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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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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.
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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.

Mentions: Finally, we simulated the response of an oscillating system with a natural frequency of 20 Hz and variable damping factors (0.05–0.6) when the system was driven by impulse input at frequencies from 1 to 60 Hz. The initial undamped amplitude was set as one and the peak amplitude relative to the initial value was extracted from the model for various stimulation frequencies and damping factors (Fig. 3).


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)

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

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

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.
Mentions: Finally, we simulated the response of an oscillating system with a natural frequency of 20 Hz and variable damping factors (0.05–0.6) when the system was driven by impulse input at frequencies from 1 to 60 Hz. The initial undamped amplitude was set as one and the peak amplitude relative to the initial value was extracted from the model for various stimulation frequencies and damping factors (Fig. 3).

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