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

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Abstract

The decade and a half following the Second World War was a particularly interesting period in human eye-movement research. The enlistment of scientists and engineers in technical projects for the war effort showed many of them the way towards practical applications. This included not only electronic devices and computers, but also instrumentation and procedures for solving problems in biology and medicine. Accompanying this development was a change in attitude in the direction of applying rigorous modes of analysis. With instrumentation derived from war surplus material and under the banner of “systems theory,” eye movements, the pupil and accommodation responses were recorded to step, pulse, ramp and sinusoidal stimuli. Transfer functions were calculated and openand closed-loop behaviour investigated. Because this was the first round, researchers did not see, or because of their physicalist biases were even unprepared and unable to see, possible mismatches between their biological systems and their analytical probe.

Though the study of human eye movements has a venerable history, a constellation of circumstances made the 1950s a particularly fertile period of advances. Up to then, progress had been sporadic. In psychology and education, eye movements were being recorded during reading and the results used in attempts to measure learning deficits (Carmichael & Dearborn, 1947). The American Optical Company marketed a moving film camera device for that purpose. There was some interest in ocular motility among neuro-ophthalmologists (Adler, 1950; Cogan, 1956) but almost none within the ranks of neuromuscular physiologists, whose focus then was on lower motor reflexes that could be studied in spinal preparations.

1. Change in mindset

The Second World War brought about a fundamental change. Large numbers of physical scientists and engineers enlisted in research efforts that may best be described as applied science. Specific examples are radar, submarine detection, control of guns, bombs, vehicles and aircraft. The projects had deterministic end points and the whole exercise was to achieve a defined goal by whatever means that could be marshalled. The war had wide popular support and almost everyone was engaged in it without reservation. As a consequence, the personnel tackling the scientific and technical projects were of the highest calibre; a whole generation of the intellectual elite became effective problem solvers who learned what was needed to achieve practical success.

In the years following the war this attitude and the hardware that resulted from the war effort began to be channelled in new directions: electronics and computers are the most prominent of these, but instrumentation and procedures for biological research also were beneficiaries. Until then, the armamentarium of neurophysiology – electrodes, stimulators, amplifiers – was one of a kind. Good academic departments had workshops in which skilled technicians laboriously hand-designed and crafted research apparatus. Reliable oscilloscopes, invaluable in this work, were just becoming more readily available. And so did microscopes, optical and electron.

Perhaps even more important was the change in the mindset that these wartime activities generated. An example will illustrate. In the 1940s mathematics programme of Sydney University, as taught by Cambridge wranglers, we used as a textbook Piaggio’s Treatise on Differential Equations (Piaggio, 1944). Here are some quotations from the Preface: “The theory of differential equations, said Sophus Lie, is the most important branch of modern mathematics If we travel along the purely analytical path, we are soon led to discuss infinite series, existence theorems and the theory of functions.” As a graduate student in 1951, I came across a textbook covering much the same ground as Piaggio’s. But Trimmer’s book (Trimmer, 1950) was entitled The response of physical systems and here are excerpts from its preface: “The book is based on material used for lectures and laboratory sessions of a course ‘Instrumentation’ ”. Trimmer goes on to write about “the emergence of a discipline called ‘system response’ ” and about “the relation of instrumentation and system response to the newly defined ‘Cybernetics’ ”

quoting Norbert Wiener’s book (Wiener, 1948). In addition to Wiener’s Cybernetics, he might have mentioned an even more seminal contemporary, Shannon’s information theory (Shannon & Weaver, 1949). Within a span of a few years, the lecture courses in differential equations changed their emphasis from existence theorems to instrumentation.

Eye movement had been a subject dear to the hearts of earlier generations of psychologists. The single most influential paper in the whole subject, clearly distinguishing between the saccades and pursuit movements, was written by R. Dodge, a Yale psychologist (Dodge, 1903) and the topic has had a presence in experimental psychology since Wundt’s time. In the 1950s one strand of it concerned itself with the steadiness of the eyes during normal fixation.

