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

1. This study identified neurons in the rhesus monkey's frontal eye field that projected to oculomotor regions of the pons and characterized the signals sent by these neurons from frontal eye field to pons. 2. In two behaving rhesus monkeys, frontal eye field neurons projecting to the pons were identified via antidromic excitation by a stimulating microelectrode whose tip was centered in or near the omnipause region of the pontine raphe. This stimulation site corresponded to the nucleus raphe interpositus (RIP). In addition, electrical stimulation of the frontal eye field was used to demonstrate the effects of frontal eye field input on neurons in the omnipause region and surrounding paramedian pontine reticular formation (PPRF). 3. Twenty-five corticopontine neurons were identified and characterized. Most frontal eye field neurons projecting to the pons were either movement neurons, firing in association with saccadic eye movements (48%), or foveal neurons responsive to visual stimulation of the fovea combined with activity related to fixation (28%). Corticopontine movement neurons fired before, during, and after saccades made within a restricted movement field. 4. The activity of identified corticopontine neurons was very similar to the activity of neurons antidromically excited from the superior colliculus where 59% had movement related activity, and 22% had foveal and fixation related activity. 5. High-intensity, short-duration electrical stimulation of the frontal eye field caused omnipause neurons to stop firing. The cessation in firing appeared to be immediate, within < or = 5 ms. The time that the omnipause neuron remained quiet depended on the intensity of the cortical stimulus and lasted up to 30 ms after a train of three stimulus pulses lasting a total of 6 ms at an intensity of 1,000 microA. Low-intensity, longer duration electrical stimuli (24 pulses, 75 microA, 70 ms) traditionally used to evoke saccades from the frontal eye field were also followed by a cessation in omnipause neuron firing, but only after a delay of approximately 30 ms. For these stimuli, the omnipause neuron resumed firing when the stimulus was turned off. 6. The same stimuli that caused omnipause neurons to stop firing excited burst neurons in the PPRF. The latency to excitation ranged from 4.2 to 9.8 ms, suggesting that there is at least one additional neuron between frontal eye field neurons and burst neurons in the PPRF. 7. The present study confirms and extends the results of previous work, with the use of retrograde and anterograde tracers, demonstrating direct projections from the frontal eye field to the pons.(ABSTRACT TRUNCATED AT 400 WORDS)

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Two subdivisions of macaque LIP process visual-oculomotor information differently

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1605879113 ◽

2016 ◽

Vol 113 (41) ◽

pp. E6263-E6270 ◽

Cited By ~ 6

Author(s):

Mo Chen ◽

Bing Li ◽

Jing Guang ◽

Linyu Wei ◽

Si Wu ◽

...

Keyword(s):

Visual Stimulation ◽

Field Potential ◽

Frontal Eye Field ◽

Express Saccades ◽

Long Distance ◽

Lateral Intraparietal Cortex ◽

Persistent Memory ◽

Deep Layers ◽

Eye Field ◽

Saccade Task

Although the cerebral cortex is thought to be composed of functionally distinct areas, the actual parcellation of area and assignment of function are still highly controversial. An example is the much-studied lateral intraparietal cortex (LIP). Despite the general agreement that LIP plays an important role in visual-oculomotor transformation, it remains unclear whether the area is primary sensory- or motor-related (the attention-intention debate). Although LIP has been considered as a functionally unitary area, its dorsal (LIPd) and ventral (LIPv) parts differ in local morphology and long-distance connectivity. In particular, LIPv has much stronger connections with two oculomotor centers, the frontal eye field and the deep layers of the superior colliculus, than does LIPd. Such anatomical distinctions imply that compared with LIPd, LIPv might be more involved in oculomotor processing. We tested this hypothesis physiologically with a memory saccade task and a gap saccade task. We found that LIP neurons with persistent memory activities in memory saccade are primarily provoked either by visual stimulation (vision-related) or by both visual and saccadic events (vision-saccade–related) in gap saccade. The distribution changes from predominantly vision-related to predominantly vision-saccade–related as the recording depth increases along the dorsal-ventral dimension. Consistently, the simultaneously recorded local field potential also changes from visual evoked to saccade evoked. Finally, local injection of muscimol (GABA agonist) in LIPv, but not in LIPd, dramatically decreases the proportion of express saccades. With these results, we conclude that LIPd and LIPv are more involved in visual and visual-saccadic processing, respectively.

