Diagnostic value of video-oculography in progressive supranuclear palsy: a controlled study in 100 patients

Background The eponymous feature of progressive supranuclear palsy (PSP) is oculomotor impairment which is one of the relevant domains in the Movement Disorder Society diagnostic criteria. Objective We aimed to investigate the value of specific video-oculographic parameters for the use as diagnostic markers in PSP. Methods An analysis of video-oculography recordings of 100 PSP patients and 49 age-matched healthy control subjects was performed. Gain of smooth pursuit eye movement and latency, gain, peak eye velocity, asymmetry of downward and upward velocities of saccades as well as rate of saccadic intrusions were analyzed. Results Vertical saccade velocity and saccadic intrusions allowed for the classification of about 70% and 56% of the patients, respectively. By combining both parameters, almost 80% of the PSP patients were covered, while vertical velocity asymmetry was observed in approximately 34%. All parameters had a specificity of above 95%. The sensitivities were lower with around 50–60% for the velocity and saccadic intrusions and only 27% for vertical asymmetry. Conclusions In accordance with oculomotor features in the current PSP diagnostic criteria, video-oculographic assessment of vertical saccade velocity and saccadic intrusions resulted in very high specificity. Asymmetry of vertical saccade velocities, in the opposite, did not prove to be useful for diagnostic purposes.

Coupling Between Horizontal and Vertical Components of Saccadic Eye Movements During Constant Amplitude and Direction Gaze Shifts in the Rhesus Monkey

When the head is free to move, changes in the direction of the line of sight (gaze shifts) can be accomplished using coordinated movements of the eyes and head. During repeated gaze shifts between the same two targets, the amplitudes of the saccadic eye movements and movements of the head vary inversely as a function of the starting positions of the eyes in the orbits. In addition, as head-movement amplitudes and velocities increase, saccade velocities decline. Taken together these observations lead to a reversal in the expected correlation between saccade duration and amplitude: small-amplitude saccades associated with large head movements can have longer durations than larger-amplitude saccades associated with small head movements. The data in this report indicate that this reversal occurs during gaze shifts along the horizontal meridian and also when considering the horizontal component of oblique saccades made when the eyes begin deviated only along the horizontal meridian. Under these conditions, it is possible to determine whether the variability in the duration of the constant amplitude vertical component of oblique saccades is accounted for better by increases in horizontal saccade amplitude or increases in horizontal saccade duration. Results show that vertical saccade duration can be inversely related to horizontal saccade amplitude (or unrelated to it) but that horizontal saccade duration is an excellent predictor of vertical saccade duration. Modifications to existing hypotheses of gaze control are assessed based on these new observations and a mechanism is proposed that can account for these data.

Effects of Reversible Inactivation of the Primate Mesencephalic Reticular Formation. II. Hypometric Vertical Saccades

Electrical microstimulation and single-unit recording have suggested that a group of long-lead burst neurons (LLBNs) in the mesencephalic reticular formation (MRF) just lateral to the interstitial nucleus of Cajal (INC) (the peri-INC MRF, piMRF) may play a role in the generation of vertical rapid eye movements. Inactivation of this region with muscimol (a GABAA agonist) rapidly produced vertical saccade hypometria (6 injections). In three of six injections, there was a marked reduction in the velocity of vertical saccades out of proportion to saccade amplitude (i.e., saccades fell below the main sequence). This was associated with a moderate increase in saccade duration. Inadvertent inactivation of the INC could not account for these observations because vertical, postsaccadic drift was not observed. Similarly, pure downward saccade hypometria, the hallmark of rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) inactivation, was always preceded by loss of upward saccades in our experiments. We also found a downward and ipsiversive displacement of initial eye position and evidence of a contraversive head tilt following piMRF injections. Saccade latency was shorter after two of six injections. Simulation of a local feedback model provided three possible explanations for vertical saccade hypometria: 1) a shift in the input to the model to request smaller saccades, 2) a reduction of LLBN input to the vertical saccade medium lead burst neurons (MLBNs), or 3) an increase in the gain of the feedback pathway. However, when the second hypothesis was coupled to a shortened duration of the saccade trigger (i.e., the discharge of the omnipause neurons), the physiological observations of piMRF inactivation could be replicated. This suggested that muscimol had targeted structures that provided both long-lead burst activity to the MLBNs in the riMLF and were critical for reactivation of the omnipause neurons. Evidence of markedly reduced vertical saccade amplitude, curved saccade trajectories, increased saccade duration, and saccades that fall below the amplitude/velocity main sequence in these monkeys closely parallels the oculomotor findings of patients with progressive supranuclear palsy (PSP).

