Author response: A new motor synergy that serves the needs of oculomotor and eye lid systems while keeping the downtime of vision minimal
2016-07-05

Full text Figures and data Side by side Abstract eLife digest Introduction Results Discussion Materials and methods References Decision letter Author response Article and author information Metrics Abstract The purpose of blinks is to keep the eyes hydrated and to protect them. Blinks are rarely noticed by the subject as blink-induced alterations of visual input are blanked out without jeopardizing the perception of visual continuity, features blinks share with saccades. Although not perceived, the blink-induced disconnection from the visual environment leads to a loss of information. Therefore there is critical need to minimize it. Here we demonstrate evidence for a new type of eye movement serving a distinct oculomotor demand, namely the resetting of eye torsion, likewise inevitably causing a loss of visual information. By integrating this eye movement into blinks, the inevitable down times of vision associated with each of the two behaviors are synchronized and the overall downtime minimized. https://doi.org/10.7554/eLife.16290.001 eLife digest Blinking lubricates the surface of the eye and prevents it from becoming too dry. People blink around 20 times per minute, but we rarely notice the gaps in our vision because the brain becomes less sensitive to visual input during each blink. Eye movements can also hinder our vision. For example, our vision could easily become blurred when we redirect our gaze to a new target. However, like during blinking, the brain blocks visual input while these movements – known as saccades – take place. Because saccades and blinking both temporarily disrupt vision, the brain synchronizes the two, which keeps this downtime to a minimum. Involuntary eye movements can also disrupt our vision. We perceive an object most clearly when its image falls on the very center of the back of the eye. If the image drifts away from this central position, our eyes make small involuntary ‘resetting’ movements to counteract the drifting. Given that these movements would compromise our vision much like saccades do, Khazali et al. wondered whether the brain might also synchronize them with blinks as well. Khazali et al. tracked the eye movements of people staring straight ahead at a red dot in an otherwise dark room. This revealed that correcting eye movements did indeed occur at the same time as blinks, but unexpectedly the movements were different from those that had been recorded in previous studies. Further experiments then confirmed that the blinks themselves triggered this new type of corrective movement, rather than the loss of vision that resulted from the blinks. Khazali et al. propose that by synchronizing the resetting movements with blinks, the brain ensures that the eyes are damp wiped and restored to their optimal positions while minimizing visual disturbance. The next challenge is to identify the circuit of neurons in the brain that underlies these eye movements and to clarify how this circuit interacts with the one that controls blinking. https://doi.org/10.7554/eLife.16290.002 Introduction We normally blink around 15 to 20 times per minute to hydrate the eyes and to protect them from potentially harmful agents (Evinger, 1995; Evinger et al., 1991). Although normal visual input is blanked out for ~300 milliseconds during blinks, we rarely perceive these gaps due to what is called blink suppression (Bristow et al., 2005; Volkmann et al., 1980; Volkmann, 1986; Manning et al., 1983), the attenuation of visual sensitivity during blinks. This mechanism is useful to eliminate the visual consequences of eye and lid movements during blinks (Ridder and Tomlinson, 1997; Volkmann et al., 1968). But it comes with the cost of losing the connection to the visual world for the duration of the blink (VanderWerf et al., 2003; Bour et al., 2000). Without compensation this loss would lead to a discontinuous visual perception. However, previous experiments in humans have shown that the visual system is able to ensure an illusion of continuity by bridging the perceptual gaps (Bristow et al., 2005; Shultz et al., 2011). Moreover, in cases quick behavioral responses may be demanded, the blink frequency may be temporarily reduced in order to provide more time for the processing of behaviorally relevant visual information. For example during reading, we blink only 4–5 instead of 15–20 times per minute (Shultz et al., 2011; Bentivoglio et al., 1997). Another mechanism, reducing the down time of the visual system is the synchronization of blinks with saccades, the latter likewise blanking out vision due to saccadic suppression (Fogarty and Stern, 1989; Zee et al., 1983; Evinger et al., 1991, 1984). Not only voluntary saccades interfere with vision but also the fast resetting movements that are part of oculomotor reflexes that stabilize the visual background. One of these reflexes is the torsional optokinetic nystagmus (tOKN) (Farooq et al., 2004). It consists of a slow phase in which the eyes pursue the rotation of the visual stimulus in order to reduce the slip of its retinal image, followed by a torsional fast