Brain stimulation reward

Brain stimulation reward (BSR) is a pleasurable phenomenon elicited via direct stimulation of specific brain regions, originally discovered by James Olds and Peter Milner. BSR can serve as a robust operant reinforcer. Targeted stimulation activates the reward system circuitry and establishes response habits similar to those established by natural rewards, such as food and sex. Experiments on BSR soon demonstrated that stimulation of the lateral hypothalamus, along with other regions of the brain associated with natural reward, was both rewarding as well as motivation-inducing. Electrical brain stimulation and intracranial drug injections produce robust reward sensation due to a relatively direct activation of the reward circuitry. This activation is considered to be more direct than rewards produced by natural stimuli, as those signals generally travel through the more indirect peripheral nerves. BSR has been found in all vertebrates tested, including humans, and it has provided a useful tool for understanding how natural rewards are processed by specific brain regions and circuits, as well the neurotransmission associated with the reward system. Brain stimulation reward (BSR) is a pleasurable phenomenon elicited via direct stimulation of specific brain regions, originally discovered by James Olds and Peter Milner. BSR can serve as a robust operant reinforcer. Targeted stimulation activates the reward system circuitry and establishes response habits similar to those established by natural rewards, such as food and sex. Experiments on BSR soon demonstrated that stimulation of the lateral hypothalamus, along with other regions of the brain associated with natural reward, was both rewarding as well as motivation-inducing. Electrical brain stimulation and intracranial drug injections produce robust reward sensation due to a relatively direct activation of the reward circuitry. This activation is considered to be more direct than rewards produced by natural stimuli, as those signals generally travel through the more indirect peripheral nerves. BSR has been found in all vertebrates tested, including humans, and it has provided a useful tool for understanding how natural rewards are processed by specific brain regions and circuits, as well the neurotransmission associated with the reward system. Intracranial self-stimulation (ICSS) is the operant conditioning method used to produce BSR in an experimental setting. ICSS typically involves subjects with permanent electrode implants in one of several regions of the brain known to produce BSR when stimulated. Subjects are trained to continuously respond to electrical stimulation of that brain region. ICSS studies have been particularly useful for examining the effects of various pharmacological manipulations on reward sensitivity. ICSS has been utilized as a means to gauge addiction liability for drugs of many classes, including those which act on monoaminergic, opioid, and cholinergic neurotransmission. These data correlate well with findings from self-administration studies on the addictive properties of drugs. In 1953, James Olds and Peter Milner, of McGill University, observed that rats preferred to return to the region of the test apparatus where they received direct electrical stimulation to the septal area of the brain. From this demonstration, Olds and Milner inferred that the stimulation was rewarding, and through subsequent experiments, they confirmed that they could train rats to execute novel behaviors, such as lever pressing, in order to receive short pulse trains of brain stimulation. Olds and Milner discovered the reward mechanisms in the brain involved in positive reinforcement, and their experiments led to the conclusion that electrical stimulation could serve as an operant reinforcer. According to B.F. Skinner, operant reinforcement occurs when a behavior is followed by the presentation of a stimulus, and it is considered essential to the learning of response habits. Their discovery enabled motivation and reinforcement to be understood in terms of their underlying physiology, and it led to further experimentation to determine the neural basis of reward and reinforcement. Since the initial discovery, the phenomenon of BSR has been demonstrated in all species tested, and Robert Heath similarly demonstrated that BSR can be applied to humans. Early studies on the motivational effects of brain stimulation addressed two primary questions: 1. Which brain sites can be stimulated to produce the perception of reward? and 2. Which drugs influence the response to stimulation and via what mechanism? Investigation of the brain reward circuitry reveals that it consists of a distributed, multi-synaptic circuit that determines both BSR and natural reward function. The natural drives that motivate and shape behavior reach the reward circuitry trans-synaptically through the peripheral senses of sight, sound, taste, smell, or touch. However, experimentally-induced BSR more directly activates the reward circuitry and bypasses transduction through peripheral sensory pathways. For this reason, electrical brain stimulation provides a tool for identifying the reward circuitry within the