August 18, 2009
Sharon Begley

Whenever I speak to educators and interested laypeople about neuroplasticity—the ability of the adult brain to change in function and structure—one of the questions I often get is whether neuroplasticity can be tapped to treat truly devastating brain diseases such as Alzheimer’s or schizophrenia. After all, neuroplasticity has been used to treat stroke, depression, dyslexia, and other diseases or injuries of the brain. The jury is still out on Alzheimer’s (though since this disease involves massive neuronal death, my bet is that the answer will, sadly, be no). But to my surprise, the answer to schizophrenia might just be yes.

In schizophrenia, which affects about 1.1 percent of American adults, patients suffer from visual and auditory hallucinations, delusions, an absence of emotion, and cognitive deficits. All told, that seemed to be just too much for an approach based on neuroplasticity, which involves retraining the brain, to handle.

But it turns out that at least some of the symptoms of schizophrenia can be lifted with brain training. In a study published in the July issue of the American Journal of Psychiatry, scientists led by Melissa Fisher of the University of California, San Francisco, describe what they call “neuroplasticity-based auditory training” to improve memory in people with schizophrenia. Basically, what they did was assign 55 patients with schizophrenia to receive a cognitive-training program developed by Posit Science or to play a computer game that required just as much time and concentration. The Posit program, similar to one the company developed to improve memory in the elderly, emphasizes basic auditory and speech perception; participants used it one hour a day, five days a week, for 10 weeks. The better they got, the harder the program got: it automatically adjusts the level of difficulty to keep the patients’ performance at a constant level so they stay engaged.

Fisher and her colleagues found that the brain-trained group showed noticeably bigger improvements in cognition and verbal working memory than the game-playing control group. A better memory would give people with schizophrenia a better chance of doing the little tasks of daily life—remembering what and when to eat, how to dress, how to behave in public—that make them more likely to hold a job and live independently.

The emphasis on auditory training reflects the belief of UCSF’s Michael Merzenich, a pioneer in neuroplasticity and cofounder of Posit, that this is the portal to improved memory and, possibly, cognition. The idea is that if you hear more clearly, then your brain makes fewer errors in encoding the information contained in speech. As Michael Green of UCLA put it in an editorial in the American Journal of Psychiatry the Posit Science approach “is unusual in that it rests heavily on neuroplasticity models … that emphasize the consequences of a poor signal-to-noise ratio” in hearing, “which leads to errors and poor performance as they are fed forward for cognitive … operations.”

It’s hard to argue with even preliminary success, odd as it seems that merely hearing better could bring about such improvements in memory (and not just memory for heard words; it improves memory for seen words as well). “This emphasis on perceptual processes is a critical insight of the Posit Science approach and a clear distinction from other cognitive-training programs,” says Green. The significance of the new study, he says, is that “it addresses cognitive training at a more basic neurobiological level than any previous strategy. We can hope that the dramatic effects they have reported will prove to be replicable and durable and that they will extend to meaningful effects for patients’ lives.”

Hope is all well and good. But schizophrenia is notable not only for its severity, but for the yawning gap between what’s known to be effective and what treatments patients actually receive. Green asks rhetorically, “if cognitive training [for schizophrenia] worked, would we not all know it by now?” In fact, researchers do know it, and some clinicians know it, but by one estimate fewer than 15 percent of schizophrenics get it (or other treatments, rehabilitation and support that would let them live independently). In fact, in a paper earlier this year in Schizophrenia Bulletin, scientists led by Robert S. Kern of the Geffen School of Medicine at the University of California, Los Angeles, were quite upbeat in their assessment of treatments for schizophrenia—none of them the problematic antipsychotic medications that in too many cases are all that people with schizophrenia receive.

Take cognitive-behavior therapy. Its basic premise is that people can be taught to think about their thoughts differently. It is effective in depression (where people are taught to think about their tendency to catastrophize—”I had a bad date; no one will ever love me because I am worthless and unlovable”). But in something as serious as schizophrenia? Yes, Kern and his colleagues find. It turns out that, with cognitive-behavior therapy, patients who hear voices and feel persecuted can learn to see these symptoms as almost normal (in that many people experience them when, say, they are sleep deprived, under extreme stress, drunk or stoned) or as “just” the manifestations of a neurobiological glitch and not real. The approach is surprisingly effective, a 2008 review found.

Similarly, exercises to improve attention, learning and memory, reasoning and problem solving—which 90 percent of people with schizophrenia have problems with—also help, as this study found, and make a meaningful difference in whether the person can live independently and hold a job. The tragedy is that—due to an overburdened medical system, inadequate insurance and an inability to pay, as well as simply ignorance about how to find help—few patients with schizophrenia receive what works. The upside is that even schizophrenia might be treated by approaches that exploit the brain’s ability to change in fundamental ways.