phase in the opposite direction. The fast phase, generally considered to rely on the brainstem premotor circuitry for saccades (Tozzi et al., 2007), ensures that the eyes stay within the mechanical limits of the plant. In view of the tight interaction of voluntary saccades and blinks we expected that also the involuntary fast phases of the tOKN might be synchronized with blinks in order to minimize the overall down time of the visual system. Here we report that the overarching goal to optimize visual perception is actually met in a surprisingly different manner. Rather than combining fast phases with blinks, the oculomotor system deploys a novel type of resetting movement which is qualitatively different from fast phases. Results Blinks reset the torsional eye position Experiments were carried out in a dark room with subjects sitting in front of a tangent screen on which visual stimuli were presented. During the whole experiment they had to fixate a red dot located straight ahead. Each experimental block consisted of four phases (see Figure 1, and Materials and methods). Figure 1 Download asset Open asset Torsional eye movements evoked by an optokinetic stimulus. (A) An example of the experimental block depicting the stimulus in the upper row and the associated torsional eye position beneath. A block consisted of four phases. ‘Fixation in darkness’ phase I was a fixation period (start from zero), followed by a optic flow phase I phase in which a large field visual stimulus rotating counterclockwise was presented on the monitor (start marked with a red line). The subsequent ‘fixation in darkness’ phase II and ‘optic flow’ phase II were identical to ‘fixation in darkness’ phase I and ‘optic flow’ phase I, respectively. Note the build-up of eye torsion during the stimulus presentation. (B) Enlarged torsional eye position from (A) showing torsional optokinetic nystagmus consisting of fast phases in green towards the zero torsional eye position and slow phases in red which follow the direction of the rotating stimulus. Notice that the eye torsional position did not return completely back to zero, i.e. it showed a hysteresis effect. https://doi.org/10.7554/eLife.16290.003 Eye position was recorded by 3-D video-oculography (for details, see Materials and methods). The mean torsional eye position during the first phase (fixation in darkness I), when only the central fixation dot was visible, was taken as reference for eye torsion (referred to as zero torsion from now on). During the ‘fixation in darkness’ phase I, which lasted for 180 s, the eye torsion fluctuated around zero by ± 2 deg (mean ± std, by averaging the individual means of subjects, calculated as the average of the eye position for the 180 s). In the second phase (optic flow I), a large field visual background (108 deg x 90 deg) appeared on the screen that rotated around the fixation dot at 30 deg/s clockwise, or, alternatively counterclockwise. When subjects were retested on other days the rotation direction experienced was the respective other one (see Materials and methods). This torsional optic flow stimulus was presented for 270 s. The eyes followed the torsional flow with a mean velocity of ~2.95 ± 2.9 deg/s (mean ± std across subjects). This following movement, the slow phase of the torsional optokinetic nystagmus (tOKN), was time and again interrupted by fast movements in the opposite direction, corresponding to the fast phases of the tOKN, which aim to move the eyes back towards zero torsion. This resetting was, however, imperfect as reflected by a gradual build-up in the direction of the optic flow until a plateau of ~3–8 deg was reached. This plateau varied between subjects and experimental blocks. This build-up is a consequence of a smaller cumulative amplitude of fast phases as compared to the cumulative amplitude of slow phases. When the optic flow phase had ended, a fixation period of 180 s duration in total darkness followed (fixation in darkness II). During this time the overall eye torsion slowly drifted back towards zero torsion, yet, usually without fully reaching it. Finally, the fourth phase (optic flow II), which replicated the stimulus conditions of phase 2, completed the experimental block. Blinks could easily be detected and distinguished from saccades in the video-oculographic records based on their characteristic signature (see Materials and methods). During the ‘optic flow’ phases I and II, once the eyes showed an optokinetic nystagmus and had gradually reached their respective plateau of up to 8 deg, we observed a change in the eye position towards zero torsion associated with each blink. We will refer to this eye movement as blink-associated resetting movement, BARM (see Figure 2B,E). The amplitudes of these BARMs were in the order of one degree (1.34 ± 1.3 deg, mean ± std across subjects). In the ‘fixation in darkness’ phase I, when only the fixation dot was present and deviations from zero were small, BARMs were also seen, but they were less frequent, more variable in direction and smaller (0.6 ± 0.89 deg, mean ± std, see Figure 2A,D). In the ‘fixation in darkness’ phase II, however, in which the visual conditions were not different from the ‘fixation in darkness’ phase