2. Micronystagmus

Some years earlier Adler and Fliegelmann had shown in inventive experiments that the eyes were never still even during intersaccadic intervals (Adler & Fliegelman, 1934). Movements, called micronystagmus, were of sufficient magnitude – up to several minutes of arc – to raise concern about their role in visual acuity. Some people theorized that they actually sharpened vision (Marshall & Talbot, 1942) while others felt that their effect would be detrimental. The general problem was seen to be of such import that considerable ingenuity was employed by several laboratories to record the micronystagmus. Electrooculography had nowhere near the required spatial resolution (Marg, 1951), and standard photography could not reliably distinguish between rotational eye movements, which would displace images on the retina, and translational movements of the whole eyeball, which would not. The procedure of choice, developed in the laboratory of both Riggs at Brown University (Riggs & Ratliff, 1950), and Ditchburn at Reading (Ditchburn & Ginsborg, 1953), involved reflecting light from a mirror attached firmly to the eye by means of tight-fitting contact lenses. Other techniques were occasionally employed, such as a drop of mercury applied to the limbus (Barlow, 1952) or even more imaginative ones utilizing light reflected from retinal structures (Cornsweet, 1958).

Floyd Ratliff, later to gain prominence as Hartline’s collaborator, devoted his PhD thesis, working under Lorrin Riggs, to recording micronystagmus during short time intervals and relating it to the measured visual acuity in these epochs (Ratliff, 1952). His conclusion was that the two were negatively correlated. The opposing view, namely that eye-movements aided acuity, was never articulated in sufficient detail to allow its empirical validation. Altogether, the topic of visual resolution was not advanced materially by these exercises, because it was shown 20 years later (Westheimer & McKee, 1975) that target movements in the velocity range of micronystagmus do not impair acuity.

Something else about micronystagmus intrigued researchers at the time, namely the possibility that it played a role in keeping the visual process active. As a result of Hartline’s work, and later Kuffler’s, on single retinal ganglion cells, it had become apparent that most neural activity occurred at the onset and offset of light stimuli, and little during steady illumination. This insight, together with the observation that afterimages fade and

that entoptic visualization of Haidinger’s brushes (Ratliff, 1958) or the Purkinje vascular tree requires temporal transients, made people wonder what vision would be like when the optical image on the retina eye was totally stabilized. Nulling out micronystagmus requires considerable experimental expertise, involving not only contact lens mirrors but also multi-stage optical paths (Ditchburn & Fender, 1955; Ditchburn & Ginsborg, 1952). In the end it was demonstrated that when there was no jiggling of the optical image on the retina, vision does indeed fade. Nowadays we would call this a manifestation of the temporal bandpass characteristics of retinal processing; transients are necessary to activate the optic nerve impulses, though the phototransductive stages of vision have good DC output. Description of experiences with stabilized vision became quite a cottage industry, especially when it was extended into the realm of colour.

3. Systems theory

A much more direct expression of the Zeitgeist of 1950s’ science and technology was the application of “systems theory” to oculomotorics, sparked predominantly by engineers and fellow-travelling physicians, biologists and psychologists. Systems theory here was not just the – still very popular – fitting of engineering models to biological data; rather it was the enveloping concept that such models capture its essence, in other words that the prime approach is to examine biological systems as if they were black boxes whose properties and the interaction between them can be satisfactorily described and analyzed by equations. A bon mot of the times is revealing: What do you find when you open the black box? Other black boxes.

At the outset, the research framework was uncomplicated: examine the eye-movement responses of a human observer as if they were manifestations of a mechanical, or perhaps opto-electronic, control system. That is, present an unambiguous stimulus in the domain of visual target position (the input) and record and analyze the resultant eye movement (the output). Adequate photomechanical and later electro-optical instrumentation could be built, utilizing the experimentalists’ major supply line: war surplus mechanical, electrical and optical components. The shelves of laboratories then were groaning with elaborate and originally very expensive lenses, mirrors, filters, gear trains, electric motors and circuit boards, which had been intended for airplanes, submarines, radar installations and such.

