Selection and Maintenance of Saccade Goals in the Human Frontal Eye Fields

2006 ◽  
Vol 95 (6) ◽  
pp. 3923-3927 ◽  
Author(s):  
Clayton E. Curtis ◽  
Mark D'Esposito
Keyword(s):  
Working Memory ◽  
Spatial Working Memory ◽  
Response Selection ◽  
Delay Period ◽  
Delayed Response ◽  
Frontal Eye Fields ◽  
Motor Processing ◽  
Visual Encoding ◽  
Prospective Coding ◽  
Response Task

In a delayed-response task, response selection marks an important transition from sensory to motor processing. Using event-related functional magnetic resonance imaging, we imaged the human brain during performance of a novel delayed-saccade task that isolated response selection from visual encoding and motor execution. The frontal eye fields (FEFs) and intraparietal sulcus (IPS) both showed robust contra-lateralized activity time-locked to response selection. Moreover, response selection affected delay-period activity differently in these regions; it persisted throughout the memory delay period following response selection in the FEF but not IPS. Our results indicate that the FEF and IPS both make important but distinct contributions to spatial working memory. The mechanism that the FEF uses to support spatial working memory is tied to the selection and prospective coding of saccade goals, whereas the role of the IPS may be more tied to retrospective coding of sensory representations.

Attenuation of Delay-Period Activity of Monkey Prefrontal Neurons by an α2-Adrenergic Antagonist During an Oculomotor Delayed-Response Task

1998 ◽  
Vol 80 (4) ◽  
pp. 2200-2205 ◽  
Author(s):  
T. Sawaguchi
Keyword(s):  
Working Memory ◽  
Target Location ◽  
Spatial Working Memory ◽  
Delay Period ◽  
Delayed Response ◽  
Peripheral Cues ◽  
Adrenergic Antagonist ◽  
Neuronal Processes ◽  
Response Task ◽  
Delayed Response Task

Sawaguchi, T. Attenuation of delay-period activity of monkey prefrontal neurons by an α2-adrenergic antagonist during an oculomotor delayed-response task. J. Neurophysiol. 80: 2200–2205, 1998. To examine the role of norepinephrine receptors in spatial working memory processes mediated by the prefrontal cortex (PFC), noradrenergic antagonists (yohimbine for α2, prazosin for α1, and propranolol for β receptors) were applied iontophoretically to neurons of the dorsolateral PFC in rhesus monkeys that performed an oculomotor delayed-response (ODR) task. The ODR task was initiated when the monkeys fixated on a central spot on a computer monitor and consisted of fixation (1 s), cue (1 of 4 peripheral cues, 0.5 s), delay (fixation cue only, 4 s), and go periods. In the go period, the subject made a memory-guided saccade to the target location that was cued before the delay period. I focused on 49 neurons that showed directional delay-period activity, i.e., a sustained increase in activity during the delay period, the magnitude of which varied significantly with the memorized target location. Iontophoretic (usually 50 nA) application of yohimbine, but not prazosin or propranolol, significantly decreased the activities of most of the neurons with directional delay-period activity ( n = 41/49, 81%). Furthermore, yohimbine attenuated the sharpness of tuning, examined by a tuning index, of delay-period activity and had a greater attenuating effect on delay-period activity than on background activity. These findings suggest that the activation of α2-adrenergic receptors in the dorsolateral PFC plays a modulatory role in neuronal processes for visuospatial working memory.