I, but the average eye position had not yet fully returned to zero torsion, BARMs were much more frequent and of larger amplitude (0.68 ± 0.79 deg mean ± std, p=0.02, fixation in darkness phase II vs. fixation in darkness phase I, see Figure 2C,F for one of the subjects; for the other subjects see Figure 2—figure supplement 1). This suggests that the probability and the amplitude of BARMs are determined by the deviation of the eyes from zero torsion, no matter if an optokinetic stimulus is present or not. In accordance with this view, we found the amplitude of BARMs to be linearly correlated with the size of the pre-blink torsional eye position, which is the deviation from zero torsion (see Figure 3A). In contrast, the amplitude of BARMs was not related to the slow phase preceding the blink, since the amplitude of the slow phase, defined by the difference of the torsional eye position between the onset of the slow phase and the onset of the blink, was not correlated with the amplitude of BARMs (see Figure 3B, for the other subjects see Figure 3—figure supplement 1). In other words, the absolute torsional eye position matters but the latest history of the slow phase does not. Although the correlation between the amplitude of BARMs and the pre-blink eye position was strongest for the ‘optic flow’ phase I and II (see Table 1), in which the optokinetic stimulus was present and the deviation from zero was largest, we found similar relationships also for the ‘fixation in darkness’ phase I and phase II. This supports the view that BARMs are not restricted to optic flow stimuli but that they are a ubiquitous phenomenon. In accordance with the correlation analysis, also the slope of the regression of the BARM amplitude as a function of the pre-blink torsional eye position was largest for the ‘optic flow’ phase I and II, intermediate for the ‘fixation in darkness’ phase II and smallest for the ‘fixation in darkness’ phase I. In order to elucidate if theses experimental phase differences were a consequence of different ranges of pre-blink torsional eye positions in the various phases, the regressions and the correlations were recalculated for exactly the same, constrained range of pre-blink torsional eye positions (−2 deg to 2 deg). Table 1 shows that the differences between phases in terms of the quality of fits and the slopes of the regression lines stayed. This indicates that the BARM amplitude is not only dependent on the pre-blink torsional eye position preceding a single BARM but additionally influenced by the average torsional eye position of a phase. It suggests a gain modulation of the linear relation between pre-blink torsional eye position and BARM amplitude according to superordinate requirements. Figure 2 with 1 supplement see all Download asset Open asset Example of blinks during fixation in darkness (A, D) and during the presentation of the optic flow pattern (B, E). In (B) the optic flow is counterclockwise, in (E) clockwise. Dotted lines demarcate the period around the blink-associated artifact of the eye position record, which was not considered for analysis (see Materials and methods). Note the torsional eye position shift towards zero after every blink during the presentation of optic flow stimulus, and less consistently in darkness. (C and F) are comparing the pre- and post-blink torsional eye position for all blinks observed in two blocks examples of subject M. https://doi.org/10.7554/eLife.16290.004 Figure 3 with 1 supplement see all Download asset Open asset The dependence of the size of eye torsion resetting on the torsional eye position before the onset of resetting is specific for BARMs. (A) The torsional shift of BARMs during optic flow and darkness, and the torsional shift of fast phase saccades during optic flow is plotted as function of the torsional eye position before the shift for the subject O. Note the strong dependence of the shift size on the pre-shift torsional eye position for BARMs (blue), but not for fast phase saccades (green). This dependence of BARMs is stronger for optic flow backgrounds (blue) than for dark backgrounds (black). The regression lines (red) are only drawn in case of significant correlations (see Materials and methods). (B) The torsional shift of BARMs and fast phase saccades is plotted as function of the amplitude of the preceding slow phase for the subject O. In contrast to (A), the torsional shift of fast phases but not that of BARMs showed a dependence on slow phases. When there are two regression lines plotted the values listed refer to the mean of values derived from both regression analyses (see Materials and methods). In (C) the mean correlation coefficients (95% confidence interval) between torsional shift and pre-shift eye position (y-axis) are plotted relative to those between torsional shift and pre-shift slow phase amplitude (x-axis) for each of the 5 subjects separately for BARMs (blue) and fast phases (green). The clear distinction between BARMs and fast phases in their torsional shift dependence on eye position (BARMs) or preceding slow phase (fast phases) is apparent. The borders of the 95% confidence interval are not visible because they are very small (see Materials and methods). (D) The