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Understanding ADHD
Understanding ADHD

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2.1.2 Brain chemistry and ADHD

Many neurotransmitters and pathways are thought to be involved in the development of ADHD symptoms. Focusing again on selective attention, acetylcholine is thought to be the most important neurotransmitter for exogenous attention, while dopamine may preferentially contribute to endogenous attention (Mueller et al., 2017). In line with this, changes in acetylcholine (cholinergic) receptor functioning have been found in the few studies that have investigated this in ADHD (Wallis et al., 2009; Johansson et al., 2013). However, research into dopamine functioning in ADHD has been central to most investigations.

Dopamine, along with serotonin and noradrenalin, is one of the monoamine transmitters. These neurotransmitters are produced by neurons making up relatively small areas within the brain, but the axons of these neurons form pathways sending signals to many other brain regions, so the effects of the neurotransmitter can be quite widespread. Certainly, ADHD is not the only condition that dopamine is thought to be involved in. Other mental health conditions in which dopamine may be involved include addiction and psychosis.

In Activity 7 you will explore neurotransmitter pathways and see how these pathways may be involved in ADHD.

Activity 7 Exploring the monoamine neurotransmitters

Timing: Allow about 30 minutes

You should now explore the pathways for the monoamine neurotransmitters dopamine, serotonin, noradrenalin and acetylcholine using the interactive below. Click on each pathway for information about the pathway and structures involved. Make notes about the start and end points of each pathway in order to complete Table 3 that follows.

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The interactive shows a side view of the brain sliced vertically to show the internal structures and various pathways.

Dopamine pathways: consist of neurons that synthesise, store and release dopamine. There are three principal dopaminergic pathways in the brain. Dopaminergic pathways and dopamine function are of particular interest in the study of ADHD, addictions and psychosis. The mesocortical pathway extends from the ventral tegmental area, a body in the brain stem, to the prefrontal cortex. The mesolimbic pathway extends from the ventral tegmental area to the amygdala and nucleus accumbens, which is located between the PFC and the brain stem. The nigrostriatal pathway extends from the substantia nigra, another body in the brain stem, to the dorsal striatum, which includes the caudate nucleus and putamen.

Serotonin pathways: consist of neurons that synthesise, store and release serotonin. Serotonergic pathways are found widely throughout the brain. Serotonergic neurons play a role in alterations of sleep-waking, as well as emotions and moods. Abnormalities within this system appear to be at the basis of depression. Raphe nuclei, which are nuclei (groups of neuronal cell bodies) within the brain stem, are the location of the cell bodies of serotonergic neurons, which project their axons very widely throughout the brain and spinal cord. Some serotonergic neurons terminate in the prefrontal cortex and some in the hippocampus, which is important in learning and memory, as well as being involved in emotion and mood.

Noradrenalin pathways: consist of neurons that synthesise, store and release noradrenalin. Noradrenergic pathways are found widely throughout the brain and are involved in many brain functions, most notably arousal and reaction to stimuli. The brain stem site of the cell bodies of noradrenergic neurons is the locus coeruleus. Noradrenergic neurons project throughout large areas of the brain and also downwards in the spinal cord. Activation in the descending pathway exerts an effect on organs and tissues involved in the autonomic reaction to stressors. Some noradrenergic neurons terminate in the prefrontal cortex.

Acetylcholine system: consist of neurons that synthesise, store and release acetylcholine. Cholinergic pathways are found widely throughout the brain and are involved in many brain functions including cognition, learning and memory. Cholinergic function is of particular interest in the study of disorders of cognition and memory, such as dementia. The pons is the site in the brain stem of the cell bodies of a group of cholinergic neurons which project their axons to a number of other brain regions and downwards in the spinal cord. The basal forebrain, at the edge of the cortex next to the brain stem, is the site of the cell bodies of a group of cholinergic neurons which project their axons widely throughout the cortex and to the hippocampus, amongst other regions. The hippocampus plays a crucial role in learning and memory. It receives axon terminals of cholinergic neurons with cell bodies in the basal forebrain. If these cholinergic neurons cease to function, as in Alzheimer's disease, the hippocampus is unable to perform its normal function. Cholinergic neurons terminate throughout the cortex. Particularly in areas of the cortex towards the front of the brain, a deficiency of cholinergic activity at these axon terminals is associated with the cognitive impairments seen in Alzheimer's disease.

Interactive feature not available in single page view (see it in standard view).
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Table 3 (interactive) Origins and end points of neurotransmitter pathways
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The table has three columns. On the left are neurotransmitters: dopamine – mesocortical pathway; dopamine – mesolimbic pathway; dopamine – nigrostriatal pathway; serotonin; noradrenalin; acetylcholine. The second column is headed ‘site of cell body (origin of pathway)’ and the third column is ‘site of neurotransmitter release (end of pathway)’.

The boxes to be dropped in are: frontal cortex and hippocampus; raphe nuclei; amygdala and nucleus accumbens; prefrontal cortex (two boxes); prefrontal cortex and hippocampus; substantia nigra; ventral tegmental area (two boxes); locus coeruleus; dorsal striatum; basal forebrain.

Table 3 (interactive) Origins and end points of neurotransmitter pathways
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Now study Figure 8 (via the interactive link below) which provides an overview of the brain regions and neurotransmitters thought to be involved in the seven cognitive domains impacted in ADHD

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Figure 8 (interactive) The brain structures involved in the different cognitive domains disrupted in ADHD. Click or tap on each domain for a reminder about what it does and to see the circuitry involved. You can also select each brain region for a summary of its function (adapted from Mueller et al., 2017).
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Clicking on the function selective attention, the ability to preferentially process one stimulus in the presence of other potentially distracting stimuli, shows that the ventral tegmental area has a direct pathway to the PFC, whilst the basal forebrain links to the sensory cortex. The sensory cortex has reciprocal links with the parietal cortex and the PFC; the parietal cortex has a reciprocal link with the PFC.

Sustained attention, the ability to continuously perform a task over a prolonged period without decline in performance, shows the locus coeruleus and basal forebrain having a pathway to the PFC.

Response precision refers to the temporal and/or spatial precision in behavioural responses to stimuli and only involves the PFC.

Cognitive flexibility, the ability to switch between tasks without significant loss of performance, involves the ventral tegmental area, the basal forebrain, the amygdala, the parietal cortex and the PFC. The basal forebrain links to the PFC and the amygdala. The ventral tegmental area links to the PFC. The parietal cortex has reciprocal links to the PFC.

Working memory, the ability to preserve a representation of information over short periods of time (i.e. seconds), has links from the ventral tegmental area and the locus coeruleus to the PFC.

Temporal information processing is the ability to accurately recognise or reproduce time intervals. It involves a link from the cerebellum to the parietal cortex, which has a two-way link with the PFC.

Response inhibition is the ability to suppress actions that are inappropriate for a given task. The raphe nuclei link to the basal ganglia and to the PFC. The basal ganglia have a two-way link to the PFC.

Figure 8 (interactive) The brain structures involved in the different cognitive domains disrupted in ADHD. Click or tap on each domain ...
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You should be able to see from Activity 7 that the involvement of various neurotransmitters and brain regions in ADHD is very complex. At present it is not clear what changes, if any, take place in ADHD for all of the different neurotransmitters and brain regions shown in Figure 8. It is likely that, as for other conditions involving brain functioning, altered connectivity between brain networks underlies some of the changes in brain functioning seen in ADHD. Investigating this altered connectivity is extremely complex and is an active area of research into this condition. 

As mentioned previously, much research has focused on the involvement of dopamine and the PFC, which will be looked at in more detail in the next section.