Commonly prescribed stimulants include methylphenidate and lisdexamfetamine, which are effective drugs that improve the level of wakefulness and energy by increasing the levels of dopamine and norepinephrine in the brain. The prevalence of the medication is 6.1% among all Americans and as high as 24.6% among boys aged 10–19 years. Stimulants are primarily prescribed for attention-deficit/hyperactivity disorder (ADHD). Still, they are also used to treat narcolepsy, traumatic brain injury, depression, and, less commonly, as appetite suppressants or to enhance cognitive and athletic performance.
The history of stimulants is extensive. Their wakefulness-promoting effects were discovered in 1929, and soldiers widely used them during World War II. In 1937, physician Charles Bradley observed that amphetamines reduced disruptive behavior in children. This observation contributed to the long-held belief that stimulants enhance attention by acting directly on attention-control regions of the prefrontal cortex. However, despite decades of extensive research, the precise neural mechanisms underlying the effects of stimulants remain incompletely understood.
Behavioral research indicates that stimulants do not consistently enhance performance. Instead, their effects follow an inverted U-shaped pattern: individuals with poorer baseline performance tend to improve, whereas high performers show little benefit or may even experience declines in performance, despite perceiving improvement. The most reliable stimulant effects include enhanced reaction times, increased motivation, reduced impulsivity, greater effort, and improved persistence, rather than enhanced intelligence or attention itself.
To gain deeper insight into the neural effects of stimulants, researchers analyzed resting-state functional MRI data from 11,875 children aged 8–11 years enrolled in the Adolescent Brain Cognitive Development (ABCD) Study. Among these children, 7.8% had been prescribed stimulants, and 6.2% had taken them before undergoing brain imaging. Of the children who met criteria for ADHD (3.7% of the cohort), 42.7% were receiving stimulant therapy.
The researchers evaluated the alterations of functional connectivity across brain networks using a data-driven, whole-brain modelling approach. Much to their surprise, no significant stimulant-related changes were observed in classic attention or cognitive control networks, despite the study having 95% statistical power to detect them. Additionally, there was also no improvement in the performance of attention and working-memory activities in healthy children on stimulants. Instead, the greatest connectivity changes were observed in sensorimotor, somatomotor–cognitive action, auditory, and salience/parietal memory networks.
The stimulants decreased connections in sensorimotor and auditory networks, whereas connections between sensorimotor and salience/memory networks were increased. The effects were quite similar to those observed in the children who were either more alert or better rested. The researchers also conducted a precision imaging drug trial in 5 healthy individuals, each receiving 40 mg of methylphenidate and undergoing up to 210 minutes of brain imaging. This independent experiment confirmed the key results observed in the larger pediatric cohort.
Notably, the brain alterations caused by stimulants reflected the influences of sleep. Changes in brain connectivity were again evident in the salience and parietal memory systems associated with dopamine– and reward-guided learning. In contrast, core attention systems, including the dorsal attention network, showed no significant changes.
In children with ADHD, stimulants improved school performance but did not enhance cognitive ability beyond normal levels or “super-normalize” brain connectivity. Overall, these findings suggest that stimulants are effective because they raise arousal, motivation, and persistence, which make dull or difficult jobs more rewarding, rather than directly enhancing attention or intelligence. This challenges the long-standing belief that stimulants primarily sharpen attention and suggests that some of their benefits may also be achieved through sufficient sleep and improved alertness.
References: Kay BP, Wheelock MD, Siegel JS, et al. Stimulant medications affect arousal and reward, not attention networks. Cell. 2025;188(26):7529-7546.e20. doi:10.1016/j.cell.2025.11.039
