| Abstract No.: | C-D3145 |
| Country: | Canada |
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| Title: | BLOCKING NMDA RECEPTOR ACTIVITY LENGTHENS RESPONSE TIME AND IMPROVES RESPONSE ACCURACY DURING VISUAL SEARCH |
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| Authors/Affiliations: | 1 Sarah Kalwarowsky; 1 Wendy Clarence; 1 Michael Warfe; 1 Emiliano Brunamonti; 1 Kelly Shen; 1 Martin Paré*;
1 Queens's University, Kingston, ON, Canada
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| Content: | Objectives: The cognitive control of action entails a decision process by which our brain is thought to temporally integrate the evidence that supports available alternatives before making a choice. This integration process is theoretically validated because neural representations of sensory evidence are inherently variable and thus unreliable at any given instant. Recent modeling work has proposed a candidate cellular mechanism in the reverberatory network dynamics mediated by the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor (Wang, Neuron, 2002). According to this hypothesis, each ensemble of neurons whose activity represents each of the different alternatives are interconnected via excitatory recurrent collaterals and the integration arises from these recurring inputs being continuously summated thanks to the relatively slow time course of the NMDA-related synaptic current. The objective of this study was to test this hypothesis by determining whether altering the function of the NMDA receptors causes predictable and consistent changes in the performance of nonhuman primates deciding which of several alternatives is the visual stimulus with the highest luminance.
Materials and Methods: We trained two monkeys (macaca mulatta) to perform a visual search task, which required them to report the location a unique target stimulus presented with seven distractors of equally lower luminance by foveating this search target after a single saccadic eye movement. The position of the target in the visual search array was varied randomly across eight positions, and the difference in luminance between target and distractor stimuli was randomly varied across low to high discriminability levels (1-128 cd/m2). Visual search performance was assessed by measuring both the accuracy and the latency of the saccades made in response to the search array presentation before and after each animal was administered an intramuscular injection of ketamine, a non-competitive NMDA antagonist. Ketamine is a dissociative anaesthetic and we used a low dose of 0.5 mg/kg, which we previously found to produce reliable, yet not debilitating, effects on visual behavior (Brunamonti et al., Soc Neurosci Abstr, 2007). We also controlled for the effects related to the procedure with injections of the vehicle (saline) alone.
Results: We found that ketamine injections significantly lengthens saccade latency and improves saccade accuracy across most of the target/distractor discriminability, thus shifting the chronometric function upward and the psychometric function leftward (lowering the discrimination threshold). Vehicle (saline) injections produced no significant changes in performance.
Conclusions: By showing that ketamine slows down the responses of nonhuman primates deciding among several alternatives, we demonstrated the importance of the NMDA receptors in the integration of visual stimulus representations underlying visual discrimination. The improved visual discrimination ability following ketamine injection suggests that lengthening the neural activity integration helps resolve small differences between alternatives. This finding argues against the hypothesis that decisions arise from a simple race between neural representations and suggests that these representations are mutually inhibiting each other. We conclude that the decisional processes underlying the selection of saccade targets in visual search rest on the competition between alternatives. |
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