A Correct. Sustained attention is hypothetically modulated by the cortico-striatal-thalamic-cortical loop involving the dorsolateral prefrontal cortex (DLPFC). Inefficient activation of the DLPFC can lead to problems following through or finishing tasks, disorganization, and trouble sustaining mental effort; the patient exhibits all of these symptoms. The dorsal anterior cingulate cortex is important in regulating selective attention, and is associated with behaviors such as losing things, being distracted, and making careless mistakes. This area is certainly also inefficient in this patient.

B Incorrect. The prefrontal motor cortex hypothetically modulates behaviors such as fidgeting, leaving one’s seat, running/climbing, having trouble being quiet.

C Incorrect. The orbital frontal cortex on the other hand regulates impulsivity, which includes symptoms such as talking excessively, blurting things out, and interrupting others.

D Incorrect. Finally, the supplementary motor area is implicated in planning motor actions; thus this brain area would be more involved in hyperactive symptoms.

A Incorrect. Research shows that the pattern of cortical maturation is similar for children with and without ADHD. Specifically, the primary sensory and motor areas attain peak cortical thickness earlier in development than do high-order association areas such as the dorsolateral prefrontal cortex.

B Correct. There are differences in the timing of cortical maturation between children with and without ADHD that are apparent as early as age 7. That is, cortical maturation in children with ADHD seems to lag behind that of healthy children. In fact, the median age by which 50% of the cortical points achieve peak thickness is delayed by 3 years in children with ADHD. Delay is most prominent in the superior and dorsolateral prefrontal regions, which are particularly important for control of attention and planning.

Interestingly, there is one brain region in which children with ADHD achieve peak cortical thickness earlier than typically developing controls: the primary motor cortex.

C and D Incorrect.

A Correct. Pulsatile delivery of stimulants can cause a frequent and rapid increase in NE and DA, and this amplifies phasic firing. Phasic firing is hypothetically associated with reward, feelings of euphoria, and abuse potential.

B Incorrect. Immediate-release stimulants rapidly increase DA and NE, thereby especially increasing phasic firing, not tonic firing. Therefore, immediate-release stimulants have a higher risk of abuse.

C and D Incorrect. Extended release formulations of stimulants lead to a gradual and sustained increase in NE and DA, thus enhancing tonic firing, which is hypothetically linked to the therapeutic effects of stimulants. They are amplifying tonic NE and DA signals, which are thought to be low in ADHD. The extended release formulations occupy the NE transporter in the prefrontal cortex with slow enough onset and for long enough to enhance tonic NE and DA signaling; however, they do not block DA transporters fast or long enough in the nucleus accumbens to increase phasic signaling, thus reducing abuse potential.

A Incorrect. In the nucleus accumbens there are only a few NE neurons and NE transporters. Inhibiting NET in the nucleus accumbens will not lead to an increase in NE or DA.

B Correct. The prefrontal cortex lacks high concentrations of DAT, so in this brain region, DA gets inactivated by NET. Therefore, inhibiting NET in the prefrontal cortex increases both DA and NE. As only a few NET exist in the nucleus accumbens, atomoxetine does not induce an increase in DA and NE in the nucleus accumbens, the reward center of the brain, thus atomoxetine does not have abuse potential.

C Incorrect. Atomoxetine does not modulate serotonin levels.

D Incorrect. The striatum and the anterior cingulate cortex are not brain areas involved in reward.