Objective: To characterize the effect of cognitive load on the excitability of circuitry connected with the subthalamic nucleus (STN) motor territory in Parkinson’s disease (PD) patients.

Background: Cognitive load in PD patients can worsen their motor signs[1,2]. However, the physiological mechanisms of this cognitive-to-motor influence are yet to be clarified. Understanding these mechanisms could help optimize deep brain stimulation (DBS) therapy to account for fluctuations in cognitive load. Previous studies have shown that single electrical pulses delivered in the STN evoked long-latency responses in the STN that may reflect the excitability of circuit loops[3-5]. These stimulation-evoked responses (sERs) exhibit large amplitude in the beta band (13-35 Hz), which has been linked to bradykinesia and rigidity. Here, we tested the hypothesis that increased cognitive load amplifies STN sERs in the beta band.

Method: The Cleveland Clinic IRB approved all patient procedures. Local field potentials (LFPs) during 2.01-2.93 Hz stimulation of the STN were recorded from the STN of five PD patients using externalized DBS leads. The LFPs were recorded off-medication during an attention task (AT) or a Wisconsin Card Sorting Task (WCST). The AT was used as a control with a lower cognitive load than the WCST. The sERs were obtained by averaging LFP segments aligned with the stimulation pulses and suppressing the artifacts[3-5]. The amplitude and frequency of the sERs were characterized using spectrograms (time-frequency maps). We assessed whether differences in the spectrograms between tasks resulted from chance using a permutation test with a correction for multiple tests in the time and frequency. Differences in spectrogram amplitudes with p<0.01 were considered significant. Preoperative MR and postoperative CT imaging was employed to confirm that stimulation was directed to the STN motor region.

Results: sERs exhibited their largest power in the beta-band in all subjects. In 4/5 patients, the amplitude of beta band sERs was higher in the WCST than in the AT.

Conclusion: Our data indicates that increased cognitive load can enhance beta band excitability of circuitry connected with the STN motor region. Since beta activity is linked to motor impairment, we further hypothesize that beta band circuit excitability mediated by cognitive load may contribute to the worsening of PD motor signs.

References: 1. Profiles of Motor-Cognitive Interference in Parkinson’s Disease—The Trail-Walking-Test to Discriminate between Motor Phenotypes [Internet]. [cited 2025 Mar 15]. Available from: https://www.mdpi.com/2076-3425/12/9/1217

2. Cognitive load amplifies Parkinson’s tremor through excitatory network influences onto the thalamus | Brain | Oxford Academic [Internet]. [cited 2025 Mar 15]. Available from: https://academic.oup.com/brain/article/143/5/1498/5827585?login=false

3. Campbell BA, Favi Bocca L, Escobar Sanabria D, Almeida J, Rammo R, Nagel SJ, Machado AG, Baker KB. The impact of pulse timing on cortical and subthalamic nucleus deep brain stimulation evoked potentials. Frontiers in Human Neuroscience [Internet]. 2022 [cited 2022 Oct 26];16. Available from: https://www.frontiersin.org/articles/10.3389/fnhum.2022.1009223

4. Escobar Sanabria D, Aman JE, Amaya VZ, Johnson LA, Farooqi H, Wang J, Hill M, Patriat R, Sovell-Brown K, Molnar GF, Darrow D, McGovern R, Cooper SE, Harel N, MacKinnon CD, Park MC, Vitek JL. Controlling pallidal oscillations in real-time in Parkinson’s disease using evoked interference deep brain stimulation (eiDBS): Proof of concept in the human. Brain Stimulation. Elsevier; 2022 Sep 1;15(5):1111–1119.

5. Frontiers | Low-frequency deep brain stimulation reveals resonant beta-band evoked oscillations in the pallidum of Parkinson’s Disease patients [Internet]. [cited 2025 Mar 15]. Available from: https://www.frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2023.1178527/full

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cognitive-load-modulates-excitability-of-subthalamic-motor-circuitry-in-parkinsons-disease/