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Topographic Maps in Human Frontal Cortex Revealed in Memory-Guided Saccade and Spatial Working-Memory Tasks

Journal of Neurophysiology ◽

10.1152/jn.00010.2007 ◽

2007 ◽

Vol 97 (5) ◽

pp. 3494-3507 ◽

Cited By ~ 121

Author(s):

Sabine Kastner ◽

Kevin DeSimone ◽

Christina S. Konen ◽

Sara M. Szczepanski ◽

Kevin S. Weiner ◽

...

Keyword(s):

Working Memory ◽

Frontal Cortex ◽

Spatial Working Memory ◽

Memory Task ◽

Topographic Maps ◽

Button Press ◽

Frontal Eye Field ◽

Topographic Organization ◽

Human Frontal Cortex ◽

Eye Field

We used fMRI at 3 Tesla and improved spatial resolution (2 × 2 × 2 mm3) to investigate topographic organization in human frontal cortex using memory-guided response tasks performed at 8 or 12 peripheral locations arranged clockwise around a central fixation point. The tasks required the location of a peripheral target to be remembered for several seconds after which the subjects either made a saccade to the remembered location (memory-guided saccade task) or judged whether a test stimulus appeared in the same or a slightly different location by button press (spatial working-memory task). With these tasks, we found two topographic maps in each hemisphere, one in the superior branch of precentral cortex and caudalmost part of the superior frontal sulcus, in the region of the human frontal eye field, and a second in the inferior branch of precentral cortex and caudalmost part of the inferior frontal sulcus, both of which greatly overlapped with activations evoked by visually guided saccades. In each map, activated voxels coded for saccade directions and memorized locations predominantly in the contralateral hemifield with neighboring saccade directions and memorized locations represented in adjacent locations of the map. Particular saccade directions or memorized locations were often represented in multiple locations of the map. The topographic activation patterns showed individual variability from subject to subject but were reproducible within subjects. Notably, only saccade-related activation, but no topographic organization, was found in the region of the human supplementary eye field in dorsomedial prefrontal cortex. Together these results show that topographic organization can be revealed outside sensory cortical areas using more complex behavioral tasks.

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Difficulty of Visual Search Modulates Neuronal Interactions and Response Variability in the Frontal Eye Field

Journal of Neurophysiology ◽

10.1152/jn.00522.2007 ◽

2007 ◽

Vol 98 (5) ◽

pp. 2580-2587 ◽

Cited By ~ 13

Author(s):

Jeremiah Y. Cohen ◽

Pierre Pouget ◽

Geoffrey F. Woodman ◽

Chenchal R. Subraveti ◽

Jeffrey D. Schall ◽

...

Keyword(s):

Multivariate Analysis ◽

Visual Search ◽

Search Task ◽

Response Variability ◽

Frontal Eye Field ◽

Search Tasks ◽

Saccade Onset ◽

Neuronal Interactions ◽

Eye Field ◽

Spiking Activity

The frontal eye field (FEF) is involved in selecting visual targets for eye movements. To understand how populations of FEF neurons interact during target selection, we recorded activity from multiple neurons simultaneously while macaques performed two versions of a visual search task. We used a multivariate analysis in a point process statistical framework to estimate the instantaneous firing rate and compare interactions among neurons between tasks. We found that FEF neurons were engaged in more interactions during easier visual search tasks compared with harder search tasks. In particular, eye movement–related neurons were involved in more interactions than visual-related neurons. In addition, our analysis revealed a decrease in the variability of spiking activity in the FEF beginning ∼100 ms before saccade onset. The minimum in response variability occurred ∼20 ms earlier for the easier search task compared with the harder one. This difference is positively correlated with the difference in saccade reaction times for the two tasks. These findings show that a multivariate analysis can provide a measure of neuronal interactions and characterize the spiking activity of FEF neurons in the context of a population of neurons.

