The absence of eye muscle fatigue indicates that the nervous system compensates for non-motor disturbances of oculomotor function

Abstract

The physical properties of our bodies are subject to change (due to fatigue, heavy equipment, injury or aging) as we move around in the surrounding environment. The traditional definition of motor adaptation dictates that a mechanism in our brain needs to compensate for such alterations by appropriately modifying neural motor commands, if the vitally important accuracy of executed movements is to be preserved. In this article we describe how a repetitive eye movement task brings about changes in eye saccade kinematics that compromise accurate motor performance in the absence of a proper compensatory response. Surgical lesions in animals and human patient studies have previously demonstrated that an intact cerebellum is necessary for the compensation to arise and prevent the occurrence of hypometric movements. Here we identified the dynamic properties of the eye plant by recording from abducens motoneurons responsible for the required movement and measured the muscle response to microstimulation of the abducens nucleus in rhesus monkeys. The ensuing results demonstrate that the muscular periphery remains intact during the fatiguing eye movement task, while internal sources of noise (drowsiness, attentional modulation, neuronal fatigue etc.) must be responsible for a diminished oculomotor performance. This finding leads to the important realization that while supervising the accuracy of our movements, the nervous system takes additionally into account and adapts to any disruptive processes within the brain itself, clearly unrelated to the dynamical behavior of muscles or the environment. The existence of this supplementary mechanism forces a reassessment of traditional views of cerebellum-dependent motor adaptation.

Figure 1.

Typical changes in eye saccade kinematics during saccadic fatigue. A, Illustrative depiction of the fatigue experiment. The selected convention was to define the first and last 10 trials as the start and end of fatigue. B, Saccade peak velocity and duration, but not amplitude, progressively change during the fatigue experiment. Left, Lines are least-squares linear fits to the three saccade metrics plotted for each consecutive trial. Right, Eye position and eye velocity individual (thin) and mean (bold) traces at the start (blue) and end (red) of the fatigue experiment. C, Eye saccade kinematics move away from their pre-fatigue main sequences. Left, Average data points at the start (blue dots) and end (red arrowheads) of one fatigue session with the pre-fatigue peak saccade velocities and durations plotted against amplitude (black dots). Middle, Same average data points for all 62 fatigue sessions. Blue lines indicate the direction of change predicted by the corresponding pre-fatigue main sequences. Right, Mean ± SD changes in peak saccade velocity and duration across all fatigue sessions were statistically different from zero (t tests, *p < 10⁻³⁰) while the mean amplitudes did not significantly (n.s.) change (t test, p = 0.91).

Figure 2.

Characterization of abducens neurons' activity. A, Recording neurons from the abducens nucleus. Top, Approximate anatomical location of the abducens nucleus in an MRI image of a rhesus monkey. Dotted lines reveal the placement and orientation of the recording chamber. Bottom, A typical saccade-related discharge pattern of an abducens neuron. The superimposed eye traces, detected action potentials and the average spike density function are aligned on saccade onset (vertical line). B, Quantitative assessment of abducens discharges. Top, Spiking rates were fitted with the two model formulations and bootstrap histograms were computed for each model parameter. Median values (red lines) and limits of the 95% confidence intervals (dotted lines) are provided. Bottom, Examples of eye traces and spike density functions recorded during three saccades of increasing amplitude. The VAF measure (mean ± SD) was used to evaluate how well the models fit the data. The predicted activity is superimposed on the actual one for the first-order (green) and second-order (orange) model fits. Dotted vertical lines indicate the onset and end of each saccade. C, Position and velocity sensitivity measures. Data from the same example neuron with least-squares linear regression fits (red lines). D, Simulation of eye plant dynamics with the first-order model showing changes in firing rates of abducens motoneurons that would be expected under the muscular and nonmuscular fatigue hypotheses. Left, Simulated motoneuron spike density profile (F) given the pre-fatigue eye position (E) and velocity (Ė) traces (in blue) with the indicated model parameters. Right, Same simulation with a slower and longer post-fatigue eye saccade (in red) in the two cases where the eye plant parameters are either modified or remain unchanged. The simulated pre-fatigue data (dotted traces) are superimposed for comparison purposes. With identical plant dynamics, the expected changes in firing rates parallel those in eye saccade kinematics, whereas in the case of modified dynamics they do not. In the latter case, the neuron's sensitivity to eye position and velocity (as measured in C) would be altered, and attempting to predict the firing rate with the pre-fatigue eye plant dynamics (as in B) would underestimate the actual rate.

Figure 3.

Eye plant dynamics are not altered by saccadic fatigue. A, Comparison of pre-fatigue and post-fatigue discharge properties of a single abducens neuron. Top, Position and velocity sensitivity data with their least-squares linear regression fits before and after the fatigue experiment. Insets provide the slopes and y-intercepts (with their 95% confidence intervals) of the regression lines. Bottom, Bootstrap distributions of the first- and second-order model parameters evaluated before (blue) and after (red) fatigue. On each histogram, the median values (thick lines) with their 95% confidence intervals (thin lines) are provided. B, Comparison of pre-fatigue and post-fatigue saccade-related properties of a population response of 62 neurons. Same measures as in A. The population activity was computed by dividing the range of saccade amplitudes into equally sized bins of 0.5°. Eye position traces and the associated spike density functions were then assigned to their corresponding bins and average saccades and firing rates were then computed across all trials and all neurons for each bin.

Figure 4.

No changes in eye plant dynamics occur during the course of fatigue. A, Progressively slower eye saccades are accompanied by parallel decreases in peak discharges of abducens neurons. Top, Average data points at fatigue start (blue dots) and end (red arrowheads) with pre-fatigue peak discharges plotted against saccade peak velocity (black dots) for one example neuron. Bottom, Same average data points for all 62 neurons normalized to the unity-slope line (dotted line) with their respective pre-fatigue velocity sensitivity regression fits [Y_n = (Y − b)/a, where Y_n is the normalized version of the peak spike density measure Y, and a and b are, respectively, the slope and y-intercept of the velocity sensitivity regression line]. B, The evaluated models predicted the activity of abducens neurons equally well throughout fatigue. Top, Eye traces and corresponding abducens neuron spike density functions of an example neuron, with superimposed first (green)- and second (orange)-order model fits, for three trials taken from the start (blue) and end (red) of a fatigue experiment. Bottom, Between the start (blue) and end (red) of the fatigue, mean (±SD) values of peak saccade velocity and duration showed significant changes (*) (t tests, p = 0.0004 and p = 0.00003, respectively), whereas those of saccade amplitude (p = 0.36) and the VAF by the first (p = 0.85)- and second (p = 0.88)-order model fits did not (n.s.).

Figure 5.

Microstimulation of the abducens nucleus confirms the absence of muscular fatigue. Top, Eye position (first row) and velocity (second row) traces of the stimulation-evoked eye movements at four different stimulus frequencies were highly similar before (blue) and after (red) a fatigue session, and after a subsequent rest period (green). The traces are aligned on saccade onset. Bottom, Mean amplitudes and peak velocities of the stimulated saccades for all 15 experimental sessions (small open squares) together with their average values (large filled squares).