Entrainment of STN neurons by cortical beta oscillations in Parkinson's disease

TY - CHAP

T1 - Entrainment of STN neurons by cortical beta oscillations in Parkinson's disease

AU - Sharott, Andrew

AU - Gulberti, Alessandro

AU - Hamel, Wolfgang

AU - Köppen, Johannes

AU - Zittel, Simone

AU - Hidding, Ute

AU - Gerloff, Christian

AU - Westphal, Manfred

AU - Engel, Andreas Karl

AU - Moll, Christian

PY - 2009/9/20

Y1 - 2009/9/20

N2 - Synchronized oscillations in the β range (10-30Hz) within cortex-basal ganglia circuits have been proposed as a pathophysiological mechanism in Parkinson’s disease (PD). Much evidence supporting this idea has come from recordings of PD patients after the implantation of electrodes for deep brain stimulation (DBS) of the subthalamic nucleus (STN). Local field potentials (LFPs) recorded postoperatively through the therapeutic DBS electrodes display β oscillations that are coherent with the frontocentral EEG and are ameliorated by dopaminergic medication. Such studies indicate that STN oscillations are driven by cortex, but this has not been verified at the level of single neurons. Here we compared the relationships between cortical and STN (units+LFP) signals using intraoperative recording.Simultaneous recordings of cortex and STN were made in 13 patients undergoing stereotactic implantation of DBS electrodes for the treatment of advanced PD. EEG recordings were referenced to give one frontocentral and two lateral dipoles. Electrocorticographic signals (ECoG) were recorded using a monopolar epidural electrode beneath the craniotomy. STN units (n = 256) were recorded from 5 simultaneously advanced microelectrodes (interelectrode distance: 2mm). STN-LFPs were taken from macroelectrodes 3mm above the microelectrode tip on three trajectories. Patients were included only if (i) 10 STN units had been recorded for over 60s each, (ii) there were units that displayed oscillations and (iii) there was significant coherence between the frontocentral EEG and STN-LFP in the β range.Analysis of spectral relationships of physiologically identified STN-LFPs verified that patients displayed core features of β oscillations in relation to the EEG described previously. Coherence was significantly higher with frontal than lateral channels and phase and directed transfer function analyses showed the EEG/ECoG leading the STN-LFP by around 20ms. Around 30% of STN single and multi-units were significantly coherent with the frontocentral EEG and showed the same anatomical and directional relationships to the EEG in the β range. The delay derived from the phase spectra, however, was longer for units, 30-90ms, than for LFPs. Phase histograms and spike triggered averaging confirmed that oscillations in the STN neurons lagged cortical β oscillations, whereas those for the STN-LFP were centered on zero.These results show that cortical β oscillations precede those STN neurons in PD patients off medication and suggest that STN-LFPs provide accurate directional information, but not precise temporal relations of STN neurons to cortex at β frequencies.

AB - Synchronized oscillations in the β range (10-30Hz) within cortex-basal ganglia circuits have been proposed as a pathophysiological mechanism in Parkinson’s disease (PD). Much evidence supporting this idea has come from recordings of PD patients after the implantation of electrodes for deep brain stimulation (DBS) of the subthalamic nucleus (STN). Local field potentials (LFPs) recorded postoperatively through the therapeutic DBS electrodes display β oscillations that are coherent with the frontocentral EEG and are ameliorated by dopaminergic medication. Such studies indicate that STN oscillations are driven by cortex, but this has not been verified at the level of single neurons. Here we compared the relationships between cortical and STN (units+LFP) signals using intraoperative recording.Simultaneous recordings of cortex and STN were made in 13 patients undergoing stereotactic implantation of DBS electrodes for the treatment of advanced PD. EEG recordings were referenced to give one frontocentral and two lateral dipoles. Electrocorticographic signals (ECoG) were recorded using a monopolar epidural electrode beneath the craniotomy. STN units (n = 256) were recorded from 5 simultaneously advanced microelectrodes (interelectrode distance: 2mm). STN-LFPs were taken from macroelectrodes 3mm above the microelectrode tip on three trajectories. Patients were included only if (i) 10 STN units had been recorded for over 60s each, (ii) there were units that displayed oscillations and (iii) there was significant coherence between the frontocentral EEG and STN-LFP in the β range.Analysis of spectral relationships of physiologically identified STN-LFPs verified that patients displayed core features of β oscillations in relation to the EEG described previously. Coherence was significantly higher with frontal than lateral channels and phase and directed transfer function analyses showed the EEG/ECoG leading the STN-LFP by around 20ms. Around 30% of STN single and multi-units were significantly coherent with the frontocentral EEG and showed the same anatomical and directional relationships to the EEG in the β range. The delay derived from the phase spectra, however, was longer for units, 30-90ms, than for LFPs. Phase histograms and spike triggered averaging confirmed that oscillations in the STN neurons lagged cortical β oscillations, whereas those for the STN-LFP were centered on zero.These results show that cortical β oscillations precede those STN neurons in PD patients off medication and suggest that STN-LFPs provide accurate directional information, but not precise temporal relations of STN neurons to cortex at β frequencies.

M3 - Conference contribution - Poster

BT - 2009 Neuroscience Meeting Planner

T2 - Neuroscience 2009

Y2 - 17 October 2009 through 21 October 2009

ER -