J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.3.374 on 1 September 1998. Downloaded from 374 J Neurol Neurosurg Psychiatry 1998;65:374–377 SHORT REPORT Functional organisation of saccades and antisaccades in the frontal lobe in humans: a study with echo planar functional magnetic resonance imaging R M Müri, O Heid, A C Nirkko, C Ozdoba, J Felblinger, G Schroth, C W Hess Abstract responsible for the correct performance of the The cortical activation pattern of saccades antisaccade task. If correct antisaccade per- and antisaccades (versus rest) in the fron- formance needs a relevant contribution from tal lobe was analysed using an echo planar the dorsolateral prefrontal cortex (for sup- imaging (EPI) technique in 10 healthy pressing the unwanted reflexive saccade to- subjects. Statistical analysis of activity in wards the visual target) we would expect an the dorsolateral prefrontal cortex dis- increased activity in the dorsolateral prefrontal closed a significantly greater activation cortex during the antisaccade versus rest during antisaccades in this region than condition, but not during the saccade (a during saccades. On the other hand, saccade towards the visual target) versus rest activity in the frontal eye fields was not condition. In this case, the activity in the fron- statistically diVerent in both tasks. These tal eye fields is expected to be the same during results confirm the important role of the both conditions. The aim of this study was, dorsolateral prefrontal cortex for the cor- therefore, to evaluate the role of these regions rect performance of antisaccades ob- in the control of the antisaccade task using tained by studies in humans with isolated functional magnetic resonance imaging lesions of the dorsolateral prefrontal cor- (fMRI). Preliminary results were presented in a tex. poster.7 (J Neurol Neurosurg Psychiatry 1998;65:374–377) Keywords: eye movements; frontal eye field; dorsolateral Methods prefrontal cortex; functional magnetic resonance imag- Ten healthy subjects (three women, seven men ing with a mean age of 31 years and a range of 24 Department of to 40 years, all right handed) who gave their http://jnnp.bmj.com/ Neurology R M Müri informed consent were examined. The study A C Nirkko Recent studies concerning the function of the was approved by the local ethics committee. C W Hess prefrontal cortex disclosed its important role Saccades and antisaccades were elicited by for many aspects of human behaviour.12 For projecting the visual targets by a video projec- Department of ocular motor control at least three important tion system on to a screen in the magnet bore. Neuroradiology regions are located in the frontal lobe: the fron- Firstly, a central fixation point was given for a O Heid tal eye fields, the supplementary eye fields, and pseudorandomised duration between 1 to 2 C Ozdoba on October 1, 2021 by guest. Protected copyright. G Schroth the dorsolateral prefrontal cortex. seconds. Then, simultaneously with the extin- Patients with lesions of the prefrontal cortex guishing of the central fixation point a lateral Department of fail to suppress unwanted responses and are visual target with a constant amplitude of 15 MR-Methodology and impaired on cognitive tests such as the degrees but randomised direction was lit for Spectroscopy, Wisconsin card sort test or the Stroop test. 700 ms; finally, the central fixation point was University of Bern, Antisaccades,3 a paradigm in which the subject shown again for the next visual stimulation. Inselspital, CH-3010 Bern, Switzerland has to make a saccade away from the presented Instruction for the saccade task was to look as J Felblinger visual target, reliably test prefrontal function in quickly and precisely as possible at the lateral ocular motor research: the task requires two visual target. For the antisaccade task, the Correspondence to: steps of cortical processing: (1) inhibition of an instruction was to look directly opposite to the Dr René M Müri, Department of Neurology, unwanted reflexive saccade in the direction of appearing visual target, and to avoid looking University of Bern, the visual target, and (2) intentional saccade to first on the visual target. If this was the case it Inselspital, CH-3010 Bern, the opposite side. It is still not clear how the was counted as an error. To reduce head move- Switzerland. Telephone 0041 632 21 11; fax 0041 632 96 frontal eye fields and the dorsolateral prefrontal ment artefacts, head restraints were used, 79; email [email protected] cortex are involved in the control of the which allowed immobilisation of the volun- antisaccade paradigm. Some authors34 argue teer’s head with lateral foam pads and a velcro Received 22 August 1997 that the frontal eye fields mainly control band across the forehead. The task perform- and in revised form 18 56 December 1997 antisaccades, whereas others have arguments ance during fMRI was