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Boosting the LTP-like Plasticity Effect of Intermittent Theta-burst Stimulation with Gamma Transcranial Alternating Current Stimulation improves Bradykinesia in Parkinson’s Disease

G. Paparella, D. Costa, M. de Riggi, L. Angelini, A. Cannavacciuolo, S. Pietracupa, A. Berardelli, A. Guerra, M. Bologna (Pozzilli

Meeting: 2025 International Congress

Keywords: Bradykinesia, Parkinson’s, Transcranial magnetic stimulation(TMS)

Category: Parkinson's Disease: Pathophysiology / molecular mechanisms of disease

Objective: We  investigated whether transcranial alternating current stimulation (tACS) applied at the gamma frequency (γ) frequency on the primary motor cortex (M1) improves long-term potentiation (LTP)-like plasticity and alleviates bradykinesia in Parkinson’s disease (PD) [1].

Background: γ -band oscillations in cortico-basal circuits are reduced in PD, and the M1 plasticity is impaired [2-4]. tACS may enhance γ oscillations and restore M1 plasticity, but its effects on motor functions remain unclear [2-4].

Method: Eighteen PD patients and 15 healthy controls (HCs) underwent two randomized sessions: intermittent theta burst stimulation (iTBS) combined with γ-tACS (iTBS-γ tACS) and sham-tACS (iTBS-sham tACS). Transcranial magnetic stimulation (TMS) assessed M1 activity at baseline, and 5, 15, and 30 minutes post-stimulation. Bradykinesia was evaluated through finger-tapping kinematic analysis at the same timepoints [3-5].

Results: At baseline, PD patients showed reduced M1 intracortical inhibition compared to HCs, alongside impaired finger-tapping (reduced velocity and amplitude, altered rhythm, and sequence effect). iTBS alone failed to indice plasticity in PD, whereas iTBS-γ tACS elicited plasticity improvements (Figure 1). Kinematic results indicated movement velocity improvements following iTBS-γ tACS in PD (Figure 2), whith no changes after iTBS-sham tACS or in HCs.

Conclusion: γ-tACS may restore M1 plasticity and improve movement in PD, highlighting the role of γ oscillations in motor deficits and supporting novel non-invasive brain stimulation therapies.

Figure 1

Figure 1

Figure 2

Figure 2

References: 1. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015 Oct;30(12):1591-601. doi: 10.1002/mds.26424.
2. Bologna M, Paparella G, Fasano A, Hallett M, Berardelli A. Evolving concepts on bradykinesia. Brain. 2020 Mar 1;143(3):727-750. doi: 10.1093/brain/awz344. PMID: 31834375; PMCID: PMC8205506;
3. Bologna M, Guerra A, Paparella G, Giordo L, Alunni Fegatelli D, Vestri AR, Rothwell JC, Berardelli A. Neurophysiological correlates of bradykinesia in Parkinson’s disease. Brain. 2018 Aug 1;141(8):2432-2444. doi: 10.1093/brain/awy155. PMID: 29901693.
4. Guerra A, Colella D, Giangrosso M, Cannavacciuolo A, Paparella G, Fabbrini G, Suppa A, Berardelli A, Bologna M. Driving motor cortex oscillations modulates bradykinesia in Parkinson’s disease. Brain. 2022 Mar 29;145(1):224-236. doi: 10.1093/brain/awab257. PMID: 34245244.
5. Paparella G, Cannavacciuolo A, Angelini L, et al. May Bradykinesia Features Aid in Distinguishing Parkinson’s Disease, Essential Tremor, And Healthy Elderly Individuals? J Park Dis. 2023;13(6):1049-1062.

To cite this abstract in AMA style:

G. Paparella, D. Costa, M. de Riggi, L. Angelini, A. Cannavacciuolo, S. Pietracupa, A. Berardelli, A. Guerra, M. Bologna (Pozzilli. Boosting the LTP-like Plasticity Effect of Intermittent Theta-burst Stimulation with Gamma Transcranial Alternating Current Stimulation improves Bradykinesia in Parkinson’s Disease [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/boosting-the-ltp-like-plasticity-effect-of-intermittent-theta-burst-stimulation-with-gamma-transcranial-alternating-current-stimulation-improves-bradykinesia-in-parkinsons-disease/. Accessed October 5, 2025.
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