Cancer patients undergoing chemotherapy experience a number of negative side effects; however, the cause of one of those reactions, commonly referred to as “chemobrain,” has never really been understood. The term actually encompasses several different types of mental impairment including a feeling of confusion, difficulty learning new tasks, short attention span, and poor short-term memory. Chemobrain affects about 70 percent of all chemotherapy patients; but until now, no one could explain why it happened.

Researchers from Rutgers University found that there are two conditions caused by prolonged treatment with chemotherapy that travel throughout the body that create chemobrain. First, there is decreased in the growth of new neurons in the hippocampus. The constant proliferation of new brain cells is necessary to maintain the ability to learn, and if the number is decreased, the individual will find it difficult to learn something new. Second, which also occurs in the hippocampus, brain rhythm known as theta activity is inhibited. When a person learns a new task, these brain rhythms aid in communication between similar brain structures that are a distance away from each other. If that communication is disrupted, as it is during chemotherapy, the person is unable to learn that task. The other important discovery these researchers made is that since the hippocampus controls learning, but not long-term memory, the chemotherapy patient will find it hard to learn a new task but will have no trouble replicating tasks that were learned prior to receiving treatment.

The Rutgers team made their findings through an analysis of the behavior of 53 adult male rats bred in the Department of Psychology at the University. The animals were injected with temozolomide (TMZ), a chemotherapy drug that has been used to treat human brain tumors for more than ten years. The rats were treated cyclically, meaning they were given a dose of 2-5 mg per kilogram of body weight once a day for three days followed by four days of recovery, for up to six weeks. The dose and method of treatment mimicked human cancer patient treatment.

The researchers evaluated changes in the rats’ learning and memory by using variations of eyeblink conditioning, a methodology for studying the brain structures that facilitate memory and learning. A classic example of conditioning training is Pavlov’s famous experiment in which he rang a bell and then gave  his dogs food. The food caused the dogs to salivate. After repeating the pairing of a ringing bell followed by food, the dogs began salivating when they heard the bell because they had learned that the bell meant food was coming and they remembered that fact each time they heard the bell.

In this experiment, the number of daily tests and the number of training days for each eyeblink conditioning was determined by the difficulty of the task the researchers tried to teach the rats. The results of these tests showed that the rats had a lot of trouble learning to associate two events if there was a period of time between the tests. However, they could learn a simple tasks if the researchers performed the tasks without any time gap.

References

Nokia MS, Anderson ML, & Shors TJ (2012). Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain. The European journal of neuroscience, 36 (11), 3521-30 PMID: 23039863

Wada, N., Kishimoto, Y., Watanabe, D., Kano, M., Hirano, T., Funabiki, K., & Nakanishi, S. (2007). Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission Proceedings of the National Academy of Sciences, 104 (42), 16690-16695 DOI: 10.1073/pnas.0708165104

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