Endogenously Generated and Visually Guided Saccades after Lesions of the Human Frontal Eye Fields Avishai Hen& Ben Gurion University of the Negev, Israel Robert Rafhl Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/6/4/400/1755171/jocn.1994.6.4.400.pdf by guest on 18 May 2021 University of California, Davis Dell Rhodes Reed College Abstract Nine patients with chronic, unilateral lesions of the dorso- toward the ipsilesional $eld had abnormally prolonged laten- lateral prefrontal cortex including the frontal eye fields (FEF) cies; they were comparable to the latencies observed for vol- made saccades toward contralesional and ipsilesional fields. untary SdCcddeS. The effect of FEF lesions on saccacles The saccades were either voluntarily directed in response to contrasted with those observed in a second experiment re- arrows in the center of a visual display, or were reflexively quiring a key press response: FEF lesion patients were slower summoned by a peripheral visual signal. Saccade latencies were in making key press responses to signals detected in the con- compared to those made by seven neurologic control patients tralesional field. To assess covert attention and preparatory set with chronic, unilateral lesions of dorsolateral prefrontal cortex the effects of precues providing advance information were sparing the FEF, and by 13 normal control subjects. In both the measured in both saccade and key press experiments. Neiher normal and neurologic cohl[rolsubjects, reflexive saccades had patient group showed any deficiency in using precues to shili shorter Latencies than voluntary sdccades . In the FEF lesion attention or to prepare saccades. patients, voluntary saccades had longer latencies toward the The FEF facilitates the generation of voluntary saccatles and contralesional field than toward the ipsilesional field. The op- also inhibits reflexive saccades to exogenous signals. FEF Ic- posite pattern was found for reflexive saccades: latencies of sions may disinhibit the ipsilesional midbrain which in turn saccades to targets in the contralesional field were shorter than may inhibit the opposite colliculus to slow reflexive s:iccades saccades summoned to ipsilesional targets. Reflexive saccades toward the ipsilesional field. INTRODUCTION saccades. Monkeys with superior colliculus lesions show an increase in saccade latency (Goldberg & Wurtz, 1972; The frontal lobes are the latest structures to develop both Schiller, Sandell, & Maunsell, 1987). In humans the SLI- phylogenetically and ontogenetically: Their development perior colliculus is involved not only in triggering re- is most advanced in the human brain and their myelin- flexive saccades (Rafal, Smith, Krantz, Cohen, & Brennan, ization is not complete until long after birth. They are 1990) but also in moving visual attention to exogenous involved in complicated activities that require planning. signals (Rafal, Henik, & Smith, 1991; Rafal, Posner, Fried- This regulation of voluntary, goal-directed behavior may man, Inhoff, & Bernstein, 1988). require modulating or adapting subcortical reflexes. It is Cortical mechanisms, on the other hand, are necclcd likely, for example, that the frontal eye fields (FEF) affect for generating voluntary saccadic eye movements under reflexive saccades generated by subcortical systems strategic guidance (Bruce & Goldberg, 1985; Deng, Gold- (Goldberg & Segraves, 1989). berg, Segraves, Ungerleider, & Mishkin, 1986; Goldberg Saccades can be reflexively summoned, as when turn- & Segraves, 1989). In early work, Holmes (1938) ob- ing toward a movement seen out of the corner of the served that patients with frontal cortex lesions have dif- eye; or they can be deployed endogenously, as when ficulty executing saccades in response to verbal looking both ways before crossing the street. Brainstem command. Luria, Karpov, and Yarbuss (1966) suggested programs involving primarily the superior colliculus are that ocular scanning patterns of these patients are con- critical in triggering reflexive, peripherally summoned trolled entirely by external stimuli rather than by instruc- 0 1994 Masacbusens Institute of Technology Journal of Cognitiue Neuroscience 64,pp. 400-41 I Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn.1994.6.4.400 by guest on 27 September 2021 tions. Recent work suggests that interactions between the the saccade is being withheld (Bruce & Goldberg, 1985). frontal cortex and the superior colliculus may arbitrate To study this aspect of preparatory set, saccade targets between external and internal demands on the oculo- were preceded by a preparatory cue (see Fig. 2). The motor apparatus (Bruce & Goldberg, 1985; Schiller et al., cue could provide correct information about the spatial 