controlled by an Accepted 5 February 1998 for the dorsolateral prefrontal cortex being adapted electro-oculography (EOG) system.8 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.3.374 on 1 September 1998. Downloaded from Functional organisation of saccades and antisaccades 375 Figure 1 Functional activation of frontal eye fields, supplementary eye fields, and dorsolateral prefrontal cortex during saccade versus rest and during antisaccade versus rest task. Three representative original EPI slices with overlaid clustered activated pixels are shown. This system allows on line registration of EOG 2.6×1.9 mm and a slice thickness of 5 mm, field during fMRI without reducing the image qual- of view 210×240 mm, matrix 90×128, TE=62 ity. The number of misdirected saccades or ms, flip angle 90 degrees, one series acquired in antisaccades was counted and calculated as the 3.56 seconds) on a 1.5 Tesla MR system percentage of errors of all performed saccades (Magnetom VISION, Siemens). Images were during the task. acquired during four cycles of alternating rest (eyes closed) or activation periods (saccades or IMAGE ACQUISITION AND ANALYSIS antisaccades), with a duration of 32 seconds Firstly, in each subject T2 weighted spin echo each, resulting in 160 images during each images of the brain were acquired for exact period. During each activation period, a mean individual anatomical localisation of the re- of 25 centrifugal and centripetal eye move- gions of interest (ROIs). Functional MRI was ments (saccades or antisaccades) were per- performed using a single shot 2D multislice formed by the subject. http://jnnp.bmj.com/ gradient echo planar imaging (EPI) technique z Score maps with the activation—rest time (axial slices in AC-PC orientation, 20 slices function shifted by one period (3.56 s) and z covering the whole brain, with a pixel size of score values >4.0—were generated and laid over the anatomical echo planar images. This Antisaccades avoids image mismatch due to diVerent distor- 100 Saccades tion eVects. Head movement artefacts were detected by screening the images in cinema on October 1, 2021 by guest. Protected copyright. 80 p < 0.0071 mode and by analysing the time course signal to detect abrupt changes of activity between 60 two consecutive images. Quantitative group analysis of activity was performed for three 40 ROIs defined in each subject using the T2 Voxels (n) Voxels weighted anatomical images: (1) The ROI of the frontal eye fields, which lies at the posterior 20 end of the middle frontal gyrus and in the pre- central sulcus or in the depth of the caudalmost 0 9 DLPC FEF part of the superior frontal sulcus ; (2) the ROI of the dorsolateral prefrontal cortex, which lies p < 0.03 anteriorly on the middle frontal gyrus10 11 Figure 2 Tukey box graph of activated clustered pixels in including cortical grey matter and fundi of the 10 subjects during saccade versus rest and antisaccade adjacent sulci. The posterior limit of the ROI versus rest task, showing median 10th, 25th, 75th, and 90th percentiles. There is a significant diVerence (1) for saccades excluded the posterior end of the middle fron- between the frontal eye fields (FEF) and the dorsolateral tal gyrus; (3) the ROI of the supplementary eye prefrontal cortex (DLPC) (p<0.03), and (2) between 12 13 antisaccades and saccades for the dorsolateral prefrontal fields (SEF), which lies on the medial side cortex (p<0.0071). of the superior frontal gyrus. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.3.374 on 1 September 1998. Downloaded from 376 Müri, Heid, Nirkko, et al Figure 3 Online EOG during fMRI showing a period of the antisaccade task. Three errors—a saccade towards the visual target, during one block of antisaccades—occurred (marked by arrows). To reduce the influence of isolated, ran- teral prefrontal cortex during the saccade task domly activated pixels, only clusters of more versus the antisaccade task (fig 2) resulted in a than four neighbouring activated pixels with z significant diVerence (p<0.0071, Mann- score values >4 were used for further analysis. Whitney U test; median: 0 voxels for saccades Statistical analysis of clustered activated pixels versus median: 16 voxels for antisaccades). The during diVerent conditions was performed by activity in the supplementary eye fields was Mann-Whitney U test. significantly increased during the antisaccade (median during antisaccades 28 voxels, range Results 0–85 voxels; median during saccades 6.5 Figure1 shows an example of an individual voxels, range 0–29 voxels; p<0.03) activation during saccades or antisaccades Analysis of EOG in six of the subjects during (versus rest) for three original echo planar the saccade task disclosed no direction error. In slices with overlaid clustered activated pixels. the antisaccade task (fig 3) a mean percentage In this subject, activity in the frontal eye fields of errors of 11% (range 4–18%) was found.