Objective: This study investigates the effects of a novel TBS paradigm on large-scale brain network connectivity in PD patients.

Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive motor dysfunction and cognitive decline. While deep brain stimulation (DBS) of the subthalamic nucleus (STN) at gamma frequencies effectively manages motor symptoms, it has been linked to cognitive deficits. Theta-burst stimulation (TBS) has shown promise in enhancing cognitive function without impairing motor control. ​​Functional magnetic resonance imaging (fMRI) is a powerful tool for assessment of brain network connectivity and has been used to characterize differences in DBS protocols.

Method: Eight PD patients [table1] with existing STN-DBS implants underwent resting-state fMRI under two stimulation conditions: (1) standard gamma-frequency and (2) theta-burst DBS [figure1]. Stimulation order was randomized, with a 10-minute washout period between conditions. We assessed connectivity within and between seven cortical networks, including the visual, somatomotor, dorsal attention (DAN), salience, limbic, control, and default mode networks (DMN).

Results: Overall network integrity was preserved in gamma and TBS stimulation paradigms, with stronger within-network connectivity compared to between-network connectivity [figure2]. However, TBS significantly increased anti-correlation between the DMN and the DAN (p = 0.0098, FDR-corrected) and between the DMN and the visual network (p =0.024, FDR-corrected), suggesting enhanced segregation of cognitive and attention networks. TBS increased connectivity between the DAN and salience network (p =0.024, FDR-corrected) [figure3].

Conclusion: Our study provides novel insights into the effects of TBS on large-scale brain network dynamics in PD patients undergoing DBS. The observed anti-correlation between the DMN and both the DAN and VIS aligns with evidence linking excessive DMN activity to cognitive interference and attentional deficits in PD, while increased DAN-SAL connectivity may help restore balance between attention and salience networks, which are often disrupted in PD and associated with cognitive rigidity and impaired motor function. These results highlight the potential of TBS as a neuromodulation approach for optimizing brain network organization in PD which may be further validated through motor and cognitive testing.

table1

figure1

figure2

figure3

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