Resonance in subthalamo-cortical circuits in Parkinson's disease - PubMed (original) (raw)

Multicenter Study

. 2009 Aug;132(Pt 8):2139-50.

doi: 10.1093/brain/awp079. Epub 2009 Apr 15.

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Multicenter Study

Resonance in subthalamo-cortical circuits in Parkinson's disease

Alexandre Eusebio et al. Brain. 2009 Aug.

Erratum in

Abstract

Neuronal activity within and across the cortex and basal ganglia is pathologically synchronized, particularly at approximately 20 Hz in patients with Parkinson's disease. Defining how activities in spatially distributed brain regions overtly synchronize in narrow frequency bands is critical for understanding disease processes like Parkinson's disease. To address this, we studied cortical responses to electrical stimulation of the subthalamic nucleus (STN) at various frequencies between 5 and 30 Hz in two cohorts of eight patients with Parkinson's disease from two different surgical centres. We found that evoked activity consisted of a series of diminishing waves with a peak latency of 21 ms for the first wave in the series. The cortical evoked potentials (cEPs) averaged in each group were well fitted by a damped oscillator function (r > or = 0.9, P < 0.00001). Fits suggested that the natural frequency of the subthalamo-cortical circuit was around 20 Hz. When the system was forced at this frequency by stimulation of the STN at 20 Hz, the undamped amplitude of the modelled cortical response increased relative to that with 5 Hz stimulation in both groups (P < or = 0.005), consistent with resonance. Restoration of dopaminergic input by treatment with levodopa increased the damping of oscillatory activity (as measured by the modelled damping factor) in both patient groups (P < or = 0.001). The increased damping would tend to limit resonance, as confirmed in simulations. Our results show that the basal ganglia-cortical network involving the STN has a tendency to resonate at approximately 20 Hz in Parkinsonian patients. This resonance phenomenon may underlie the propagation and amplification of activities synchronized around this frequency. Crucially, dopamine acts to increase damping and thereby limit resonance in this basal ganglia-cortical network.

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Figures

Figure 1

Figure 1

Shape and distribution of the cortical evoked potentials. (A) Example of cEP in Case 1 from Group 1 (see

Supplementary Table 1

) OFF-drug during 5 Hz stimulation. The time period over which cEP amplitude was averaged in B and C is indicated by the grey box. The initial portion of the trace (up to ∼ 5 ms) is dominated by stimulation artefact. (B and C) Scalp maps of peak amplitudes of cEPs of 15–30 ms latency averaged across all seven patients in OFF-drug (B) and ON-drug (C) states for each stimulation frequency. Where necessary data were flipped so that scalp maps correspond to right hemisphere stimulation.

Figure 2

Figure 2

Fittings and parameters of the oscillator OFF- and ON-drugs. (A) Fitting of cEP traces averaged across seven patients in Group 1 in OFF- and ON-drug states for each stimulation frequency by the function for an impulse forced damped oscillator. Both the raw (black) and filtered (green) traces are indicated along with the fitted function (pink) (r = correlation coefficient for each fit). Stimulation artefacts at < 5 ms latency are deleted for clarity. (B) Undamped amplitude in both drug states (_P_-values corrected for multiple comparisons: *P < 0.05; **P < 0.005; ***P < 0.0001) (C) Example fits in two Parkinson's disease patients (Cases 2 and 3) stimulated at 5 Hz.

Figure 3

Figure 3

Simulation of response of an oscillating system with a natural frequency of 20 Hz showing dependency of resonance phenomena on damping factor. Changes in damping factor of the same degree as seen with the shift from the OFF- to ON-drug state, are sufficient to have a major effect on the amplitude of oscillations during stimulation at 20 Hz. Note there is a dip in amplitude with stimulation at 15 Hz that parallels the dip in undamped amplitude in Fig. 2B. White horizontal lines indicate a damping factor of 0.18 (ON) and 0.14 (OFF), as in patient Group 1, and vertical lines indicate 5 and 20 Hz stimulation.

Figure 4

Figure 4

Fittings and parameters of the oscillator OFF- and ON-drugs in an independent Parkinson's disease patient group. Fitting of cEP traces averaged across eight patients in Group 2 in OFF- and ON-drug states for 5 and 20 Hz stimulation by the function for an impulse forced damped oscillator. Both the raw (black) and filtered (green) traces are indicated along with the fitted function (pink) (r = correlation coefficient for each fit). Stimulation artefacts at ∼ 5 ms latency are deleted for clarity.

References

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