Non-invasive Modulation of Language Networks in Patients with Parkinson’s Disease: Resting state functional connectivity analysis
DOI: Pending DOI
Synopsis
Communication deficits in Parkinson’s disease (PD) involve language network disruptions. This double-blind, sham-controlled interim analysis (N=24) tested a 10-day anodic tDCS protocol over the F7 coordinate paired with language training. Global measures showed non-significant trends, but node-to-node analysis revealed successful target engagement of two connections from the inferior frontal gyrus. Significant Time x Group interactions emerged for the between-network intra-frontal connectivity and the ventral projection track, with robust post-stimulation increases in the active group. Results suggest that anodic F7 tDCS acts as a neuroplastic network integrator, offering a promising tool for language-focused neurorehabilitation in PD.
Background
Communication impairments in Parkinson’s disease (PD) extend far beyond motor speech deficits, frequently involving higher-order linguistic processes such as syntactic comprehension and lexical retrieval1. Cognitive and language processing heavily relies on the synchronized orchestration of two major neural pathways: the dorsal language network, responsible for phonological and syntactic processing, and the ventral language network, serving for semantic mapping and comprehension2,3. Neurodegenerative progression in PD disrupts frontostriatal connectivity, with recent evidence suggesting network-specific connectivity reductions4,5. Anodic transcranial direct current stimulation (tDCS) focusing on key structural nodes within these language networks could present a promising therapeutic tool to modulate cortical excitability6. However, the systemic neuromodulatory capacity of this paradigm to reinforce connectivity within targeted dual-stream networks in PD remains to be elucidated. Our aim is to assess whether targeting the left inferior frontal gyrus, which is a critical hub for language processing, via tDCS while synergistically paired with concurrent behavioral language training, could exploit mechanisms of activity-dependent neuroplasticity to reinforce neural pathways and drive functional network reorganization.
Methods
In this randomized, double-blind, sham-controlled interim analysis, 24 patients with Parkinson’s disease received either active or sham anodic tDCS over the F7 coordinate (targeting the inferior frontal gyrus; 20 min/day, 2mA, 10 consecutive days) during tailored language training. Resting-state fMRI connectivity was assessed at baseline and immediately post-intervention. Extracted metrics included global within-network connectivity for the dorsal and ventral language streams, between-network connectivity, and localized node-to-node connectivity across 10 specific network nodes of the dual-stream model (5 within the dorsal stream and 5 within the ventral stream), primarily anchored at the stimulated frontal operculum and inferior frontal gyrus pars triangularis.
Results
The preliminary analysis revealed successful focal target engagement. Significant Time × Group interactions emerged for the specific intra-frontal integration bridge between the dorsal and ventral language networks, directly adjacent to the stimulation site (i.e., between the inferior frontal gyrus pars triangularis and the frontal operculum; F (2, 42) = 3.32, p = .046, ηp2 = 0.136) and in the fronto-temporal ventral projection pathway (connecting the inferior frontal gyrus pars triangularis to the fusiform gyrus; F (2, 42) = 3.3, p = .046, ηp2 = 0.136). The active tDCS group showed robust post-stimulation connectivity increases compared to sham. Although the global within-network and between-network functional connectivity measures did not demonstrate statistically significant Time × Group interaction effects (p > .05), exploratory within-group analyses highlighted promising directional trends. The active tDCS group exhibited a significant post-stimulation increase in global ventral connectivity (MD = 0.11, SE = 0.03, p = .009) and between-network connectivity (MD = 0.11, SE = 0.03, p = .006), whereas the sham group remained statistically unchanged (p > .05). Preliminary exploratory brain-behavior partial correlations between these localized fMRI changes and neuropsychological language test scores (verbal fluency, naming) did not reach statistical significance at this interim stage (p > .05).
Discussion
The protocol demonstrated both safety and feasibility. These preliminary findings provide compelling evidence of successful target engagement. The stimulation specifically reinforced the local fronto-opercular bridge and its immediate downstream visual-semantic projection track. This anatomical modulation aligns with the concept of activity-dependent neuroplasticity, as these specific pathways were actively recruited by the concurrent language task6. The current absence of direct behavioral correlations is attributable to the restricted statistical power of this interim cohort. Unblinding the full sample will clarify whether these localized connectivity improvements ultimately translate into stable communication enhancements. In light of the documented language network disruptions in PD, these results suggest that achieving such focal target engagement via tDCS could be a promising approach for language-focused neurorehabilitation in PD.
Disclosures
This work was supported by the Czech Health Research Council (AZV ČR), grant NU23J‑04‑00005. No authors have financial or commercial relationships that could be perceived as potential conflicts of interest
References
1 Smith, K. M., & Caplan, D. N. (2018). Communication impairment in Parkinson's disease: Impact of motor and cognitive symptoms on speech and language. Brain and Language, 185, 38–46. https://doi.org/10.1016/j.bandl.2018.08.002
2 Hickok, G., & Poeppel, D. (2007). The cortical organization of speech processing. Nature Reviews Neuroscience, 8(5), 393–402. https://doi.org/10.1038/nrn2113
3 Saur, D., Kreher, B. W., Schnell, S., Kümmerer, D., Kellmeyer, P., Vry, M. S., Umarova, R., Musso, M., Glauche, V., Abel, S., Huber, W., Rijntjes, M., Hennig, J., & Weiller, C. (2008). Ventral and dorsal pathways for language. Proceedings of the National Academy of Sciences, 105(46), 18035–18040. https://doi.org/10.1073/pnas.0805234105
4 Baggio, H. C., Sala-Llonch, R., Segura, B., Marti, M. J., Valldeoriola, F., Compta, Y., Tolosa, E., & Junqué, C. (2014). Functional brain networks and cognitive deficits in Parkinson's disease. Human Brain Mapping, 35(9), 4620–4634. https://doi.org/10.1002/hbm.22499
5 Nováková, L., Gajdoš, M., Marková, J., Martinkovičová, A., Košútzká, Z., Švantnerová, J., Valkovič, P., Cséfalvay, Z., & Rektorová, I. (2023). Language impairment in Parkinson's disease: fMRI study of sentence reading comprehension. Frontiers in Aging Neuroscience, 15, Article 1117473. https://doi.org/10.3389/fnagi.2023.1117473
6 Nasios, G., Dardiotis, E., & Messinis, L. (2019). From Broca and Wernicke to the Neuromodulation Era: Insights of brain language networks for neurorehabilitation. Behavioural Neurology, 2019, Article 9894571. https://doi.org/10.1155/2019/9894571