Frontal cortex-like functions of the subthalamic nucleus

Abstract

The subthalamic nucleus (STN) has been considered a motor structure for a long time. Over the last 20 years, anatomical and behavioral data have highlighted the position of the STN within a prefrontal-associative and a limbic loops, suggesting that the STN should play a critical role in frontal functions such as attention, inhibitory control (including impulsive action, compulsivity, impulsive choice), and motivation. Here we will review the work highlighting these functions of the STN.

Keywords: attention; basal ganglia; behavioral inhibition; compulsion; deep brain stimulation; impulsivity; motivation; subthalamic nucleus.

Figure 1

Schematic representation of the impulsive action processes in the stop task and the 5-CSRTT (premature responses) from lesion and pharmacological manipulations. Colored bands surrounding each structure highlight the impulsive-like effect of the lesion of the given structure. Hatched–shaded bands indicate no effect of excitotoxic lesion, but an effect under pharmacological manipulation or other conditions). Gray structures indicate that no information is available. Arrows materialize anatomical connections between regions. CG, cingulate cortex; PL, pre-limbic cortex; IL, infra-limbic cortex; OFC, orbito-frontal cortex; HPC, hippocampus; DMStr, dorso-medial striatum; NAcbC, nucleus accumbens core; NAcbS, nucleus accumbens shell; GP, globus pallidus; BLA, basolateral amygdale; STN, subthalamic nucleus; VP, ventral pallidum.

Figure 2

Schematic representation of the impulsive action and perseveration/compulsivity processes in the stop task and the 5-CSRTT (premature responses and perseverative responses) from lesion and pharmacological manipulations. Colored bands surrounding each structure highlight the impulsive-like effect of the lesion of the given structure. Hatched–shaded bands indicate no effect of excitotoxic lesion, but an effect under pharmacological manipulation or other conditions). Gray structures indicate that no information is available. Arrows materialize anatomical connections between regions. CG, cingulate cortex; PL, pre-limbic cortex; IL, infra-limbic cortex; OFC, orbito-frontal cortex; HPC, hippocampus; DMStr, dorso-medial striatum; NAcbC, nucleus accumbens core; NAcbS, nucleus accumbens shell; GP, globus pallidus; BLA, basolateral amygdale; STN, subthalamic nucleus; VP, ventral pallidum.

Figure 3

Schematic representation of the impulsive action, perseveration/compulsivity, and impulsive choice processes in the stop task, the 5-CSRTT (premature responses and perseverative responses) and the delay-discounting task from lesion and pharmacological manipulations. Colored bands surrounding each structure highlight the impulsive-like effect of the lesion of the given structure. Hatched–shaded bands indicate no effect of excitotoxic lesion, but an effect under pharmacological manipulation or other conditions). Gray structures indicate that no information is available. Arrows materialize anatomical connections between regions. CG, cingulate cortex; PL, pre-limbic cortex; IL, infra-limbic cortex; OFC, orbito-frontal cortex; HPC, hippocampus; DMStr, dorso-medial striatum; NAcbC, nucleus accumbens core; NAcbS, nucleus accumbens shell; GP, globus pallidus; BLA, basolateral amygdale; STN, subthalamic nucleus; VP, ventral pallidum (from Eagle and Baunez, 2010).

Figure 4

Effects of bilateral high frequency stimulation (HFS) of the STN on motivation to work for either food (A) or intravenous cocaine (B) in control [OFF stimulation (empty bars)] and stimulated rats (black bars) performing a progressive ratio schedule of reinforcement. Rats were required to produce an increasing number of lever presses to obtain the given reward. The number of rewards obtained is illustrated on the upper part of the graph, while the last ratio reached is illustrated on the lower part. (taken from Rouaud et al., 2010). Vertical bar: SEM. ***p < 0.05 and p < 0.01 respectively compared with control group (OFF stimulation condition).