Stimulant drug action in attention deficit hyperactivity disorder (ADHD): inference of neurophysiological mechanisms via quantitative modelling.
OBJECTIVE
To infer the neural mechanisms underlying tonic transitions in the electroencephalogram (EEG) in 11 adolescents diagnosed with attention deficit hyperactivity disorder (ADHD) before and after treatment with stimulant medication.


METHODS
A biophysical model was used to analyse electroencephalographic (EEG) measures of tonic brain activity at multiple scalp sites before and after treatment with medication.


RESULTS
It was observed that stimulants had the affect of significantly reducing the parameter controlling activation in the intrathalamic pathway involving the thalamic reticular nucleus (TRN) and the parameter controlling excitatory cortical activity. The effect of stimulant medication was also found to be preferentially localized within subcortical nuclei projecting towards frontal and central scalp sites.


CONCLUSIONS
It is suggested that the action of stimulant medication occurs via suppression of the locus coeruleus, which in turn reduces stimulation of the TRN, and improves cortical arousal. The effects localized to frontal and central sites are consistent with the occurrence of frontal delta-theta EEG abnormalities in ADHD, and existing theories of hypoarousal.


CONCLUSIONS
To our knowledge, this is the first study where a detailed biophysical model of the brain has been used to estimate changes in neurophysiological parameters underlying the effects of stimulant medication in ADHD.
Rowe
D L
DL
School of Physics, University of Sydney, Camperdown, NSW 2006, Australia. drowe@physics.usyd.edu.au
Robinson
P A
PA
Gordon
E
E
D000293:Adolescent; D001143:Arousal; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D003712:Dendrites / Q000187:drug effects; D003913:Dextroamphetamine / Q000627:therapeutic use*; D004569:Electroencephalography; D006801:Humans; D008125:Locus Coeruleus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D008959:Models, Neurological; D013787:Thalamic Nuclei / Q000187:drug effects / Q000503:physiopathology
D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D003913:Dextroamphetamine