Neurons in the Monkey's Subthalamic Nucleus Differentially Encode Motivation and Effort

Abstract

The understanding of the electrophysiological properties of the subthalamic nucleus (STN) neurons is crucial since it represents the main target of deep brain stimulation for the treatment of Parkinson's disease and obsessive-compulsive disorders. The study of its nonmotor properties could shed light on the cognitive and motivational alterations possibly encountered after stimulation. In this study, we recorded the activity of STN neurons in two male behaving monkeys (Macaca mulatta) while they performed a visuomotor motivational task in which visual cues indicated which amount of force was required to obtain which amount of reward. Our results evidenced force- and reward-modulated neurons. After the occurrence of the visual stimuli, the force-modulated neurons mainly fired when a high effort was required. Differently, the activity of the population of reward-modulated neurons encoded the motivational value of the stimuli. This population consisted of neurons increasing or decreasing their activity according to the motivational ranking of the task conditions. Both populations could play complementary roles, one in the implementation of the difficulty of the action and the other in enhancing or slowing its execution based on the subjective value of each condition.SIGNIFICANCE STATEMENT An increasing number of studies confers a role to the subthalamic nucleus (STN) in motivational and reward-related processes. However, the electrophysiological bases of such properties at the neuronal level remain unclear. The present study investigated the modulation of STN neuronal activity in monkeys performing a motivational task in which the force to produce and the reward obtained were manipulated. We found two main populations of neurons, one modulated by the effort required and the other integrating the motivational subjective value of the stimuli. This last population could help at improving decision-making to act or not, depending on the subjective value set by the motivational context. This highlights the pivotal role of STN in the valuation of cost/benefit for decision-making processes.

Keywords: effort; electrophysiology; monkey; motivation; reward; subthalamic nucleus.

Figure 1.

Task design and localization of the subthalamic nucleus recordings. A, Task design. A trial started when the monkey applied a basal force on the lever and maintained it during a 1 s preparatory period after which a pair of visual stimuli appeared on the screen (occurrence of the visual stimuli). In response to these stimuli, the monkey had to increase its pressing force until it reached the required force range materialized by a rectangle and a gauge on the screen (the time to reach the target force being the cue threshold period), and held its force for 1 s (i.e., holding period) to obtain the reward. B, Table illustrating the combinations of visual stimuli. Four possible pairs of visual stimuli indicated to the animal the force to be developed and the size of the upcoming reward. Green represented the force (F or f) and red the reward (R or r), a circle meant small (f or r), and a square meant large (F or R). The example condition shown in A was low force/large reward. C, Left, MR image from Monkey Y (left) and Monkey M (right), respectively, at +13 and +14 mm from the midpoint of the interaural line. Both images have been reoriented to fit the electrode track (Monkey Y: anteroposterior angle, −4.5°; lateral angle, 18°; Monkey M: anteroposterior angle, 6°; lateral angle, 17°).

Figure 2.

Behavioral performance of both monkeys. A, RTs of the monkeys in the four conditions of the task. Solid black lines, high force; dashed black lines, low force. The error bars represent the SEM. The stars indicate the influence of force and reward on the animal reaction time (two-way ANOVA: **p < 0.01, ***p < 0.001). B, Acceptance level of the animals in the four conditions of the task (fR, FR, fr, and Fr). The stars indicate a significant difference between the proportions of accepted trials on the total number of trials performed in a given condition (Pearson's χ²: *p < 0.05, ***p < 0.001). C, Mean of the force developed on the lever along the trial by the animals in the four conditions of the task. Black lines, High force; gray lines, low force; thick lines, large reward; thin lines, small reward. The dashed vertical line represents the occurrence of the visual stimuli.

Figure 3.

Distribution of the FSI and RSI, average activity of STN neurons among the task conditions, and comparison of cue versus RT alignment. A, Scatter plots of force versus reward selectivity indices for each individual neuron during the cue-threshold period. FSIs > 0 indicate higher modulation in the high-force conditions. RSIs > 0 indicate higher modulation in the large-reward conditions. The color of the dots indicates the significance of a modulation (force, reward, or interaction effect) in the GLM analysis. Filled green circles represent the neurons showing a force effect. Unfilled red circles represent the neurons showing a reward effect. Black crosses represent neurons showing an interaction effect, and small gray dots represent neurons without modulation by the task factors (n. s. for non significant). The superimposed histograms represent the distribution of the FSI (green) and the RSI (red) of the 78 neurons. B, Average spike density (σ = 30) of the whole population (n = 78) of STN neurons. The horizontal dashed line represents the baseline activity, and the four solid color lines represent the four conditions of the task (purple, fR; orange, FR; green, fr; blue, Fr). The vertical dashed line represents the occurrence of the visual cues. C, Same representation as in A for a period of 150 ms from the reaction time. D, Average spike density (σ = 50) of the whole population with all conditions combined. The vertical dashed line represents the occurrence of the visual cues for the activity represented in blue, and the RT for the activity represented in gray. The activity is slightly higher (<1 Hz) when aligned on the RT but clearly triggered by the cue onset. For scaling reasons, a neuron with an RSI higher than 2 is not represented on the scatter plot in A an C.