Spatial working memory assessment by a visual-manual delayed response task: a controlled study in schizophrenia

1999 ◽  
Vol 275 (1) ◽  
pp. 9-12 ◽  
Author(s):  
P Stratta ◽  
E Daneluzzo ◽  
P Prosperini ◽  
M Bustini ◽  
M.G Marinangeli ◽  
...  
Keyword(s):  
Working Memory ◽  
Spatial Working Memory ◽  
Controlled Study ◽  
Delayed Response ◽  
Memory Assessment ◽  
Response Task ◽  
Delayed Response Task

Prefrontal Task-Related Activity Representing Visual Cue Location or Saccade Direction in Spatial Working Memory Tasks

2002 ◽  
Vol 87 (1) ◽  
pp. 567-588 ◽  
Author(s):  
Kazuyoshi Takeda ◽  
Shintaro Funahashi
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Spatial Working Memory ◽  
Delay Period ◽  
Neuron Activity ◽  
Delayed Response ◽  
Related Activity ◽  
Visual Cue ◽  
Response Period ◽  
Dorsolateral Prefrontal

To examine what kind of information task-related activity encodes during spatial working memory processes, we analyzed single-neuron activity in the prefrontal cortex while two monkeys performed two different oculomotor delayed-response (ODR) tasks. In the standard ODR task, monkeys were required to make a saccade to the cue location after a 3-s delay, whereas in the rotatory ODR (R-ODR) task, they were required to make a saccade 90° clockwise from the cue location after the 3-s delay. By comparing the same task-related activities in these two tasks, we could determine whether such activities encoded the location of the visual cue or the direction of the saccade. One hundred twenty one neurons exhibited task-related activity in relation to at least one task event in both tasks. Among them, 41 neurons exhibited directional cue-period activity, most of which encoded the location of the visual cue. Among 56 neurons with directional delay-period activity, 86% encoded the location of the visual cue, whereas 13% encoded the direction of the saccade. Among 57 neurons with directional response-period activity, 58% encoded the direction of the saccade, whereas 35% encoded the location of the visual cue. Most neurons whose response-period activity encoded the location of the visual cue also exhibited directional delay-period activity that encoded the location of the visual cue as well. The best directions of these two activities were identical, and most of these response-period activities were postsaccadic. Therefore this postsaccadic activity can be considered a signal to terminate unnecessary delay-period activity. Population histograms encoding the location of the visual cue showed tonic sustained activation during the delay period. However, population histograms encoding the direction of the saccade showed a gradual increase in activation during the delay period. These results indicate that the transformation from visual input to motor output occurs in the dorsolateral prefrontal cortex. The analysis using population histograms suggests that this transformation occurs gradually during the delay period.

Activity in Human Frontal Cortex Associated with Spatial Working Memory and Saccadic Behavior

2000 ◽  
Vol 12 (supplement 2) ◽  
pp. 2-14 ◽  
Author(s):  
Bradley R. Postle ◽  
Jeffrey S. Berger ◽  
Alexander M. Taich ◽  
Mark D'Esposito
Keyword(s):  
Working Memory ◽  
Frontal Cortex ◽  
Signal Intensity ◽  
Spatial Working Memory ◽  
Delay Period ◽  
Delayed Response ◽  
Related Activity ◽  
Memory Condition ◽  
Fmri Signal ◽  
Spatio Temporal

We examined, with event-related fMRI, two hypotheses about the organization of human working memory function in frontal cortex: (1) that a region immediately anterior to the frontal eye fields (FEF) (superior frontal cortex, SFC) is specialized for spatial working memory (Courtney, et al., 1998); and (2) that dorsolateral prefrontal cortex (PFC) plays a privileged role in the manipulation of spatial stimuli held in working memory (Owen, et al., 1996; Petrides 1994). Our delayed-response task featured 2-D arrays of irregularly arranged squares that were highlighted serially in a random sequence. The Forward Memory condition required maintenance of the spatio-temporal sequence, the Manipulate Memory condition required reordering this sequence into a new spatially defined order, the Guided Saccade condition required saccades to highlighted squares in the array, but no memory, and the Free Saccade condition required self-paced, horizontal saccades. The comparison of fMRI signal intensity associated with 2-D saccade generation (Guided Saccades) versus fMRI signal intensity associated with the delay period of the working memorials condition revealed no evidence for greater working memory-related activity than saccade-related activity in SFC in any individual subject, nor at the level of the group, and greater 2-D saccade than delay-period activity in three of five subjects. These results fail to support the hypothesis that spatial working memory-related activity is represented preferentially in a region of SFC anterior to the FEF (Courtney, et al., 1998). The comparison of maintenance versus manipulation of spatio-temporal information in working memory revealed significantly greater activity associated with the latter in dorsolateral PFC, but not in ventrolateral PFC or in SFC. These results suggest that the delay-related function of SFC is limited to the maintenance of spatial information, and that this region does not support the nonmnemonic executive control functions supported by dorsolateral PFC. These results also indicate that the preferential recruitment of dorsolateral PFC for the manipulation of information held in working memory applies to tasks employing spatial stimuli, as well as to tasks employing verbal stimuli (D'Esposito, et al., 1999); Petrides et al., 1993; Postle et al., 1999).

