Ординатура / Офтальмология / Английские материалы / Age-Related Changes of the Human Eye_Cavallotti, Cerulli_2008

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In this chapter the neuroanatomical and neurophysiological background of the blink circuit and the consequences of aging will be discussed. Eyelid and eye kinematics are described for healthy subjects and patients with facial movement disorders. Attention will be paid to the blink rate, which can be used as an external parameter of the condition of the blink circuit and the brain structures influencing the circuit in health and disease. Reflex blinks give important information and are excellent experimental models for the assessment of internal networks and nuclei. The reflex blink circuit is the most commonly used neuronal blink circuit model for the study of how relatively simple lid movements are controlled and generated by the central nervous system.

Several focal dystonia will be discussed in relation to blinking, and finally reflex blinking will be used as a tool to determine the consequences of cerebellar diseases on the precise timing in the onset of eyelid movement after a stimulus.

Because it is impossible to discuss in this chapter all the different aspects of brain, brainstem, and cranial nerve function related to blinking and aging, a selection of subjects was made focusing on the most common movement disorders.

Neuroanatomical and Neurophysiological Background

of the Blink Circuit

In humans, eyelid responses mainly result from the neuronal activity of two different motor systems: the facial and the oculomotor systems.6-8

The facial motor system innervates facial muscles, including the orbicularis oculi muscle. The orbicularis oculi muscle is a sphincter muscle and can be divided into an orbital portion, a preseptal portion, and a pretarsal portion.8 The orbicularis oculi muscle fibers are relatively short and heterogeneous in length.3 The muscle fibers are arranged parallel to the rims of the eyelids.

The oculomotor system innervates five of the six extraocular muscles; the inferior oblique muscle, the recti superior, inferior, and medial muscles, and the levator palpebrae superioris muscle. The levator palpebrae superioris muscle contains a unique levator slow-twitch fiber type,9 and the levator aponeurosis connects this muscle with the upper eyelid.

Efferently, the motoneurons that innervate the orbicularis oculi muscle are located in the ipsilateral intermediate subnucleus of the facial motor nucleus.8 The motoneurons of the levator palpebrae superioris are located in the central caudal nucleus (CCN) of the oculomotor nucleus.7

A population of CCN motoneurons subserves both levator muscles and is probably involved in synchronizing eyelid movement.

Afferently, the orbicularis oculi muscle, like all facial muscles, lacks sensory innervation.7 Sensory innervation via the muscle spindle was found in the levator palpebrae superioris muscle of a human fetus.10 This result confirms the retrograde tracing study in the levator palpebrae superioris muscles of the monkey, in which primary sensory neurons were detected in the gasserian ganglion.7

Fig. 19.2 An area in the pontomedullary reticular formation, the dorsal part of the medullary reticular nucleus, subserve both the facial and oculomotor systems

of the medullary reticular nucleus, premotor neurons of the superior colliculus were observed.14 In another study inhibitory glutamic acid decarboxylase (GAD) premotor neurons of the facial motor nucleus were located in the paralemniscal zone of the midbrain tegmentum.15 This study does not describe an exclusive blink premotor area, as the retrograde tracer injections comprised almost the whole facial nucleus.

Numerous studies have exposed the mechanisms of coordination of the levator palpebrae superioris muscles during lid saccades. Compelling neuroanatomical and neurophysiological data exist on levator palpebrae superioris muscle innervation during lid saccades.16-18 Little is known about the pathways of premotor neurons of the central caudal nucleus that innervate the levator palpebrae superioris muscle during blinking.

Fig. 19.3 Separated areas in the reticular formation and cervical spinal cord were found to initiate only an eyelid or an eye movement during blinking

Neuronal tracing studies in humans, monkeys, and cats reveal that the medial longitudinal fasciculus17 and the interstitial nucleus of Cajal serve as premotor areas for lid saccades.18 In cats, retrograde tracer injections in the interstitial nucleus of Cajal did not result in labeling of a specific neuron population in the pontomedullary reticular formation, a candidate location for the “eye blink generator.” This finding indicates that the location of the blink generator for eye movements is entirely different from that of the “eye blink generator.” Further investigations are needed to localize the pathway(s) between the “blink” levator premotor neurons and the “eye blink generator.”

The eye movement component during blinking is initiated by neurons of the lateral superior colliculus portion.19 The afferent pathways of the eye movement component run via the gasserian ganglion to the sensory trigeminal complex towards the deep layers of the lateral superior colliculus portion.20-21 The neuronal pathways between the superior colliculus and specific areas of the lateral reticular formation were explored by neuronal tracing studies in rats.13-14

Connections between higher brain areas and the brainstem, including the intermediate stations, are speculative. An extensive neuronal tracing study of the monkey

motor cortex and facial motor nuclei revealed that the representation regions of the upper and lower face, located in the gyrus precentralis of the motor cortex, project directly to the facial motor nucleus. The upper face region projects mainly bilaterally and the lower face region projects contralaterally to the facial motor subnuclei.22-23 Further analysis revealed that other higher brain structures are involved in blinking. Basal ganglia and probably the noradrenergic system24-25 can modulate the blink reflex. In Parkinson’s patients the dopaminergic system is disturbed, which results in a higher blink rate with deviated blink profiles26 and lid saccadic metrics.27

