Stimulation of the substantia nigra influences the specification of memory-guided saccades

Abstract

In the absence of sensory information, we rely on past experience or memories to guide our actions. Because previous experimental and clinical reports implicate basal ganglia nuclei in the generation of movement in the absence of sensory stimuli, we ask here whether one output nucleus of the basal ganglia, the substantia nigra pars reticulata (nigra), influences the specification of an eye movement in the absence of sensory information to guide the movement. We manipulated the level of activity of neurons in the nigra by introducing electrical stimulation to the nigra at different time intervals while monkeys made saccades to different locations in two conditions: one in which the target location remained visible and a second in which the target location appeared only briefly, requiring information stored in memory to specify the movement. Electrical manipulation of the nigra occurring during the delay period of the task, when information about the target was maintained in memory, altered the direction and the occurrence of subsequent saccades. Stimulation during other intervals of the memory task or during the delay period of the visually guided saccade task had less effect on eye movements. On stimulated trials, and only when the visual stimulus was absent, monkeys occasionally (∼20% of the time) failed to make saccades. When monkeys made saccades in the absence of a visual stimulus, stimulation of the nigra resulted in a rotation of the endpoints ipsilaterally (∼2°) and increased the reaction time of contralaterally directed saccades. When the visual stimulus was present, stimulation of the nigra resulted in no significant rotation and decreased the reaction time of contralaterally directed saccades slightly. Based on these measurements, stimulation during the delay period of the memory-guided saccade task influenced the metrics of saccades much more than did stimulation during the same period of the visually guided saccade task. Because these effects occurred with manipulation of nigral activity well before the initiation of saccades and in trials in which the visual stimulus was absent, we conclude that information from the basal ganglia influences the specification of an action as it is evolving primarily during performance of memory-guided saccades. When visual information is available to guide the specification of the saccade, as occurs during visually guided saccades, basal ganglia information is less influential.

Keywords: action; decision making; delay period; eye movements; inhibition; memory; movement preparation; vision.

Fig. 1.

Experimental task. A: schematic view of the lateral surface of a monkey brain. Electrical stimulation targeted the substantia nigra pars reticulata (nigra) as shown by the electrode in the brain schematic. The 5 large squares show the spatial arrangement of the memory-guided saccade task. The centrally located black circle indicates the fixation point (fp). The peripherally located black circle shows 1 example target location. The small square around the circles indicates the eye position criterion required for assessment of performance accuracy. The arrow indicates a correct saccade. The gray rectangles below the screen image show the timing of the electrical stimulation that occurred in the first set of experiments in 2 monkeys. B: temporal arrangement of the memory-guided saccade task. The gray rectangle labeled “fixation point” indicates the time and duration of fixation; the gray rectangle labeled “target” shows the time and duration of the visual stimulus, and the gray rectangles labeled “stim” show the time and duration of the electrical stimulation. The line labeled “eye” shows a schematic of the eye position. C: same as in B for the 2nd set of experiments in which visually guided and memory-guided saccades were interleaved with stimulation only during the delay period; this panel shows the memory-guided saccade condition. D: same as in C for the visually guided saccade condition.

Fig. 2.

Nigral stimulation during the delay period influences saccades. An example recording and stimulation site show that electrical stimulation of the nigra well before the onset of a saccade influences the occurrence of subsequent saccades. A: raster plot and spike density function (σ = 12 ms) of the neuron recorded at the site. Each tick indicates the time of an action potential; each row of ticks is 1 trial of the delayed saccade task. Left trace is aligned on the onset of the target (vertical dashed line and arrowhead); right trace is aligned on saccade onset (vertical dashed line and arrowhead). The position traces below the rasters are horizontal (H eye) and vertical eye positions (V eye). Downward movement is shown leftward by convention. er7a is a file identifier. B: control (no stimulation) eye position traces plotted from the time the saccade started to 300 ms at the site where the neuron shown in A was recorded. C: same as in B for the condition in which stimulation occurred during the visual (encoding) interval. D: same as in B for the condition in which the stimulation occurred during the delay period (maintenance). E: same as in B for the condition in which the stimulation occurred during the presaccade (retrieval) interval. Contralateral (contra) and ipsilateral (ipsi) hemifields are indicated with respect to the site of stimulation. See Fig. 1 for stimulation intervals relative to the task events. er7b is a file identifier.

Fig. 3.

Stimulation of the nigra during the visual, delay, and presaccade intervals in the memory-guided saccade task. The mean saccadic endpoints for each of the 28 experiments from 2 animals are plotted. Different colors indicate different target positions. The size of the circles indicates the frequency of the endpoints that were within 5° of the target location. Triangles show the data points for the example data shown in Fig. 2. A: endpoints when no stimulation occurred (control). B: endpoints when stimulation occurred during the visual interval. C: endpoints when stimulation occurred during the delay interval. D: endpoints when stimulation occurred during the presaccade interval. Data are taken from correct trials.

