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Stop Animal Exploitation NOW!
S. A. E. N.
"Exposing the truth to wipe out animal experimentation"

Government Grants Promoting Cruelty to Animals

Massachusetts Institute of Technology, Cambridge, MA

EARL K. MILLER - Primate Testing - 2006

Grant Number: 5R01NS035145-10
Project Title: Integrative functions of primate prefrontal cortex
PI Information: PROFESSOR EARL K. MILLER, ekmiller@mit.edu 

Abstract:
"Divide and conquer" seems to dominate many neural analyses: There are specialized systems for analyzing different types of information. Cognition requires synthesizing their results. To plan and execute complex, goal-directed behaviors we must learn "the rules of the game": predictive relationships between disparate sensory events, environmental context, the possible actions and consequences. This depends on brain systems specialized for learning and memory: the prefrontal cortex (PFC), basal ganglia (BG) and hippocampal systems (HS). Damage to any of these systems, or their disconnection, impairs rule learning. Previous studies have shown that neural correlates of acquisition and/or representation of concrete (specific) rules and higher-level abstract rules (general principles) are prevalent in the PFC, a brain region central to rule-based behaviors. But our understanding is limited by our lack of knowledge about the respective contributions of, and PFC interactions with, the other critical systems: the BG and HS. The main goal of this project is to provide that knowledge. We plan to simultaneously study neural activity from up to 28 electrodes implanted these systems while monkeys larn and follow concrete rules )conditional visuomoter associations between an object and a saccade direction) and follow abstract rules (matching and non-matching rules applied to new stimuli). This will afford a precise assessment of the respective contributions of the PFC, BG, and GS to complex goal-directed behaviors and insight into the underlying neural circuitry. Our specific aims are: 1. To compare and contrast the neural representation of concrete rules in the PFC with anatomically and functionally-related systems (BG and HS). 2. To assess the relative contributions of PFC, BG and HS to rule acquisition by comparing neural correlates of their learning. 3. To compare and contrast the neural representation of abstract rules in the PFC with the BG, and HS. As rule learning is fundamental to all higher-order behavior, data from this project has the potential to impact on our understanding of a wide range of behaviors and human and human disorders. The ability to glean rules and principles from experience is disrupted in a variety of neuropsychiatric disorders such as autism and schizophrenia. By identifying brain structures important for these abilities, discerning their relative roles, and uncovering their neural mechanisms, we can open a path to drug therapies designed to alleviate their dysfunction.

Thesaurus Terms:
basal ganglia, brain mapping, hippocampus, learning, memory, neuroanatomy, prefrontal lobe /cortex
brain electrical activity, cognition, electrophysiology, neural information processing
Macaca mulatta, behavioral /social science research tag, electrode, electronic recording system, magnetic resonance imaging, single cell analysis, stereotaxic technique

Institution: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
77 MASSACHUSETTS AVE
CAMBRIDGE, MA 02139
Fiscal Year: 2006
Department: BRAIN AND COGNITIVE SCIENCES
Project Start: 01-JAN-1997
Project End: 30-JUN-2007
ICD: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
IRG: IFCN

The Journal of Neurophysiology Vol. 88 No. 2 August 2002, pp. 929-941

Copyright 2002 by the American Physiological Society

Visual Categorization and the Primate Prefrontal Cortex: Neurophysiology and Behavior

David J. Freedman,1,2,5 Maximilian Riesenhuber,3,4,5 Tomaso Poggio,3,4,5 and Earl K. Miller1,2,5

1Center for Learning and Memory, 2The Institute of Physical and Chemical Research-Massachusetts Institute of Technology Neuroscience Research Center, 3Center for Biological and Computational Learning and 4McGovern Institute for Brain Research, 5Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Subjects
Two female adult rhesus monkeys (Macacca mulatta) weighing 6.0 and 7.5 kg were used in this study. Using previously described methods (Miller et al. 1993 ), they were implanted with a head bolt to immobilize the head during recording and with recording chambers. Eye movements were monitored and stored using an infrared eye-tracking system (Iscan, Cambridge, MA). All surgeries were performed under sterile conditions while the animals were anesthetized with isoflurane. The animals received postoperative antibiotics and analgesics and were handled in accord with National Institutes of Health guidelines and the recommendations of the Massachusetts Institute of Technology Animal Care and Use Committee.

Recording techniques
Electrode penetration sites were determined using magnetic resonance imaging scans obtained prior to surgery. The recording chambers were positioned stereotactically over the lateral prefrontal cortex such that the principal sulcus and ventrolateral prefrontal cortex were readily accessible.

Behavioral tasks
The monkeys performed a delayed match-to-category task that required them to judge whether two successive stimuli were from the same category (Fig. 2). The trial began when the monkey grasped a metal bar and fixated a small (0.3) white spot at the center of a CRT screen. They were required to maintain gaze within a 2 square window around the fixation spot for the entire trial. After the initial 500 ms of fixation, a sample image was presented at the center of the screen for 600 ms, followed by a 1,000-ms delay. Then a choice image appeared. If the sample and choice stimuli were from the same category (a category match), the monkeys were required to release the lever before the stimulus disappeared 600 ms after its onset to receive a juice reward.  

Please email: EARL K. MILLER, ekmiller@mit.edu to protest the inhumane use of animals in this experiment. We would also love to know about your efforts with this cause: saen@saenonline.org

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Rats, mice, birds, amphibians and other animals have been excluded from coverage by the Animal Welfare Act. Therefore research facility reports do not include these animals. As a result of this situation, a blank report, or one with few animals listed, does not mean that a facility has not performed experiments on non-reportable animals. A blank form does mean that the facility in question has not used covered animals (primates, dogs, cats, rabbits, guinea pigs, hamsters, pigs, sheep, goats, etc.). Rats and mice alone are believed to comprise over 90% of the animals used in experimentation. Therefore the majority of animals used at research facilities are not even counted.

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