scholarly journals Parallel processing of working memory and temporal information by distinct types of cortical projection neurons

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jung Won Bae ◽  
Huijeong Jeong ◽  
Young Ju Yoon ◽  
Chan Mee Bae ◽  
Hyeonsu Lee ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Delay Period ◽  
Temporal Information ◽  
Projection Neurons ◽  
Delayed Response ◽  
Subcortical Structures ◽  
Cortical Projection ◽  
Different Types ◽  
Response Task

AbstractIt is unclear how different types of cortical projection neurons work together to support diverse cortical functions. We examined the discharge characteristics and inactivation effects of intratelencephalic (IT) and pyramidal tract (PT) neurons—two major types of cortical excitatory neurons that project to cortical and subcortical structures, respectively—in the deep layer of the medial prefrontal cortex in mice performing a delayed response task. We found stronger target-dependent firing of IT than PT neurons during the delay period. We also found the inactivation of IT neurons, but not PT neurons, impairs behavioral performance. In contrast, PT neurons carry more temporal information than IT neurons during the delay period. Our results indicate a division of labor between IT and PT projection neurons in the prefrontal cortex for the maintenance of working memory and for tracking the passage of time, respectively.

Prefrontal Cortical Representation of Visuospatial Working Memory in Monkeys Examined by Local Inactivation With Muscimol

2001 ◽  
Vol 86 (4) ◽  
pp. 2041-2053 ◽  
Author(s):  
Toshiyuki Sawaguchi ◽  
Michiyo Iba
Keyword(s):  
Working Memory ◽  
Functional Organization ◽  
Visual Fields ◽  
Local Injection ◽  
Delayed Response ◽  
Visually Guided ◽  
Visuospatial Working Memory ◽  
Prefrontal Cortical ◽  
Response Task ◽  
Spatial Locations

In primates, dorsolateral areas of the prefrontal cortex (PFC) play a major role in visuospatial working memory. To examine the functional organization of the PFC for representing visuospatial working memory, we produced reversible local inactivation, with the local injection of muscimol (5 μg, 1 μl), at various sites ( n = 100) in the dorsolateral PFC of monkeys and observed the behavioral consequences in an oculomotor delayed-response task that required memory-guided saccades for locations throughout both visual fields. At 82 sites, the local injection of muscimol induced deficits in memory-guided saccades to a few specific, usually contralateral, target locations that varied with the location of the injection site. Such deficits depended on the delay length, and longer delays were associated with larger deficits in memory-guided saccades. The injection sites and affected spatial locations of the target showed a gross topographical relationship. No deficits appeared for a control task in which the subject was required to make a visually guided saccade to a visible target. These findings suggest that a specific site in the dorsolateral PFC is responsible for the working memory process for a specific visuospatial coordinate to guide goal-directed behavior. Further, memoranda for specific visuospatial coordinates appear to be represented in a topographical memory mapwithin the dorsolateral PFC to represent visuospatial working memory processes.

