Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity and impulsivity that begins in childhood and can persist into adulthood. ADHD is associated with dysfunction in several areas of the brain involved in executive functions like attention, inhibitory control and working memory. However, there is no single “damaged” part of the brain that causes all of the symptoms of ADHD. It is the complex interactions between multiple brain regions and neurotransmitter systems that lead to the behavioral manifestations of ADHD.
The Prefrontal Cortex
One of the brain regions most strongly implicated in ADHD is the prefrontal cortex (PFC), which is located at the very front of the brain. The PFC is the control center of the brain, responsible for higher-order cognitive functions like planning, organization, reasoning, problem solving, inhibition, emotional regulation and working memory. Numerous imaging studies have shown that individuals with ADHD have decreased blood flow and lower metabolic activity in the PFC compared to neurotypical controls. The PFC undergoes rapid development during childhood and adolescents, which may explain why ADHD symptoms often improve with age as this region matures.
Specific sub-regions of the PFC that are affected in ADHD include:
– The dorsolateral prefrontal cortex (DLPFC) – involved in working memory, attention, planning and impulse inhibition. The DLPFC shows hypoactivation in ADHD.
– The ventrolateral prefrontal cortex (VLPFC) – plays a role in inhibitory control over inappropriate behaviors and responses. Studies show the VLPFC has reduced activation in people with ADHD.
– The anterior cingulate cortex (ACC) – monitors conflict and performance. The ACC is underactivated in individuals with ADHD and is linked to their excessive distractibility.
Evidence of PFC Dysfunction in ADHD
Several lines of evidence confirm the central role of PFC abnormalities in ADHD:
– Children with ADHD often perform poorly on neuropsychological tests of executive function that require PFC-mediated cognition.
– People with ADHD symptoms following PFC injury after stroke or traumatic brain injury.
– Functional MRI scans show hypoactivation of the PFC in those with ADHD during tasks of inhibition, working memory and attention.
– The severity of ADHD symptoms correlates with the degree of PFC dysfunction on brain scans.
Treatment with ADHD medications like stimulants enhances PFC structure and function, leading to improved symptoms.
The Basal Ganglia
The basal ganglia are a group of structures deep within the brain that help regulate movement and cognition. Multiple studies have identified abnormalities in the basal ganglia of those with ADHD. The main components of the basal ganglia include:
– The caudate nucleus – controls cognition, motor planning, motivation and reward perception. People with ADHD have reduced volume in the caudate.
– The putamen – regulates motor movements and learning. Individuals with ADHD exhibit anatomical differences in the putamen.
– The globus pallidus – involved in voluntary motor activities. Structural and functional irregularities in this region are linked to ADHD.
Role of the Basal Ganglia
The basal ganglia modulate cortical signals that influence executive functioning. Dysfunction in the basal ganglia may contribute to:
– Hyperactivity and impulsivity – Disruption between the basal ganglia and PFC leads to disinhibition of motor activity.
– Inattention – Signaling abnormalities from the basal ganglia to PFC could impair ability to sustain focus.
– Cognitive inflexibility – Altered basal ganglia activity makes it difficult to rapidly shift between tasks or behaviors.
The Cerebellum
The cerebellum is located at the base of the brain and originally thought to only control balance and motor coordination. But we now know the cerebellum plays a crucial role in cognitive processes and emotion regulation as well. People with ADHD have been found to have smaller total cerebellar volume along with regional cerebellar abnormalities.
Cerebellum Functions Disrupted in ADHD
– Attention – The cerebellum has reciprocal connections with the PFC and is vital for attentional control. Cerebellar dysfunction could manifest as distractibility and lack of attention.
– Timing – The cerebellum regulates precise timing of behaviors and cognitive events. Disruptions here may lead to inconsistent task performance.
– Error detection – The cerebellum monitors ongoing behaviors and detects errors. This helps explain impulsivity and disinhibition seen in ADHD.
– Working memory – Cerebellar activation occurs during working memory tasks. Impairments may impact the ability to hold and manipulate information in mind.
Neurotransmitter Systems
ADHD is not solely due to structural abnormalities in the brain, but also involves imbalances in key neurotransmitters:
Dopaminergic System
– Dopamine is critical for motivation, arousal, reward-processing and motor control.
