Ordinary chronic stress can impair our ability to shift attention flexibly, according to a recent study of stressed-out medical students. The study found that stress achieves this temporary remodeling of the brain by reducing the connectivity of an attention-regulating area of the prefrontal cortex.
“It’s reassuring that this attention-shifting deficit seems to go away after stress is reduced, but such deficits are similar to what we see in a number of stress-related psychiatric disorders, so we need to know more about it,” says the study’s first author, Conor Liston, a neuroscientist and a psychiatry resident at New York-Presbyterian Hospital. The study was released Jan. 12 on the Proceedings of the National Academy of Science Web site.
Liston and his colleagues used functional magnetic resonance imaging (fMRI), as well as a behavioral test, to measure attention-shifting performance in 20 students before they took the all-important U.S. Medical Licensing Exam. The students’ stress levels were verified using a standard self-assessment questionnaire.
Compared with a matched control group of 20 relatively nonstressed med-student subjects, the exam-stressed students scored significantly lower on a task in which they had to flexibly shift their attention from one visual stimulus to another. Their fMRI responses during the task also implied a reduction in the strength of the connection between the dorsolateral prefrontal cortex and other regions within a brain network normally engaged during attention-shifting.
Four relatively low-stress weeks after their exams, the medical students performed the same tests again. This time, their performance no longer differed significantly from that of controls—suggesting that the neural change caused by stress had reversed itself after the stress abated.
“This study is the first to show how this common behavioral experience in people may relate to weaker brain network connections,” says Amy Arnsten, a neuroscientist at Yale University who has done work in this area. “Importantly, the effects of stress were fully reversible, similar to those seen in animals.”
Liston and other researchers had shown in recent years that rats, too, become impaired on attention-shifting tests when subjected to chronic stress. Bruce McEwen, an expert on stress and the brain at New York’s Rockefeller University and co-author of the med-student study, notes that in the rat experiments the attention-shifting deficits were associated with shrinkages of the dendrites of neurons in a region that corresponds roughly to the human dorsolateral prefrontal cortex. Such a shrinkage implies a reduced connectivity with surrounding brain areas. “That, too, is reversible if you stop the stress and let the animal recover over a couple of weeks,” McEwen adds. [McEwen is a science advisor for stories that appear on this Web site.]
Accentuating the Limbic
Work by McEwen’s, Arnsten’s and other laboratories in recent years suggests that chronic stress tends to increase the influence of more instinctive, limbic networks involved in fear and desire at the expense of more highly evolved, prefrontal-based networks designed to moderate behavior according to long-range goals.
“We call it ‘adaptive plasticity’ because in the short run it probably serves the animal well to be more wary and aggressive in a dangerous situation,” says McEwen. “When it doesn’t reverse itself after the danger has passed, then you’ve got problems.”
This loss of flexibility is a symptom of anxiety disorders and depression; people with these disorders typically find it hard to shift their focus away from fearful or otherwise negative thoughts. Evidence suggests that drug addiction, too, empowers limbic craving activity and at the same time weakens the inhibitory influence of the dorsolateral prefrontal cortex.
Stress is known to play a role in all of these conditions. Although the mechanisms by which it boosts some regions and impairs others are not yet clear, Arnsten and colleagues have shown in animal experiments that, for example, stressful conditions can raise levels of the neurotransmitters norepinephrine and dopamine in prefrontal regions. These raised levels in turn may alter the sensitivity of the neurons in those regions, effectively reducing their influence over behavior.
Whether chronic-stress-induced changes in prefrontal neurotransmitter levels eventually lead to actual dendritic shrinkage remains to be seen. “This is still a new area that we don’t know much about,” says Liston. “But the ultimate goal is to design targeted interventions aimed at exploiting the finding that a stress effect like this is reversible.”
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