This Is Your Brain on ADHD, Part I: Dopamine & Reward

It was 1968 when the diagnostic criteria for what is now called ADHD first appeared in the Diagnostic and Statistical Manual (DSM), the book used for diagnosing “mental disorders.” Although the criteria for ADHD have changed over time, they have always been based almost exclusively on observations of behavior. The problem with this approach is that it only describes how ADHD looks; it does not define what Attention Deficit Hyperactivity Disorder really is. Although there seems to be little doubt that its symptoms reflect activity in the human brain, the DSM has never described what that activity might be or where in the brain it may occur. The same can be said about all the conditions listed in the manual. This is the reason why, in 2015, the National Institute of Mental Health announced that it would no longer fund research focused on the behavioral symptoms of mental disorders. Rather, it would only support scientific studies that explore the human brain with the goal of describing and explaining these disorders in neurological terms as specific processes occurring in specific parts of the brain.

More than two decades before the change in NIMH policy, neuroscientists had already begun to look at ADHD in this way, utilizing such tools as positron emission tomography (PET) scans, functional magnetic resonance imaging (fMRI), and genetic analysis to study activity within the ADHD brain. Thus far, they appear to have arrived at three broad conclusions: first, that most ADHD is hereditary in origin, deriving from gene variations passed down within families; second, that ADHD appears somehow related to anomalies in brain development, brain structure, and/or brain function; and third, that thus far there is no consensus as to which of those anomalies fully explain ADHD.

Despite the lack of definitive evidence, there are a number of intriguing hypotheses, and in the three parts of this blog I have summarized what I have read about some of them.

Dopamine,
The most widely accepted neurological explanation for ADHD is that it has something to do with how the brain processes dopamine, one of the chemicals that are integral to how we think, feel, and behave. Dopamine is a neurotransmitter, a molecule that helps carry messages from one brain neuron to another. Molecules of this chemical are stored in axons, the transmitting structures of a neuron, and released when electrical current flows through the cell. They then travel across synapses, spaces between neurons, to dendrites, the receiving structures of other neurons. There the molecules bond to receptor sites. This triggers the same process in the receiving cell, which then becomes another sending neuron. The result is a chain like the pony express that relays messages from one part of the brain to another. Once the dopamine molecule has delivered its message, it is released by the receiving neuron and retrieved for re-use by the sending neuron. This part of the process is called reuptake. Scientists estimate that each of our brains has about four hundred thousand dopamine molecules. Although this is a small number in comparison to our 100 billion neurons, dopamine is nonetheless a chemical with a powerful impact on what we do and why we do it.

Dopamine’s travels from neuron to neuron occur along predictable pathways that link specific structures within the brain. Two of these are of particular importance in our daily lives. One, the nigrostriatal pathway, is involved with motor planning, the brain’s ability to conceive, organize, and coordinate the actions of our muscles and limbs. The other, the mesolimbic pathway, is central to our system of reward and motivation. According to many neuroscientists, inefficiencies in this second pathway may lie at the very heart of ADHD.

The Reward System
In the late 1800’s Russian scientist Ivan Pavlov made a discovery that has shaped how we think today about learning and reward. While studying behaviors of dogs, Pavlov noted that when his lab assistant placed food in front of them, the dogs began to salivate. He considered this behavior an instinctive response to something desirable – in effect, to a reward – and it was the outcome he had fully expected. What he had not expected was that over time the dogs would come to salivate the moment the lab assistant came into sight with food and, eventually, even when the assistant appeared without any food at all. Pavlov regarded this behavior as not only instinctive but also as learned. The dogs’ response had initially occurred at the time the reward was delivered. Gradually, however, it had shifted to an earlier time when the dogs had learned to recognize a signal that predicted the reward. In other words, the response was no longer to the reward itself but, instead, to a reward prediction.

In the 1930’s, B.F. Skinner took the experiment further. He introduced rats to a “Skinner Box,” where they would unintentionally press a lever and release a food pellet. In short order they learned to release the pellet by pressing the lever intentionally. Thereafter, as soon as they entered the box, the previously docile rats would appear to become excited, making a mad dash for the lever. Like Pavlov’s dogs, they had shifted their response from the reward itself to their learned prediction of it. Unlike Pavlov’s subjects, however, the rats’ response was more than instinctive and learned. It was also purposeful. The same phenomenon – purposeful response to reward prediction – occurs in humans, and recent dopamine research helps to explain why.

According to neuroscientists, the presence or prediction of a reward triggers the firing activity of our dopamine-producing cells, which typically occurs in short bursts. Dopamine is then released from a midbrain structure known as the ventral tagmental area. From there, it travels forward along the mesolimbic pathway to the prefrontal cortex (which manages such functions as analytic thinking, decision making, and intentional behavior) as well as the nucleus accumbens (which processes motivation, aversion, incentive satisfaction, and positive reinforcement). During this sequence the brain engages in a process called Reward Prediction Error (RPE), wthat guides its learning about the reward. Initially, RPE results in an overestimate or underestimate of the satisfaction a person will feel in the future as a result of the reward. With repetition, the reward system is able to eliminate RPE and encode an accurate prediction of the reward’s value. From then onward, the prediction rather than the reward will be the event that triggers the release of dopamine. Depending on the type of receptor where the neurotransmitter attaches, the response to the reward prediction will either be the activation of a behavior (e.g., attention) or the inhibition of one (e.g., an impulse).

ADHD and Reward Processing
How does all this relate to ADHD? Several recent research reports have strongly suggested that while the reward system may work as described above in neurotypical children, it seems to work differently in those with ADHD. A 2009 study sponsored by NIMH found that in comparison with the dopamine pathways of a control group, those of ADHD subjects exhibited a reduction or deficiency in dopamine release and reuptake. The researchers hypothesized that this deficiency may be associated with symptoms of inattention. Another 2009 study, this one sponsored by the U.S. Department of Energy, reported that relative to controls, the ADHD participants had lower levels of dopamine receptors in the nucleus accumbens and midbrain. The researchers suggested this as a reason for the ADHD brain’s deficient dopamine system. In addition to these studies, there are many others supporting the argument that we ADHD people do not seem to produce and process our dopamine as efficiently as do most people.

Yet another 2009 research project, this one reported in the journal Neuropharmacology, offered an intriguing interpretation of the dopamine studies. The authors hypothesized a condition they called Dopamine Transfer Deficit (DTD), which they suggested is typical of many ADHD children. In essence, they described this condition as a reduced capacity of the ADHD child’s reward system to transfer responses from a reward itself to the earlier cues predicting the reward; in other words, the system does not correct for Reward Prediction Error. As a result, the child is more likely to be motivated more by receiving the reward than by anticipating it. According to the authors, DTD might explain the most consistent finding of the dopamine studies: a stronger preference in ADHD subjects for immediate rewards over delayed reinforcement. It might also explain why so many ADHD children would choose to play a video game for a short period right now rather than do homework first and be rewarded later with a much longer period of screen time.

As mentioned above, the dopamine theory is the most extensively researched and best supported explanation of the ADHD brain. However, there are also other explanations based on data about other parts of the brain. These are the subject of Part II.



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