_HEALTH MEDICINE Neurobiology

_Focus on Focus

Researchers in Drexel’s Waterhouse Laboratory are zeroing in understanding the role that norepinephrine and Ritalin play in sustaining mental focus.

_Barry Waterhouse

Waterhouse is a professor of neurobiology and anatomy and vice dean of biomedical graduate and postgraduate studies

Actively engaged in research for more than 30 years, the Waterhouse Laboratory at Drexel employs a broad variety of techniques to address fundamental questions in behavioral neurobiology. Barry Waterhouse, the lab’s founder, keeps the focus on the central monoaminergic systems in the brain —in particular, the norepinephrine and serotonin transmitter pathways.

Norepinephrine and serotonin are primarily neuromodulatory agents involved in regulating neural circuits in the brain according to the behavioral demands placed on the organism. Waterhouse explains that norepinephrine is high during behaviors that require the organism to be alert and attentive to environmental cues—“when you are in situations that require focused attention,” he explains, “working on a math problem, driving a car, flying an airplane.” This system is less active when a person becomes drowsy or falls asleep.

Serotonin, on the other hand, is associated with maintaining homeostasis in brain circuits. There is not an exact correlation to behavior, but Waterhouse notes that the serotonin system has been linked to stress, anxiety and post-traumatic stress disorder.

The serotonin and norepinephrine systems are often implicated in a variety of neuropsychiatric disorders and the drugs used to treat these conditions have major influences on the operations of these pathways. Zoloft and Prozac elevate serotonin levels in the brain, while drugs like Ritalin—commonly prescribed for treating Attention Deficit Hyperactivity Disorder—elevate norepinephrine in the brain.

Currently, researchers in the Waterhouse Laboratory are interested in understanding the basic anatomy, physiology and molecular biology of the norepinephrine system and what role it plays in sustained and flexible attention. As it turns out, norepinephrine via the actions of Ritalin regulates rodent performance in laboratory tests of attention. In a sustained attention task, rats are required to remain vigilant to a light cue in order to receive a reward. In the flexible attention task the experimenter periodically changes the rules of the test so that the rat recognizes it must change its behavior in order to receive a reward—in other words, the rat has to be flexible in its cognitive ability.

The research team has discovered that rats perform better in both tasks, supporting the idea that Ritalin improves cognitive function regardless of an ADHD diagnosis. Unfortunately, this can lead to off-label use of the drug as an increasingly popular cognitive enhancing agent.

Though Waterhouse and his team are extensively studying the effects of Ritalin on the norepinephrine system, the greatest focus of this effort is on the prefrontal cortex. Waterhouse explains, “[The prefrontal cortex] is the seat of executive function—assigning value to our actions, making decisions, and attending to things when we’re supposed to.” Importantly, this area of the brain also allows us to “change our strategies so we don’t perseverate on tasks at the exclusion of attending to other important activities or events.”

The ability to focus intensely—but change focus when required—is a prefrontal cortex function greatly affected by Ritalin. Though researchers have seen these effects, they do not know how Ritalin causes the change. Waterhouse explains, “We know norepinephrine is involved but we don’t know precisely how.” In this case, the drug is being used as both a tool and focal point for research, since the broader goal is to understand how the transmitter system regulates cognitive function in the prefrontal cortex under a variety of behavioral conditions.