Where is the brain’s reward system located?
If the reward system was a movie it would have three major locations and two leading roles. The locations are each complex entities in their own right but work together to make things even more confusing.
The locations are the prefrontal cortex, the basal ganglia and the thalamus. The leading roles are two neurotransmitters: dopamine and GABA.
The first location is the prefrontal cortex. It is both easy and hard to find. Let’s start at the top and work our way down.
As you know, the brain has four major lobes (frontal, temporal, occipital and parietal). The frontal lobe has three major components: the motor cortex (to move your muscles), the premotor cortex (for planning movements) and the prefrontal cortex.
This prefrontal cortex has three parts too. The dorsolateral portion houses rules about rules. It is the last region of the brain to myelinate. It helps integrate information from all the other parts of the brain, and uses that data for high level motor planning. The dorsolateral cortex is involved in working memory, decision making and comparing inputs. You don’t blurt out what you’re thinking because your dorsolateral region helps inhibit your impulses. On the other hand, when you lie it’s because of your dorsolateral cortex. Our tendency is to tell the truth. When we want to lie, we have to use brain power to make up the lies. When you suffer from sleep deprivation, it is the dorsolateral region that is mad at you. Tumors in this region produce schizophrenia-like symptoms.
The dorsolateral cortex is directly bi-directionally connected to the orbitofrontal region, which houses rules about when you should switch what you are doing. When the orbitofrontal area is damaged, patients suffer from lack of control. They swear excessively, become hypersexual, have poor social interactions. They can’t judge social awkwardness, have poor emotional regulation and display compulsive behavior common in ADHD and OCD.
The orbitofrontal cortex is involved in three major issues related to reward: Alzheimer’s, gambling, and drug abuse. It is one of the brain regions where the neuro-tangles of Alzheimer’s occur. Something happens to the neurons and they get tangled up and die. The result is poor emotional regulation and a lack of intuitive judgement. Rewards seem to be overvalued and punishment (or loss) is underestimated.
The orbitofrontal region is involved in comparing expected and actual outcomes, and evaluating reward and punishment expectations. Damage to the orbitofrontal area results in compulsive behavior. For example, it shown a button labels DON’T PRESS, patients can’t stop themselves from pressing it. The inability of gamblers to effectively evaluate their losses is correlated with damage to the orbitofrontal cortex.
Similarly, the orbitofrontal portion of the prefrontal cortex allows you to switch rules when you need to. When the region is damaged, patients can’t switch away from an activity even though they can articulate that they should. They get stuck. They continue to pursue losing hands.
The orbitofrontal cortex is also involved in drug addiction. In addition to the compulsive use of drugs, cravings are associated with activity in this region. During cocaine withdrawal, the more you crave, the more activity there is in it.
As withdrawal continues, the orbitofrontal area activity drops to below normal levels. Three to four months after stopping cocaine use, the orbitofrontal region is not working as well as non-drug users. A similar pattern occurs in alcoholics.
Since the orbitofrontal cortex is involved in evaluating the emotional value of reinforcers, this might lead to an increased motivation to take a drug.
The three prefrontal cortex parts (dorsolateral, orbitofrontal and ventromedial) all work together. The orbitofrontal and dorsolateral are directly interconnected by neurofibers. The orbitofrontal and ventromedial portions are anatomically inseparable. All three do somewhat different functions but are so intertwined it is difficult to say when they aren’t working together.
“All roads lead to Rome” is a great metaphor for the thalamus. In the days of Caesar Augusus, all roads led to a monument (Milliarium Aureum) in the middle of Rome. Distance along any road was measured from this monument, so the saying should really be that “all roads lead away from Rome.” Both directions work for the thalamus. Everything directly or indirectly comes to or is sent from the thalamus complex.
The thalamus sends and receives input to most regions of the cortex. This thalamus-cortico-thalamus loop provides a complex feedback system. Specialized cells in the thalamus oscillate in response to the rhythmic patterns of neural input. The level of oscillation correlates with the level of cortical response.
In addition to being the processor of incoming stimuli and the filter for outgoing traffic, the thalamus is the center of pain perception. It regulates sleep, consciousness, alertness, and every sensory input but smell. One region (the LGN) accepts all the inputs of the eyes and transfers them to the occipital lobe. Another nucleus (the MGN), transfers all of the auditory inputs to the temporal lobe. Degeneration of the thalamus results in permanent insomnia and eventually death.
The hypothalamus is part of the thalamus complex. It runs much of your life. When the bark of a big dog scares you, it is the hypothalamus that triggers your fight-flight response. When you are hunger or thirsty, the hypothalamus is at work. If you have a menstrual period, it is caused by the cyclical properties of the hypothalamus. The hypothalamus is involved in sleep, circadian rhythms, and body temperature, among others. It is the major link between neurons and hormones.
The thalamus is in the center of the head and just above the midbrain (substantia nigra, inferior colliculi, superior colliculi, etc.). Neurons extend out in all directions. It is the Rome of your brain.
In addition to the prefrontal cortex and the thalamus, the basal ganglia is a major component of the brain’s reward system. It’s basal (basement) because it is located under the cerebrum. It’s ganglia (neuron cluster or swelling) because it is not a single structure but several entities that work together as a single unit.
