visual Stimulation, Working Memory, and Attention

Recent studies suggest that trial-to-trial variability of neuronal spiking responses may provide important information about behavioral state. Observed changes in variability during sensory stimulation, attention, motor preparation, and visual discrimination suggest that variability may reflect the engagement of neurons in a behavioral task. We examined changes in spiking variability of frontal eye field (FEF) neurons in a change detection task requiring monkeys to remember a visually cued location and direct attention to that location while ignoring distracters elsewhere. In this task, the firing rates (FRs) of FEF neurons not only continuously reflect the location of the remembered cue and select targets, but also predict detection performance on a trial-by-trial basis. Changes in FEF response variability, as measured by the Fano factor (FF), showed clear dissociations from changes in FR. The FF declined in response to visual stimulation at all tested locations, even in the opposite hemifield, indicating much broader spatial tuning of the FF compared with the FR. Furthermore, despite robust spatial modulation of the FR throughout all epochs of the task, spatial tuning of the FF did not persist throughout the delay period, nor did it show attentional modulation. These results indicate that changes in variability, at least in the FEF, are most effectively driven by visual stimulation, while behavioral engagement is not sufficient. Instead, changes in variability may reflect shifts in the balance between feedforward and recurrent sources of excitatory drive.

Position effect on apparent helical propensities in the C-peptide helix

A search has been made for position effects on apparent helix propensities when another amino acid is substituted for alanine in the C-peptide helix of ribonuclease A. Three internal alanine residues (Ala4, Ala5, Ala6) are used as sites for substitution. Five amino acids, Glu, His, Arg, Lys and Phe, are substituted singly in individual peptides at each of these three positions, and the pH profiles of helix content for the substituted peptides have been determined. The effect of using an acetyl or a succinyl amino-terminal-blocking group has also been determined for each substitution. A strong position effect is found at Ala5: the helix content of the substituted peptide is significantly higher for substitution at position 5 than at positions 4 or 6 in almost all cases. The reason for the position 5 effect is unknown. The results also show that electrostatic interactions often influence substitution experiments, and they provide data on the variability of substitution experiments made with a natural sequence peptide.