Ординатура / Офтальмология / Английские материалы / Eye Movements A Window on Mind and Brain_Van Gompel_2007

traces from one subject performing anti-saccades in the MR scanner during the eventrelated experiment. The error rates of individual subjects ranged from 4 to 35% (16% ± 3 4% [mean ± standard error of the mean], median 11%). Subjects did not show significant differences in the percentage of errors between leftward (48.1%) and rightward (51.9%) stimulus presentations (paired t-test, p = n s). Black traces show correct trials in which the subject looked away from a stimulus whereas grey traces show error trials in which the subject initially looked towards the stimulus before generating an anti-saccade.

As previously described (Ford et al., 2005) the mean SRT differed significantly between correct anti-saccades (355 ms) and error anti-saccades (326 ms). The SRT of anti-saccade errors indicates they were not express saccades. Correct anti-saccades had significantly longer mean SRTs than anti-saccade errors (paired t-test, p < 0 05).

2.2. Functional imaging data

2.2.1. Blocked design experiment

BOLD signal intensities were compared for anti-saccade blocks and pro-saccade blocks utilizing the GLM across data collected from 10 subjects (p < 0 01, corrected for multiple comparisons; see Section “Methods” for details). As shown in the group statistical activation map in Figure 2, significantly greater activation for anti-saccade blocks than pro-saccade blocks was exhibited bilaterally in areas corresponding to the FEF, the SEF, the ACC, the right DLPFC and bilaterally in an area in the parieto-occipital sulcus (POS). In contrast, pro-saccade blocks elicited greater BOLD signal activation than anti-saccade blocks bilaterally in an area in the superior frontal gyrus (SFG).

2.2.2. Event-related experiment

The regions functionally mapped in the blocked experiment demonstrated differential BOLD signal activations between blocks of proand anti-saccades. These functionally localized regions of cortex from the blocked experiment were then further examined by analyzing BOLD activations from correct and error anti-saccades in the event-related experiment.

Analysis of event-related trials during the mean of the 10s preparatory period before stimulus presentation and saccade execution showed no areas with significantly greater activation for error anti-saccades compared with correct anti-saccades; however, one area in the SFG located in Brodmann’s area (BA) 9 did approach significance. There were, however, three areas localized in the blocked experiment which showed significantly greater activation for correct anti-saccades compared with errors. Figure 3a shows the group average BOLD signal time courses for correct anti-saccades (black line) and error anti-saccade (grey lines) for ACC which showed significantly higher BOLD activation for correct anti-saccades than error anti-saccades during the instruction period (paired t-test, <0 05). The grey shaded area shows the data points included in the mean (see Figure 3B).

As shown in Figure 4a, significantly higher BOLD signal activation was also found for the correct anti-saccade instruction period compared with the error anti-saccade instruction period in the right DLPFC and the SEF (paired t-test, p < 0 05). In contrast, Figure 3(c, d) shows the group average BOLD signal time courses for left FEF which failed to show significant differences between correct anti-saccades and error anti-saccades during the instruction period. All other areas localized in the block experiment failed to show any significant differences in mean preparatory BOLD activation between correct antisaccades and errors (see Figure 4b).

3. Discussion

The present study had two main goals. First, to compare BOLD signal activations elicited by rapid blocked trial presentations of proand anti-saccades to those elicited by slow event-related trial presentations. It is important to recognize the potential differences between rapid trial presentations frequently used in single-neuron recording experiments conducted with monkeys and the event-related design used here to examine preparatory processes within a given trial. An event-related design utilizing a long preparatory period (in this case 10 s) and a 12 s inter-trial interval may not be directly comparable to electrophysiological experiments in which a trial may take place in the order of 1–2 s. It is possible that the preparation to make an eye movement that takes place in the order of 200 ms (Everling and Munoz 2000) is not reflective of the same process we have measured in this paradigm with our long preparatory period. Here, by demonstrating that we can localize similar cortical regions using rapid trials presentations in our blocked experiment to those localized using our event-related design (see Ford et al., 2005), we have further supported this event-related technique to dissociate processes taking place within a trial.

The second goal was to compare directly the prestimulus activations between correct anti-saccades and errors in cortical areas localized in a rapidly presented blocked experimental paradigm, utilizing a new analysis that makes no assumptions about the particular temporal waveform shape of the BOLD signal response during each event-related trial. Our previous analysis of this event-related data utilized multiple GLM predictor curves to model the BOLD signal response during preparatory and saccade periods (Ford et al., 2005). Although fruitful, we had hoped that by conducting this new analysis and examining the BOLD signal activation in a variety of areas independently of a model that assumes a hypothesized waveform shape, we could increase the sensitivity of our analysis. We have shown in this study that a number of cortical areas that exhibit differences in BOLD activation levels between blocks of proand anti-saccades demonstrate differences during the preparatory period of event-related trials between correct anti-saccades and errors. The new blocked design experiment yielded similar results to those found using only the event-related data. Our previous analysis found increased preparatory period activation for correct anti-saccades vs errors in the right DLPFC, ACC and pre-SEF. Here, we supported these results demonstrating that right DLPFC, ACC and a similar

area in SEF (see Figures 3 and 4) showed the same pattern of BOLD signal activation even when localized independently using a new, rapidly presented blocked experimental paradigm. However, we failed to find significant differences in additional areas.

