The coupling of electrical signals in the brain — as it responds to levodopa and is associated with motor improvements — may provide ways to better assess the clinical state of people with Parkinson’s disease, and improve the efficacy of deep brain stimulation (DBS), according to new research.
The researchers say coupling patterns may enable broader insight into Parkinson’s, and have potential use as a biomarker.
The study, “Distinct subthalamic coupling in the ON state describes motor performance in Parkinson’s disease,” appeared in the journal Movement Disorders.
The human brain displays repetitive patterns of neural activity, or electrical pulses, due to the communication between brain nerve cells (neurons). These are called brainwaves.
Measuring a type of electrical pulses called local field potentials (LFPs) from the subthalamic nucleus (STN) — a brain region hyperactive in Parkinson’s patients — has shown the existence of frequency bands, or wave oscillations, that correlate with motor impairment and respond to medication.
The interactions between high- and low-frequency brain waves — cross-frequency coupling — also has been increasingly studied. This is particularly evident in unmedicated patients. Yet, what these interactions mean is still scarcely understood.
A team at the University of Houston addressed how these bands are changed by medication, as well as their coupling, via a 24-hour monitoring period that included three trials. Those trials involved nine people (seven men, ages 39-70 years) with idiopathic Parkinson’s, meaning the disease with no known cause. The participants underwent local field potential recording three weeks after deep brain stimulation of the subthalamic nucleus. The recordings were then correlated with motor improvements over three treatment cycles.
Clinical and behavioral assessments were made within 30 minutes prior to taking levodopa, which controls Parkinson’s symptoms. Similar evaluations were then done within 30 minutes after the participants said they felt the medication kicking in, in terms of motor function (verbal on state).
Specifically, the clinicians used the Unified Parkinson’s Disease Rating Scale to assess numerous symptoms: hand and foot tremors (item 20); upper and lower extremity rigidity (item 22); and finger tapping, hand open and close, hand pronation and supination — which means flipping the palm face up or face down — and leg agility (items 23–26).
A computer-based task also was used, with a keyboard. Participants had to press the left and right arrow keys sequentially and as fast as possible, for 30 seconds, using the index and middle fingers. The total number of keypresses was then analyzed.
The results showed that bradykinesia — slowness of movement — and keyboard scores differed between “off” and “on” states, meaning the periods before and after taking levodopa and regaining motor control. However, these responses did not correlate in all patients. Two patients showed eased bradykinesia yet minimal-to-no improvement in the performance of the keyboard task.
The data also showed distinct peaks across different bands. In the off state, the activity of low-beta (13-22Hz) and high-frequency oscillations (200-300Hz) was higher than normal. It was either suppressed, or shifted to a different frequency, after taking levodopa. Among other findings, six patients also showed a peak in the gamma range (50–200 Hz).
The investigators also found that, in the off state, the amplitude or signal strength of high-frequency oscillations was coupled with a specific parameter — called phase — of low-beta bands in all participants.
After the transition to the on state, this coupling shifted to a different subset of beta bands (22-30Hz) and high-frequency oscillations (300-400Hz). It also was linked with more pronounced improvements in the keyboard task scores. Only two patients failed to show this coupling after taking levodopa. That could be due to suboptimal dose, the team said.
Overall, the findings show that cross frequency coupling also exists in treated patients. “So in effect we have ‘cleared coupling’s name’ and showed the frequencies involved in coupling impacts whether its effects are negative or positive,” Musa Ozturk, the study’s lead author, said in a press release.
“Together with the differences in the ON-state coupling according to the degree of motor improvement, our observations suggest that [cross-frequency coupling] patterns provide a broader insight into [Parkinson’s], and have potential utility as a biomarker for the clinical state of patients,” the researchers said.
One potential application is deep brain stimulation.
“We can now make the closed-loop stimulator adaptive to sense a patient’s symptoms, so it can make the adjustments to the fluctuations in real time, and the patient no longer has to wait for weeks or months until the doctor can adjust the device,” said Nuri Ince, PhD, the study’s senior author.
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