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

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).

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

Journal of Neurophysiology ◽

10.1152/jn.00249.2001 ◽

2002 ◽

Vol 87 (1) ◽

pp. 567-588 ◽

Cited By ~ 105

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.

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

Journal of Neurophysiology ◽

10.1152/jn.1998.80.4.2200 ◽

1998 ◽

Vol 80 (4) ◽

pp. 2200-2205 ◽

Cited By ~ 36

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.

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

Journal of Neurophysiology ◽

10.1152/jn.01120.2005 ◽

2006 ◽

Vol 95 (6) ◽

pp. 3923-3927 ◽

Cited By ~ 61

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.

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Neuronal Activity Throughout the Primate Mediodorsal Nucleus of the Thalamus During Oculomotor Delayed-Responses. II. Activity Encoding Visual Versus Motor Signal

Journal of Neurophysiology ◽

10.1152/jn.00995.2003 ◽

2004 ◽

Vol 92 (3) ◽

pp. 1756-1769 ◽

Cited By ~ 33

Author(s):

Yumiko Watanabe ◽

Shintaro Funahashi

Keyword(s):

Working Memory ◽

Information Processing ◽

Spatial Working Memory ◽

Memory Task ◽

Neuron Activity ◽

Delayed Response ◽

Related Activity ◽

Response Period ◽

Motor Information ◽

Saccade Direction

We collected single-neuron activity from the mediodorsal (MD) nucleus of the thalamus, examined the information that was represented by task-related activity during performance of a spatial working memory task, and compared the present results with those obtained in the dorsolateral prefrontal cortex (DLPFC). We used two oculomotor delayed-response (ODR) tasks. In the ordinary ODR task, monkeys were required to make a memory-guided saccade to the location where a visual cue had been presented 3 s previously, whereas in the rotatory ODR task, they were required to make a memory-guided saccade 90° clockwise from the cue direction. By comparing the best directions of the same task-related activity between the two tasks, we could determine whether this activity represented the cue location or the saccade direction. All cue-period activity represented the cue location. In contrast, 56% of delay-period activity represented the cue location and 41% represented the saccade direction. Almost all response-period activity represented the saccade direction. These results indicate that task-related MD activity represents either visual or motor information, suggesting that the MD participates in sensory-to-motor information processing. However, a greater proportion of delay- and response-period activities represented the saccade direction in the MD than in the DLPFC, indicating that more MD neurons participate in prospective information processing than DLPFC neurons. These results suggest that although functional interactions between the MD and DLPFC are crucial to cognitive functions such as working memory, there is a difference in how the MD and DLPFC participate in these functions.

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Abnormal brain activity patterns during spatial working memory task in patients with end-stage renal disease on maintenance hemodialysis: a fMRI study

Brain Imaging and Behavior ◽

10.1007/s11682-020-00383-7 ◽

2020 ◽

Author(s):

Jinzhuang Huang ◽

Lei Xie ◽

Ruiwei Guo ◽

Jinhong Wang ◽

Jinquan Lin ◽

...

Keyword(s):

Working Memory ◽

Frontal Cortex ◽

Spatial Working Memory ◽

Brain Activity ◽

Activity Patterns ◽

Parietal Lobule ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients ◽

Back Task

Abstract Hemodialysis (HD) is associated with cognitive impairment in patients with end-stage renal disease (ESRD). However, the neural mechanism of spatial working memory (SWM) impairment in HD-ESRD patients remains unclear. We investigated the abnormal alterations in SWM-associated brain activity patterns in HD-ESRD patients using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) technique during n-back tasks. Twenty-two HD-ESRD patients and 22 well-matched controls underwent an fMRI scan while undergoing a three-load n-back tasks with different difficulty levels. Cognitive and mental states were assessed using a battery of neuropsychologic tests. The HD-ESRD patients exhibited worse memory abilities than controls. Compared with the control group, the HD-ESRD patient group showed lower accuracy and longer response time under the n-back tasks, especially in the 2-back task. The patterns of brain activation changed under different working memory loads in the HD-ESRD patients, showing decreased activity in the right medial frontal gyrus and inferior frontal gyrus under 0-back and 1-back task, while more decreased activation in the bilateral frontal cortex, parietal lobule, anterior/posterior cingulate cortex and insula cortex under 2-back task. With the increase of task difficulty, the activation degree of the frontal and parietal cortex decreased. More importantly, we found that lower activation in frontal cortex and parietal lobule was associated with worse cognitive function in the HD-ESRD patients. These results demonstrate that the abnormal brain activity patterns of frontal cortex and parietal lobule may reflect the neural mediation of SWM impairment.

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

Neuroscience Letters ◽

10.1016/s0304-3940(99)00726-0 ◽

1999 ◽

Vol 275 (1) ◽

pp. 9-12 ◽

Cited By ~ 10

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

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

Journal of Cognitive Neuroscience ◽

10.1162/jocn.1992.4.1.58 ◽

1992 ◽

Vol 4 (1) ◽

pp. 58-68 ◽

Cited By ~ 166

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.

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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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