Disruption of Fixation Reveals Latent Sensorimotor Processes in the Superior Colliculus

Abstract

Executive control of voluntary movements is a hallmark of the mammalian brain. In the gaze-control network, this function is thought to be mediated by a critical balance between neurons responsible for generating movements and those responsible for fixating or suppressing movements, but the nature of this balance between the relevant elements-saccade-generating and fixation-related neurons-remains unclear. Specifically, it has been debated whether the two functions are necessarily coupled (i.e., push-and-pull) or independently controlled. Here we show that behavioral perturbation of ongoing fixation with the trigeminal blink reflex in monkeys (Macaca mulatta) alters the effective balance between fixation and saccade-generating neurons in the superior colliculus (SC) and can lead to premature gaze shifts reminiscent of compromised inhibitory control. The shift in balance is primarily driven by an increase in the activity of visuomovement neurons in the caudal SC, and the extent to which fixation-related neurons in the rostral SC play a role seems to be linked to the animal's propensity to make microsaccades. The perturbation also reveals a hitherto unknown feature of sensorimotor integration: the presence of a hidden visual response in canonical movement neurons. These findings offer new insights into the latent functional interactions, or lack thereof, between components of the gaze-control network, suggesting that the perturbation technique used here may prove to be a useful tool for probing the neural mechanisms of movement generation in executive function and dysfunction.

Significance statement: Eye movements are an integral part of how we explore the environment. Although we know a great deal about where sensorimotor transformations leading to saccadic eye movements are implemented in the brain, less is known about the functional interactions between neurons that maintain gaze fixation and neurons that program saccades. In this study, we used a novel approach to study these interactions. By transient disruption of fixation, we found that activity of saccade-generating neurons can increase independently of modulation in fixation-related neurons, which may occasionally lead to premature movements mimicking lack of impulse control. Our findings support the notion of a common pathway for sensory and movement processing and suggest that impulsive movements arise when sensory processes become "motorized."

Keywords: fixation; impulsivity; microsaccades; sensorimotor integration; superior colliculus; visuomovement neurons.

Figure 1.

Behavior in control and perturbation conditions. a, Schematic of the delayed-saccade task. The red arrows indicate that blink-perturbation times preceded target appearance. The temporal traces in the bottom rows are schematics of typical eye-position profiles in the absence of perturbation (control, black) and with perturbation leading to premature (gold) and regular latency saccades (red). Radial position is plotted. Hence all deflections are positive. b, Histograms for the distribution of saccade reaction times with regular (right) and early (left) latencies for control (top) and perturbation (bottom) trials. The offset of fixation point represents the GO cue. c, Proportion of errors in the perturbation condition (ordinate) plotted against the control condition (abscissa). Each point represents a session. Symbols represent individual subjects. The unity line is on the diagonal. The inset replots the same data on log–log axes for better visualization.

Figure 2.

Population activity in the caudal SC. a, Population average (mean ± SEM) of caudal SC neurons (normalized) for the control (black) and perturbation (red) conditions. The tick marks near the base of the figure indicate time points at which the difference between the two conditions was significantly different (Wilcoxon signed-rank test, p < 0.01). The color of the tick mark indicates the condition in which activity was higher. The bottom row shows mean eye-position traces in the two conditions. b, Scatter plots of individual neuron activities (n = 94) during the target-evoked response period (left; a, dark-shaded epoch), delay period (middle; a, intermediate-shaded epoch), and saccade period (right; a, light-shaded epoch) in the perturbation condition plotted against the control condition. Unity line is on the diagonal. Each symbol corresponds to a different monkey. Activity was enhanced during the target and delay epochs but not during the saccade epoch for a majority of neurons.

Figure 3.

Latent visual response in putative movement neurons. a, VMI (see Materials and Methods) calculated from perturbation trials plotted against VMI from control trials. VMI significantly decreased in perturbation trials (neurons became more “visual”). Note that neurons in the light-shaded rectangle that would typically be classified as “movement” neurons based on activity in the control condition (VMI, >0.6) become visuomovement neurons under perturbation. The histogram shows the distribution of VMI differences between the two conditions. b, Top, Population activity of 11 movement neurons, defined as those with VMI >0.9 (a, dark-shaded region), in control and perturbation conditions. Bottom, Activity of an exemplar movement neuron showing strong unmasking of a latent visual response following the perturbation. c, Modulation index in perturbation trials relative to control trials plotted as a function of VMI in control trials. The correlation was significantly positive, i.e., more movement-like cells were more likely to be modulated by the perturbation during the visual epoch.

