Acquisition and baseline performance of working memory tasks by adolescent rhesus monkeys

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Brain research (Impact Factor: 2.84). 03/2011; 1378:91-104. DOI: 10.1016/j.brainres.2010.12.081
Source: PubMed


Adolescence is a transitional stage of development characterized by protracted refinements in the neural circuits required for adult level proficiency of working memory. Because impaired working memory is a hallmark feature of several psychiatric disorders that have their onset during adolescence, model systems that can be used to assess the maturation of working memory function, and of disease-related risk factors that disrupt its development, are of particular importance. However, few studies have investigated the maturation of working memory in nonhuman primates. Thus in the present study, we adapted two working memory tests that are among the most widely used in human and adult nonhuman primates, for adolescent rhesus monkeys. Using a touch-screen apparatus, monkeys were trained on a spatial delayed-response task to assess spatial working memory and a delayed match-to-sample task to assess object working memory. The results indicate that adolescent rhesus monkeys readily and efficiently acquire the ability to perform touch-screen based, complex tests of working memory. These data establish that distinct components of adult prefrontal cortex-dependent cognitive functions can be effectively modeled and evaluated in adolescent monkeys. As such, this approach should be useful for assessing the influence of environmental risk factors on the protracted maturation of working memory in adolescent macaques.

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Available from: Christopher D Verrico, Oct 09, 2015
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    • "Measurements of behavioral performance in nonspatial delayed-match-to-sample tasks have been interpreted as showing that monkeys remember the sample using working memory, that is, they use selective memorization (Miller and Desimone 1994; Amit et al. 2003; Schneider et al. 2009; Verrico et al. 2011). However, this interpretation has been made even when the delayed-match-to-sample task does not include intervening distractors (Schneider et al. 2009; Verrico et al. 2011), which are critical for distinguishing selective memorization from the neighborhood strategy. Even tasks that included intervening distractors often did not repeat those images as the test image (Miller et al. 1993; Woloszyn and Sheinberg 2009). "
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    ABSTRACT: Seven monkeys performed variants of two short-term memory tasks that others have used to differentiate between selective and nonselective memory mechanisms. The first task was to view a list of sequentially presented images and identify whether a test matched any image from the list, but not a distractor from a preceding list. Performance was best when the test matched the most recently presented image. Response rates depended linearly on recency of repetition whether the test matched a sample from the current list or a distractor from a preceding list, suggesting nonselective memorization of all images viewed instead of just the sample images. The second task was to remember just the first image in a list selectively and ignore subsequent distractors. False alarms occurred frequently when the test matched a distractor presented near the beginning of the sequence. In a pilot experiment, response rates depended linearly on recency of repetition irrespective of whether the test matched the first image or a distractor, again suggesting nonselective memorization of all images instead of just the first image. Modification of the second task improved recognition of the first image, but did not abolish use of recency. Monkeys appear to perform nonspatial visual short-term memory tasks often (or exclusively) using a single, nonselective, memory mechanism that conveys the recency of stimulus repetition.
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    • "The animals used in this study will also be included in a longitudinal study exploring the effects of long-term THC administration on age-related improvement in WM ability, thus the animals had only 4–5 weeks of baseline training before THC/vehicle administration (Verrico et al, 2011). This approach ensured that (1) the monkeys understood how to perform the tasks, (2) performance accuracy increased in a delay-dependent manner from the first to last week of baseline training, and (3) performance accuracy was well below ceiling levels. "
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    ABSTRACT: Among adolescents, the perception that cannabis can cause harm has decreased and use has increased. However, in rodents, cannabinoid administration during adolescence induces working memory (WM) deficits that are more severe than if the same exposure occurs during adulthood. As both object and spatial WM mature in a protracted manner, although apparently along different trajectories, adolescent cannabis users may be more susceptible to impairments in one type of WM. Here, we evaluate the acute effects of a range of doses (30-240 μg/kg) of intravenous Δ⁹-tetrahydrocannabinol (THC) administration on the performance of spatial and object WM tasks in adolescent rhesus monkeys. Accuracy on the object WM task was not significantly affected by any dose of THC. In contrast, THC administration impaired accuracy on the spatial WM task in a delay- and dose-dependent manner. Importantly, the THC-induced spatial WM deficits were not because of motor or motivational impairments. These data support the idea that immature cognitive functions are more sensitive to the acute effects of THC.
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    ABSTRACT: The human ability to flexibly adapt to novel circumstances is extraordinary. Perhaps the most illustrative, yet underappreciated, form of this cognitive flexibility is rapid instructed task learning (RITL)-the ability to rapidly reconfigure our minds to perform new tasks from instructions. This ability is important for everyday life (e.g., learning to use new technologies) and is used to instruct participants in nearly every study of human cognition. We review the development of RITL as a circumscribed domain of cognitive neuroscience investigation, culminating in recent demonstrations that RITL is implemented via brain circuits centered on lateral prefrontal cortex. We then build on this and the recent discovery of compositional representations within lateral prefrontal cortex to develop an integrative theory of cognitive flexibility and cognitive control that identifies mechanisms that may enable RITL within the human brain. The insights gained from this new theoretical account have important implications for further developments and applications of RITL research.
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