Figure 4.

Distributions of the FSIs and RSIs during the cue-threshold period and average spike density of STN neurons showing a force or a reward effect. Same representation as in Figure 3. A, Indices distribution and average spike-density for the neurons showing a reward effect. Left, Scatter plot of force selectivity versus reward selectivity indices for the neurons showing a force effect (n = 19; green filled circles). The black line represents the Pearson's correlation between the FSI and RSI of the 19 neurons. The gray arrow indicates the neuron taken as an example on the right panel of the figure. Middle, The average spike density shows the higher activity in the high-force conditions after the occurrence of the cues (materialized by the vertical line at time 0). Right, Raster plot of a cell showing a force effect. Each line represents a trial, and each dot represents the occurrence of a spike. The trials are sorted among the four conditions. In this example, the activity is higher in the high-force conditions than in the low-force conditions after the occurrence of the visual cues. B, Distribution and average spike density of indices for the neurons showing a reward effect. Left, Top, Scatter plot of force versus reward selectivity indices for the neurons showing a reward effect (n = 15; empty red circles). For scaling reasons, a neuron with an RSI higher than 2 is not represented on the scatter plot. The black line represents the Pearson's correlation between the RSI and FSI of the 15 neurons, revealing a significant correlation. The gray arrows indicate the neurons taken as example on the right panel of the figure. Middle, The average spike density of the separated populations of neurons showing a reward effect. Middle, Top, Average spike density of the neurons with a positive RSI (n = 9) showing higher activity in the large-reward conditions after the occurrence of the cues (materialized by the vertical line at time 0), but also decreasing response with the high force. Middle, Bottom, Average spike density of the neurons showing a negative RSI (n = 6) showing lower activity in the large-reward conditions after the occurrence of the cues (materialized by the vertical line at time 0), but also increasing slightly with the high force. Left, Bottom, Boxplot representing the average activity during the cue-threshold period and among the four conditions of the task of both subpopulations of reward-modulated neurons RSI⁺ and RSI^–. The boxplots illustrate the influence of the force on the reward-modulated neurons. Only for RSI^– is the effect of force significant. Purple, fR; orange, fR; green, fr; blue, Fr. Right, Raster plots of neurons showing a positive (top) and a negative (bottom) reward effect at the occurrence of the cues. The influence of the force on the reward-modulated neurons is visible at the population level and at the single-cell level.

Figure 5.

Dynamic encoding of relevant information of the task along the trial. A, Results obtained following the training of a classifier at a time t₁ (y-axis) and testing this classifier at a time t₂ (x-axis) for the decoding of the task condition. Left, Bidimensional map of the decoding accuracy in which each pixel represents the decoding accuracy at t₂ with a training of the classifier performed at t₁. The higher decoding accuracy along the main diagonal shows the dynamic decoding of the task condition. The black lines indicate the occurrence of the visual cues. Middle, The black curve represents the decoding accuracy along the main diagonal, at lag 0 (when t₁ = t₂) for the whole population of recorded neurons. Right, Similar representation analyzing separately the neurons showing a force effect (green), a reward effect (red), and the remaining ones (gray). The thick lines at the bottom of the plots represent the significance of the decoding accuracy above the chance level (at 25%, four conditions). The time is the beginning of the first of five significant consecutive bins based on the same analysis performed with a shuffle of the condition labels. B, C, Same representation as in A for the decoding of the amount of reward (B) and the amount of force (C). The trials are pooled between the small-reward (fr and Fr) conditions and the large-reward (fR and FR) conditions for the decoding of the amount of reward. Inversely, they are pooled between the low-force (fr and fR) conditions and the high-force conditions (Fr and FR) for the decoding of the amount of force. The chance level represented by the black line is 50% in both cases.

Figure 6.

Topography of the neuronal recordings in the subthalamic nucleus. The three bidimensional plots on the left represent the projections of each recorded cell from the midpoint of the interaural line. Top left, AP versus laterality, horizontal view. Top right, Depth versus laterality, coronal view. Bottom left, Depth versus AP, sagittal view. Right, Three-dimensional reconstruction of the cell distribution and theoretical boundaries of the STN based on the atlas of Saleem and Logothetis (2007). The filled circles represent the neurons recorded in Monkey Y, and the filled squares represent the neurons recorded in Monkey M. The ellipsoids on the bidimensional plots represent the 95% of the cell distribution for each population of cells. Green, Neurons showing a force effect (n = 19); red, neurons showing a reward effect (n = 15); black, remaining neurons (n = 45).