M+Neural+Circuits+of+Reward

Chapter 2

Anatomical connectivity studies provide a key element for understanding the neural networks involved in evaluating environmental stimuli that transform this information into actions, thus leading to expected outcomes. The reward circuit is a central component of the network that drives incentive-based learning, appropriate responses to stimuli, and good decision making. The idea that there is an anatomically identifi able reward circuit initially came from experiments that demonstrated rats would work for electrical stimulation in specifi c brain sites 51 and was later supported by pharmacological manipulation of those sites through intracranial injections of drugs of abuse. 8 Although this circuit included several brain regions, the orbital (OFC) and anterior cingulate cortices (ACC), the n. accumbens (NAcc), and the ventral tegmental area (VTA) dopamine neurons are central. 29,60,62,71 Recent studies extend the striatal and midbrain reward-related areas to include the entire ventral striatum (VS) and the dopamine neurons of the substantia nigra, pars compacta (SNc). * The VS receives its main cortical input from the OFC and ACC, and a massive dopaminergic input from the midbrain. The VS projects to the ventral pallidum (VP) and to the VTA-SN, which in turn project back to the prefrontal cortex (PFC), via the medial dorsal nucleus (MD) of the thalamus. These structures are part of the corticobasal ganglia system and are at the center of the reward circuit ( fi gure 2.1 ). 25

//Schematic illustrating key structures and pathways of the reward circuit. Black arrow = input from the// //vmPFC; dark gray arrow = input from the OFC; light medium gray arrow = input from the dACC; light// //gray arrow = input from the dPFC; white arrows = other main connections of the reward circuit. Amy,// //amygdala; dACC, dorsal anterior cingulate cortex; dPFC, dorsal prefrontal cortex; Cd, caudate nucleus;// //Hipp, hippocampus; MD, medial dorsal nucleus of the thalamus; OFC, orbital frontal cortex; Pu, putamen;// //S, shell; SN, substantia nigra; STN, subthalamic n.; Thal, thalamus; VP, ventral pallidum; VTA, ventral// //tegmental area; vmPFC, ventral medial prefrontal cortex.//

While the reward circuit is now considered part of the corticobasal ganglia network, historically, the basal ganglia was considered solely part of the sensory – motor control system. 47 The conceptual change from a purely sensory – motor function to a more complex set of functions can be traced to the demonstration that an additional (and separate) functional loop, the limbic loop, exists within the basal ganglia. 30 The idea of separate cortical loops in the basal ganglia was subsequently expanded to include several parallel and segregated functional loops (limbic, associative, and sensorimotor). 1 Although this concept has dominated the fi eld for the past 20 years, several studies demonstrate integration across these circuits. Network crosstalk between limbic associative functions is consistent with the idea that adaptive behaviors require a combination of reward evaluation and associative learning to develop appropriate action plans and inhibit inappropriate choices. Not surprisingly, the idea of motivation-to-movement interface through basal ganglia circuits was developed soon after the discovery of the limbic component to the basal ganglia. 43,46 Thus, the ventral corticobasal ganglia network, while at the heart of reward processing, does not work in isolation. 3,5,12,23,24 In fact, within each station of the circuit there are interfaces between pathways that allow communication between different parts of the reward circuit and between the reward circuit and the associative circuit.

Prefrontal Cortex and Its Projections to the Striatum
The PFC comprises multifunctional regions involved in reinforcement-based learning and decision making. Different prefrontal cortical areas and corresponding striatal regions are involved in these various aspects of motivation and learning, and pathophysiology in the circuit is associated with sadness and depression, pathological risk taking, addictive behaviors, and obsessive-compulsive disorder. 15,38,41,50,69 The PFC is a complex and heterogenous region, but can broadly be divided into (1) the orbitofrontal cortex, or OFC (lateral OFC and part of insular cortex); (2) a ventral, medial prefrontal cortex, or vmPFC (medial OFC, subgenual ACC, and area 10); (3) the dorsal anterior cingulate cortex, or dACC (area 24); and (4) the dorsal prefrontal cortex, or dPFC (areas 9 and 46). 10,25,52