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Frontal Eye Field Neurons Orthodromically Activated From the Superior Colliculus

Journal of Neurophysiology ◽

10.1152/jn.1998.80.6.3331 ◽

1998 ◽

Vol 80 (6) ◽

pp. 3331-3335 ◽

Cited By ~ 71

Author(s):

Marc A. Sommer ◽

Robert H. Wurtz

Keyword(s):

Electrical Stimulation ◽

Superior Colliculus ◽

Direct Evidence ◽

Visual Stimulation ◽

Saccadic Eye Movements ◽

Frontal Eye Field ◽

Anatomical Studies ◽

Eye Field ◽

To Receive ◽

Stimulation Of

Sommer, Marc A. and Robert H. Wurtz. Frontal eye field neurons orthodromically activated from the superior colliculus. J. Neurophysiol. 80: 3331–3333, 1998. Anatomical studies have shown that the frontal eye field (FEF) and superior colliculus (SC) of monkeys are reciprocally connected, and a physiological study described the signals sent from the FEF to the SC. Nothing is known, however, about the signals sent from the SC to the FEF. We physiologically identified and characterized FEF neurons that are likely to receive input from the SC. Fifty-two FEF neurons were found that were orthodromically activated by electrical stimulation of the intermediate or deeper layers of the SC. All the neurons that we tested ( n = 34) discharged in response to visual stimulation. One-half also discharged when saccadic eye movements were made. This provides the first direct evidence that the ascending pathway from SC to FEF might carry visual- and saccade-related signals. Our findings support a hypothesis that the SC and the FEF interact bidirectionally during the events leading up to saccade generation.

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Spatial Processing in the Monkey Frontal Eye Field. II. Memory Responses

Journal of Neurophysiology ◽

10.1152/jn.2001.86.5.2344 ◽

2001 ◽

Vol 86 (5) ◽

pp. 2344-2352 ◽

Cited By ~ 101

Author(s):

Marc M. Umeno ◽

Michael E. Goldberg

Keyword(s):

Receptive Field ◽

Visual Stimulation ◽

Spatial Location ◽

Frontal Eye Field ◽

Short Term ◽

Response Latencies ◽

Memory Response ◽

Visual Cells ◽

Field Response ◽

Eye Field

Monkeys and humans can easily make accurate saccades to stimuli that appear and disappear before an intervening saccade to a different location. We used the flashed-stimulus task to study the memory processes that enable this behavior, and we found two different kinds of memory responses under these conditions. In the short-term spatial memory response, the monkey fixated, a stimulus appeared for 50 ms outside the neuron's receptive field, and from 200 to 1,000 ms later the monkey made a saccade that brought the receptive field onto the spatial location of the vanished stimulus. Twenty-eight of 48 visuomovement cells and 21/32 visual cells responded significantly under these circumstances even though they did not discharge when the monkey made the same saccade without the stimulus present or when the stimulus appeared and the monkey did not make a saccade that brought its spatial location into the receptive field. Response latencies ranged from 48 ms before the beginning of the saccade (predictive responses) to 272 ms after the beginning of the saccade. After the monkey made a series of 16 saccades that brought a stimulus into the receptive field, 21 neurons demonstrated a longer term, intertrial memory response: they discharged even on trials in which no stimulus appeared at all. This intertrial memory response was usually much weaker than the within-trial memory response, and it often lasted for over 20 trials. We suggest that the frontal eye field maintains a spatially accurate representation of the visual world that is not dependent on constant or continuous visual stimulation, and can last for several minutes.

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Frontal Eye Field Sends Delay Activity Related to Movement, Memory, and Vision to the Superior Colliculus

Journal of Neurophysiology ◽

10.1152/jn.2001.85.4.1673 ◽

2001 ◽

Vol 85 (4) ◽

pp. 1673-1685 ◽

Cited By ~ 105

Author(s):

Marc A. Sommer ◽

Robert H. Wurtz

Keyword(s):