– The dopamine transporter and D2/D4 receptors are implicated in ADHD pathophysiology.
– Individuals with ADHD show enhanced dopamine transporter density, leading to excessive reuptake and dopamine deficiency in synapse.
– Stimulant medications boost dopamine signaling, thereby improving symptoms.
Noradrenergic System
– Norepinephrine is important for alertness, concentration and regulating the signal-to-noise ratio during cognitive tasks.
– People with ADHD display abnormal cell architecture in the locus coeruleus, source of norepinephrine.
– Some ADHD medications (atomoxetine) selectively target the noradrenergic system.
Serotonergic System
– Serotonin modulates mood, aggression, appetite, sleep and impulse control.
– Imaging studies show individuals with ADHD have reduced serotonin synthesis in the orbital frontal cortex.
– Serotonin reuptake inhibitors may help treat comorbid anxiety, depression and oppositional behaviors in ADHD.
Brain Network Connectivity
While certain isolated brain regions show abnormalities in ADHD, it is really the complex interactions between multiple neural networks that gives rise to ADHD symptoms:
ADHD-Related Brain Networks
| Network | Function |
|---|---|
| Cognitive control | Focused attention, impulse inhibition |
| Reward | Motivation, reinforcement-driven behaviors |
| Salience | Detection of relevant internal/external stimuli |
– Dysfunction arises from poor coordination between the networks, rather than one single deficit.
– Problems with motivation and reward perception, for example, stem from miscommunication between cognitive control and reward circuits.
– ADHD involves widespread reduced connectivity within and between critical brain networks.
The Default Mode Network
The default mode network (DMN) is a set of brain regions active during restful introspection. In people with ADHD, the DMN shows excessive connectivity, meaning it remains turned “on” during tasks when it should deactivate.
– Failure to suppress DMN leads to attention lapses, distraction and mind wandering.
– Stimulant medications normalize DMN over-connectivity in ADHD.
– Mindfulness-based approaches may help strengthen ability to disengage DMN.
Neuroimaging Evidence
Here is a summary of the structural and functional brain imaging findings in ADHD:
Structural MRI
| Brain Region | Structural Differences in ADHD |
|---|---|
| Prefrontal cortex | Reduced volume |
| Basal ganglia | Smaller caudate, globus pallidus |
| Cerebellum | Overall smaller volume |
| Corpus callosum | Decreased white matter integrity |
Functional MRI
| Brain Region | Functional Differences in ADHD |
|---|---|
| Prefrontal cortex | Hypoactivation during cognitive tasks |
| Basal ganglia | Altered activity and connectivity |
| Cerebellum | Reduced activation |
| Reward circuits | Enhanced ventral striatal reactivity to rewards |
Genetic Factors
ADHD has a strong genetic component, although environmental influences are also involved. First-degree relatives of individuals with ADHD have a 20-35% increased risk of developing the disorder. Several genes implicated in ADHD play a role in dopamine and serotonin signaling pathways:
ADHD-Linked Genes
| Gene | Protein Encoded |
|---|---|
| DRD4 | Dopamine D4 receptor |
| DRD5 | Dopamine D5 receptor |
| DAT1 | Dopamine active transporter |
| 5-HTT | Serotonin transporter |
– The 7-repeat variant of DRD4 is associated with increased ADHD risk.
– The 10-repeat polymorphism in DAT1 may increase ADHD susceptibility.
– Interactions between multiple genes and environment determine ADHD onset.
Conclusion
In summary, ADHD does not stem from a single focal brain lesion, but rather involves abnormalities in:
– The prefrontal cortex and its regulation of executive functions
– Basal ganglia and their role in motivation and movement
– The cerebellum and its modulation of cognition and behavior
– Neurotransmitter systems, especially dopamine and norepinephrine
– The interconnections between large-scale brain networks
– How genes influence cellular processes and neural signaling
While certain circuits are clearly implicated, ADHD results from dysregulation of multiple interacting brain regions and systems. Ongoing research continues to uncover the intricate neurological underpinnings of ADHD.