The basal ganglia is the brake of the brain. It works on the disinhibition principle. Basically, it says “No, No, No, No” until it receives an input that releases the brake. It balances the excitatory inputs of the cerebellum to make your dance movements smooth. It balances the cortical activity to calm you down. It balances the thalamus activity to help regulate your emotions.
Balance is important. Too little braking initiates multiple uncontrolled simultaneous activities. This is what happens in Huntington’s disease. In contrast, Parkinson’s disease is the result of too much braking. It makes it difficult to initiate movements.
The basal ganglia is composed of two major structures and two smaller ones. The striatum is the largest structure. It looks like two blobs of gray separated by large white stripe. It receives inputs from many brain areas but only outputs to other parts of the basal ganglia.
The striatum coordinates multiple aspects of cognition, including action planning, decision making, motivation, reinforcement and reward. The striatum is activated by novel, intense or unexpected stimuli. Its activity is associated with reward and aversive stimuli. Huntington’s is a genetic disorder that causes damage to the striatum.
Its dorsal aspect of the striatum is composed of the caudate and putamen, which together look like a backward “at” sign (@). The putamen, the center circle or “a” of the at-sign, is the outermost portion of the basal ganglia. It interconnects with the thalamus and many brain regions. It is involved in the learning of skills and movements, and is one of the regions damaged by Parkinson’s disease.
The caudate (semicircular tail) is also damaged by Parkinson’s. In addition to regulating motor functions, the caudate is involved in procedural learning (do this before that) and making associations. It is plays a major role in the reward system (cortico-basal ganglia-thalamic loop).
The ventral (opposite of dorsal) striatum is composed the olfactory bulb and the nucleus accumbens. The olfactory bulb is the primary region for processing smell. The interaction of the olfactory bulb and the basal ganglia explains why smells can produce such strong emotions.
The nucleus accumbens is sometimes called the pleasure center of the brain. Remember those rat studies where they pressed a lever to get more brain stimulation? The probes were placed in the nucleus accumbens.
But pleasure and reward in humans is not that simple. The nucleus accumbens plays a major role in the cognitive processing of motivation, pleasure, reward, reinforcement, aversion and addiction. It plays a minor role in processing fear, impulsivity, encoding motor skills and the placebo effect. It is particularly good at encoding new motor programs that help us get future rewards.
The nuclei (one in each hemisphere) each has two parts: a shell and a core. The shell processes want (motivational salience) and influences the perception of rewards and reinforcements. It responds both to drugs and naturally rewarding stimuli.
Stimulating the nucleus accumbens strengthens associations between a drug and its environmental cues. Even after stopping its use, the look, smell, who you are with, lighting and environmental cues associated with taking cocaine and amphetamines continue to trigger an emotional response. These triggers can last for months or years. Alcohol use has similar effect.
In addicts, the nucleus accumbens appears to release seratonin, dopamine and perphas other neurotransmitters. This release correlates with drug cravings. The prefrontal cortex also seems to be activated by or causes cravings.
After the striatum, the pallidum is the second large component of the basal ganglia. It receives input from the striatum and sends inhibitory output (GABA) to a number of motor-related areas.
The pallidum is involved in planning and inhibiting movements. This includes movements that are voluntary and those well-practiced movements that are more subconscious. As a balance to the cerebellum, the pallidum allows smooth and controlled movement.
The dorsal portion of the pallidum (the globus pallidus) contains very large neurons that form a 3-D cluster of flat discs. It directly outputs to the substantia nigra.
3. Substantia nigra
Located in the midbrain (the region between the limbic system and spine), the substania nigra is closer to the pons than anywhere else. It receives input from the globus pallidus and outputs to many brain structures. It also supplies the striatum with dopamine.
The substantia nigra impacts both movement and emotion. It is probably best known for its connection with Parkinson’s disease. As we age, we lose a few of the dopamine neurons in the substatia nigra. We have plenty so it it’s really a problem until we have lost 70-80% of them. The premature and massive loss of dopamine neurons in the substantia nigra causes Parkinson’s symptoms.
The most prevalent neurotransmitters in the brain are glutamate and GABA. Glutamate is an excitatory neurotransmitter. It accounts for 90% of the neurons in the brain. It is the “GO, GO, GO” signaler of the brain. In contrast GABA, which is synthesized from glutamate, is the “STOP, STOP, STOP” signaler of the brain. It accounts for about 9% of the brain’s neurons. The basal ganaglia primarily outputs GABA.
When something happens that you want to remember, your brain releases several neurotransmitters to mark it as important. This is true of good things and bad things. Anything that seems important. One of those neurotransmitters is dopamine.
Dopamine is released from an area under the cortex and above the spine. It is either part of the substatia nigra or next to it. This VTA (ventral tegmental area) isn’t as much a nucleus (cluster of gray matter) as it is a borderless region or zone. You’ll find it next to hypothalamus, the red nucleus, the pons and the substantia nigra.
You probably know that the pons connects the cerebrum to the cerebellum, and back again. It and the red nucleus help you coordinate your movements and swing your arms when you walk.
From the VTA, dopamine neurons connect first to the nucleus accumbens, and then head for the prefrontal cortex, with branches leading to most portions of the brain.
Next we look at how the brain’s reward system works.