One novel finding of particular interest that has not yet been discussed is an area detected bilaterally in the SFG which showed a unique pattern of activation, with higher activation for blocks of pro-saccades as compared with blocks of anti-saccades. This area was both functionally and anatomically distinct from the cortical area we localized in the prefrontal cortex we refer to as DLPFC. Our previous analysis examining only data from slow event-related trials also localized a bilateral area in the SFS which showed an increase in the BOLD signal preceding anti-saccade errors compared with correct anti-saccades. The current analysis indicated that indeed this area did show a similar pattern of activation (higher activation for errors than correct anti-saccades during the preparatory period) but this difference was not found to be significant, although this comparison did approach significance. This activation appears to be located in BA 9 based on Petrides and Pandya (2001), and based on the combined, robust findings of our current and previous analysis deserves further examination. Previous research combining magnetoencephalography and positron emission tomography has suggested that BA 9 may be the source of the human motor readiness potential (Pedersen et al., 1998). It may be the case that our finding of increased activation in BA 9 on pro-saccade trials reflects the increased motor preparation involved in the performance of voluntary visually guided saccades, as compared with anti-saccade trials in which the automatic pro-saccade must be inhibited. This increase in motor preparation may also explain the trend towards an increase in activation in this area on error anti-saccade trials, in which the automatic pro-saccade to the visual stimulus was not inhibited.

Overall, our new comparison between blocks of proand anti-saccades found differences in areas corresponding to the FEF, SEF, ACC, DLPFC and POS and SFG (see Figure 2 and Table 1). The comparison between event-related correct and error

Table 1

Peak Activations for Comparisons

anti-saccades during the preparatory period revealed significant differences in only three areas, the right DLPFC, ACC and SEF (see Figures 3 and 4) but not in the FEF, POS, or SFG. Although our new analysis did not detect differences in cortical areas beyond those demonstrated to show differences in our previous event-related analysis (Ford et al., 2005), we have succeeded in providing a valuable comparison between a rapidly presented blocked trial design and our slow event-related design utilizing long preparatory periods.

Our findings indicate that we can localize similar cortical regions using rapid trials presentations in a blocked design experiment to those localized using a event-related design with a long preparatory period and long inter-trial intervals (see Ford et al., 2005). In doing so, we have further supported our findings indicating a large network of frontal and posterior areas is modulated during the performance of anti-saccade compared with pro-saccade trials; however, it is the activation of more localized frontal cortical areas prior to stimulus presentation, which is associated with subjects’ performance in the anti-saccade task.

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Abstract

Listing’s law can be achieved in two ways. First, neural activation of extraocular muscles could be encoded by the central nervous system. However, this requires complex calculations of the central nervous system. Secondly, Listing’s law could be implemented by the anatomical structure of the ocular motor plant and then neural commands have to be encoded only in two dimensions.

Simulations with a dynamical model show that commutative eye movements can be generated solely by the anatomical structure of the eye globe. A necessary condition then is that during eye rotations to a specific location the extraocular muscles are kept in the same plane. In patients with congenital nystagmus (CN), rotations of the eye do not obey Listing’s law. Simulations with the dynamical model demonstrate that this could be explained an aberrant anatomical structure, resulting in cross-talk between the horizontal, vertical and torsional planes.

1. Listing’s law

Eye rotation in three dimensions (3D) should obey Listing’s law, that is, all rotation axes describing the orientation of the eye lie in a single plane, called Listing’s plane (Donders, 1876; Von Helmholtz, 1924). In this manner commutative eye rotations are ensured, which means that the sequence of consecutive rotations does not influence the final eye position and there will be no build-up of torsion. Mathematically, eye movements then are described with rotation vectors. Rotation vectors define eye orientation as a single rotation, with an angle around an axis n, using the ‘right-hand rule’, from a reference orientation to the current orientation. The axis and angle are used to define the rotation vector r as:

The components rx, ry and rz indicate clockwise, vertical and horizontal rotation, respectively. The reference orientation is chosen as looking straight ahead with a zero torsional

component: rref = 0 0 0 .

In healthy subjects previous experimental findings of smooth pursuit and saccades show that under normal conditions within an accuracy of about 1–2 rotation axes describing the orientation of the eye are restricted to one single plane (Ferman, Collewijn, & Van den Berg, 1987c; Haslwanter et al., 1995; Straumann, Zee, Solomon & Kramer, 1996; Tweed and Vilis, 1987), that is Listing’s plane. Exceptions to this rule, that is violations of Listing’s law, occur for vestibularly generated eye movements (Tweed et al., 1999) and under special or pathological conditions (Nakayama and Balliet, 1977; Raphan, 1998). Furthermore, with convergence the primary position of both eyes generally changes. This implies that Listing’s plane rotates with respect to the fronto-parallel plane (Bruno and Van den Berg, 1997; Mok, 1992; Van Rijn & Van den Berg, 1993).

There are two possibilities for the ocular motor system to obey Listing’s law. First, neural activation of extraocular muscles could be specifically encoded by the central nervous system such that it compensates for non-commutativity of ocular rotations. A model has been developed (Tweed & Vilis, 1987, 1990; Tweed, Cadera, & Vilis, 1990; Tweed et al., 1999) that uses a non-commutative, rotational operator (quaternion), to generate innervation of the extraocular muscles. Since in the latter model complex neuronal computations are required, Schnabolk and Raphan (1994) developed an alternative