Neural Control of the Eyelid

Although the position of the upper eyelid is actively controlled by several muscles, eyelid closure (blink) is itself a passive movement of the eyelid. It occurs when innervation of the levator palpebrae muscle (LPM) ceases [1]. In addition to the LPM inhibition, connective tissue (canthal tendons, superior transverse ligament) serves as an elastic force that is stretched during upgaze and released during downgaze. Voluntary firm closure of the eyelid is supplied by the orbicularis oculi (OO) muscles, which are innervated by the facial nerve [2]. The OO muscle is, however, not active during lid movements that accompany vertical eye movements [2, 3]. Eyelid opening is largely controlled by the strong LPM, which is innervated by the superior branch of the third cranial (oculomotor) nerve. In contrast, the superior tarsal (Müller) muscle is supplied by sympathetic efferents and regulates the width of the palpebral fissure. The LPM contains singly (but not multiply) innervated fibers that enable tonic activity [4]. Both fast-twitch and slow-twitch fibers of the LPM are rich in mitochondria and help to resist fatigue. In addition, the frontal muscle helps to retract the lid in maximal upgaze.

The motoneurons of the LPM lie in the central caudal nucleus (CCN) of the oculomotor nucleus complex in the midbrain. This uniquely unpaired nucleus is located midline between the caudal pole of the oculomotor nucleus and the rostral pole of the trochlear nucleus [5]. Since motoneurons of both LPMs intermingle within the CCN, any lesion of the CCN affects both eyelids.

Lid-Eye Coordination

Eyelid and vertical eye movements are tightly coupled to avoid visual disturbances on upward gaze and to protect the eye on downward gaze. Accordingly, the neuronal activity of LP and superior rectus motoneurons [6] and also the dynamic properties of lid and eye saccades are very similar in their temporal profile, which is also reflected in electromyographic (EMG) recordings. The gain and phase shift of the eye and lid movement are similar during sinusoidal smooth pursuit. In contrast, during saccades the lid starts about 5 ms later than the eye but reaches the peak velocity at about the same time as the eye [7]. Lid movements that accompany saccadic eye movements between the straight ahead position and the lower visual field are larger than lid movements that accompany saccadic eye movements between the straight ahead position and the upper visual field [7]. Lid saccades are not as conjugate as saccades [8]. During fixation periods, lid position is quite unstable; the lids perform idiosyncratic eye movements that can amount to up to 5 [7]. The tight coupling of lideye coordination may be changed by additional factors. The magnitude of OO-EMG activity is reduced, when a saccade is made to a previously cued

spatial location. Thus, the modulation of gaze-evoked OO-EMG activity does not appear to depend on the presence of visual information per se, but results from an extraretinal signal [9]. Moreover, the tonic lid position and the tonic activity of the LPM depend on the state of alertness. The lid involuntarily lowers with increasing fatigue [10].

Levator motoneurons discharge at a steady rate. This increases linearly with the elevating lid position. Upward lid saccades are caused by a burst of activity in the LP motoneurons. Lid velocity increases with amplitude, saturating at about 450 /s [11]. LPM pause in firing during downward lid saccades, which are entirely due to the elastic forces.

The eye and lid movement dissociate during a blink, and eye-lid coupling is discontinued. In contrast to superior rectus motoneurons, LP motoneurons cease firing [6]. Additional inhibition of the basal tonic LPM activity is required. This inhibition is presumably received from the nucleus of the posterior commissure (nPC) [12]. Physiologically, the inhibition of LPM precedes and outlasts the OO activation by about 10 ms [7]. Only during forced voluntary eye closure does OO activity precede LPM inhibition [13].

Due to the tight coupling of eye-lid coordination, the supranuclear areas for vertical eye movements are likely to also be involved, e.g. the interstitial nucleus of Cajal (iC) and the rostral interstitial nucleus of the medial longitudinal fascicle (riMLF). A small region, the M group, has been identified to be a supranuclear center of eye-lid coordination, at least for saccades. It is caudal and medial from the riMLF in the cat [14], monkey, and human [15]; from there, it projects to the superior rectus and the inferior oblique subnuclei. For this reason, the M group is thought to control the eyelids and eyes bilaterally [15], thus allowing close synchronicity of both eyelids. The CCN receives input from the nPC, the riMLF, and the superior colliculus (SC). Accordingly, disorders of eye-lid coordination in the absence of LPM or superior rectus paresis are likely to be caused by lesions of the M group or the nPC (see below).

The nPC is located bilaterally adjacent to the posterior commissure [16]. Experimental and clinical nPC lesions elicit vertical upward gaze palsy and lid disorders [17]. Lid retraction is the most frequent sign [18–21]. Single vertical saccade-related neurons have been identified in the nPC [22], but their relation to lid movements has not yet been investigated. The nPC receives afferents from the frontal eye field (FEF) and SC, and projects to the neural integrator for vertical and torsional eye movements (iC) [23, 24], the riMLF, SC, and the paramedian pontine reticular formation (PPRF) [16]. It has reciprocal connections with the M group [25] and lesions involving the nPC [21] or the M group [26] may impair supranuclear inhibition of the CCN, leading to lid retraction and discoupling of eye-lid coordination.