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Grant Number: 5R01EY012389-07
Project Title: Diencephalic Mechanisms of Visuomotor Integration
PI Information: ASSISTANT PROFESSOR TERRENCE R. STANFORD, stanford@wfubmc.edu 

Abstract: DESCRIPTION (provided by applicant): Decisions about where to look within a typical visual scene are governed by the relative salience of individual stimuli and current behavioral objectives. To date, the majority of studies examining the cognitive control of visual orienting have targeted frontal cortex. However, there is growing evidence to suggest that signals related to working memory and decision-making are critically dependent on interactions between frontal cortex and subcortical structures such as the basal ganglia, cerebellum, and thalamus. Thalamus is unique among these subcortical structures; in addition to providing direct input to cortex, its constituent nuclei mediate the influences of both the basal ganglia and cerebellum on their respective cortical targets. Despite its critical anatomical position, virtually nothing is known about the nature of the information represented in central thalamus. The current experiments seek to fully characterize the central thalamic representations of cognitive factors relevant for producing visually-guided saccadic eye movements. The proposed studies will be the first to examine the potential importance of central thalamic nuclei, and the subcortical-cortical interactions they mediate, to the cognitive control of goal-directed saccadic eye movements. In doing so, these experiments will help to define the essential neural substrates for visuomotor cognition.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
eye movement, neural information processing, saccade, sensorimotor system, thalamic nuclei, thalamus, visual perception
basal ganglia, behavior prediction, cerebellum, decision making, goal oriented behavior, neural transmission, neurophysiology, prefrontal lobe /cortex, sensory discrimination, short term memory, space perception, visual stimulus
Macaca mulatta, behavioral /social science research tag, electrode, histology, oscillography, stereotaxic technique

Institution: WAKE FOREST UNIVERSITY HEALTH SCIENCES
MEDICAL CENTER BLVD
WINSTON-SALEM, NC 27157
Fiscal Year: 2006
Department: NEUROBIOLOGY AND ANATOMY
Project Start: 01-FEB-1999
Project End: 30-JUN-2009
ICD: NATIONAL EYE INSTITUTE
IRG: CVP

Quantitative Assessment of the Timing and Tuning of Visual-Related, Saccade-Related, and Delay Period Activity in Primate Central Thalamus
 
Melanie T. Wyder^1,*, Dino P. Massoglia^2,* and Terrence R. Stanford<sup>2

1</sup> Program in Neuroscience, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157; ² Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157

Submitted 23 January 2003; accepted in final form 24 April 2003
J Neurophysiol 90: 2029-2052, 2003

Surgical procedures
All surgical and experimental protocols complied with the National Institutes of Health Guide for the Care and Use of Laboratory Animals, USDA regulations, and the policies set forth by the Wake Forest University School of Medicine Animal Care and Use Committee (ACUC). Three rhesus monkeys (Macaca mulatta) were prepared for chronic single-unit recording. Each monkey underwent two sterile surgical procedures while under general isoflurane anesthesia. During the first surgery, an MRI-compatible titanium post was attached to the skull using titanium screws and orthopedic bone cement. Also at this time, a preformed loop of Teflon-coated stainless steel wire (eye coil) was implanted beneath the conjuctiva to circumscribe the cornea of one eye (Judge et al. 1980 ). During subsequent training/recording sessions, the post served to restrain the monkey's head, whereas the eye coil provided an analog signal of eye position (Fuchs and Robinson 1966 ; Robinson 1963 ). Recovery from the initial surgery required 2–4 wk, during which time analgesics and antibiotics were administered as required.
 
Fully recovered animals were trained on the behavioral task (see following text). Once trained to a criterion level of performance, a second surgery was performed to place an MRI-compatible recording cylinder (Crist Instrument) over the oculomotor thalamus (OcTh). A presurgical MRI was carried out to optimize the stereotaxic coordinates of the cylinder for individual monkeys. The recording cylinder was positioned over a small craniotomy (about 15 mm diameter) and secured with titanium screws and bone cement. Daily recording sessions began on full recovery (2–3 wk).

Recording procedures
Eye position was recorded using the search coil method (Fuchs and Robinson 1966 ; Robinson 1963 ). Briefly, the monkey sat in a primate chair with head restrained at the center of a pair of orthogonal (horizontal and vertical) magnetic fields. The magnetic fields induced current to flow within the surgically implanted eye coil. This current, when decomposed into horizontal and vertical components, yielded analog signals proportional to the angular relationships between the eye coil and the horizontal and vertical magnetic fields, respectively (i.e., eye position). Horizontal and vertical eye positions were sampled and stored at 500 Hz.
Neural activity was recorded using parylene-coated, tungsten microelectrodes (Micro Probe) having impedances between 1.0 and 1.5 M at 1 kHz. Activity was amplified, filtered (300 Hz to 4 kHz), and monitored using an oscilloscope and an audio monitor. The action potentials of single neurons were isolated using a time/amplitude window discriminator and spike times stored at a resolution of 10 µs. Electrodes were advanced through a dura-piercing cannula and advanced to OcTh by hydraulic microdrive. Generally, the electrode was advanced rapidly to 15 mm below the surface of the dura and then more slowly to detect landmark changes in background activity. A "quiet" period as the electrode passed through the lateral ventricle was followed by a return of activity on entry into dorsal thalamus. Within the thalamus, oculomotor regions were identified by observing/listening for modulations that coincided with task events (see Experimental design, below). We recorded from any isolated neuron that appeared to be modulated in association with any phase of the task.

Experimental design
During training and subsequent recording sessions, monkeys were seated in a primate chair in a very dimly lit room. The stimulus display consisted of an array of light-emitting diodes (LEDs). The distance between adjacent LEDs was either 1 or 2 in., which, at a viewing distance of 57 in., corresponded to 1 or 2° of visual angle (Cartesian coordinates), respectively. Maximum horizontal and vertical stimulus eccentricities were 24 and 21°, respectively. Standard operant methods were used to train monkeys to look toward visual targets for liquid reward (drop of water or juice). Neural data presented in this report were collected primarily in association with performance of a visually guided delayed-saccade task, diagrammed in Fig. 1. Each trial began with the presentation of a central fixation stimulus (left), which the monkey had to acquire within 500 ms. After a variable interval (300–700 ms), a second stimulus was illuminated at an eccentric location (middle). The monkey was required to withhold eye movement to the eccentric stimulus until the fixation light was extinguished (GO signal, right). This interval, the delay period, ranged from 500 to 1000 ms. Once given the GO signal, the monkey was required to look to the target within 500 ms and maintain fixation on the target for an additional fixed interval (200 or 500 ms) to obtain a liquid reward.

* Fuchs and Robinson 1966