Other suprasegmental structures, such as the primary motor cortex, supplementary motor area, dorsolateral prefrontal cortex, posterior parietal cortex, visual cortex, central thalamus, and cerebellum are connected with the facial motor nucleus.28

The cerebellum, besides its function in motor learning and memory, is also important for the control of fine motor movements, the balance control.29 The cerebellar cortex, like the motor cortex, contains a homunculus of the body. It is known that the hemispheral lobule VI represents the area of eyelid-related movements.30-31 Direct projections from lobule VI towards brainstem regions involved in blinking have not yet been found. The common opinion is that lobule VI is connected with one of the deep cerebellar nuclei, the interpositus nucleus. The interpositus nucleus is connected with the red nucleus,32 which projects to the reticular part of the blink circuit.11

Recently a neurophysiological study in a group of cerebellar ataxia patients showed aberrant timing of blink reflex (unpublished results).

Blink Rate

Humans blink for the first time in the fetal stage at 33 weeks menstrual age. The fetal “spontaneous” blink rate is 6 blinks per hour;33 at birth the blink rate increases up to 4 blinks per minute. In adults the spontaneous blink rate is about 14 blinks per minute in the rest position, and by the age of 89 the blink rate increases to 31 blinks per minute.34 Thus throughout life the blink rate increases about 300-fold! Blink rate can dramatically be reduced to 0 to 3 blinks per minute in patients with the Steel-Richardson-Olszewski syndrome or slightly decreased in Parkinson patients26,35 and remarkably increased to over 50 blinks per minute in patients with cranial dystonia.36

Gender can influence the blink rate; men blink faster and suppress blinks better than women.37 In addition, the blink rate can be changed by numerous other neuropathological conditions.

External factors like the time of day, environment, humidity, emotional state, mental load, or activity can also influence blinks and blink rate. A study of the influence of humidity on blinking revealed that an elderly group with a mean age of 71 tended to blink less frequently than a young group with a mean age of 22, although the differences were not significant.38 Because the groups were small and rather variable in age, analysis of larger groups is necessary to gain significant differences.

blinks.6 These eyelid responses are used as a measure of associative motor learning and memory.39 Conditioned blink responses are longer in duration, have longer lid closure duration, the maximal downward amplitude is lower, and the neural mechanisms underlying the eyelid movement are different. Therefore it is questioned whether these “blinks” can be defined as blinks and not as conditioned eyelid movements: CEMs.

Eyelid movement during blinking can be translated into three vectors: the vertical and horizontal displacement, and retraction. The vertical displacement is the most important one, but horizontal displacement is also a crucial factor in eyelid movement. The contraction of the eyelid during blinking slightly changes the 3-D position of eyelid tissues and retracts the eye between 1.0 and 2.0 mm.40

The origin and kinematics of horizontal displacement during eyelid movement has recently encouraged a discussion about the performance of eyelid surgery in ptosis patients.41 An important issue in this discussion between ophthalmologists and plastic reconstructive surgeons was agreement on the definition of the primary position of the eye when the subject looks straight forward.42 This center position is crucial for detailed reconstruction of “normal” lid movement in these ptosis patients. The vertical and horizontal eyelid displacement can be observed with an eye tracker or video camera in order to obtain the eyelid movement during a blink.

The kinematics of eyelids are best investigated with electromagnetic recordings in combination with orbicularis oculi electromyography (OO-EMG) recordings.43 Surface EMG recordings made with a wide-frequency band allow measuring of the low frequencies involved in eyelid movement. This method may also be useful to characterize blink disturbances.44 There is a risk of signal recording from nearby muscles because of volume conduction.45 Other tools used for examining eyelid kinematics are the high-speed video camera and electroencephalography.46

Of all blinks, reflex blinks are the least variable in duration, maximal downward amplitude, and maximal downward velocity. Blinks elicited by acoustic click have the shortest duration and latency, followed by blinks elicited by electrical stimulation of the supraorbital nerve or an air puff on the cornea. Spontaneous blinks have the longest duration and greatest variability.43

Simultaneous eye movements occur in all three types of blinks.12 In general, about 4 ms after the onset of eyelid closure, the eye movement starts. The direction of the eye movement runs from the initial gaze position, down towards the nose, smoothly followed by a lateral upward movement towards the initial gaze position.1 Another active movement where eyelids and eyes act simultaneously is the lid saccade. During a saccade the eyelid follows the eye independent of the goal position of the saccade. Since saccades require eye and eyelid movement coordination they should be regulated by a common neuronal structure or “saccadic

generator.”

The kinematics of eyelid closure are good tools to investigate the influence of aging on blinking. Sun and coworkers34 demonstrated disorders of blink systems in a group of subjects aged 50 years or older. These authors observed an age-related reduction in the relationship between the peak velocity and the amplitude during a blink, the so-called main sequence slope. This was interpreted as a reduction in