Facilitation of Working Memory in Humans by a D2 Dopamine Receptor Agonist

1992 ◽  
Vol 4 (1) ◽  
pp. 58-68 ◽  
Author(s):  
Monica Luciana ◽  
Richard A. Depue ◽  
Paul Arbisi ◽  
Arthur Leon
Keyword(s):  
Working Memory ◽  
Receptor Agonist ◽  
Spatial Working Memory ◽  
Receptor Activation ◽  
Facilitatory Effect ◽  
Delayed Response ◽  
General Role ◽  
Da Receptors ◽  
Nonspecific Effects ◽  
Response Performance

Recent studies on the neurobiology of cognition have focused on the ability of the prefrontal cortex (PFC) to support processes of working memory, i.e, mnemonic processes by which information relevant for a correct response is temporarily maintained to be reevaluated or updated on a trial-by-trial basis. Of most recent interest is the role played by dopamine (DA) in spatial working memory processes of the principal sulcal region of the PFC. Although D1 DA receptors appear to modulate these mnemonic processes in monkeys, several lines of research suggest that D2 DA receptors could also be relevant to cognitive functions. Therefore, we assessed the effects of a specific D2 receptor agonist (bromocriptine) and placebo on visuospatial delayed response performance in human subjects. During delay periods of 0 or 8 sec, subjects were required to remember the spatial location of rapidly presented visual cues displayed in peripheral vision within a 360° circumference. The extent to which D2 receptor activation by bromocriptine facilitated working memory in the 8–sec delay condition relative to placebo performance was assessed. As a means of providing validation of bromocriptine's D2 receptor effect, maximum inhibition of prolactin (PRL) secretion, which is inhibited specifically by activation of D2 receptor sites, was determined. Additionally, tasks having no working memory component were administered to rule out nonspecific effects of bromocriptine on sensory, arousal, attentional, and motor factors. Results demonstrated a significant facilitatory effect of bromocriptine on spatial delayed response performance (i.e., 8–sec delay performance). Results could not be explained by nonspecific effects of bromocriptine. Thus, findings of this study suggest that spatial working memory is facilitated by D2 receptor activation. The role that DA may play in human cognitive processes is discussed within the larger theoretical framework of DA's general role in the facilitation of goal-directed behavior. In the case of cognition, DA may facilitate processes that serve to guide motivated behavior through complex environments.

Temporally Irregular Mnemonic Persistent Activity in Prefrontal Neurons of Monkeys During a Delayed Response Task

2003 ◽  
Vol 90 (5) ◽  
pp. 3441-3454 ◽  
Author(s):  
Albert Compte, ◽  
Christos Constantinidis ◽  
Jesper Tegnér ◽  
Sridhar Raghavachari ◽  
Matthew V. Chafee ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Power Spectrum ◽  
Spike Train ◽  
Temporal Structure ◽  
Spike Trains ◽  
Delay Period ◽  
Delayed Response ◽  
Persistent Activity ◽  
Response Task ◽  
Delayed Response Task

An important question in neuroscience is whether and how temporal patterns and fluctuations in neuronal spike trains contribute to information processing in the cortex. We have addressed this issue in the memory-related circuits of the prefrontal cortex by analyzing spike trains from a database of 229 neurons recorded in the dorsolateral prefrontal cortex of 4 macaque monkeys during the performance of an oculomotor delayed-response task. For each task epoch, we have estimated their power spectrum together with interspike interval histograms and autocorrelograms. We find that 1) the properties of most (about 60%) neurons approximated the characteristics of a Poisson process. For about 25% of cells, with characteristics typical of interneurons, the power spectrum showed a trough at low frequencies (<20 Hz) and the autocorrelogram a dip near zero time lag. About 15% of neurons had a peak at <20 Hz in the power spectrum, associated with the burstiness of the spike train; 2) a small but significant task dependency of spike-train temporal structure: delay responses to preferred locations were characterized not only by elevated firing, but also by suppressed power at low (<20 Hz) frequencies; and 3) the variability of interspike intervals is typically higher during the mnemonic delay period than during the fixation period, regardless of the remembered cue. The high irregularity of neural persistent activity during the delay period is likely to be a characteristic signature of recurrent prefrontal network dynamics underlying working memory.

