Abstract: DESCRIPTION (provided by applicant): The fast pace and increased psycho-social stress of life in developed countries is correlated with a large increase in affective disorders. Thirty-seven million Americans suffer from a form of anxiety or depression (Narrow et al., 1998; Robins and Regier, 1990). Conventional treatments are only partially successful in combating these disorders because the neural mechanisms underlying normal and pathological emotion are not fully understood. One well-established finding is that the amygdala, a cluster of deep brain nuclei, is a key structure in the complex brain circuit of emotions. In this circuit, incoming signals from all sensory modalities converge in the amygdala where they are converted into modulatory signals directed at memory structures and to autonomic centers of emotional response. The goal of this project is to use neurophysiological techniques to elucidate the neural mechanisms that underlie the differentiation of emotional stimuli, the formation of emotional memories, and the orchestration of somatic and autonomic responses in the primate amygdala

Thesaurus Terms:
amygdala, emotion, memory, neural information processing, neuropsychology
arousal, heart rate, psychophysiology, visual stimulus
Macaca mulatta, behavioral /social science research tag, neuropsychological test, predoctoral investigator

Institution: UNIVERSITY OF ARIZONA
PO BOX 3308
TUCSON, AZ 857223308
Fiscal Year: 2006
Department: DIVISION OF NEUROBIOLOGY
Project Start: 09-SEP-2005
Project End: 08-SEP-2007
ICD: NATIONAL INSTITUTE OF MENTAL HEALTH
IRG: ZRG1

Neural Responses to Facial Expression and Face Identity in the Monkey Amygdala

K. M. Gothard¹, F. P. Battaglia², C. A. Erickson³, K. M. Spitler¹ and D. G. Amaral<sup>4

1</sup>Department of Physiology, College of Medicine, The University of Arizona, Tucson, Arizona; ²Graduate School of Neurosciences Amsterdam, Faculty of Science, Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands; ³Helen Wills Neuroscience Institute, University of California–Berkeley, Berkeley; and ⁴Department of Psychiatry and Behavioral Sciences, The California National Primate Research Center and The Music Intelligence Neural Development Institute, University of California–Davis, Sacramento, California

Submitted 12 July 2006; accepted in final form 2 November 2006
J Neurophysiol 97: 1671-1683, 2007

Surgical procedures
All surgical procedures were carried out in compliance with National Institutes of Health guidelines and were approved by the IACUC at the University of Arizona. Two adult male rhesus monkeys (Macaca mulatta) (monkeys S and H) were surgically prepared for multielectrode recordings from the amygdala using a two-step surgical procedure. For both surgical procedures the monkeys were preanesthetized with ketamine (10–15 mg/kg), administered intramuscularly, and brought to surgical levels of anesthesia with isoflurane (1–1.5%) supplemented with fentanyl (7–10 µg • kg–1 • h–1). During the first procedure, monkeys were implanted with three titanium tripod plates, custom-manufactured by Thomas Recording (Giessen, Germany). Each tripod plate had an elevated center with a threaded screw hole and three flat radial support arms emerging at 120° intervals. The three support arms were 10 mm long, 2 mm wide, and were perforated at the end to accommodate a 2-mm-diameter bone screw. The arms were bent to match the curvature of the skull and affixed to the bone with screws. Two plates were affixed posteriorly, 15 mm lateral from midline and approximately 20 mm posterior from the interaural line. The third plate was affixed straddling the midline 2 cm anterior to the interaural line. The temporalis muscle and the scalp were closed over the plates and the bone was allowed to heal and grow around the plates (about 4–12 mo). Once substantial bone growth had occurred around the screws and the arms of the plates (verified by CT scan), the second procedure was undertaken in which the scalp above the plates was perforated and small threaded head posts (3-mm-diameter shaft, 15-mm length, 5-mm-diameter spherical head) were screwed into the center of each of the tripod plates. The posts served as anchors for a removable stainless steel ring that was secured in a rigid frame during experiments. Such an arrangement distributed the torque generated by head immobilization across the three head posts.
During the second surgical procedure, a recording chamber was secured with bone screws and bone cement to the skull above the amygdala. The chamber was placed at stereotaxic coordinates calculated from a structural MRI carried out before surgery. Magnetic search coils were also implanted in the left eye of one of monkey (S) following standard procedures (Judge et al. 1980 ; Robinson 1963 ). After a 10-day recovery period, monkeys were trained to tolerate head immobilization and to fixate on objects presented on a computer monitor. When behavioral training was complete, a 6- to 8-mm-diameter craniotomy was performed within the chamber.

Behavioral training
The monkeys were trained to fixate on a white square that subtended 0.5 degree of visual angle (dva). The eye movements of monkey S were tracked with a resolution of 0.25 dva and were digitized at 500 Hz using an analog eye tracker (DNI, Newark, DE). Eye movements of monkey H were monitored with the infrared eye tracker (Iscan, Burlington, MA) with a resolution of 0.5 dva. Both eye trackers were connected to the CORTEX experimental control system (NIMH-supported freeware from the website: http://www.cortex.salk.edu) . When the eyes were fixated for 150 ms at the white square, the fixation icon was removed from the monitor and a stimulus image, subtending 12 dva, was displayed. The monkeys were allowed to freely scan the image, with the requirement to maintain gaze within the boundaries of the image. If this requirement was met for the entire duration of the display (500 ms or 1 s) the monkeys received a 0.5- to 1-ml reward droplet. The reward consisted of a paste of mashed granola, rice cereal, and fruit juice or simple fruit juice mixed with applesauce. To disambiguate the effect of the reward from the effect of the stimuli, monkeys received a reward on only 50% of the trials, so that each image was followed an equal number of times by reward or no reward. The duration of the intertrial interval (ITI) was 1 s. When the monkey's eyes moved outside the boundary of the image, the trial was terminated by removing the image from the monitor. Error trials were not rewarded and were followed by a 2-s time-out period. Error trials were excluded from the analysis. To prevent habituation and blunting of the emotional response to face stimuli, the sets of images used for training or used during the period when we searched for neurons in the amygdala did not contain monkey faces or images intended for presentation during neurophysiological recordings.