The primate prefrontal cortex plays a central role in the perception of sensory information and the planning of intelligent behavior, evidenced by the profound cognitive deficits following prefrontal injury and the mental illnesses associated with prefrontal malfunction. Previous neurophysiological studies in primates have sought to understand the involvement of the prefrontal cortex in cognitive functions and have indeed revealed prefrontal activation during execution of a large variety of behavioral tasks. Much less is known, however, on how the prefrontal cortex operates under more natural conditions, before animals have been heavily conditioned to perform a stereotypical task, and how training itself modifies neuronal responses and neural circuitry. In fact, the fundamental organization of sensory information within the prefrontal cortex has been under debate, as training in different tasks has resulted in quite distinct patterns of prefrontal activation. We have recently initiated a series of experiments examining the principles of prefrontal intrinsic connectivity as well as experiments examining neuronal responses of monkeys naive to behavioral training. Taking advantage of the methodological advancements and preliminary findings of these studies, we propose to test the nature of prefrontal encoding of visual information before and after training. Experiments will first test whether neurons in the dorsolateral and ventrolateral prefrontal cortex encode the spatial locations and features of visual stimuli presented passively and having no significance for the monkeys. The same monkeys will subsequently be trained in cognitive tasks that require them to identify and remember the spatial locations and features of these stimuli, allowing us to test whether single neurons are able to integrate spatial and feature information after training. We will use microelectrode arrays to record neural and to determine changes in the patterns of neuronal activation and in the functional connectivity between neurons. In the last few years, training human patients in similar tasks has emerged as a means of restoring cognitive function compromised after traumatic brain injury or stroke and ameliorating the effects of genetic brain disorders. Our results will shed light on the underlying neural circuit changes following cognitive training and offer insights on the design of better intervention strategies for the remediation of these conditions.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY017077-04
Application #
7539900
Study Section
Special Emphasis Panel (ZRG1-IFCN-A (91))
Program Officer
Steinmetz, Michael A
Project Start
2006-01-01
Project End
2010-11-30
Budget Start
2008-12-01
Budget End
2010-11-30
Support Year
4
Fiscal Year
2009
Total Cost
$313,512
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Constantinidis, Christos; Qi, Xue-Lian (2018) Representation of Spatial and Feature Information in the Monkey Dorsal and Ventral Prefrontal Cortex. Front Integr Neurosci 12:31
Riley, Mitchell R; Qi, Xue-Lian; Zhou, Xin et al. (2018) Anterior-posterior gradient of plasticity in primate prefrontal cortex. Nat Commun 9:3790
Constantinidis, Christos; Funahashi, Shintaro; Lee, Daeyeol et al. (2018) Persistent Spiking Activity Underlies Working Memory. J Neurosci 38:7020-7028
Zhou, Xin; Constantinidis, Christos (2017) Fixation target representation in prefrontal cortex during the antisaccade task. J Neurophysiol 117:2152-2162
Tang, Hua; Riley, Mitchell R; Constantinidis, Christos (2017) Lateralization of Executive Function: Working Memory Advantage for Same Hemifield Stimuli in the Monkey. Front Neurosci 11:532
Murray, John D; Bernacchia, Alberto; Roy, Nicholas A et al. (2017) Stable population coding for working memory coexists with heterogeneous neural dynamics in prefrontal cortex. Proc Natl Acad Sci U S A 114:394-399
Riley, Mitchell R; Qi, Xue-Lian; Constantinidis, Christos (2017) Functional specialization of areas along the anterior-posterior axis of the primate prefrontal cortex. Cereb Cortex 27:3683-3697
Constantinidis, Christos; Klingberg, Torkel (2016) The neuroscience of working memory capacity and training. Nat Rev Neurosci 17:438-49
Zhou, Xin; Zhu, Dantong; Qi, Xue-Lian et al. (2016) Neural correlates of working memory development in adolescent primates. Nat Commun 7:13423
Riley, Mitchell R; Constantinidis, Christos (2015) Role of Prefrontal Persistent Activity in Working Memory. Front Syst Neurosci 9:181

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