Objective: to investigate whether dopaminergic therapy modulates IHI and bradykinesia asymmetry in PD.

Background: previous evidence demonstrated a reduced interhemispheric inhibition (IHI) in Parkinson’s disease (PD), possibly related to the asymmetry of motor symptoms^1,3,5. However, the effects of dopaminergic treatment on interhemispheric disinhibition and motor correlates in PD, have never been investigated.

Method: we enrolled seventeen PD patients (mean age ± standard deviation – SD: 67.5±9.2 years) and 15 healthy controls (HCs) (mean age ± SD: 64±8.1 years). Patients were studied with and without their dopaminergic therapy^2,5 (ON and OFF sessions, mean LEDD ± SD: 483.8±173.2). Paired-pulse transcranial magnetic stimulation (TMS) served to measure IHI, with an interstimulus interval (ISI) between the conditioning (CS) and the test stimulus (TS) of 10 (short-latency IHI, sIHI) and 40 ms (long-latency IHI, lIHI)^1,2,4,5. Objective finger-tapping measurements were obtained bilaterally with a motion analysis system⁵. We compared data between patients and HCs, and between patients ON and OFF medication using t-tests. We also calculated asymmetry indices (AI) of neurophysiological data. Correlations analysis was performed to test possible relations between TMS and kinematic data.

Results: as compared to HC, PD OFF medication had a reduced sIHI from the most to the less affected hemisphere (p=0.02). Finger tapping was slower, more irregular and characterised by the sequence effect in PD OFF medication as compared to HCs (all p<0.05). Interhemispheric imbalance quantified by the sIHI-AI correlated with the sequence effect of the less affected side in patients OFF medication (R=-0.5, p<0.03). Although improving movement velocity (p=0.009), dopaminergic treatment did not modify sIHI or the sequence effect (R=0.23, p>0.05).

Conclusion: we here provided further evidence on the pathophysiological role of interhemispheric disinhibition in bradykinesia asymmetry in PD with a focus on the effects of dopaminergic treatment.

References: 1. Li JY, Espay AJ, Gunraj CA, Pal PK, Cunic DI, Lang AE, Chen R. Interhemispheric and ipsilateral connections in Parkinson’s disease: relation to mirror movements. Mov Disord. 2007 Apr 30;22(6):813-21. doi: 10.1002/mds.21386. PMID: 17290459.
2. Lizarraga KJ, Saravanamuttu J, Baarbé JK, Lang AE, Chen R. Interhemispheric pathways in agenesis of the corpus callosum and Parkinson’s disease. Brain Stimul. 2020 Mar-Apr;13(2):360-362. doi: 10.1016/j.brs.2019.11.003. Epub 2019 Nov 4. PMID: 31727582.
3. Malling ASB, Morberg BM, Wermuth L, Gredal O, Bech P, Jensen BR. The effect of 8 weeks of treatment with transcranial pulsed electromagnetic fields on hand tremor and inter-hand coherence in persons with Parkinson’s disease. J Neuroeng Rehabil. 2019 Jan 31;16(1):19. doi: 10.1186/s12984-019-0491-2. PMID: 30704504; PMCID: PMC6357382.
4. Bologna M, Caronni A, Berardelli A, Rothwell JC. Practice-related reduction of electromyographic mirroring activity depends on basal levels of interhemispheric inhibition. Eur J Neurosci. 2012 Dec;36(12):3749-57. doi: 10.1111/ejn.12009. Epub 2012 Oct 4. PMID: 23033874.
5. 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.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-effects-of-dopaminergic-treatment-on-interhemispheric-disinhibition-and-bradykinesia-asymmetry-in-parkinsons-disease/