The first order of business was to identify closed-loop responses to step, pulse, ramp, sinusoidal stimuli and so on. In this round, a great deal of clarity was obtained: there is a reaction time (delay) between onset of stimulus and onset of response of the order of 120 ms. Of the two classes of movement that are utilized, saccades are discretely deployed ballistiform with a step-like forcing function, while pursuit movements can be smoothly modified. An important step in systems theory is to understand the role of feedback, where the difference between the actual and the needed response is detected and utilized for correction. It was usually supposed that the intent is to foveate a target appearing (or attracting attention) in the peripheral visual field and hence, in this formulation, the error

is angular distance of the target from the fovea. A popular engineering model at the time was the sampled-data system, in which the error was sampled at discrete time intervals (Jury, 1958). Needless to say, this can cause complicated, oscillatory behaviour. This kind of thinking leads to the next step: open the loop, that is, record the system’s response to an error signal that is maintained, regardless of the resultant response. If the input is sinusoidal in a good range of temporal frequencies, such an approach can be particularly revealing, because now one obtains a Bode plot of gain and phase changes. The descriptor is called transfer function and if the input and the output remain expressed in the form of sinusoidal functions, the behaviour of the whole system in any other situation can be predicted by mere multiplication. In an equivalent approach, the elemental function is a brief pulse and the computational procedure is only marginally more complicated.

Engineering-minded people were thrilled with this development, because it gave them the chance to transfer to high-level biology many of the techniques and insights that they had so successfully employed in the design of aircraft and war materiel. The name of the discipline, servoanalysis, speaks volumes. Its origin in the world of inanimate things does not mean that it is entirely mechanistic. Thresholds, noise, dead-space in the realm of error detection, these are just a few of the concepts that had also to be contended with, and that were regarded by the engineering mind of the researchers merely as further challenges to their ingenuity. It was felt that when these were mastered, the human oculomotor system would be characterized by diagrams with boxes connected by arrows, each element representing an expression in terms of mathematically definable symbols. In preparation for this goal, many laboratories were conducting experiments to measure openand closed-loop transfer functions. Unsurprisingly, major players in this arena were the talented members of the MIT electronics laboratory, an outgrowth of the wartime Radiation Laboratory, and publisher of a 28-volume series of textbooks with such titles as Waveforms, Thresholds Signals and Theory of Servomechanisms (James, Nichols, & Phillips, 1947). For reasons which may have to do with a particular reading of dialectical materialism, many laboratories in the then “eastern bloc” had the term “cybernetics” in their name. A particularly successful venture in Germany, the Max-Planck Institute for Biocybernetics in Tuebingen, housed a group formed by Werner Reichardt, where this kind of thinking was applied most productively to insect flight.

The investigation of the vestibular and vestibulo-ocular apparatus, which is very amenable to this kind of analysis, followed a somewhat separate track at the time, presumably because, for aeronautical and astronautical considerations, it was the focus of concentration in military centres. Only in the 1960s, when it became widely apparent just how intertwined the vestibular and oculomotor systems were, did the two research streams merge.

Incidentally, while we are here talking about oculo-motility, a parallel development took place in the domain of visual sensory functions. In the mid-1950s two seminal papers by engineers were published: in 1954, DeLange subjected the temporal aspect of the human light sense to an analysis by sinusoidal flashes (DeLange, 1954) and Otto Schade in 1956 did the same for its spatial aspects using sinusoidal gratings (Schade, 1956). A significant difference between these studies and the oculomotor ones should be mentioned.

In the latter, one measured a true transfer function, obtaining the ratio of measured input and output amplitudes. In the psychophysical studies one uses the observer’s subjective detection threshold as a fixed measure of output and plots the stimulus amplitude needed to generate it.

These modes of investigation perfectly mirrored the prevailing approach to science. They were, of course, pervaded by the analytical and mechanistic mindframe immanent in the science of the time. I would argue that they were necessary stages, productive, centred on the then current state of knowledge, confirming the discipline’s standing midway between neurophysiology and cognition. Criticism of lack of a holistic predisposition are out of place, because there were no precedents for success in such a direction, vide the floundering of Gestalt psychology as a heuristic movement.

4. Limitations to the approach

The problem lies in an entirely different direction. If the use of the engineers’ system theory in eye-movement research suffered from a fatal flaw, it was that deep down it is inapplicable, and not on philosophical grounds of reductionism, but because the two are a poor match. This came home to me in two wallops in the summer of 1952 when working on my PhD thesis entitled “The Response of the human oculomotor system to visual stimuli in the horizontal plane”. I had fitted a second-order differential equation to saccades, regarding them as responses to a step forcing function. That worked well, but the simple corollary, viz. that the shape of the responses should be the same for saccades of all amplitudes, was not borne out: saturation of peak velocity started already with about 20-deg saccades (Westheimer, 1954b).Unfortunately, non-linearities enter the biological systems research as soon as you open the door. Not long after that, while recording responses to periodic square-wave and sinusoidal stimuli, I realized that, lo and behold, after just a handful of cycles, there no longer was a reaction time. Responses were synchronous or even preceded the stimulus (Westheimer, 1954a). Prediction was taking place and one could no longer rightly talk of the response to a stimulus in a systems-theoretical way.

