Differences in neuronal activity of subthalamic nuclei in asymmetric manifestation of Parkinson’s disease
Authors: Pavlovsky P. N. , Gamaleya A. A. , Sedov A. S. 
Published: May 2024

Parkinson’s disease (PD) is a widely prevalent condition that has spurred extensive research into identifying its biological markers. Different models posit that various patterns of subthalamic nucleus (STN) activity may constitute such markers, but as yet, none have been established definitively. One major limitation of human studies in this area is the lack of a reliable control group.
Therefore, patients with asymmetric motor symptoms in Parkinson’s disease are of great interest. I.I. Koloman and A.Sh. Chimagomedova [1] demonstrated that motor malfunctions’ asymmetry is indicative of asymmetry in the degenerative process within the substantia nigra. Additionally, while the disease normally manifests unilaterally, only a limited number of patients maintain notable distinctions in motor symptom severity as the condition advances.
In our study, we analyzed the single-unit activity (SUA) and local field potentials (LFP) recordings obtained duringdeep brain stimulation (DBS) surgeries in 12 patients. Neurologists assessed the severity of bradykinesia, rigidity, and tremor using the UPDRS 3 scale to meet the inclusion criteria, and the difference between hemibodies for each symptom had to be at least 25%. The median disease duration at the time of surgery ranged from 6 to 22 years. The subthalamic nucleus that exhibits more pronounced disturbances on the contralateral side of the body is labeled as “affected”, while the opposite STN, acting as the conditional control, is labeled as “nonaffected”.
For analysis, we used a hierarchical clustering method following Ward’s algorithm [2] to classify the recorded neurons into three groups based on their activity type: tonic, burst, and pause cells. We observed no significant differences in neuron activity between hemispheres, as well as the predicted hyperactivity of affected STN neurons outlined by the classical model [3] of basal ganglia functioning. However, the research demonstrates a significant increase in pause neurons and decrease in burst neurons within the affected nucleus. Furthermore, both of these types were found to be situated in the upper half of the STN, which is recognized as the motor region of the nucleus. Our hypothesis is that as the disease advances, some STN neurons (specifically burst neurons in our sample) modify their activity patterns towards a more rhythmic activity (pause neurons in our sample). This supports the notion that rhythmic STN neuron activity is linked to Parkinson’s disease [4].
LFPs were analyzed by estimating oscillation synchrony (o-scores) in multiple spectral bands following 1/f correction. Parkinson’s disease is typically associated with boosted oscillation power in the beta range (13–30 Hz). Our findings established that the power of oscillations in the low-frequency beta range (13–20 Hz) were indeed increased in the affected nucleus, but, in contrast to expectations, the power in the high-frequency part (20–30 Hz) of the band was significantly lower.
This is in line with the modern theory of distinct physiological functions of oscillations in these subbands [5]. Additionally, we noticed a rise in frequency spectrum in the alpha range (8–12 Hz) and a decrease in the gamma range (30–60 Hz) in the impacted nucleus.
Our findings indicate that a more rhythmic burst neuron activity mode and an increased number of pause neurons in the motor zone of the STN can serve as a marker for PD. Increased power oscillation in alpha and low-frequency beta bands, along with reduced synchronization in high-beta and gamma bands, may also be linked to this disorder. However, further investigation is necessary to determine their association with disease symptoms.