Prefrontal Cortex ◽

Superior Colliculus ◽

Visual Memory ◽

Target Location ◽

Visual Stimulation ◽

Visual Space ◽

Frontal Eye Field ◽

Visual Response ◽

Eye Field ◽

Output Neurons

Many neurons within prefrontal cortex exhibit a tonic discharge between visual stimulation and motor response. This delay activity may contribute to movement, memory, and vision. We studied delay activity sent from the frontal eye field (FEF) in prefrontal cortex to the superior colliculus (SC). We evaluated whether this efferent delay activity was related to movement, memory, or vision, to establish its possible functions. Using antidromic stimulation, we identified 66 FEF neurons projecting to the SC and we recorded from them while monkeys performed a Go/Nogo task. Early in every trial, a monkey was instructed as to whether it would have to make a saccade (Go) or not (Nogo) to a target location, which permitted identification of delay activity related to movement. In half of the trials (memory trials), the target disappeared, which permitted identification of delay activity related to memory. In the remaining trials (visual trials), the target remained visible, which permitted identification of delay activity related to vision. We found that 77% (51/66) of the FEF output neurons had delay activity. In 53% (27/51) of these neurons, delay activity was modulated by Go/Nogo instructions. The modulation preceded saccades made into only part of the visual field, indicating that the modulation was movement-related. In some neurons, delay activity was modulated by Go/Nogo instructions in both memory and visual trials and seemed to represent where to move in general. In other neurons, delay activity was modulated by Go/Nogo instructions only in memory trials, which suggested that it was a correlate of working memory, or only in visual trials, which suggested that it was a correlate of visual attention. In 47% (24/51) of FEF output neurons, delay activity was unaffected by Go/Nogo instructions, which indicated that the activity was related to the visual stimulus. In some of these neurons, delay activity occurred in both memory and visual trials and seemed to represent a coordinate in visual space. In others, delay activity occurred only in memory trials and seemed to represent transient visual memory. In the remainder, delay activity occurred only in visual trials and seemed to be a tonic visual response. In conclusion, the FEF sends diverse delay activity signals related to movement, memory, and vision to the SC, where the signals may be used for saccade generation. Downstream transmission of various delay activity signals may be an important, general way in which the prefrontal cortex contributes to the control of movement.

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Differences in Noradrenaline Receptor Expression Across Different Neuronal Subtypes in Macaque Frontal Eye Field

Frontiers in Neuroanatomy ◽

10.3389/fnana.2020.574130 ◽

2020 ◽

Vol 14 ◽

Author(s):

Max Lee ◽

Adrienne Mueller ◽

Tirin Moore

Keyword(s):

Working Memory ◽

Long Range ◽

Pyramidal Neuron ◽

Pyramidal Neurons ◽

Inhibitory Interneuron ◽

Receptor Expression ◽

Frontal Eye Field ◽

Receptor Subtypes ◽

Visual Spatial ◽

Eye Field

Cognitive functions such as attention and working memory are modulated by noradrenaline receptors in the prefrontal cortex (PFC). The frontal eye field (FEF) has been shown to play an important role in visual spatial attention. However, little is known about the underlying circuitry. The aim of this study was to characterize the expression of noradrenaline receptors on different pyramidal neuron and inhibitory interneuron subtypes in macaque FEF. Using immunofluorescence, we found broad expression of noradrenaline receptors across all layers of the FEF. Differences in the expression of different noradrenaline receptors were observed across different inhibitory interneuron subtypes. No significant differences were observed in the expression of noradrenaline receptors across different pyramidal neuron subtypes. However, we found that putative long-range projecting pyramidal neurons expressed all noradrenaline receptor subtypes at a much higher proportion than any of the other neuronal subtypes. Nearly all long-range projecting pyramidal neurons expressed all types of noradrenaline receptor, suggesting that there is no receptor-specific machinery acting on these long-range projecting pyramidal neurons. This pattern of expression among long-range projecting pyramidal neurons suggests a mechanism by which noradrenergic modulation of FEF activity influences attention and working memory.