Fig. 4.

Stimulation of the nigra during the visual, delay, and presaccade intervals in the memory-guided condition. A, D, G, and J: the normalized vectors of memory-guided saccades are drawn as arrows. Each black arrow is an average of at least 10 saccades. The red arrows show the example result from Fig. 2. The lengths 1 and 2 indicate the length of the saccades relative to the idealized saccade length. The direction of the arrows shows the direction of the saccade relative to the direction of an idealized saccade direction (see text for details). For the plot in A, the saccades that were made on trials without stimulation are normalized to the idealized saccades. B: distribution of the differences in saccade angles between the idealized saccades and the nonstimulated saccades. C: same as in B for saccade lengths. D: same as in A for saccades made while nigral stimulation occurred during the visual interval. E and F: same as in B and C for saccade trials in which stimulation occurred during the visual interval. G: same as in A for saccades made with stimulation during the delay period. H and I: same as in B and C for saccades made with nigral stimulation during the delay period. J: same as in A for saccades made with stimulation during the presaccade interval. K and L: same as in B and C for saccades made with stimulation during the presaccade interval. **P < 0.05, indicating that the distribution was significantly more variable with stimulation than without. All eye movements are from correct trials.

Fig. 5.

Stimulation of the nigra reduces saccade probability. The number of saccades made with stimulation is normalized to the number made without stimulation, and this ratio is plotted for each of the stimulation conditions from the memory-guided saccade task. Data from the encoding, maintenance, and retrieval conditions come from 2 monkeys and 28 stimulation sites. Data for the random interval condition come from the same 2 monkeys and only 20 of the 28 sites. No stim is the no-stimulation condition, visual is stimulation during the encoding phase, delay is stimulation during the maintenance phase, presaccade is stimulation during the retrieval phase, and random delay is from the condition in which the stimulation occurred for a fixed length of 200 ms at random intervals during the delay period. Contralateral and ipsilateral refer to the direction of the saccades made relative to the hemisphere that was stimulated. **P ≤ 0.001.

Fig. 6.

Nigral stimulation during the delay period of visually guided and memory- guided saccades influences only memory-guided saccades. A: visually guided saccade trajectories without stimulation (visual no stim) are plotted from the time of the fixation point offset for 300 ms. B: same as in A for the condition in which stimulation occurred (visual stim). C: same as in A for memory-guided saccades (memory no stim). D: same as in B for memory-guided saccades (memory - stim). H_Aug12_2010b is a file identifier.

Fig. 7.

Stimulation of the nigra during the delay period of memory-guided saccades alters the variability of saccadic eye movement endpoints. The arrangement is the same as in Fig. 3, although these data are from the 2nd set of experiments and monkeys (2 monkeys, 41 sites). Triangles show the data points from the example data shown in Fig. 6. Data are from correct and error trials. A: visually guided trials without stimulation (visual no stim). B: memory-guided trials without stim (memory no stim). C: visually guided trials with stimulation during the delay period (visual with stim). D: memory-guided trials with stimulation during the delay period (memory with stim). Contralateral and ipsilateral are indicated with respect to the site of stimulation. Note that for some of these trials the eye movement endpoints showed large rotations with stimulation in the memory condition (green circle in the middle of orange circles in D; purple circle next to black and red circles).

Fig. 8.

Stimulation of the nigra during the delay period alters the variability of saccadic eye movement endpoints and lengths of saccades in the absence of visual information. The arrangement is identical to that of Fig. 4. Data are from experiments in which both the memory-guided and visually guided saccade tasks were performed. Visual no stim indicates visually guided trials without stimulation of the nigra; visual stim indicates trials in which stimulation occurred. Memory no stim indicates trials in which memory-guided saccades were performed and stimulation of the nigra did not occur; memory stim indicates trials in which nigral stimulation occurred. **P < 0.05, indicating that the distribution was significantly more variable with stimulation than without. The red arrows show the example result that appears in Fig. 6.

Fig. 9.

Stimulation of the nigra reduces saccade probability in the absence of visual information. The number of saccades made with stimulation during the delay period was normalized to the number made without stimulation, and this ratio was plotted for the memory-guided saccade task and the visually guided saccade task. Data are from 41 stimulation sites in 2 monkeys. No stim is the no-stimulation condition, stim is the stimulation condition, and mem is the memory condition. Values are means; error bars indicate SE. *P < 0.01, indicating a statistically significant reduction in saccade frequency with stimulation.

Fig. 10.

Stimulation of the nigra during the delay period increases saccade latency in the absence of visual information. The cumulative probability of a saccade with a particular latency is plotted against time. Cyan functions show the stimulation latencies, and black functions show the no-stimulation latencies. These data are from the correct trials from 41 stimulation sites in 2 monkeys. A: saccades directed to the hemifield contralateral to the hemisphere that was stimulated. B: saccades directed to the hemifield ipsilateral to the hemisphere that was stimulated.