System Saccadometer applications

The neural structures that control saccades comprise nearly every level of the brain, and neurological and physiological disorders have a variety of effects on the saccadic parameters that are characteristic of their origin. These effects may be divided into two types, saccadic velocity and saccadic latency.

Saccadic velocity

The lower levels of the saccadic system – the brainstem, the motor neurons and their axons and endplates, the muscles themselves – determine the saccadic time-course. Saccades are stereotyped movements, and saccadic velocity is notably constant under physiological conditions across all humans at a given age, comparable for instance to the constancy of core body temperature at 37°C. At the same time it is highly and specifically responsive to all kinds of disturbances at this level, at which the motor commands to the contractile muscular fibres are generated and delivered, so that saccadic velocity is a most sensitive indicator of even slight disturbances within the neuromuscular system.

The reason is that this level of saccadic control is a highly evolved one. Saccades are some of the fastest movement that the body makes, often less than 25ms in duration and with the eye reaching velocities of up to 800deg/s. Very precise temporal patterns of firing have to be created by the brainstem to achieve precise movements so quickly. It is striking that whereas the firing rate accompanying the maximum contraction of skeletal muscles dopes not typically exceed 30Hz, during moderate-sized saccades the frequency may reach 600Hz. This demands extremely high bandwidth from the saccadic system as a whole, more than an order of magnitude (ten fold) higher than is usually required for skeletal muscle. Thus any disturbance in the neuromuscular system is manifested as the reduction of the bandwidth of the neuromuscular system as whole. This is why impairment of saccadic dynamics is one of the very first signs of nearly every neuromuscular pathology right at its onset, observable long before the appearance of symptoms in other parts of the neuromuscular system.

A further reason why the saccadic system is often the most sensitive indicator of disturbances of bandwidth is the invariance of the mechanical properties of the 'plant' – the inertia of the eye, and the elasticity and viscosity of the mechanical structures (muscle and connective tissue) that connect it to the orbit. Mechanical inertia of the eye itself is so small that it does not significantly influence eye movement. In fact, because the mechanics are dominated by viscosity, the velocity profile of the saccade can be considered as equivalent to the profile of the force generated by the agonist muscles. This means that without having to insert needle electrodes into the muscle trunk or dissecting one of the muscle attachment and connecting it to a force transducer, we can record precisely and non-invasively the time-course of the muscle activation.

Saccadic latency

The second way in which saccades are controlled is at a completely different, higher, level in the brain. Clearly, it is not enough to be able to generate precise and rapid saccades: they need to be correctly directed to objects in the outside world that are of importance. Corresponding to this, there is direct descending control of the oculomotor brainstem from midbrain regions such as the colliculus, whose function is to translate position in the visual world into a correctly-directed eye movement; and these midbrain regions are themselves under descending control, both inhibitory and excitatory, from cortical and basal ganglia areas whose function is to recognise potential oculomotor targets, and evaluate which of them should be the goal for the next saccade. The study of these high-level neural mechanisms of decision has been an enormous focus of interest in recent years, and it turns out that the measurement of reaction time or latency, both for saccades and other kinds of movement, can provide detailed quantitative information about the functioning of these Bayesian decision mechanisms. In particular, analysis of the way in which latency varies from trial to trial, generating a stochastic latency distribution, allows estimation of the underlying decision parameters such as level of excitability, rate of information processing, and spontaneity. These measures can be extremely sensitive: for instance, a recent study demonstrated specific impairment of the rate of information processing in response to doses of anaesthetic representing only a small fraction of what is needed to induce anaesthesia. An advantage of studying saccadic latency is that – unlike most neurocognitive tests - it provides separate and symmetrical measures for the two hemispheres, so that one side can act as a control for the other. Work in progress has demonstrated the utility of this approach in evaluating peri-operative cerebral impairment in endarterectomy. Other recent studies have shown its utility in the diagnosis of Huntington’s and Parkinson’s disease, and ongoing work in Maastricht has demonstrated very large effects that can be used to compare the efficacy of conventional medication for PD and deep brain stimulation of the subthalamic nucleus in human patients. Other studies are looking at the effects of conditions that would not normally be regarded as neurological, but have consequences for saccadic latency: storage disorders such as Gaucher’s disease, and liver pathology.

Thus, these two measures – latency and velocity – together provide information about the functional status of two entirely distinct levels of the brain. Previously, using the physiological features of the saccadic eye movements for medical diagnosis was restricted by very limited access to the clinical eye movement laboratories; now measurements can be made at the bedside, in the clinic or even in the waiting room. We believe that this opens up exciting possibilities for quantitative neurology, and all over the world the saccadometer is now being used for precise measurements of brain function in clinical settings.

From a medical perspective

Clinicians are already familiar with the diagnostic value of disturbed ocular motility, especially in the field of neurology and ophthalmology. The widely used procedure of ocular motility examination is based on direct observation of eye movements in response to a visual stimuli presented by doctor to the subject manually, like "Please follow my finger tip". In this way many kinds of so called slow oculomotor responses including OKN and VOR can be evaluated partly without instrumentation.

But the important exception is saccadic eye movement, because of its high speed and short duration. Violations of saccadic correctness have a high potential value for differential diagnosis of a wide range of conditions, from neuromuscular diseases, right at the early stage of its development, right up to frontal lobe dysfunction, and non-neurological conditions, including the effects of vascular and cardiac surgery, as well as neurological conditions. Unfortunately its observation and analysis requires instrumentation, which until now was available only in specialised clinical laboratories. The Saccadometer is a highly specialised measuring system dedicated exclusively to saccadic measurement. It is non-invasive and comfortable for the subject; because it generates its own stimuli by projection, no special screens are needed for the targets, and the patient’s head does not have to be restrained in any way. It is simple to use with minimal training: it does not require the operator to possess knowledge of ocular motility testing, usually necessary when performing the saccadic examination in the specialised clinical laboratories. Nor does it require an understanding of eye movement measurement technology, necessary for proper adjustment of most systems. The readout from the Saccadometer is a single number, representing the duration of a saccade of given amplitude, which has a direct physiological meaning, analogous to determining a patient’s fever with an electronic thermometer. More detailed information is stored automatically during measurement sessions and can be downloaded at the end of the day to a laptop for quantitative analysis of velocity and latency profiles, including sophisticated determination of the underlying decision performance by the cortex.

For all these reasons we can expect that this instrument will be widely used by general practitioners as well as hospital clinicians. As can be seen on the both pictures, the Saccadometer is a pocket size battery powered instrument. Optionally the optically isolated computer interface and the advanced software for saccadic analysis is available. It has the potential to become a widely used diagnostic instrument like the sphygmomanometer or the stethoscope.