The Triplets Learning Task (TLT) may help determine the extent of dopamine loss in patients with Parkinson’s disease (PD), results of a pilot study hint.

The TLT tests implicit learning, a type of learning that occurs without awareness or intent and that relies on the caudate nucleus, an area of the brain affected by dopamine loss.

The test is a sequential learning task that doesn’t require complex motor skills, which tend to decline in people with PD. In the TLT, participants see 4 open circles, see 2 red dots appear, and are asked to respond when they see a green dot appear. Unbeknownst to them, the authors note, the location of the first red dot predicts the location of the green target. Participants learn implicitly where the green target will appear, and they become faster and more accurate in their responses.

Katherine R. Gamble, psychology PhD student at Georgetown University in Washington, DC, and colleagues had 27 patients with mild to moderate PD receiving dopaminergic medication and 27 healthy controls matched for age and education take the TLT on several occasions.

Patients with PD implicitly learned the dot pattern with training, as did controls, but a loss of dopamine appeared to “negatively impact” that learning compared with healthy older adults, Gamble noted in an interview with Medscape Medical News.

“Their performance began to decline toward the end of training, suggesting that people with Parkinson’s disease lack the neural resources in the caudate, such as dopamine, to complete the learning task,” she added in a conference statement.

Gamble reported the findings here at Neuroscience 2013, the annual meeting of the Society for Neuroscience.

Implicit Learning

In this study, participants responded to 6 “epochs” of the TLT, for a total of 1500 trials. All patients had been diagnosed with PD by a neurologist, and all were receiving treatment with anti-PD medication when they took the test.

Their results showed “significant implicit sequence learning” on the TLT test, the researchers report. Learning increased over the first 5 epochs of training, they note; patients continued to respond more quickly to high- vs low-probability triplets, but this plateaued between periods 5 and 6.

“We suggest that in people with PD, learning is intact early in training because less affected regions of the brain (eg, the hippocampus) can support learning,” they conclude. “However, PD-related dopamine deficits appear later in training when the caudate becomes more important.”

The TLT “may be a noninvasive way to evaluate the level of dopamine deficiency in PD patients, and which may lead to future ways to improve clinical treatment of PD patients,” said Steven E. Lo, MD, associate professor of neurology at Georgetown University Medical Center and a coauthor of the study, in a statement.

The researchers are now testing how implicit learning may differ by different PD stages and drug doses.

Evaluating Dopamine Deficiency

Asked to comment on this pilot study, Lidia Gardner, PhD, assistant professor, Department of Neurology, University of Tennessee Health Science Center in Memphis, said the “simple implicit learning test might be potentially a useful tool for neuropsychologists. I would like to know if there is any correlation between the disease progression and the time required for TLT training.”

However, she told Medscape Medical News, “Until a strong correlation is established, most physicians would shy away from using it as a diagnostic tool for the loss of dopamine neurons. However, in addition to other clinical tests it could be useful.”

“Currently, the loss of dopamine neurons can be visualized with PET [positron emission tomography] using 18F-DOPA or other radio-tracers. This technique can give a relatively close assessment of dopamine neurons in PD patients. A simple and inexpensive test (in comparison to PET or SPECT [single-photon emission computed tomography]) is always welcome in healthcare administration,” Dr. Gardner said.