Classical conditioning could link disorders and brain dysfunction, researchers suggest

Classical conditioning response--one of the most primordial and basic units of learning ever studied--may help researchers better understand, and possibly treat, some human pathologies. Studies are finding a link between how quickly people learn a classical conditioning response and some disorders, including Alzheimer's disease, autism and obsessive-compulsive disorder.

As any introductory psychology student learns, Pavlov first identified classical conditioning in the 1920s when he noticed that dogs learned to salivate when they heard a bell ring after he'd paired the bell tone with food a number of times. Since then, researchers have used animal models to work through most of the behavioral and neurological pathways by which the learning occurs.

"Classical conditioning is so well established on a behavioral and neural basis that it allows us to start making predictions about how conditioning will be affected by certain pathologies," says Indiana University psychologist Joseph Steinmetz, PhD. "It's a two-way street. Conditioning experiments can help us better understand the pathologies and the pathologies may help us better understand conditioning."

In fact, classical conditioning is so well understood and so similar in animals and humans, it's ideal for studies trying to link human disorders to brain dysfunction, says Temple University psychologist Diana Woodruff-Pak, PhD, who has found a connection between conditioning and Alzheimer's disease. Researchers can develop theories using animals and then test them in humans, using identical conditioning paradigms.

Slowing with aging

Woodruff-Pak, who studies aging, became interested in classical conditioning 15 years ago when she met University of Southern California psychologist Richard Thompson, PhD. He had long worked on conditioning and had discovered that it occurred primarily within the brain's cerebellum. After discussing their research, the two believed that classical conditioning might be an interesting paradigm with which to pursue the study of cognitive aging.

It was. Working in Thompson's lab, Woodruff-Pak and Williams College psychologist Paul Solomon, PhD, soon discovered that as animals age, they learn a conditioned response significantly more slowly than they did in their youth. The conditioning paradigm they used was classical eye-blink conditioning: By pairing a tone with an air puff to the eye, participants unconsciously learn to blink when they hear the tone, even if it's not accompanied by the air puff.

In the late 1980s researchers discovered a link between Alzheimer's disease and impairment in the brain cells that produce the neurotransmitter acetylcholine. Earlier work by Solomon provided a link between this finding and eye-blink conditioning: He discovered that young rabbits that were given the drug scopolamine--which blocks acetylcholine--learn the conditioned eye-blink response more slowly than normal for rabbits their age. Subsequently, Solomon found that the same thing happened in people given scopolamine.

Because Alzheimer's disease impairs cells that produce acetylcholine--in essence causing a chemical environment in the brain similar to that caused by scopolamine--researchers hypothesized that people with the disorder would condition more slowly than other people their age. They were right. In Woodruff-Pak's first study 19 of the 20 Alzheimer patients were poor conditioners: Over the course of 100 pairings of the tone and the air puff, the Alzheimer patients produced few conditioned responses. In contrast, people of the same age who didn't have Alzheimer's disease produced 30 to 40 conditioned responses. Solomon found the same results in an independent study.

"It's an absolutely striking difference between people with Alzheimer's disease and age-matched controls," says Woodruff-Pak.

Eventually, Alzheimer patients will learn the conditioned response, she and Solomon have found. But it takes them much longer. "Their machinery for learning is not obliterated. It's disrupted," she says.

A distorted signal

The link between conditioning and Alzheimer's disease can help pinpoint deficits in Alzheimer patients and may also have implications for the neural mechanisms behind classical conditioning, says Solomon.

Although exactly how Alzheimer's disease affects classical conditioning is unclear, the disorder likely causes a disruption in the chain of neural changes that occur during the learning process, say researchers.

And it's likely the disruption emanates from the hippocampus. Studies in animals find that if signals from the hippocampus are distorted, conditioning takes longer than if the hippocampus is intact. This implies that the hippocampus plays a modulatory role in conditioning, says USC's Thompson. It also implies that the acetylcholine deficits in Alzheimer patients have their roots in the hippocampus.

Drug companies are already capitalizing on the link between Alzheimer's and eye-blink conditioning: They're testing cognition-enhancing drugs in animals and watching the effect on conditioning. Drugs that work may prove useful in delaying the onset of Alzheimer's.

And Woodruff-Pak has preliminary evidence that the slow-down in classical conditioning may occur several years before any overt signs of Alzheimer's disease, making it a candidate for a noninvasive screening technique. In one of her studies she found that eight people without Alzheimer's disease conditioned as poorly as Alzheimer patients. Three years later, five of them had developed dementia. None of the people who conditioned normally became demented.

These findings look promising, says William Jagust, MD, director of the University of California at Davis Alzheimer's Center. But before they're definitive, classical conditioning needs to be put through serious clinical tests in large samples of people--something Woodruff-Pak hopes to do soon.

Autism and OCD

While learning a conditioned response slows dramatically in Alzheimer patients, it appears to do just the opposite in people with obsessive-compulsive disorder (OCD) and people with autism, finds Indiana University's Steinmetz and his colleagues.

In a series of studies Steinmetz conducted with Indiana University's Dick McFall, PhD, JoAnne Tracy, PhD, Sushmita Ghose and Tamara Stecher, the researchers found that under some conditions people with symptoms of OCD condition three times faster than people without OCD.

"Normally, people show consistent conditioned responses after about 10 to 15 trials," says Steinmetz. "Our OCD subjects showed consistent conditioned responses after as few as three to five trials."

This finding implies that people with OCD make associations between neutral and aversive stimuli more quickly than people without the disorder, says Steinmetz. That's consistent with theories that people with OCD, and perhaps more general anxiety disorders, may suffer from a general susceptibility to aversive conditioning, he says.

In another series of studies conducted several years ago Steinmetz showed that people with autism condition much faster than people without autism and execute early, mis-timed conditioned responses.

In fact, people with autism seem to overattend to the conditioned stimuli, which may facilitate conditioning and cause the mis-timed learned responses, says Steinmetz. This finding may have implications for teaching children with autism how to cope with their disorder, he says.

The research linking human pathology to classical conditioning is truly exciting, says Bruce Overmier, PhD, of the University of Minnesota. It's a classic example of how research on the very basic mechanisms of learning can lead to practical information about the human condition.

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