We have for the first time identified cells that appear to carry a signal related to the strabismus angle. These cells were identified within the supraoculomotor area in the strabismic monkeys. It is highly likely that these cells are the same as those that have been reported to encode the vergence angle in normal animals.17–19
First, the anatomical locations of these cells correspond very well to the midbrain near-response region identified before. We were also able to verify the location of the recording via histological reconstruction of electrode track penetrations. Second, the neuronal response characteristics correspond very well to the near response cells of the normal animal. Near-response cells in the normal animal show modulation related to vergence (difference in position of the two eyes) but not to conjugate eye movements. Similarly, cells in our sample show responses related to the strabismus angle (difference in position of the two eyes—) but not conjugate eye movements (). Finally, we encountered many more near-response cells than far-response cells, similar to the distribution reported earlier.
A significant finding in our study is that the response characteristics of the near-response cells in the strabismic monkey are altered from the normal animal. The threshold (vergence angle at which the neuron commences firing) for the normal animals is close to 0.0°, while the threshold for the strabismic monkeys was approximately −40° and −27° (40° and 27° of exotropia or divergence) respectively. We suggest that the fact that SOA cells show significant levels of activity even in the divergent state is evidence that these cells are indeed involved in maintaining the state of strabismus. The reduced thresholds can perhaps be explained from within a recently developed framework for binocular control.20,21
Thus, King and colleagues proposed that the neural integrators encoded monocular eye position and that they provided inputs to the SOA such that SOA activity encoded the difference in position of each eye. In the normal monkey, during a conjugate eye movement, SOA activity would simply provide a DC signal to the medial rectus motoneurons that may be referred to as the “vergence tone.” During a vergence movement (again in the normal monkey), the SOA cells provide a required positional command to the medial rectus motoneurons that eventually helps to adduct each eye. Our data are compatible with the idea that the SOA cells do not encode a “vergence” command per se
; rather, they encode the difference between the positions of the two eyes (strabismus angle). If they were simply encoding vergence, we might not have expected to observe the reduced thresholds and we might have predicted that these cells would be silent in the exotropic state. We, of course, cannot comment on whether the difference signal is arriving from monocular neural integrators, but it stands to reason that there is some representation of each eye’s position upstream of the SOA. Note that we cannot rule out the classical Hering model for binocular control, wherein the SOA supplies a vergence command to medial rectus motoneurons. If the thresholds of the SOA cells were adaptively altered (a vergence offset) in the strabismic animals toward the divergent (exotropic) direction, then any modulation of SOA cell activity could be the source of the vergence command that leads to observed change in eye misalignment. There is in fact some evidence that SOA cells can adapt to different levels of tonic vergence. Morley and colleagues showed that relationship between SOA cell activity and vergence was altered in approximately 70% of cells following phoria adaptation.22
Perhaps a similar adaptive mechanism can cause reduced thresholds in the strabismic monkeys.
The second difference between the normal and strabismic animals’ SOA activity was the reduced sensitivities (). We suggest that the reduced sensitivity for vergence could manifest as a reduced vergence tone in extraocular muscle and therefore result in the monkeys maintaining an exotropic state. In support of our hypothesis, the strabismic animal with the lower sensitivity had a larger exotropia and a more reduced threshold. Note that we are not claiming that the SOA activity is the reason that the animals developed an exotropia in the first place. Rather, we suggest that the SOA cells are the substrate that helps maintain the divergent state.
Several studies have shown that many of the SOA cells encode not only the vergence angle but also ocular accommodation.23,24
Unfortunately, we did not have the technical capability to monitor or control levels of accommodation in our animals. Potentially some of the misalignment sensitivity measures developed here for the SOA cells could be contaminated by sensitivity to accommodation. However, it is highly unlikely that the observed differences in threshold and sensitivity of the SOA population of the strabismic monkeys compared to the normal animals is driven by changes in the accommodative component alone.