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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.
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