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Modulation of shifting receptive field activity in frontal eye field by visual salience

Journal of Neurophysiology ◽

10.1152/jn.01054.2010 ◽

2011 ◽

Vol 106 (3) ◽

pp. 1179-1190 ◽

Cited By ~ 22

Author(s):

Wilsaan M. Joiner ◽

James Cavanaugh ◽

Robert H. Wurtz

Keyword(s):

Visual Field ◽

Receptive Field ◽

Visual Stimulation ◽

Receptive Fields ◽

Spatial Location ◽

Substantial Contribution ◽

Frontal Eye Field ◽

Central Visual Field ◽

Eye Field ◽

The Stability

In the monkey frontal eye field (FEF), the sensitivity of some neurons to visual stimulation changes just before a saccade. Sensitivity shifts from the spatial location of its current receptive field (RF) to the location of that field after the saccade is completed (the future field, FF). These shifting RFs are thought to contribute to the stability of visual perception across saccades, and in this study we investigated whether the salience of the FF stimulus alters the magnitude of FF activity. We reduced the salience of the usually single flashed stimulus by adding other visual stimuli. We isolated 171 neurons in the FEF of 2 monkeys and did experiments on 50 that had FF activity. In 30% of these, that activity was higher before salience was reduced by adding stimuli. The mean magnitude reduction was 16%. We then determined whether the shifting RFs were more frequent in the central visual field, which would be expected if vision across saccades were only stabilized for the visual field near the fovea. We found no evidence of any skewing of the frequency of shifting receptive fields (or the effects of salience) toward the central visual field. We conclude that the salience of the FF stimulus makes a substantial contribution to the magnitude of FF activity in FEF. In so far as FF activity contributes to visual stability, the salience of the stimulus is probably more important than the region of the visual field in which it falls for determining which objects remain perceptually stable across saccades.

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Functional properties of corticotectal neurons in the monkey's frontal eye field

Journal of Neurophysiology ◽

10.1152/jn.1987.58.6.1387 ◽

1987 ◽

Vol 58 (6) ◽

pp. 1387-1419 ◽

Cited By ~ 281

Author(s):

M. A. Segraves ◽

M. E. Goldberg

Keyword(s):

Superior Colliculus ◽

Visual Stimulation ◽

Visual Stimuli ◽

Frontal Eye Field ◽

Related Activity ◽

Minimum Threshold ◽

Strong Activity ◽

Visual Component ◽

Behavioral Tasks ◽

Eye Field

1. We examined the activity of identified corticotectal neurons in the frontal eye field of awake behaving rhesus monkeys (Macaca mulatta). Corticotectal neurons were antidromically excited using biphasic current pulses passed through monopolar microelectrodes within the superior colliculus. The activity of single corticotectal neurons was studied while the monkey performed behavioral tasks designed to test the relation of the neuron's discharge to visual and oculomotor events. 2. Fifty-one frontal eye field corticotectal neurons were examined in two monkeys. Current thresholds for antidromic excitation ranged from 6 to 1,200 microA, with a mean of 330 microA. Antidromic latencies ranged from 1.2 to 6.0 ms, with a mean of 2.25 ms. 3. Fifty-three percent of the identified corticotectal neurons were classified as having movement-related activity. They had little or no response to visual stimuli, but very strong activity before both visually guided and memory-guided saccades. An additional 6% of corticotectal neurons had visuomovement activity, combining both a visual- and a saccade-related response. In each case, visuomovement neurons antidromically excited from the superior colliculus had movement-related activity, which was much stronger than the visual component of their response. 4. Twenty-two percent of the corticotectal neurons were primarily responsive to visual stimulation of the fovea. These included both neurons responding to the onset and neurons responding to the disappearance of a light flashed on the fovea. 5. The remaining 20% of the corticotectal neurons were a heterogeneous group whose activity could not be classified as movement, visuomovement or foveal. Their responses included postsaccadic, anticipatory, and reward-related activity, as well as activity modulated during certain directions of smooth-pursuit eye movements. One neuron was unresponsive during all of the behavioral tasks used. There were no corticotectal neurons that could be classified as primarily responsive to peripheral visual stimuli. 6. Histological reconstructions of electrode penetrations localized corticotectal neurons to layer V of the frontal eye field. For 22 corticotectal neurons tested, each had its minimum threshold for antidromic excitation within the superior colliculus, as judged by either histological confirmation, or surrounding neuronal responses recorded through the stimulation microelectrode. The majority of these neurons had minimum threshold sites within the intermediate layers, a few minimum threshold sites were located within the superficial or deep collicular layers.(ABSTRACT TRUNCATED AT 400 WORDS)

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