The prefrontal cortex guides behaviors, thoughts, and feelings using
representational knowledge, i.e., working memory. These fundamental
cognitive abilities subserve the so-called executive functions: the
ability to inhibit inappropriate behaviors and thoughts, regulate our
attention, monitor our actions, and plan and organize for the future.
Neuropsychological and imaging studies indicate that these prefrontal
cortex functions are weaker in patients with
attention-deficit/hyperactivity disorder and contribute substantially to
attention-deficit/hyperactivity disorder symptomology. Research in
animals indicates that the prefrontal cortex is very sensitive to its
neurochemical environment and that small changes in catecholamine
modulation of prefrontal cortex cells can have profound effects on the
ability of the prefrontal cortex to guide behavior. Optimal levels of
norepinephrine acting at postsynaptic ?-2A-adrenoceptors and dopamine
acting at D1 receptors are essential to prefrontal cortex function.
Blockade of norepinephrine ?-2-adrenoceptors in prefrontal cortex
markedly impairs prefrontal cortex function and mimics most of the
symptoms of attention-deficit/hyperactivity disorder, including
impulsivity and locomotor hyperactivity. Conversely, stimulation of
?-2-adrenoceptors in prefrontal cortex strengthens prefrontal cortex
regulation of behavior and reduces distractibility. Most effective
treatments for attention-deficit/hyperactivity disorder facilitate
catecholamine transmission and likely have their therapeutic actions by
optimizing catecholamine actions in prefrontal cortex.
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