Theta-Frequency Deep Brain Stimulation of the Subthalamic Nucleus: Enhancing Working Memory in Parkinson’s Disease
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Philipps-Universität Marburg
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Abstract
In this study we investigated the effect of theta-frequency (6Hz) deep brain stimulation (DBS) in the subthalamic nucleus (STN) on working memory (WM) in Parkinson’s disease (PD) patients. WM deficits is common cognitive impairment in PD and WM is integral to higher-order cognitive processes. WM deficit like all other non-motor symptoms of PD significantly reduces patient's quality of life. Based on previous evidence supporting the role of theta-frequency stimulation in STN on cognitive function, and the critical role of theta oscillation in WM processes, we hypothesized that theta frequency stimulation could enhance WM performance in PD patients.
We implemented a randomized, single-blind, crossover design to evaluate 20 PD patients with bilateral STN-DBS implants. We assessed WM performance using modified Sternberg WM task during five stimulation conditions: theta (6 Hz), beta (15 Hz), low gamma (70 Hz), high gamma (130 Hz), and baseline (off-stimulation).
Our results demonstrated that theta-frequency stimulation improved WM performance compared to all other frequencies and baseline. These enhancements occurred independently of motor symptom modulation, indicating the cognitive specificity of theta-frequency stimulation in the STN. Furthermore, our connectivity analyses revealed that the observed WM performance during theta-frequency stimulation were associated with stronger structural connectivities from the STN to the dorsolateral prefrontal cortex (DLPFC). This connectivity was both frequency- and task-specific.
We also found that patients with lower baseline WM performance exhibited greater improvements during theta stimulation, suggesting that baseline cognitive function influences the efficacy of theta-frequency DBS. These findings emphasize the importance of tailoring DBS protocols to individual cognitive profiles to optimize therapeutic outcomes.
Our study establishes theta-frequency DBS as a targeted and frequency-specific intervention for addressing WM deficits in PD. By leveraging the effect of theta-frequency stimulation on the STN-PFC connectivity, we provide a foundation for developing dual- or adaptive-frequency DBS protocols that address both motor and non-motor symptoms. Future research should evaluate the long-term effects of theta-frequency stimulation, investigate the neural dynamics of theta oscillations in STN-PFC networks, and refine patient-specific DBS protocols to enhance cognitive and motor outcomes.
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Created: 2025Issued: 2025-08-11Updated: 2025-08-11
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Medizin
Language
eng
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DoctoralThesis
Keywords
Deep brain stimulationtheta stimulationdorsolateral prefrontal cortextheta oscillationworking memorysubthlamic nucleus
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610
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Narges Salehi: Theta-Frequency Deep Brain Stimulation of the Subthalamic Nucleus: Enhancing Working Memory in Parkinson’s Disease. : Philipps-Universität Marburg 2025-08-11. DOI: https://doi.org/10.17192/z2025.0405.