central nervous system with some degree of anatomical and neurochemical specificity. Studies involving these two forms of laboratory reward showed stimulation of a broad range of limbic and diencephalic structures could be rewarding as well as implicated the dopamine-containing neurons of the mesolimbic dopamine system in motivational function. The motivational effect of intracranial self-stimulation varies substantially depending on the placement site of the surgically implanted electrode during electrical stimulation, and animals will work to stimulate different neural sites depending on their current state. Often, animals that work to initiate brain stimulation will also work to terminate the stimulation. The relationship between BSR and natural rewards (e.g. food, water and copulation) has long been debated, and much of the early research on BSR is focused on their respective similarities and differences. BSR is facilitated through the same reinforcement pathway activated by natural rewards. Self-stimulation can exert robust activation of central reward mechanisms due to more direct action than natural rewards, which initially activate peripheral nerves. BSR to the medial forebrain bundle (MFB) through either electrical or chemical means activates key components of the reward pathway also activated by natural rewards. When specific regions of the hypothalamus are electrically stimulated, it elicits reward-related behaviors such as eating, drinking, or copulation responses. Natural rewards are associated with a state of deprivation which results from unmet needs or desires (e.g. hunger). These states drive instinctual, motivated behaviors like food consumption. It has been argued that this is not the case with BSR, as it does not meet an intrinsic survival-based need. BSR also notably lacks an established neural representation in memory that naturally facilitates the learning of reward expectancy. Both of these effects lead to diminished response rate for BSR in the early trials of a series; however, experiments have also shown that extinguished behavior can be quickly reinstated by a priming stimulation that refreshes the short-term association involved in reward expectancy. Studies on BSR indicate that reinforcing brain stimulation may activate the natural pathways associated with natural drives as well as stimulate the reinforcement pathways that are usually activated by natural rewards. Rats will perform lever-pressing at rates of several thousand responses per hour for days in order to obtain direct electrical stimulation of the lateral hypothalamus. Multiple studies have demonstrated that rats will perform reinforced behaviors at the exclusion of all other behaviors. Experiments have shown rats will forgo food to the point of starvation in order to work for brain stimulation or intravenous cocaine when both food and stimulation are offered concurrently for a limited time each day. Rats will also cross electrified grids to press a lever, and they are willing to withstand higher levels of shock to obtain electrical stimulation than to obtain food . Satiation experiments in rats have revealed that BSR does not produce satiety. Olds demonstrated that this lack of satiation associated with BSR allows animals to self-stimulate to sheer exhaustion and that satiation is dependent on the location of the electrical stimulation. In a 48-hour satiation test, rats with hypothalamic electrodes self-stimulated to exhaustion and showed no intrinsic satiation tendencies, whereas telencephalic electrodes showed radical slowing of self-stimulation after 4 to 8 hours. The insatiability of BSR is closely related to the strength of drive. While a natural reward, like food, is met with a feeling of being full (satiety), BSR does not have a comparable correlate. This allows for BSR to be experienced indefinitely, or in the case of ICSS, until exhaustion. Addiction is a chronic brain disorder consisting of compulsive drug-taking and seeking that is maintained despite detrimental effects on various aspects of life including health, relationships, and work. Laboratory procedures can establish compulsive self-administration habits of seeking and ingesting that qualify as addictive behaviors. Rodents and non-human primates have been shown to work in a compulsive manner to receive intravenous injections of stimulants, and when access to the drugs is not limited, they will self-administer drugs to the point of severe weight loss and death. Similar to self-administration behavior, responding for intracranial brain stimulation has a highly compulsive component which is characteristic of an addicted state. BSR is hypothesized to be so effective in establishing compulsive habits due to its more direct activation of the reward pathway, bypassing transmission through sensory pathways which occurs in response to natural rewards. Delayed reinforcement following a response for BSR decreases how strongly this behavior is reinforced and to what extent it continues. A delay of one second, for example, between a lever-press and reward delivery (stimulation) can reduce response levels. BSR offers insights into the neural circuitry involved in reinforcement and compulsive behavior.