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Resonance in subthalamo-cortical circuits in Parkinson's disease.

Eusebio A, Pogosyan A, Wang S, Averbeck B, Gaynor LD, Cantiniaux S, Witjas T, Limousin P, Azulay JP, Brown P - Brain (2009)

Bottom Line: 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.Our results show that the basal ganglia-cortical network involving the STN has a tendency to resonate at approximately 20 Hz in Parkinsonian patients.Crucially, dopamine acts to increase damping and thereby limit resonance in this basal ganglia-cortical network.

View Article: PubMed Central - PubMed

Affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London, UK.

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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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.
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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.

Mentions: In order to determine the reproducibility of our core findings in patient Group 1 we repeated the experiment in an independent population of eight Parkinson's disease patients (Group 2) from a different surgical centre (Marseille). The cEPs were recorded during 5 Hz STN stimulation both in OFF- and ON-drug states. As before, the cEPs averaged over the ipsilateral and mesial sensorimotor cortex, consisted of a series of diminishing waves with a peak latency of 21.6 ± 0.6 ms for the first consistent wave. The fitted grand average cEP (r = 0.9 OFF and 0.95 ON, P < 0.00001, for both) had a natural frequency of 21.8 ± 0.1 Hz OFF and 20.8 ± 0.1 Hz ON (P < 0.00001) and a damping factor of 0.13 ± 0.01 OFF drugs increasing by 85% to 0.24 ± 0.01 ON-drugs (P < 0.00001; Fig. 4). As before the undamped amplitude of cEPs was greater during stimulation at 20 Hz (3.9 ± 0.3 µV at 20 Hz) than during 5 Hz stimulation OFF (P = 0.002; Fig. 4). The only major difference between this cohort of Parkinson's disease patients and those reported above was a higher undamped amplitude OFF (2.8 ± 0.1 µV; P < 0.00001 OFF Group 1 versus Group 2) that increased even further ON-drugs during 5 Hz stimulation (4.4 ± 0.2 µV; P < 0.00001 Group 2 OFF versus ON).Figure 4


Resonance in subthalamo-cortical circuits in Parkinson's disease.

Eusebio A, Pogosyan A, Wang S, Averbeck B, Gaynor LD, Cantiniaux S, Witjas T, Limousin P, Azulay JP, Brown P - Brain (2009)

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.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2714058&req=5

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.
Mentions: In order to determine the reproducibility of our core findings in patient Group 1 we repeated the experiment in an independent population of eight Parkinson's disease patients (Group 2) from a different surgical centre (Marseille). The cEPs were recorded during 5 Hz STN stimulation both in OFF- and ON-drug states. As before, the cEPs averaged over the ipsilateral and mesial sensorimotor cortex, consisted of a series of diminishing waves with a peak latency of 21.6 ± 0.6 ms for the first consistent wave. The fitted grand average cEP (r = 0.9 OFF and 0.95 ON, P < 0.00001, for both) had a natural frequency of 21.8 ± 0.1 Hz OFF and 20.8 ± 0.1 Hz ON (P < 0.00001) and a damping factor of 0.13 ± 0.01 OFF drugs increasing by 85% to 0.24 ± 0.01 ON-drugs (P < 0.00001; Fig. 4). As before the undamped amplitude of cEPs was greater during stimulation at 20 Hz (3.9 ± 0.3 µV at 20 Hz) than during 5 Hz stimulation OFF (P = 0.002; Fig. 4). The only major difference between this cohort of Parkinson's disease patients and those reported above was a higher undamped amplitude OFF (2.8 ± 0.1 µV; P < 0.00001 OFF Group 1 versus Group 2) that increased even further ON-drugs during 5 Hz stimulation (4.4 ± 0.2 µV; P < 0.00001 Group 2 OFF versus ON).Figure 4

Bottom Line: 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.Our results show that the basal ganglia-cortical network involving the STN has a tendency to resonate at approximately 20 Hz in Parkinsonian patients.Crucially, dopamine acts to increase damping and thereby limit resonance in this basal ganglia-cortical network.

View Article: PubMed Central - PubMed

Affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London, UK.

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.

Show MeSH
Related in: MedlinePlus