The reward circuit: linking primate anatomy and human imaging

Abstract

Although cells in many brain regions respond to reward, the cortical-basal ganglia circuit is at the heart of the reward system. The key structures in this network are the anterior cingulate cortex, the orbital prefrontal cortex, the ventral striatum, the ventral pallidum, and the midbrain dopamine neurons. In addition, other structures, including the dorsal prefrontal cortex, amygdala, hippocampus, thalamus, and lateral habenular nucleus, and specific brainstem structures such as the pedunculopontine nucleus, and the raphe nucleus, are key components in regulating the reward circuit. Connectivity between these areas forms a complex neural network that mediates different aspects of reward processing. Advances in neuroimaging techniques allow better spatial and temporal resolution. These studies now demonstrate that human functional and structural imaging results map increasingly close to primate anatomy.

Figure 1

Schematic illustrating key structures and pathways of the reward circuit. Red arrow=input from the vmPFC; dark orange arrow=input from the OFC; light orange arrow=input from the dACC; yellow arrow=input form the dPFC; brown arrows other main connections of the reward circuit. Amy=amygdala; dACC=dorsal anterior cingulate cortex; dPFC=dorsal prefrontal cortex; Hipp=hippocampus; LHb=lateral habenula; hypo=hypothalamus; OFC=orbital frontal cortex; PPT=pedunculopontine nucleus; S=shell, SNc=substantia nigra, pars compacta; STN=subthalamic nucleus.; Thal=thalamus; VP=ventral pallidum; VTA=ventral tegmental area; vmPFC=ventral medial prefrontal cortex.

Figure 2

Expected value of monetary rewards activates the ventral cortico-basal ganglia circuit. Panels indicate activation significantly correlated with expected value in the mPFC (anterior=45), NAcc (anterior=12), and VTA (anterior=−15). Although the midbrain and VS are sensitive to anticipated reward magnitude, the MFPC is also sensitive to anticipated reward probability (not shown here; adapted from Knutson et al, 2005).

Figure 3

Schematic illustrating the connections of the VS. Blue arrows=inputs; gray arrows=outputs; Amy=amygdala; BNST=bed nucleus stria terminalis; dACC=dorsal anterior cingulate cortex; Hipp=hippocampus; hypo=hypothalamus; MD=medio-dorsal nucleus of the thalamus; OFC=orbital frontal cortex; PPT=pedunculopontine nucleus; S=shell; SNc=substantia nigra, pars compacta; STN=subthalamic nucleus; Thal=thalamus; VP=ventral pallidum; VS=ventral striatum; VTA=ventral tegmental area; vmPFC=ventral medial prefrontal cortex.

Figure 4

Schematic chartings of labeled fibers after injections into different prefrontal regions. (a) vmPFC injection site (area 25), (b) OFC injection site (area 11), (c) dACC, (d) dPFC injection site (area 9/46). The focal projection fields are indicated in large solid black shapes. Diffuse projection fibers are found outside of the focal projection fields (as illustrated in the photomicrograph in (d)).

Figure 5

Schematics showing convergence of cortical projections from different reward-related regions and dorsal prefrontal areas. (a) Medio-frontal view of a 3D reconstruction illustrating convergence of inputs from PFC inputs. (b) 2D section through the striatum illustrating regions of convergence. (c) Distribution of diffuse fibers from different PFC regions. (d) Diffuse fibers are superimposed onto the focal projections, showing the interface between diffuse and focal projections. ACC=dorsal anterior cingulate cortex; dPFC=dorsal lateral prefrontal cortex; OFC=orbital prefrontal cortex; vmPFC=ventral medial prefrontal cortex. red=inputs from vmPFC; dark orange=inputs from OFC; light orange=inputs from dACC; yellow=inputs from dPFC.

Figure 6

Anatomical schemes for parcellating the striatum based on structural landmarks. Top: Ventral and dorsal striatum (adapted from Mawlawi et al, 2001); Bottom: nucleus NAcc, caudate, and putamen (adapted from Breiter et al, 2001).

Figure 7

Propagation of gain prediction error from rostral to dorsal striatal regions over time. Lines depict neural responses to gain (+$5.00; black) vs nongain (+$0.00; gray) outcomes during trials in which subjects had earlier anticipated winning an uncertain large gain (ie, $5.00 with 66% chance of hitting) in the monetary incentive delay task (Knutson et al, 2003). The white band indicates the onset of gain vs nongain feedback (lagged by 4 s to account for the hemodynamic delay). Stars indicate a significant difference between activation for gain vs nongain feedback (p<0.01). Note that gain prediction error differences appear in the mPFC and NAcc immediately, but not in the dorsomedial caudate until 2 s later, and not in the putamen until 4 s later (n=40 subjects, unpublished data).

Figure 8

Schematic illustrating the connections of the VP. Blue arrows=inputs; gray arrows=outputs; DP=dorsal pallidum; hypo=hypothalamus; LHb=lateral habenula; MD=medio-dorsal nucleus of the thalamus; PPT=pedunculopontine nucleus; SN=substantia nigra; STN=subthalamic nucleus; Thal=thalamus; VP=ventral pallidum; VTA=ventral tegmental area.

Figure 9

Schematic illustrating the organization (a) and connections (b) of the midbrain dopamine cells. Red cells=connections with VS regions; yellow cells=connections with dorsal caudate nucleus; blue cells=connections with motor control striatal areas. BNST=bed nucleus stria terminalis; CeA=central amygdala nucleus; Amy=amygdala; Hipp=hippocampus; PPT=Pedunculopontine nucleus; SNc=substantia nigra, pars compacta; VP=ventral pallidum; VTA=ventral tegmental area.

Figure 10

Schematic illustrating the complex connections between the striatum and SN. The arrows illustrate how the VS can influence the dorsal striatum through the midbrain dopamine cells. Colors indicate functional regions of the striatum based on cortical inputs. Midbrain projections from the shell target both the VTA and ventromedial SNc. Projections from the VTA to the shell form a ‘closed,' reciprocal loop, but also project more laterally to impact on dopamine cells that project to the rest of the VS, forming the first part of a feed forward loop (or spiral). The spiral continues through the striato-nigro-striatal projections through which the VS impacts cognitive and motor striatal areas through the midbrain dopamine cells; red=inputs from the vmPFC; orange=inputs from the OFC and dACC; yellow=inputs from the dPFC; green and blue=inputs from motor control areas.

Figure 11

Three networks of integration through cortico-basal ganglia pathways. (1) Fibers from different prefrontal areas converge within subregions of the striatum. (2) Through the organization of striato-nigro-striatal (SNS) projections, the VS can influence the dorsal striatum. (3) The nonreciprocal cortico-thalamic projection carries information from reward-related regions, through cognitive, and motor controls. dACC=dorsal anterior cingulate cortex; dPFC=dorsal prefrontal cortex; OFC=orbital frontal cortex; vmPFC=ventral medial prefrontal cortex. Red=vmPFC pathways; dark orange=OFC pathways; light orange=dACC pathways; yellow=dPFC pathways; green=output to motor control areas.