Brain Advance Access originally published online on May 30, 2006
Brain 2006 129(7):1758-1767; doi:10.1093/brain/awl143
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Single subthalamic nucleus deep brain stimuli inhibit the blink reflex in Parkinson's disease patients
1 Department of Neurology, Santa Maria University Hospital, Lisbon Faculty of Medicine, Institute of Molecular Medicine Lisbon, Portugal 2 Department of Neurology, IDIBAPS (Institut d'Investigació Biomèdica August Pi i Sunyer), Universitat de Barcelona Barcelona, Spain 3 Department of Neurosurgery, Hospital Clínic, Universitat de Barcelona Barcelona, Spain 4 Department of Neurorehabilitation, Hospital Hochzirl Innsbruck, Austria
Correspondence to: Josep Valls-Solé, EMG Unit, Neurology Department, Hospital Clínic, Villarroel, 170, Barcelona 08036, Spain. E-mail: jvalls{at}clinic.ub.es
The disordered output from the basal ganglia to the pontine tegmentum nuclei is considered responsible for a number of abnormalities in brainstem reflexes in patients with Parkinson's disease. One of the most conspicuous of these abnormalities is the reduced inhibition of the blink reflex by a prepulse stimulus. The circuit of prepulse inhibition involves structures and fibre groups that can be reached by stimuli applied through the electrodes implanted in the subthalamic nucleus for deep brain stimulation (STNDBS). In seven Parkinson's disease patients we examined whether single STNDBS induced prepulse effects on the blink reflex and how they compared with the effects induced by single auditory and somatosensory stimuli. Prepulse inhibition was determined by measuring the percentage inhibition induced in the R2 component of the orbicularis oculi response to supraorbital nerve stimuli. The inter-stimuli intervals (ISI) between the prepulse and the supraorbital nerve stimuli were 0 to 30 ms and 100 ms for single STNDBS and 100 ms for auditory and somatosensory modalities. The results obtained with acoustic and somatosensory stimuli were compared with those obtained from a group of 20 age-matched healthy subjects. Single STNDBS induced significant inhibition of the R2 in all patients at ISIs between 10 and 30 ms, with a mean percentage inhibition of 94% at the ISI of 30 ms. On the contrary, significant inhibition by auditory or somatosensory stimuli was induced in only two out of the seven patients. The mean percentage inhibition at the ISI of 100 ms was 37% for auditory and 40% for somatosensory stimuli, well below reference limits for prepulse inhibition in control subjects (61%). Single STNDBS induces significant prepulse inhibition of the blink reflex in Parkinson's disease patients who have abnormally reduced auditory and somatosensory prepulse effects. This finding helps define the prepulse circuit in humans and the eventual site of its dysfunction in Parkinson's disease.
Key Words: subthalamic nucleus; deep brain stimulation; prepulse inhibition; blink reflex; Parkinson's disease
Abbreviations: DBS, deep brain stimulation; GPi, globus pallidus internum; ISI, inter-stimulus interval; nRPC, nucleus reticularis pontis caudalis; OOc, orbicularis oculi; PPTg, pedunculopontine tegmental nucleus; SNr, substantia nigra pars reticulata; STN, subthalamic nucleus; STNDBS, subthalamic nucleus deep brain stimulation
Received March 29, 2006. Revised April 27, 2006. Accepted April 28, 2006.
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