Excitatory pathways are shown in orange and the reciprocal inhibitory pathways are shown in blue. The particular pathway shown emanates from the frontal eye field (FEF), which projects through the anterior limb of the internal capsule, decussates to the opposite side at the midbrain-pontine junction, and then innervates the paramedian pontine reticular formation (PPRF). From there, projections directly innervate the lateral rectus (ipsilateral to the PPRF). A second decussation, back to the side of origin of FEF activation, via the MLF, innervates the medial rectus subnucleus of cranial nerve III and then neurons here project to innervate the medial rectus muscle. The right FEF command to trigger a saccade culminates in conjugate eye movements to the left. According to Herring's law, the horizontal yoke pair, the medial and lateral recti, are activated in synchrony.

This figure illustrates the projections involved during the activation of the left lateral semicircular canal. For instance, during a leftward rotation of the head while attempting to maintain straight ahead gaze, axons from left lateral canal (on the right side of the figure) canal neurons project to ipsilateral vestibular nucleus (primarily the medial) which then projects across the brainstem to innervate the opposite right abducens (VI) nucleus. This nucleus has two populations of neurons; a direct projection to the same side lateral rectus (right) and an interneuronal projection that crosses back to the left side via the MLF and then innervates the medial rectus subnucleus of cranial nerve III, which ultimately innervates the left medial rectus muscle.

Axons from anterior semicircular canal neurons project to the ipsilateral vestibular nucleus and from there decussate across the brainstem to innervate the contralateral inferior oblique nucleus of cranial nerve III (and then the muscle itself) and the ipsilateral superior rectus muscle via a second decussation from the superior rectus subnucleus on the right, which completely crosses back to the left (on the right side of the figure). The excitatory pathways are shown in orange and the reciprocal inhibitory pathways are shown in blue. Activation of both canals (as with pitching the head downward and attempting straight ahead fixation) will result in cancellation of the torsional vector components, but addition of the vertical vector components resulting in upward movement of the eyes.

Axons from the canal project to the ipsilateral vestibular nuclei and then decussate to innervate the contralateral inferior rectus subnucleus of the oculomotor complex of cranial nerve III and the trochlear nucleus. The trochlear neurons then exit the brainstem posteriorly and decussate back to the left side innervating the superior oblique muscle. Activation of both canals (as with pitching the head upward and attempting straight ahead fixation) will result in cancellation of the torsional vector components, but addition of the vertical vector components resulting in downward movement of the eyes.

In this example, a left head tilt results in a counterclockwise (with respect to the examiner) torsional counterroll of the upper poles of the eyes. This response is mediated by a crossed otolith projection to the extorters in the patient's right eye (the inferior oblique and inferior rectus muscles) and a double crossed projection to the intorters of the left eye (the superior oblique and superior rectus muscles). These slow phases are punctuated by torsional fast phases that are mediated by the rostral interstitial nucleus of the medial longitudinal fasciculus. The interstitial nucleus of Cajal (INC) is also shown (without connections). This important midbrain structure contains circuitry important for neural integration of vertical and torsional gaze, eye-head coordination during roll movements, and contains inhibitory burst neurons for vertical eye movements.³ Lesions of these otolith projections result in the opposite reciprocal effects leading to intorsion and elevation of the right eye and extorsion and depression of the left eye, the so-called skew deviation. If the lesion occurs prior to the otolith pathway decussation (here on the left) then the lower left eye is on the side of the lesion. Alternately, if the lesion is within this pathway after the decussation (in the pons or midbrain), then the higher eye is on the side of the lesion.

These fundus photographs show the extorsion (upper pole of the eye rotated away from the nose or toward the left shoulder) of the left eye (OS), with the disc-macular line rotated clockwise (according to the examiner), and the right eye (OD) intorted (upper pole of the eye toward the nose or toward the left shoulder) with the macular-disc line rotated clockwise (again, according to the examiner). A lesion within the otolith projections in the medial longitudinal fasciculus at the level of the left medulla (the side of the lower eye) or right pons or midbrain (side of the higher eye) would result in this appearance.

Note the severe vertical misalignment of the two eyes. This abnormality is the consequence of otolith disruption and is supranuclear in mechanism (ductions were intact for all individual eye muscles).

The lesion was at the level of the left midbrain (after the decussation of the rightward originating otolith pathways) and involved the medial longitudinal fasciculus. Also note the enlarged left pupil, which exhibited the characteristics of near-light dissociation.

Volitional saccadic pathway with a lesion in the right MLF that results in an INO during an attempted saccade to the patient's left.

In this case a rightward (upward tracing) 20 deg saccade results in interocular disconjugacy (note separation of the two tracings). Observe that the right eye (OD in blue) achieves the 20 deg target rapidly, whereas the left eye (OS in red) lags behind. The ratio of the eyes when the abducting right eye achieves the target to the position of the adducting eye at that time is referred to as the first pass amplitude (FPA). Ultimately both eyes achieve the fixation target, the final amplitude (FA). During the trajectory of the saccade, the divergence of the two eyes can result in loss of stereoscopy, diplopia (transiently), difficulty reading, visual blur, and risk of fall while turning, or motor vehicle accident with head turning while driving.

The patient was unable to elicit saccades to the right (i.e., a right gaze palsy), and had evidence of a right internuclear ophthalmoparesis (INO) upon attempted gaze to the left. In this photograph, the patient is looking straight ahead. We can observe an exotropia, the so-called paralytic pontine exotropia with the left eye in exo (the only remaining movement possible). In this circumstance, there is an attempted leftward preference. However, only left eye abduction is possible given the right INO (with slowing and significant ocular limitation). Below is the T2-weighted axial MRI showing the responsible lesion involving the right pontine tegmentum (arrow).

Note the exotropic appearance of both eyes (i.e., wall-eyed). Attempted gaze to the right or left revealed adduction slowing and limitation consistent with bilateral INO. There was also reduced vertical smooth pursuit and vertical vestibulo-ocular reflexes (both pathways course through the MLF).

Both images were derived from patients with multiple sclerosis and bilateral internuclear ophthalmoparesis. Both lesions demonstrate the eloquence principal of periventricular demyelinating lesions that are localized to the brainstem, in contrast to the non-eloquence of many cerebral periventricular lesions (that often do not correspond to any concomitant clinical manifestations).