Cortical afferent inhibition abnormalities reveal cholinergic dysfunction in Parkinson’s disease: A reappraisal

Raffaele Nardone*, Francesco Brigo, Viviana Versace, Yvonne Höller, Frediano Tezzon, Leopold Saltuari, Eugen Trinka, Luca Sebastianelli

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

7 Citations (Scopus)


Parkinson’s disease (PD) is a multisystem neurodegenerative disorder affecting, besides the dopaminergic function, multiple neurotransmission systems, including the cholinergic system. Central cholinergic circuits of human brain can be tested non-invasively by coupling peripheral nerve stimulation with transcranial magnetic stimulation (TMS) of motor cortex; this test is named short latency afferent inhibition (SAI). SAI abnormalities have been reported in PD patients with gait disturbances and many non-motor symptoms, such as visual hallucinations (VHs), REM sleep behavior disorder (RBD), dysphagia, and olfactory impairment. The findings of these TMS studies strongly suggest that cholinergic degeneration is an important contributor to a number of clinical features of PD. TMS and neuropsychological raise the possibility that the presence of RBD, VHs and olfactory dysfunction indicate increased risk of cognitive impairment in patients with PD. Longitudinal studies of the patients are required to verify whether SAI abnormalities can predict a future severe cognitive decline. TMS can provide simple measures that may represent suitable biomarkers of cholinergic neurotransmission in PD. SAI studies enable an early recognition of PD patients with cholinergic system degeneration, and this might allow future targeted cholinergic treatment approaches, in addition to dopaminergic therapy, to ameliorate non-motor and motor clinical symptoms in PD patients.

Original languageEnglish
Pages (from-to)1417-1429
Number of pages13
JournalJournal of Neural Transmission
Issue number11
Publication statusPublished - 1 Nov 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017, Springer-Verlag GmbH Austria.

Other keywords

  • Parkinson’s disease
  • Short latency afferent inhibition
  • Transcranial magnetic stimulation


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