The Prefrontal Cortex Is Out of Tune in Attention-Deficit/Hyperactivity Disorder
Issue: The different symptoms of attention-deficit/hyperactivity disorder are hypothetically linked to inefficient information processing in various areas of the prefrontal cortex.
Pyramidal neurons, shaped like a triangular pyramid, are key regulators of neuronal networks in the prefrontal cortex.1-3 These cortical networks send messages that can be either accepted as signals or ignored as noise.1-4 When the prefrontal cortex is functioning properly, pyramidal neurons within these networks can tell the difference between signals and noise. However, in attention-deficit/hyperactivity disorder (ADHD), pyramidal neurons seem to have problems distinguishing signals from noise.1,2 Another way to state this is that pyramidal neurons and their prefrontal cortex networks are "out of tune" (see Figures 1 and 2). (n = 12)
Take-Home Points
- In ADHD, pyramidal neurons in the prefrontal cortex are hypothetically "out of tune," causing either deficient signals, excessive noise, or both.
- Specific malfunctioning brain areas within the prefrontal cortex theoretically mediate the various symptoms of ADHD.
- Inefficient information processing in related areas of prefrontal cortex may also cause the specific symptoms of the common comorbidities of ADHD, such as bipolar disorder, anxiety disorders, conduct disorder, and oppositional defiant disorder.
Theoretically, such problems with information processing in prefrontal cortex may be caused in part by imbalances in various neurotransmitters.1-7 Norepinephrine, for example, may be particularly important in enhancing signals, whereas dopamine may be particularly important in reducing noise.1,2,4-7 (These concepts were discussed in the last Brainstorms.7) In this issue, we discuss the potential link of dopamine and norepinephrine imbalances at key neurotransmitter receptors that result in problems differentiating signals from noise in prefrontal cortex in ADHD. We also discuss where in the prefrontal cortex specific symptoms of ADHD may be hypothetically mapped (see Figure 3).
References
1. Stahl SM. Stahl’s Essential Psychopharmacology. 3rd ed. New York, New York: Cambridge University Press; 2008
2. Stahl SM, Mignon L. Stahl’s Illustrated: Attention Deficit Hyperactivity Disorder. New York, New York: Cambridge University Press. In press
3. Goldman-Rakic PS. The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive. Philos Trans R Soc Lond B Biol Sci 1996;351(1346):1445-1453
4. Vijayraghavan S, Wang M, Birnbaum SG, et al. Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory. Nat Neurosci 2007;10:376-384
5. Arnsten AFT. Catecholamine and second messenger influences on prefrontal cortical networks of "representational knowledge": a rational bridge between genetics and the symptoms of mental illness. Cereb Cortex 2007;(suppl 1):i6-i15
6. Ramos BP, Arnsten AFT. Adrenergic pharmacology and cognition: focus on the prefrontal cortex. Pharmacol Ther 2007;113:523-536
7. Stahl SM. Norepinephrine and dopamine regulate signals and noise in the prefrontal cortex [Brainstorms]. J Clin Psychiatry 2009;70(5):617-618