differential dependence of torsional shift on pre-shift eye position and pre-shift slow phase amplitude for BARMs is indicated by clearly different 2D linear regression fits (based on the ‘optic flow’ phases, subject O). The tilt of the plane and the change of the darkness of color along the torsional eye position axis illustrates the major role of pre-shift eye position for the torsional shift. (E) For fast phases (clockwise optic flow, subject O) the plane is tilted and the darkness of color changes along the slow phase amplitude axis demonstrating the major role of pre-shift slow phase amplitude for the torsional shift by fast phases. (F) Similar to (C) the slopes of the 2D regression analysis are shown for all subjects separately for BARMs and fast phases. The distinction between both is reproduced. https://doi.org/10.7554/eLife.16290.006 Table 1 Relationship between torsional shifts of BARM’s and pre-blink eye position for different experimental phases and ranges of pre-blink eye torsion. The steeper slopes and larger correlation coefficients for the ‘optic flow’ phase I and II are also observed when restricting the range of pre-blink eye torsion. Also the steeper slopes and larger correlation coefficients in the ‘fixation in darkness’ phase II as compared to the ‘fixation in darkness’ phase I are maintained when analyzing the restricted range for pooled data from all subjects and experimental blocks. https://doi.org/10.7554/eLife.16290.008 PhaseRegression slope (mean ± std)Correlation (mean ± std)P-value of the correlationsfixation in darkness phase I−0.26 ± 0.09−0.33 ± 0.1p<0.005optic flow phase I and II−0.62 ± 0.163−0.73 ± 0.19p<0.005fixation in darkness phase II−0.28 ± 0.15−0.48 ± 0.1p<0.005fixation in darkness phase I (−2° to 2°)−0.08 ± 0.09−0.18 ± 0.14p<0.005optic flow phase I and II (−2° to 2°)−0.43 ± 0.1−0.60 ± 0.25p<0.005fixation in darkness phase II (−2° to 2°)0.12 ± 0.07−0.25 ± 0.08p<0.005 Are BARMs, in fact, fast phases coinciding with blinks? The occurrence of BARMs during the ‘fixation in darkness’ phases I and II argues against this objection. In these phases there was no optokinetic stimulus present that could give rise to a fast phase optokinetic response. Moreover, the fixation in darkness period I did not follow a preceding exposure to an optokinetic stimulus, excluding fast phases as hangovers of earlier optokinetic stimulation. Further evidence for a qualitative difference between BARMs and fast phases comes from an analysis that we performed for fast phases in analogy to the one for BARMs described before. In the case of fast phases, the preceding slow phase amplitude, i.e. the difference between the onset and the offset of the slow phase explains a large part of the amplitude of the following fast phase (r = −0.35 ± 0.1 mean ± std. across subjects, Figure 3 and Figure 3—figure supplement 1, mean slope of 0.33). On the other hand, the torsional eye position at the onset of the fast phase has little if any influence on the size of the fast phase amplitude (correlations are only weak and inconsistent: significant correlation in 3 out of 5 subjects, r = −0.18 ± 0.09 mean ± std. across subjects, see Figure 3 and Figure 3—figure supplement 1). This is very different from BARMs, in which – as said earlier - it is the pre-blink torsional eye position which determines the size of the BARM. Moreover, the amplitude of the fast phases are dependent on the optic flow direction. This is why they form two separated clusters in plots of fast phase amplitude as function of the direction of the optic flow. Fitting these two clusters requires separate linear regressions yielding different regression slopes and offsets in comparison with fitting them as one pool (see Materials and methods). On the other hand, BARMs form a continuous distribution with similar regression slopes and offsets independent of the direction of the optic flow. This was confirmed by having almost no difference between the regression slopes produced by fitting blinks as two separated pools, depending on the optic flow direction, and by fitting them as one (see details in Figure 3, Figure 3—figure supplement 1 legends and Materials and methods). We conclude that BARMs and fast phases are functionally two distinct entities (see Figure 3C and F). Blink-associated resetting of eye torsion is realized by a specific type of eye movement Although functionally distinct from fast phases, BARMs could nevertheless be a kinematic product of the saccade machinery, simply working under a different control command (torsional eye position instead of slow phase amplitude). Alternatively, they could be modifications of blink-associated eye movements that occur during fixation and that have been described in studies of visual fixation in the of optic flow. movements are and and are usually as an oculomotor the and function of blinks et al., et al., et al., the of these two requires information on the of the eye movements BARMs. However, the eye lid during the blinks from the information This is why we the experiment before in subjects, to and (see Materials and methods). This the of eye position in all independent of whether the eyes were or We observed and eye movements during blinks very similar