Early experiences not only shape adult lives, but they might also protect against future cognitive problems resulting from brain damage, according to neurobiologists studying the mental abilities of rats with brain lesions. Typically, these lesions impair a rat's ability to focus and filter out distractions. But scientists now have evidence that an early behavioral intervention could prevent this effect.
Researchers at the State University of New York Downstate Medical Center, the Nathan S. Kline Institute for Psychiatric Research, and New York University have demonstrated how just teaching young rats to focus on relevant cues could protect against cognitive decline related to their brain injuries. The finding appears August 22 in Neuron
"We never imagined you could do something for these animals that could essentially compensate for a major developmental defect," says neuroscientist Daniel Weinberger at the Lieber Institute for Brain Development at Johns Hopkins University. Weinberger, who is unaffiliated with the study, calls this work a totally novel approach and discovery.
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In a healthy brain, cognitive control allows an individual to devote resources toward a specific object and tune in to only the correct cues. This is what, for example, allows you to pay attention when your boss is talking to you despite the appearance of five new e-mails in your inbox and a ringing telephone. This control deteriorates, however, as a consequence of certain brain injuries and in certain mental disorders such as schizophrenia.
For this study, researchers induced a brain injury in rats by injecting seven-day old pups with neuron-killing acid. Specifically, they targeted a region of the brain called the ventral hippocampus. The hippocampus is a region implicated in memory; it also neighbors the brain's cognitive command center, the prefrontal cortex. Rats that receive this injection possess normal cognitive functioning in their youth and adolescence, but as they enter adulthood, they show sharp cognitive and behavioral changes. These changes occur because as the brain continues to develop, the injury's damage is amplified.
The scientists first compared the cognitive control of healthy adult rats with those that had brain lesions. They placed rats on a rotating arena. Rats had to attend to cues in the room to orient themselves and avoid a region of the arena that would send a mild electric shock to their feet. As expected, adult rats with normal brains learned to avoid getting zapped much more quickly than those with lesions.
After demonstrating the normal cognitive deficits in these rats, the researchers added an additional level of comparison. They trained a group of adolescent rats—some with and some without lesions—to attend to relevant stimuli in a rotating arena. As adults, the trained rats were compared with damaged- and normal-brain rats that had received no training. Researchers placed these rats in a new study environment: a T-shape maze in which certain branches of the maze would be electrified. As in the previous experiment, untrained lesioned animals struggled to avoid the electrified areas. Brain-damaged rats with training, however, performed at the same level as healthy rodents. These adults had retained cognitive control even after maturation.
In addition, the researchers examined the rats' brain activity using electrodes. The scientists found that untrained lesioned individuals display low synchrony, meaning neurons fired in an uncoordinated manner, in the brain's inter-hippocampal region. But the trained rats—with or without lesions—displayed very similar, synchronous brain activity.
"That was very impressive to me," says neurobiologist and co-author André Fenton at New York University. He adds that the results have optimistic implications for humans as well—presenting how the brain's ability to grow and adapt could overcome an intense biological insult with purely behavioral training.
As the co-authors detail in Neuron, their finding may be particularly encouraging to researchers and psychiatrists who study schizophrenia. In fact, this particular rat model was developed to explore a possible explanation of the disorder's developmental course—in which an early injury to the brain leads to symptoms expressed in maturity.
Duke University psychologist Richard Keefe, who was not involved in this study, explains that there is a growing body of evidence to suggest that cognitive deficits in schizophrenia precede and may influence psychotic symptoms. "It is a bold notion that we will eventually prevent schizophrenia by combinations of pharmacological behavioral treatments that will help to 'teach' those at risk to avoid the cognitive processes that lead to psychosis, and how to fortify healthy cognitive processes," Keefe says. In addition, the work of Fenton and his colleagues complements ongoing research in schizophrenia that suggests intervening at the earliest signs—when symptoms such as social withdrawal become apparent—could alter the disorder's course.
Given the nebulous nature of schizophrenia and limitations of a rat model, however, a more immediate implication could be the importance of cognitive training in general. The findings make a case for teaching mindfulness and cognitive behavioral therapy. "Experience can change outcomes in really profound ways," Fenton says. "It's best not to do nothing with your brain."