scholarly journals A theory of working memory without consciousness or sustained activity

2016 ◽  
Author(s):  
Darinka Trübutschek ◽  
Sébastien Marti ◽  
Andrés Ojeda ◽  
Jean-Rémi King ◽  
Yuanyuan Mi ◽  
...  
Keyword(s):  
Working Memory ◽  
Visual Masking ◽  
Target Location ◽  
Chance Level ◽  
Delayed Response ◽  
Conscious Perception ◽  
Neural Firing ◽  
Beta Band ◽  
Sustained Activity ◽  
Response Task

AbstractWorking memory and conscious perception are thought to share similar brain mechanisms, yet recent reports of non-conscious working memory challenge this view. Combining visual masking with magnetoencephalography, we demonstrate the reality of non-conscious working memory and dissect its neural mechanisms. In a spatial delayed-response task, participants reported the location of a subjectively unseen target above chance-level after a long delay. Conscious perception and conscious working memory were characterized by similar signatures: a sustained desynchronization in the alpha/beta band over frontal cortex, and a decodable representation of target location in posterior sensors. During non-conscious working memory, such activity vanished. Our findings contradict models that identify working memory with sustained neural firing, but are compatible with recent proposals of ‘activity-silent’ working memory. We present a theoretical framework and simulations showing how slowly decaying synaptic changes allow cell assemblies to go dormant during the delay, yet be retrieved above chance-level after several seconds.

scholarly journals Chemogenetic actuator drugs impair prefrontal cortex-dependent working memory in rhesus monkeys

2019 ◽  
Author(s):  
Nicholas A. Upright ◽  
Mark G. Baxter
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Rhesus Monkeys ◽  
Memory Performance ◽  
Memory Function ◽  
Muscarinic Acetylcholine Receptor ◽  
Designer Drugs ◽  
Delayed Response ◽  
Response Task ◽  
Delayed Response Task

AbstractThe most common chemogenetic neuromodulatory system, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), uses a non-endogenous actuator ligand to activate a modified muscarinic acetylcholine receptor that is no longer sensitive to acetylcholine. It is crucial in studies using these systems to test the potential effects of DREADD actuators prior to any DREADD transduction, so that effects of DREADDs can be attributed to the chemogenetic system rather than the actuator drug. We investigated working memory performance after injections of three DREADD agonists, clozapine, olanzapine, and deschloroclozapine, in male rhesus monkeys tested in a spatial delayed response task. Performance at 0.1 mg/kg clozapine and 0.1 mg/kg deschloroclozapine did not differ from mean performance after vehicle in any of the four subjects. Administration of 0.2 mg/kg clozapine impaired working memory function in three of the four monkeys. Two monkeys were impaired after administration of 0.1 mg/kg olanzapine and two monkeys were impaired after the 0.3 mg/kg dose of deschloroclozapine. We speculate that the unique neuropharmacology of prefrontal cortex function makes the primate prefrontal cortex especially vulnerable to off-target effects of DREADD actuator drugs with affinity for endogenous monoaminergic receptor systems. These findings underscore the importance of within-subject controls for DREADD actuator drugs to confirm that effects following DREADD receptor transduction are not due to the actuator drug itself, as well as validating the behavioral pharmacology of DREADD actuator drugs in the specific tasks under study.Significance StatementChemogenetic technologies, such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), allow for precise and remote manipulation of neuronal circuits. In the present study, we tested monkeys in a spatial delayed response task after injections of three actuator drugs – clozapine, olanzapine, and deschloroclozapine. We found that monkeys showed significant working memory impairments after 0.2 mg/kg clozapine, 0.1 mg/kg olanzapine, and 0.3 mg/kg deschloroclozapine compared to vehicle performance. In monkeys that showed impairments, these deficits were particularly apparent at longer delay periods. It is imperative to validate the drugs and dosages in the particular behavioral test to ensure any behavior after DREADD transduction can be attributed to activation of the receptors and not administration of the actuator drug itself.

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