Objective: To delineate hemisphere-specific, local, and network-level mechanisms underlying stimulation-induced speech impairment after subthalamic deep brain stimulation (STN-DBS).

Background: STN-DBS can improve but also worsen speech, suggesting that stimulation can modulate cortico–basal ganglia speech networks. However, the network mechanisms underlying these effects remain poorly understood.

Method: 25 patients with STN-DBS were assessed OFF medication during chronic stimulation and during a blinded randomized protocol in which stimulation amplitudes were systematically varied across 8 stimulation conditions above and below an individually defined speech-impairment threshold, yielding 190 right- and 189 left-hemispheric stimulation conditions. Speech was evaluated using phonation, diadochokinesis, and reading tasks. Acoustic features were combined into a Composite Dysarthria Index and compared with blinded patient self-ratings.

Results: Speech modulation increased dose-dependently and was more pronounced with left-sided stimulation. Objective biomarkers correlated with blinded self-ratings (R=0.53, p<0.001). Under chronic stimulation, the left-hemispheric speech “sweet spot” localized to the dorsolateral sensorimotor STN at the motor–associative interface (R=0.71, p=0.02) and was associated with motor STN–globus pallidus externus connections (R=0.52, p=0.01). In contrast, the right-hemispheric sweet spot was located more ventroanteriorly within associative STN (R=0.50, p=0.02), but no speech-improving pathways survived validation. Speech-worsening regions extended beyond STN borders into lateral, dorsomedial, and ventromedial territories. In the left hemisphere, speech impairment was linked to corticobulbar projections, pallidothalamic and cerebellothalamic tracts, and hyperdirect connections to prefrontal and anterior cingulate regions. Right-hemispheric impairment was largely confined to motor effector circuitry.

Conclusion: Stimulation-induced speech impairment reflects engagement of an extended, left-lateralized cortico-subcortical network, whereas right-hemispheric effects are largely restricted to motor pathways. These findings provide a mechanistic framework for hemisphere-specific, volume- and fiber-informed STN-DBS programming and highlight the potential of digital speech biomarkers to guide image-informed and adaptive neuromodulation strategies aimed at preserving communication.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/network-determinants-of-stimulation-induced-speech-impairment-after-subthalamic-dbs-in-parkinsons-disease/