Parkinson’s disease is characterized by motor impairments such as tremors, stiffness, and slowness of movement. However, it also causes less visible symptoms such as problems with memory, attention, and language, which also significantly affect people’s quality of life. Now, new research from Stanford Medicine reveals the brain mechanisms behind one of the most common, but often overlooked symptoms of the disease: difficulty speaking.
Using brain imaging of Parkinson’s patients, researchers have identified specific connections in the brain that may determine the severity of speech difficulties. The findings have been published in the Proceedings of the National Academy of Sciences and may help explain why some Parkinson’s treatments that have been developed primarily to treat motor symptoms can improve speech problems, while others make them worse.
“Parkinson’s disease is a very common neurological disorder, but it’s generally thought of as a motor disorder,” said Weidong Cai, a clinical associate professor of psychiatry and behavioral sciences and senior author of the new study. “There’s been a lot of research on how treatments like medications and deep brain stimulation can improve motor function in patients, but there was little understanding about how these treatments affect cognitive function and speech.”
About 9 in 10 patients with Parkinson’s have difficulty speaking, a complex neurological process that requires both motor and cognitive control. Patients may have a weak voice, slur their words, stammer or stutter. “Speech is a complex process that involves multiple cognitive functions, such as receiving auditory feedback, organizing thoughts and producing the final vocal output,” Cai explained.
Improving speech function in patients with Parkinson’s
The researchers set out to study how levodopa, a common Parkinson’s drug that replaces dopamine lost due to the disease, affects overall cognitive function. They focused on the subthalamic nucleus, a small pumpkin seed-shaped region located deep within the brain.
The subthalamic nucleus is known for its role in inhibiting motor activity, but there are hints of its involvement in other functions. For example, deep brain stimulation, which uses implanted electrodes to stimulate the subthalamic nucleus, has been shown to be an effective way to relieve motor symptoms in Parkinson’s patients, although a common side effect is worsening speech problems.
In this study, 27 participants with Parkinson’s disease and 43 healthy controls, all over 60 years of age, underwent standard tests of motor and cognitive function. The participants with Parkinson’s disease performed the tests both with and without their medication. As expected, the medication improved motor function in the patients, and those with the most severe symptoms improved the most.
The cognitive functioning test offered a surprise. The test, known as the Symbol-Digit Modalities Test, is administered in two forms: oral and written. Patients are given a series of nine symbols, each paired with a number (for example, a plus sign for the number 7). They are then asked to translate a string of symbols into numbers, either by speaking or writing their answers, depending on the version of the test.
“By identifying key neural maps and connections that predict speech improvement, we can create more effective and personalized treatment plans for patients with Parkinson’s disease.”
The patients’ performance on both versions of the cognitive test was, overall, barely affected by the medication. But when they shifted the focus away from the group and looked more closely, the researchers noticed that the subset of patients who performed particularly poorly on the oral version of the test without medication improved their oral performance with the medication. Their scores on the written test did not change significantly.
“It was quite interesting to find this dissociation between the written and oral versions of the same test,” Cai said. The dissociation suggested that the medication was not improving general cognitive functions like attention and working memory, but was instead selectively improving speech. “Our research revealed a previously unrecognized impact of dopaminergic drugs on the speech function of Parkinson’s patients,” said Vinod Menon, professor of psychiatry and behavioral sciences and director of the Stanford Cognitive and Systems Neuroscience Laboratory and senior author on the study.
The researchers then analyzed the participants’ functional magnetic resonance imaging (fMRI) scans, looking at how the subthalamic nucleus interacted with brain networks dedicated to various functions, including hearing, vision, language and executive control. They found that different parts of the subthalamic nucleus interacted with different networks.
In particular, they found that improvements on the oral version of the test correlated with improved functional connectivity between the right side of the subthalamic nucleus and the brain’s language network. Using a statistical model, they were even able to predict a patient’s improvement on the oral test based on changes in their brain’s functional connectivity.
“We found that these drugs influence speech by altering functional connectivity between the subthalamic nucleus and crucial language networks,” Menon said. “This finding opens new avenues for therapeutic interventions specifically designed to improve speech without impairing other cognitive abilities.”
This recently discovered interaction between the subthalamic nucleus and the language network could act as a biological marker of speech behavior, both in Parkinson’s disease and in other speech disorders, such as stuttering. Such a biomarker could be used to monitor treatment outcomes and inspire new therapies.
The findings also provide a detailed map of the subthalamic nucleus, which could guide neurosurgeons performing deep brain stimulation to avoid damaging an area critical to speech function. “By identifying key neural maps and connections that predict speech improvement, we can create more effective treatment plans that are precise and personalized for patients with Parkinson’s disease,” Menon concluded.
