Neurobiology

Neuroimaging studies have associated various structural,1-6 functional,7,8 electrical activity9 and chemical10,11 correlates with attention-deficit hyperactivity disorder (ADHD) in children, adolescents and adults.

Structural

Brain imaging studies have associated structural abnormalities with ADHD in children and adolescents,1-6,12,13 including:

  • Delayed cortical development12,13
  • Cortical thinning, and reductions in the volume of grey and white matter5,6,12
  • Reductions in the volume of several regions of the brain, including: the posterior inferior vermis; splenium of the corpus callosum; total and right cerebral volume; right caudate; right global pallidus; right anterior frontal region; cerebellum; temporal lobe; and pulvinar2,3,14,15 (Figure).

Regions of the brain implicated in ADHD in children and adolescents1-6,8,13,15,16

Regions of the brain implicated in ADHD in children and adolescents

Brain abnormalities associated with ADHD in children and adolescents may persist into adulthood.17-21 MRI studies in adults have yielded similar evidence as described above with regards to reduction in the volume of several regions of the brain, cortical thickness, and grey matter;19,20 particularly in the frontal cortex of the brain, compared with controls;18-21 as well as structural abnormalities in connecting brain cells within networks that regulate attention and emotion.22

Functional

Brain structures implicated in ADHD correspond to brain networks, including some involving frontal regions, and some that support executive function and attention (Figure).23

Functional circuits involved in the pathophysiology of ADHD as identified in a review of the neurobiology of ADHD23

Functional circuits involved in the pathophysiology of ADHD as identified in a review of the neurobiology of ADHD

Activation abnormalities are associated with ADHD in children, adolescents and adults,24,25 with meta-analyses demonstrating significant activation reductions in various frontal regions of the brain including the anterior cingulate; dorsolateral prefrontal and inferior prefrontal cortices; and related regions including the basal ganglia, thalamus, and areas of parietal cortex.8

Furthermore, atypical functional network connectivity in the default mode network (a network of brain regions that are active during resting) has been observed in children and adolescents with ADHD.26

In addition, there is some evidence that patterns of under- and over-activation of certain regions of the brain differ between children and adolescents versus adults, as indicated by a meta-analysis of 55 fMRI studies which compared children, adolescents and adults with ADHD with healthy controls (Table).7

Activation patterns in the brain as indicated by a meta-analysis of 55 fMRI studies7  
Age group     Regions associated with over-activation Regions associated with under-activation
Children and adolescents 
  • right angular gyrus
  • middle occipital gyrus
  • posterior cingulate cortex
  • midcingulate cortex
  • frontal regions (bilaterally)
  • putamen (bilaterally)
  • right parietal region
  • right temporal region
 
 Adults
  • right angular gyrus
  • middle occipital gyrus
  • right central sulcus
  • precentral gyrus
  • middle frontal gyrus

Electrical activity

A meta-analysis of worldwide studies reported that quantitative electroencephalography (EEG; the recording of electrical activity along the scalp) may be used to identify changes in brain electrical activity. An increase in the theta/beta (two EEG frequency bands) ratio was observed in all studies included in the review.27 Further research is required to substantiate EEG findings for use as a biomarker in ADHD diagnosis.28 Individual EEG patterns associated with ADHD are under early investigation for utility in personalising neurofeedback protocols — computer-assisted training to self-regulate brainwave activity — as non-pharmacological treatment options for ADHD.29

Chemical

Delayed maturation of certain dopaminergic neural pathways has been observed in children and adolescents with ADHD,30 as well as an imbalance in the levels of both dopamine and noradrenaline in the brains of children, adolescents and adults with ADHD compared with healthy controls.10,11,31,32 Dopamine and noradrenaline have been implicated in influencing impulsivity,10 and dopamine in influencing inattention.11

Emerging evidence also suggests possible roles for other signalling systems in the neurobiology of ADHD. Deficiencies in glutamate signalling in some regions of the brain may have a modulatory role in adults with ADHD.33,34 Furthermore, polymorphisms in the serotonin transporter gene have been associated with differential response to ADHD treatment,35 and the presence of comorbid conduct disorder in children and adolescents with hyperkinetic disorder (an alternative description of ADHD).36


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ADHD can continue to affect patients’ functioning and quality of life beyond childhood into adolescence and adulthood

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