Right at the beginning of a systems-theoretical analysis of a reasonably tractable biological apparatus – one that could be given straightforward unambiguous stimuli, that had easily measurable responses, that had no load and did not suffer from parametric feedback via muscle spindles – the limitations of the approach had to be confronted head-on.

Books such as Trimmer’s in the very first chapter warned about possible non-linearities and the consequent intractability, but in their treatment of systems such books sailed right on as if in real life non-linearities could be ignored. So one proceeded to deal with oculomotor, accommodation and pupil responses staying entirely within the mode of linear analysis. Of course, one has to start somewhere and in the application of the formulations to electrical and mechanical systems one can indeed go a long linear distance before one is pulled up. Most practitioners of oculomotor research came from physics or

engineering or, even if their original training was in medicine, had strong biases in that direction. However, the first thing any clinician or practicing biologist learns is that in their domain nothing is straightforward or linear and, when there is a poor fit between the biological preparation and the analytical probe, to proceed with caution, or to look for other avenues.

This underlying problem did not entirely disappear when the next stage of oculomotor research took over in the 1960s. A more nuanced approach was followed in the exploration of eye-movement responses, taking account of the perceptual and cognitive dimensions by examining the various strategies that human observers employ. When confronted with predictive responses, engineers would just insert an operator in their equations that shifted the response backward in time, as if that constituted a step in the scientific understanding of the system. Experimental psychologists were more aware of the kind of explanations and constructs that would have standing in such a research area.

In addition, a clearer picture began to emerge of the neural pathways through which oculomotor responses operate. Control of the intra-ocular musculature is largely confined to brainstem neurons and responses to some stimuli do not involve the cortex. Hence it is quite appropriate to talk of the “pupillary reflexes” in the traditional, Sherringtonian parlance and expect a servoanalytic approach to be not entirely out of place at the outset (Stark & Sherman, 1957). But this kind thinking begins to fail in the case of ciliary muscle and accommodation responses. Fincham, the most significant contributor to our understanding of the accommodation mechanism, still thought that focusing was a reflex akin to pupillary constriction (Fincham, 1951). But it soon became clear that the error signal, the crucial element in any servomechanism, could not be handled by unsophisticated midbrain structures (Campbell & Westheimer, 1959). And once the cerebral cortex becomes involved, with its vast interrelation and plasticity, engineering formulations, no matter how clever and elegant, become inadequate.

As modern neurophysiological exploration with microelectrodes gained ground in the 1950s, especially in the hands of Eccles and other members of the revived Sherrington motor-research school, it started also to be applied to the oculomotor system. Whereas the spinal reflexes could be studied in the encéphale isolé preparation, studies of the neural paths of oculomotor system needed the experimental animal to remain alert and behaving. Once the technical problems of recording neuronal firing when a visual stimulus elicited an eye movement were solved, an enormous and very productive enterprise developed. At the outset there still was much servo-analytical modelling, but soon the realities of the intricate neural apparatus began to assert themselves and the researchers in this discipline settled down to the long haul of unravelling the intricate midbrain and cerebellar circuitry involved in translating to the eye muscles the animal’s intention to place a particular retinal target on the fovea. This research is continuing apace.

In retrospect, one aspect of the 1950s eye-movement enterprise constituted its major limitation. Even if open-loop transfer functions could be established with some semblance of linearity, generality and validity, they are still intended to describe only the performance in a servomechanistic setting: keeping a target on the fovea as it experiences displacements. But in a richly textured visual world, a conscious observer’s oculomotor

behaviour depends on many more influences. The current movement towards “natural scenes” is trying to encompass them. Will the problems in such multi-layered research environment make the next-generation of scientist look back with nostalgia to a time when their predecessors’ aim was merely to succeed with operators and transfer functions from engineering handbooks?

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