Fast Intracortical Sensory-Motor Integration: A Window Into the Pathophysiology of Parkinson's Disease

Raffaele Dubbioso, Fiore Manganelli, Hartwig Roman Siebner, Vincenzo Di Lazzaro

33 Citationer (Scopus)

Abstract

Parkinson's Disease (PD) is a prototypical basal ganglia disorder. Nigrostriatal dopaminergic denervation leads to progressive dysfunction of the cortico-basal ganglia-thalamo-cortical sensorimotor loops, causing the classical motor symptoms. Although the basal ganglia do not receive direct sensory input, they are important for sensorimotor integration. Therefore, the basal ganglia dysfunction in PD may profoundly affect sensory-motor interaction in the cortex. Cortical sensorimotor integration can be probed with transcranial magnetic stimulation (TMS) using a well-established conditioning-test paradigm, called short-latency afferent inhibition (SAI). SAI probes the fast-inhibitory effect of a conditioning peripheral electrical stimulus on the motor response evoked by a TMS test pulse given to the contralateral primary motor cortex (M1). Since SAI occurs at latencies that match the peaks of early cortical somatosensory potentials, the cortical circuitry generating SAI may play an important role in rapid online adjustments of cortical motor output to changes in somatosensory inputs. Here we review the existing studies that have used SAI to examine how PD affects fast cortical sensory-motor integration. Studies of SAI in PD have yielded variable results, showing reduced, normal or even enhanced levels of SAI. This variability may be attributed to the fact that the strength of SAI is influenced by several factors, such as differences in dopaminergic treatment or the clinical phenotype of PD. Inter-individual differences in the expression of SAI has been shown to scale with individual motor impairment as revealed by UPDRS motor score and thus, may reflect the magnitude of dopaminergic neurodegeneration. The magnitude of SAI has also been linked to cognitive dysfunction, and it has been suggested that SAI also reflects cholinergic denervation at the cortical level. Together, the results indicate that SAI is a useful marker of disease-related alterations in fast cortical sensory-motor integration driven by subcortical changes in the dopaminergic and cholinergic system. Since a multitude of neurobiological factors contribute to the magnitude of inhibition, any mechanistic interpretation of SAI changes in PD needs to consider the group characteristics in terms of phenotypical spectrum, disease stage, and medication.

OriginalsprogEngelsk
Artikelnummer111
TidsskriftFrontiers in Human Neuroscience
Vol/bind13
Sider (fra-til)1-14
Antal sider14
ISSN1662-5161
DOI
StatusUdgivet - 1 apr. 2019

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