Figure 4.

Population activity in the rostral SC. a, Top, Population average of rostral SC neurons (normalized) in the two conditions. Colors and tick marks same as in Figure 2. The bottom row shows mean eye-position traces. b, Individual subject population means of rostral SC neurons. Activity was strongly suppressed in Monkey BB whereas Monkeys BL and WM showed transient increase in rostral SC activity (not significant, Wilcoxon rank-sum test, p > 0.05). c, Scatter plot of the individual neurons' activities (n = 44) during the delay period (shaded epoch in a) in the perturbation condition plotted against the control condition. Plot follows the scheme in Figure 2b.

Figure 5.

Microsaccade behavior of individual animals. a, Microsaccade rate as a function of time relative to target onset for each of the three monkeys in control (top row) and perturbation (middle row) trials. Monkey 1 (BB) rarely made microsaccades at any time after acquiring fixation of the central fixation target. The other two monkeys show a characteristic microsaccade rate profile with transient inhibition of microsaccades following target onset. The dramatic reduction in microsaccade occurrence in perturbation trials just before target onset is an anomaly due to the inability to detect microsaccades during the blink owing to the blink-related eye movement. b, Rostral SC activity (same as Fig. 4b, middle column) is shown in the bottom row for comparison. It is possible that the actual microsaccade rate increases during this period (suggested by the increase in rostral SC activity, particularly in Monkey WM).

Figure 6.

Behavior and population activity for alternative perturbations. a, Left, Histogram of saccade reaction times as in Figure 1b for control (top) and the target-blank perturbation (bottom) trials. Right, Proportion of errors in the target-blank perturbation condition plotted against the control condition. Each point represents a session; symbols correspond to different monkeys. The unity line is on the diagonal. b, Same as a, but for the ear-puff perturbation. c, Population activity (mean ± SEM) of caudal SC (top) and rostral SC (middle) neurons for each of the four conditions (control, black; blink, red; target blank, blue; ear puff, green). The activity is plotted only for the matched subset of neurons for which we had data for all four conditions. The tick marks of a particular color indicate time points at which the corresponding condition had a higher activity relative to the control condition (Wilcoxon rank-sum test, p < 0.01). Specific comparisons are enclosed by thin lines of the relevant color. The bottom row shows mean eye-position traces.

Figure 7.

Microsaccade behavior during alternative perturbations. a, Microsaccade rate as a function of time relative to target onset for two monkeys in control (top row; data in black), target-blank (second row; data in blue), and ear-puff (third row; data in green) conditions. Just like in the blink perturbation trials (Fig. 5), Monkey BB rarely made microsaccades at any time after acquiring fixation of the central fixation target. Monkey BL showed a characteristic microsaccade rate profile with transient inhibition of microsaccades following target onset. Since there is no blink to occlude microsaccades in the target blank trials (blue histogram), the observed reduction in microsaccade occurrence just before target onset could possibly be attributed to the reduction in rostral SC activity (bottom row). b, The bottom row plots rostral SC activity during the three conditions. The color configuration follows from above. The tick marks of a particular color indicate time points at which the corresponding condition had a higher activity relative to the control condition (Wilcoxon rank-sum test, p < 0.01). Specific comparisons are enclosed by thin lines of the relevant color.

Figure 8.

Population activity during premature saccades. Normalized population average activity (mean ± SEM) of caudal (top row) and rostral (middle row) SC neurons for control trials (black), blink perturbation trials with regular latency saccades (red), and blink perturbation trials with early saccades (gold). Note that for the gold trials, the activity in both middle and right panels reflects saccade occurrences, but is aligned with respect to different events (target onset and saccade onset, respectively). The two sets of significance bars below the spike density profiles, enclosed by dashed black and colored lines, indicate time points at which the condition corresponding to the respective color had higher (colored bars) or lower (black bars) activity relative to the control condition. The significance bars above the spike densities, enclosed by dashed red and gold lines, indicate time points at which activity in the gold trials was higher (gold bars) or lower (red bars) compared with the red trials; the arrows indicate first times at which they significantly separated from each other (Wilcoxon rank-sum test, p < 0.01). The shaded vertical rectangle indicates the early visual epoch, 50–150 ms after target onset. The bottom row shows the mean vectorial eye position in the three conditions.