Quantitative Analysis of Substantia Nigra Pars Reticulata Activity During a Visually Guided Saccade Task

Several lines of evidence suggest that the pars reticulata subdivision of the substantia nigra (SNr) plays a role in the generation of saccadic eye movements. However, the responses of SNr neurons during saccades have not been examined with the same level of quantitative detail as the responses of neurons in other key saccadic areas. For this report, we examined the firing rates of 72 SNr neurons while awake-behaving primates correctly performed an average of 136 trials of a visually guided delayed saccade task. On each trial, the location of the visual target was chosen randomly from a grid spanning 40° of horizontal and vertical visual angle. We measured the firing rates of each neuron during five intervals on every trial: a baseline interval, a fixation interval, a visual interval, a movement interval, and a reward interval. We found four distinct classes of SNr neurons. Two classes of neurons had firing rates that decreased during delayed saccade trials. The firing rates of discrete pausers decreased after the onset of a contralateral target and/or before the onset of a saccade that would align gaze with that target. The firing rates of universal pausers decreased after fixation on all trials and remained below baseline until the delivery of reinforcement. We also found two classes of SNr neurons with firing rates that increased during delayed saccade trials. The firing rates of bursters increased after the onset of a contralateral target and/or before the onset of a saccade aligning gaze with that target. The firing rates of pause-bursters increased after the onset of a contralateral target but decreased after the illumination of an ipsilateral target. Our quantification of the response profiles of SNr neurons yielded three novel findings. First, we found that some SNr neurons generate saccade-related increases in activity. Second, we found that, for nearly all SNr neurons, the relationship between firing rate and horizontal and vertical saccade amplitude could be well described by a planar surface within the range of movements we sampled. Finally we found that for most SNr neurons, saccade-related modulations in activity were highly variable on a trial-by-trial basis.

Discharge Characteristics of Vestibular Saccade Neurons in Alert Monkeys

Kaneko, Chris R. S. and Kikuro Fukushima. Discharge characteristics of vestibular saccade neurons in alert monkeys. J. Neurophysiol. 79: 835–847, 1998. We previously described a class of neurons, located in and around the interstitial nucleus of Cajal of the cat, that discharged during vestibular stimulation and before saccades. We called these neurons vestibular saccade neurons (VSNs). In the present study, we characterized similar neurons in the monkey. These neurons discharged before vertical saccades and during vertical vestibular stimulation as well as vertical smooth pursuit. Like cat VSNs, the discharge metrics of these VSNs were poorly related to saccade metrics and showed only occasional, weak sensitivity to eye position. They discharged most intensely (on-direction) for movements that were either upward or downward, and their on-directions were consistent during pitch and pursuit but not for eye position. For saccades, the correlation coefficient of number of spikes and vertical saccade size varied from 0.08 to 0.90 with a mean of ∼0.6. The average sensitivity (i.e., slope) of the number of spikes and vertical saccade size linear regression was 0.3 ± 0.2 spike/deg. Average correlations between peak discharge rate and peak saccade velocity and between burst duration and saccade duration were 0.5 and 0.4; sensitivities were 0.2 ± 0.2 spike per s per deg/s and 0.6 ± 0.5 ms/ms, respectively. Average vestibular sensitivities during 0.5 Hz, ±10° sinusoidal pitch while the animals suppressed their vestibular ocular reflex were 0.97 spike/s per deg/s for up VSNs and 0.66 spike/s per deg/s for down VSNs. The average static position sensitivity for the population of 39 VSNs tested was 0.55 spike/s per deg. The average gain for VSNs tested during 0.5 Hz, ±10° sinusoidal smooth pursuit tracking was 1.4 spike/s per deg/s. As we could not identify analogous neurons in the region of the monkey ponto-medullary junction, we conclude that horizontal on-direction VSNs do not exist in the monkey. We discuss a possible functional role for VSNs and similar neurons described in previous studies and conclude that these neurons are most likely involved with the process of neural integration (in a mathematical sense) of velocity-coded inputs from a variety of oculomotor subsystems and are not a pivotal element in saccade generation.