Muscimol-Induced Inactivation of Monkey Frontal Eye Field: Effects on Visually and Memory-Guided Saccades

Abstract

Muscimol-induced inactivation of the monkey frontal eye field: effects on visually and memory-guided saccades. Although neurophysiological, anatomic, and imaging evidence suggest that the frontal eye field (FEF) participates in the generation of eye movements, chronic lesions of the FEF in both humans and monkeys appear to cause only minor deficits in visually guided saccade generation. Stronger effects are observed when subjects are tested in tasks with more cognitive requirements. We tested oculomotor function after acutely inactivating regions of the FEF to minimize the effects of plasticity and reallocation of function after the loss of the FEF and gain more insight into the FEF contribution to the guidance of eye movements in the intact brain. Inactivation was induced by microinjecting muscimol directly into physiologically defined sites in the FEF of three monkeys. FEF inactivation severely impaired the monkeys' performance of both visually guided and memory-guided saccades. The monkeys initiated fewer saccades to the retinotopic representation of the inactivated FEF site than to any other location in the visual field. The saccades that were initiated had longer latencies, slower velocities, and larger targeting errors than controls. These effects were present both for visually guided and for memory-guided saccades, although the memory-guided saccades were more disrupted. Initially, the effects were restricted spatially, concentrating around the retinotopic representation at the center of the inactivated site, but, during the course of several hours, these effects spread to flanking representations. Predictability of target location and motivation of the monkey also affected saccadic performance. For memory-guided saccades, increases in the time during which the monkey had to remember the spatial location of a target resulted in further decreases in the accuracy of the saccades and in smaller peak velocities, suggesting a progressive loss of the capacity to maintain a representation of target location in relation to the fovea after FEF inactivation. In addition, the monkeys frequently made premature saccades to targets in the hemifield ipsilateral to the injection site when performing the memory task, indicating a deficit in the control of fixation that could be a consequence of an imbalance between ipsilateral and contralateral FEF activity after the injection. There was also a progressive loss of fixation accuracy, and the monkeys tended to restrict spontaneous visual scanning to the ipsilateral hemifield. These results emphasize the strong role of the FEF in the intact monkey in the generation of all voluntary saccadic eye movements, as well as in the control of fixation.

Top–Down Attentional Deficits in Macaques with Lesions of Lateral Prefrontal Cortex

“…Numerous other studies have shown that unilateral lesions or reversible deactivation of the FEF and other parts of PFC often cause a transient contralateral neglect, which is typically most evident for orienting into the peripheral visual field or when there are competing stimuli in the unaffected parts of the visual field (extinction) (Welch and Stuteville, 1958;Crowne et al, 1981;Collin et al, 1982;Dias and Segraves, 1999;Iba and Sawaguchi, 2003;Schiller and Tehovnik, 2003;Wardak et al, 2006). Given that the neglect after a lesion typically resolves within a few days or weeks, and the deactivation effects last only hours, we could not observe such neglect in the present study because testing of the animals did not begin for several months after the lesions.…”

Cortical and cerebellar activation induced by reflexive and voluntary saccades

“…Studies on FEF and SEF lesions in human patients and nonhuman primates suggest that both areas are either not dominantly involved in the generation of reXexive saccades or that damage can be compensated for on a behavioral level by other areas, such as the brainstem (Schiller et al 1980;van der Steen et al 1986;Lee and Tehovnik 1995;Sommer and Tehovnik 1997;Schiller and Chou 1998;Dias and Segraves 1999). However, lesions of the PEF in non-human primates (Lynch and McLaren 1989) and humans (PierrotDeseilligny 1991) considerably delay the onset of reXexive saccades, suggesting that the PEF might be more essential than the FEF or SEF for the adequate performance of reXexive saccades (Gaymard et al 1998).…”

Dual Diffusion Model for Single-Cell Recording Data From the Superior Colliculus in a Brightness-Discrimination Task

“…Each monkey received preoperative training followed by an aseptic surgery to implant a subconjunctival wire search coil, a plastic cilux recording cylinder aimed at the SC, and a titanium receptacle to allow the head to be held stationary during behavioral and neuronal recordings. All of these methods have been described in detail elsewhere (Dias and Segraves 1999;Helminski and Segraves 2003). Surgical anesthesia was induced with the short-acting barbituate thiopental (5-7 mg/kg iv) and maintained using isoflurane (1.0 -2.5%) inhaled through an endotracheal tube.…”