1987; Schiller, True, & Conway, 1980). Surgical lesions direction of the forthcoming required response (infor- of frontal lobes in humans produce a deficit in inhibiting mative cue) or supply no directional information (neutral “reflexive glances” (Guitton, Buchtel, & Douglas, 1985) cue). The advance information provided by a informative and unilateral lesions of the FEF may shorten latencies cue should allow the subject to prepare to respond to of reflex saccades to targets in the contralesional field the target, shortening the latency to respond compared (Pierrot-Deseillgny, Rivaud, Penet, & Rigolet, 1987). to neutral cue trials. It was predicted that FEF lesions Single cell recordings provide evidence for a specific might cause a loss of facilitation from advance informa- role of the frontal eye fields in endogenous saccade tion, at least for endogenously generated saccades. Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/6/4/400/1755171/jocn.1994.6.4.400.pdf by guest on 18 May 2021 generation (Bruce & Goldberg, 1985; Goldberg & Se- graves, 1989). These show that the FEF contains cells that respond in temporal correlation with purposive saccades RESULTS even in the absence of an exogenous visual stimulus. In Experiment 1: Saccade Task addition, some cells show anticipatory activity preceding Normal Control Subjects a cue fir saccade execution if the monkey could predict the dimensions of the saccade. Bruce and Goldberg con- Saccade latencies for the control subjects were subjected cluded that “The frontal eye fields may be the means by to a three-way repeated measures analysis of variance. which cortical decisions can access the brainstem’s sac- The three within-subject factors were target type (central cade generator. In contrast, the superior colliculus may arrow vs. peripheral target), cue validity (informative VS. provide a direct and rapid mechanism whereby visual neutral cue), and saccade direction (right vs. left). Mean stimuli can trigger saccades” (pp. 632-633) (Bruce & reaction times for target type and cue validity, averaged Goldberg, 1985). over saccade direction, are presented in Table 2. Thus, the FEF may be necessary both for endogenously Saccade latencies were shorter to a peripheral target generating voluntary saccades, and for inhibiting more than from a central arrow [F(1,12)= 7.00,p < 0.051, and automatic brainstem mechanisms that generate reflexive were shorter following informative cues [F(1,12) = saccades summoned by exogenous signals. The present 118.53, p < O.OOl]. A target type X validity interaction work measured the latencies of these two types of sac- [F(1,12) = 7.27, p < 0.051 obtained because saccade cades in patients with chronic unilateral lesions of the latencies were shorter to peripheral than to central t;ir- dorsolateral prefrontal cortex. Patients whose lesions in- gets following neutral cues [F(1,12) = 9.72,p < 0.011, volved the superior dorsolateral prefrontal cortex, in- but not following informative cues. Saccade latencies cluding areas thought to include FEF, were compared to were shorter when saccades were made to the right than two groups of control subjects: age-matched normal sub- when they were made to the left [right = 334 msec, jects, and other neurologic patients with lesions of dor- left = 349 msec; F(1,12) = 11.82,p < 0.0051. Saccade solateral prefrontal cortex sparing the FEF (see Table 1 direction did not interact with effects of target type or and Fig. 1). Visually guided saccades were made to a validity. bright signal appearing 10” eccentric to fixation. Endog- enously generated saccades were directed by a central Patients symbol (an arrow head pointing to left or to right) that appeared at fixation (see Fig. 2). It was predicted that Saccade latencies of the patients were subjected to a four- FEF lesions would increase the latencies of endogenously way analysis of variance. The three within-subject factors generated sdccades to the contralesional field, and might were target type (central arrow vs. peripheral target ), decrease the latencies of reflexive saccades to the con- cue validity (informative vs. neutral cue), and field to tralesional field. To determine whether any obtained ef- which saccades were directed (ipsilesional vs. contrale- fects are specific to oculomotor responses, a second sional field). The between groups factor was subject experiment required the same subjects to make a choice group (FEF vs. NFEF). Mean saccade latencies for the reaction time (RT) key press response to the same stim- various conditions are presented in Table 3. uli. The two patient groups did not differ in mean saccade In addition to studying the role of the FEF in saccade latencies [F(1,14) = 1.54, p > 0.21. As in the control execution, a second goal