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.

scholarly journals Effects of Memory Load and Distraction on Performance and Event-Related Slow Potentials in a Visuospatial Working Memory Task

1997 ◽  
Vol 9 (6) ◽  
pp. 743-757 ◽  
Author(s):  
Gina M. Geffen ◽  
Margaret J. Wright ◽  
Heather J. Green ◽  
Nicole A. Gillespie ◽  
David C. Smyth ◽  
...  
Keyword(s):  
Working Memory ◽  
Memory Load ◽  
Brain Activity ◽  
Memory Task ◽  
Delayed Response ◽  
Visuospatial Working Memory ◽  
Computer Screen ◽  
Slow Potentials ◽  
The Difference ◽  
Response Task

Brain electrical activity related to working memory was recorded at 15 scalp electrodes during a visuospatial delayed response task. Participants (N = 18) touched the remembered position of a target on a computer screen after either a 1 or 8 sec delay. These memory trials were compared to sensory trials in which the target remained present throughout the delay and response periods. Distractor stimuli identical to the target were briefly presented during the delay on 30% of trials. Responses were less accurate in memory than sensory trials, especially after the long delay. During the delay slow potentials developed that were significantly more negative in memory than sensory trials. The difference between memory and sensory trials was greater at anterior than posterior electrodes. On trials with distractors, the slow potentials generated by memory trials showed further enhancement of negativity, whereas there were minimal effects on accuracy of performance. The results provide evidence that engagement of visuospatial working memory generates slow wave negativity with a timing and distribution consistent with frontal activation. Enhanced brain activity associated with working memory is required to maintain performance in the presence of distraction.

scholarly journals Errors in visuospatial working memory across space and time

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Linjing Jiang ◽  
Hoi-Chung Leung
Keyword(s):  
Working Memory ◽  
Functional Organization ◽  
Human Subjects ◽  
Visual Space ◽  
Visual Pathway ◽  
Visually Guided ◽  
Visuospatial Working Memory ◽  
Space And Time ◽  
Functional Topology ◽  
2D Space

AbstractVisuospatial working memory (VSWM) involves cortical regions along the dorsal visual pathway, which are topographically organized with respect to the visual space. However, it remains unclear how such functional organization may constrain VSWM behavior across space and time. Here, we systematically mapped VSWM performance across the 2-dimensional (2D) space in various retention intervals in human subjects using the memory-guided and visually guided saccade tasks in two experiments. Relative to visually guided saccades, memory-guided saccades showed significant increases in unsystematic errors, or response variability, with increasing target eccentricity (3°–13° of visual angle). Unsystematic errors also increased with increasing delay (1.5–3 s, Experiment 1; 0.5–5 s, Experiment 2), while there was little or no interaction between delay and eccentricity. Continuous bump attractor modeling suggested neurophysiological and functional organization factors in the increasing unsystematic errors in VSWM across space and time. These findings indicate that: (1) VSWM representation may be limited by the functional topology of the visual pathway for the 2D space; (2) Unsystematic errors may reflect accumulated noise from memory maintenance while systematic errors may originate from non-mnemonic processes such as noisy sensorimotor transformation; (3) There may be independent mechanisms supporting the spatial and temporal processing of VSWM.

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

Brain Basis of Developmental Change in Visuospatial Working Memory

2006 ◽  
Vol 18 (7) ◽  
pp. 1045-1058 ◽  
Author(s):  
K. Suzanne Scherf ◽  
John A. Sweeney ◽  
Beatriz Luna
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Cognitive Abilities ◽  
Anterior Insula ◽  
Anterior Cingulate ◽  
Delayed Response ◽  
Visuospatial Working Memory ◽  
Brain Circuitry ◽  
Brain Changes ◽  
Performance Enhancing

Although brain changes associated with the acquisition of cognitive abilities in early childhood involve increasing localized specialization, little is known about the brain changes associated with the refinement of existing cognitive abilities that reach maturity in adolescence. The goal of this study was to investigate developmental changes in functional brain circuitry that support improvements in visuospatial working memory from childhood to adulthood. We tested thirty 8- to 47-year-olds in an oculomotor delayed response task. Developmental transitions in brain circuitry included both quantitative changes in the recruitment of necessary working memory regions and qualitative changes in the specific regions recruited into the functional working memory circuitry. Children recruited limited activation from core working memory regions (dorsal lateral prefrontal cortex [DLPFC] and parietal regions) and relied primarily on ventromedial regions (caudate nucleus and anterior insula). With adolescence emerged a more diffuse network (DLPFC, anterior cingulate, posterior parietal, anterior insula) that included the functional integration of premotor response preparation and execution circuitry. Finally, adults recruited the most specialized network of localized regions together with additional performance-enhancing regions, including left-lateralized DLPFC, ventrolateral prefrontal cortex, and supramarginal gyrus. These results suggest that the maturation of adult-level cognition involves a combination of increasing localization within necessary regions and their integration with performance-enhancing regions.

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.

scholarly journals Dissociative Effects of Methylphenidate in Nonhuman Primates: Trade-offs between Cognitive and Behavioral Performance

2012 ◽  
Vol 24 (6) ◽  
pp. 1371-1381 ◽  
Author(s):  
Abigail Z. Rajala ◽  
Jeffrey B. Henriques ◽  
Luis C. Populin
Keyword(s):  
Working Memory ◽  
Target Location ◽  
Memory Performance ◽  
Memory Task ◽  
Delayed Response ◽  
Impaired Performance ◽  
Healthy Humans ◽  
Trade Offs ◽  
Accuracy And Precision ◽  
Response Task

Low doses of methylphenidate reduce hyperactivity and improve attention in individuals with attention deficit hyperactivity disorder (ADHD) as well as in healthy humans and animals. Despite its extensive use, relatively little is known about its mechanisms of action. This study investigated the effects of methylphenidate on working memory performance, impulsivity, response accuracy and precision, and the ability to stay on task in rhesus monkeys using an oculomotor delayed response task. Methylphenidate affected task performance in an inverted-U manner in all three subjects tested. The improvements resulted from a reduction in premature responses and, importantly, not from improvement in the memory of target location. The length of time subjects participated in each session was also affected dose dependently. However, the dose at which the length of participation was maximally increased significantly impaired performance on the working memory task. This dissociation of effects has implications for the treatment of ADHD, for the nonprescription use of methylphenidate for cognitive enhancement, and for furthering the basic understanding of the neural substrate underlying these processes.

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