Neural Responses in ADHD

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By HH Patel, M.Pharm.Reviewed by Maryam Mahdi, B.Sc.

Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric condition characterized by symptoms including impulsiveness, inattentiveness, and hyperactivity.

These symptoms are particularly common in all children at some stage of their growth. However, their intensity and persistence over a lengthy period of time signals a warning bell.

Previously classified as the disorder of childhood (affecting 5% children worldwide), ADHD is now known to occur in adolescents and sometimes in adults as well.

Image Credit: Suzanne Tucker / Shutterstock

Neurological Changes in the Brain

The exact cause of ADHD is unknown, however scientists have identified various risk factors which are considered to be associated with the occurrence of ADHD. The theory of ADHD having a genetic trigger is almost unanimous because of the patterns of ADHD observed among individuals of the same families.

The brains of ADHD patients are differently wired compared to those without ADHD. The levels of noradrenaline and dopamine neurotransmitters are usually altered in individuals with ADHD. Patients are also reported to have relatively smaller frontal brains. Also, other anatomical features of the brains of ADHD patients are such that the perfusion of blood to the frontal brain is often less than normal. This further contributes to the inability to execute some executive functions, a typical feature of ADHD.

Neural Responses to Reward

Apart from inattentiveness and hyperactivity, children with ADHD are also found to have impaired reward processing. Studies in this domain have indicated that children with ADHD are more risk-taking and fond of immediate receipt of rewards. They are also more sensitive towards the outcome of reward-based performance.

To understand the underlying anatomical aspects of these behaviors, a study with a total of 350 subjects was conducted comparing adolescents and young adults with ADHD, their unaffected siblings, and impulsive control subjects without ADHD. Functional magnetic resonance imaging (fMRI) was used to observe the neural response to reward anticipation and receipt. The participants were asked to press a button as quickly as possible in response to a cue indicating the possibility of reward. The response time, hit rate, and accuracy of response were evaluated statistically. Also the fMRI images were analyzed.

The results showed increased neural responses in the anterior frontal cortex, anterior cingulate, and cerebellum during reward anticipation and in the occipital cortex, orbitofrontal cortex, and ventral striatum during reward receipt in ADHD patients compared to the control group. The frontostriatal circuitry (including the above mentioned regions) of unaffected siblings responded in a similar manner as that of ADHD patients. This, in a way, validated the fact that ADHD is a familial disorder. Even though these results were in contrast with some previously conducted studies, they provided a landmark for further research in this area.

Neural Responses to Anticipation of Monetary Loss

Another similar study with a smaller sample size of 56 adult subjects was conducted to compare the anticipation of negative outcomes of a performance (monetary loss). Adult patients with ADHD were matched to healthy subjects of the same age group. fMRI and skin conductance measurements were recorded during the study.

Researchers showed that during skin conductance test, the neural responses in anticipation of loss were more profound compared with the anticipation of monetary gain in ADHD patients. They showed increased response in left anterior insula, bilateral amygdalae, and in left temporal pole compared to healthy individuals. The responses were more intense during negative anticipation compared to those during anticipation of monetary benefit. This might also be attributed to the repeated failures in lives of these ADHD patients. Scientists considered the anatomical changes to be translated into an increased risk-seeking behavior, albeit this needs to be validated in future studies.

Association of ADHD with MAOA genotype

In a population-based study, scientists dug deeper into the genotype analysis associated with neural responses in adolescents with ADHD in the monetary incentive delay model. ADHD symptoms and the possibility of their association with single nucleotide polymorphism (rs12843268) was studied separately in males and females.

The MAOA gene was determined to have X-linked nature, and it only affected males. Further investigation of revealed an association of MAOA with ADHD symptoms. The frontostriatal activation patterns were found to be governed by rs12843268 genotype in adolescent boys.

Neural Responses to Vocal Anger

Difficulties in understanding visual emotional impulses were investigated across many studies. Further to this, a pilot study aimed at comparing the vocal perception of anger in ADHD patients to those to undiagnosed individuals with milder symptoms was carried out. The study included 50 subjects of ranging from 6 to 11 years of age. Prior to assessing their ability to comprehend vocal anger stimuli, their hearing abilities were assessed using audiometric tests.

When subjected to a pattern of random vocal stimuli (neutral, appreciative, angry, happy, sad, etc.), children with ADHD were found to be less accurate in recognizing vocal anger compared to those without ADHD. The neural responses were considered atypical, and could be seen as pre-attentive hyper-responsiveness to anticipated vocal anger stimuli.

Even though the current research provides a great deal of information around neural responses in ADHD, the results are often ambiguous and non-reproducible due to smaller sample sizes. Therefore, larger epidemiological studies providing a broader picture are required.