to previous of blink-associated eye movements during fixation in the of torsional optic flow et al., et al., et al., The analysis of torsional eye movements during blinks showed across out of subjects had blink-associated eye of two clearly distinct ± ± ± ± mean ± std In one the two were not clearly because they were most (see Figure 5 for in Figure for subject the of the first was from blink onset ± mean ± std, all ± with an amplitude of degree ± deg, all ± deg). The torsional of the first was clockwise. the eye was this to an eye It was by a movement as compared to the pre-blink the described for blinks during fixation et al., et al., et al., we found this first not only in the ‘fixation in darkness’ phase I and II, when the subject had to fixate in darkness, but also in the ‘optic flow’ phase I and II when the optic flow was The of this first did not change between phases most the direction of it was not by the direction of the optic flow, which would be if it had a role (see Figure The only relation between the first torsional and BARMs was found in ‘optic flow’ phase I and II, in which the torsional amplitude was larger when the optic flow in the same direction, i.e. clockwise, as compared to the counterclockwise direction. This was reflected by a correlation between the amplitude of the first and the amplitude of BARMs (r = based on the four subjects with two In other words, the influence of the optic flow on the first was with the optic flow direction. For this it for the of BARMs. Figure Download asset Open asset of eye movements during blinks with The and torsional eye movements observed during blinks are shown in different experimental phases. are eye movements from blocks in which the optic flow during the ‘optic flow’ phase I rotated blocks with optic flow. The same color is to eye movements in the two darkness phases, which the ‘fixation in darkness’ phase I or followed by the ‘fixation in darkness’ the one with or optic flow. the comparison of eye movement during blinks with the overall eye position during a phase, the in each the mean eye position for the whole duration of the respective experimental phase. Note that the torsional eye movement response consists of two distinct the first one is and across the phases, the following second is opposite to the overall eye position of a phase in accordance with a role in resetting the eye torsion to For the torsional is by the difference in the of the The eye are to the velocity of the first Eye are plotted from before and after that lines the mean and of blinks from the eye (see Materials and methods). the time for the eye position after the blink to green lines with were the mean ± std experimental blocks for Note that the second during the and it after the of the which could be during lid and not at the offset of the (see Materials and methods). The blink the in to with around before the onset of the The opposite was found for the second velocity was reached ± (mean ± std across subjects and phases) after the velocity of the first in the ‘fixation in darkness’ phase I and II. Although the velocity was different in the ‘optic flow’ phase I and II, velocity was reached after a similar (see Figure Therefore it is to the 2 in flow phases to be of the same as the one in optic flow phases. is the that the torsional direction of the second on the direction of the optic flow. expected for a mechanism, it was opposite to the optic flow. Moreover, the amplitude of the torsional was larger during optic flow phases, when there was more need for as compared to flow phases. a matter of fact, the torsional amplitude of the second correlated with the amplitude of BARMs, the latter as in the records by comparing pre- and post-blink eye torsion. This correlation could be for all phases and subjects (fixation in darkness phase r = optic flow phase I and r = fixation in darkness phase r = based on pooled data from four out of subjects). Finally, we found no relationships between the amplitude of BARMs and the and eye movements the blink. In it is the second which the to the BARMs by eye Moreover, the second of and eye One namely if this second of BARMs is to blinks or a type of saccades. a kinematic of view, an eye movement as a saccade if the between its amplitude and velocity the first for saccades et al., A of the fast phases of the tOKN in the ‘optic flow’ phases I and II showed the expected almost linear of velocity with amplitude The two blink in their on the and in the between amplitude and the first of blink-associated eye movements recorded with did - as expected - not a of velocity on amplitude for all subjects, the second the of a saccadic eye movement not that different from that of fast phases the regression was to for all (see Materials and and Figure in kinematic terms BARMs are a type of saccade that can be distinguished from fast phases because of their very different Figure 5 Download asset Open asset Eye movement velocity as a function of BARMs The velocity of the eye movements is drawn on the vs. their amplitude on the The first of blink related torsional movement is drawn in green the second (BARMs) in red and the fast phase of tOKN in The 5 from 5 The 3 the experimental phases with the of the