Exercise Benefits the Healthy and Diseased Brain

Report from Neuroscience 2016
Moheb Costandi, M.Sc.
December 12, 2016

“What’s good for the heart is good for the brain.”

That’s the advice a physician might give to older patients who are concerned about staying mentally sharp as they get older. We know very well that physical activity keeps the heart healthy, and in recent years we have begun to understand how exercise affects the brain.

Exercise induces neuroplasticity, a collective term referring to various structural and functional brain changes that occur in response to experience. In a symposium at the 46th annual meeting of the Society for Neuroscience in San Diego in November, researchers in the field discussed how exercise benefits the brains of healthy older adults and those of people with psychiatric and neurological diseases.

Psychologist Kirk Erickson of the University of Pittsburgh explained that most of us experience age-related decline in cognitive function, with abilities such as inductive reasoning, perceptual speed, and verbal memory declining sharply from about 60 years of age. Physical activity offers significant protection against age-related cognitive decline, however, and can improve mental function in older adults.

He then described a number of longitudinal intervention studies performed in his lab investigating the underlying mechanisms by which exercise benefits brain structure and function in healthy older adults.

In 2009, Erickson and his colleagues reported that higher levels of aerobic exercise in elderly adults are associated with increased volume of the hippocampus, a brain structure known to be critical for memory formation, and that this in turn is related to enhanced spatial memory (See One Man’s Continuing Contribution to the Science of Memory). They went on to show that higher fitness levels are also associated with greater prefrontal cortex volume and better executive function, and that exercise enhances the integrity of white matter tracts throughout the brain.

Thus, exercise appears to have a protective effect on the brain’s gray and white matter, making both more resilient to the effects of aging. Until recently, it was thought that the distribution of white matter in the brain was highly stable, but we now know that it can change rapidly in response to experience. And although studies consistently show that exercise increases expression of growth factor BDNF, it’s still not clear exactly how the observed volume increases occur; they could be due to the production of new brain cells, the formation of new synaptic connections, or a combination of both.

“I believe that exercise affects every organ of the body, and it’s very likely that there are a multitude of pathways by which it affects the brain,” said Erickson, “but we can now begin to think about how changes at the molecular and cellular level influence behavioral outcomes.”

Erickson added that we still know very little about individual differences in how exercise affects the brain, and that people generally dislike the term “exercise,” which may discourage them from participating in research. He and his colleagues are now recruiting participants for the REACT! trial, a pilot study that will compare the effects of African dance and an educational discussion group on brain health, fitness levels, and quality of life in older African Americans, who are at higher risk of age-related cognitive decline than other populations.

Psychiatrist Sarah McEwan of the University of California, Los Angeles described her studies into how exercise benefits brain function in people diagnosed with schizophrenia. Schizophrenia is a severe, long-term mental health condition with symptoms that include delusions of persecution or grandeur, visual and auditory hallucinations, and disordered patterns of thought and behavior.

Previous studies have shown that people who have had schizophrenia for between 5 and 20 years have less grey matter volume in the dorosolateral prefrontal cortex. “This part of the brain is important for higher order processes such as top-down control, attention, and problem-solving,” McEwan said. “Although anti-psychotics are excellent for treating voices and delusions, there’s nothing to treat the core cognitive dysfunctions, which are the most debilitating aspects of the disease.”

Last year, McEwan’s lab published the first empirical study to examine the benefits of regular physical activity for patients in the early stages of the disease. They scanned the brains of 14 young adults who were experiencing their first schizophrenic episode, and found that those who reported having low levels of physical activity had reduced grey matter volume in the prefrontal cortex and hippocampus compared with the “high activity” group. Patients who reported greater levels of overall physical activity also performed slightly better on tests of verbal memory and social cognition.

Together, these preliminary findings suggest that exercise-based interventions could improve brain health and cognitive function in patients experiencing their first schizophrenic episode. The findings need to be replicated in a larger study, however, and they do not address the effects of exercise in patients who have had the disease for longer periods of time.

“Patients deemed to be at high risk of developing schizophrenia tend to be more sedentary,” McEwan added, “and the first psychotic episode seems to be an excellent window during which we can try to intervene and improve patients’ prognosis later on in life.”

Other recent research suggests that exercise can also be of benefit to people diagnosed with Parkinson’s disease (PD), a progressive neurodegenerative disorder caused by the death of dopamine-producing neurons in the midbrain. PD leads to involuntary, shaky movements and other motor problems, as well as cognitive deficits.

Neurologist Giselle Petzinger of the University of Southern California and her colleagues have been examining rodent models of Parkinson’s and translating their findings to studies in humans.

In the mouse models, neuronal death reduces dopamine levels in the striatum, a deep brain structure involved in reward, motivation, and movement, which normally receives inputs from the midbrain. This is accompanied by loss of dendritic spines, the tiny, finger-like protuberances at which neuronal signaling takes place.

Petzinger and her colleagues have shown that treadmill exercise reverses the loss of dendritic spines in the striatum in a mouse model of Parkinson’s by promoting the formation of new synaptic connections. And in a small pilot study of patients with early Parkinson’s published in 2013, they showed that intensive treadmill training elevates dopamine receptor levels in the striatum, and also improved patients’ postural control.

At the meeting, Petzinger presented preliminary evidence that exercise induces changes in neural circuits involved in attention. She noted, however, that some forms of exercise involve motor learning, and that this is likely to contribute to the protective effects.

Petzinger argues that exercise does not benefit overall brain health, but rather that different forms of exercise induce changes in specific neural circuits. She is now involved in a larger study comparing the effects of cardiovascular training and skill-based exercises in people with Parkinson’s.

“What we’re beginning to see is some evidence that both cardiovascular fitness and motor-related fitness seem to be associated with improved prefrontal cortex-related cognition,” she said. “We can now tease apart how exercise type may impact specific circuits and brain areas involved in cognition.”