Improved alpha-beta power reduction via combined electrical and ultrasonic stimulation in a parkinsonian cortex-basal ganglia-thalamus computational model

Abstract Objective. To investigate computationally the interaction of combined electrical and ultrasonic modulation of isolated neurons and of the Parkinsonian cortex-basal ganglia-thalamus loop. Approach. Continuous-wave or pulsed electrical and ultrasonic neuromodulation is applied to isolated Otsuka plateau-potential generating subthalamic nucleus (STN) and Pospischil regular, fast and low-threshold spiking cortical cells in a temporally alternating or simultaneous manner. Similar combinations of electrical/ultrasonic waveforms are applied to a Parkinsonian biophysical cortex-basal ganglia-thalamus neuronal network. Ultrasound-neuron interaction is modelled respectively for isolated neurons and the neuronal network with the NICE and SONIC implementations of the bilayer sonophore underlying mechanism. Reduction in α-β spectral energy is used as a proxy to express improvement in Parkinson’s disease by insonication and electrostimulation. Main results. Simultaneous electro-acoustic stimulation achieves a given level of neuronal activity at lower intensities compared to the separate stimulation modalities. Conversely, temporally alternating stimulation with 50 Hz electrical and ultrasound pulses is capable of eliciting 100 Hz STN ﬁring rates. Furthermore, combination of ultrasound with hyperpolarizing currents can alter cortical cell relative spiking regimes. In the Parkinsonian neuronal network, continuous-wave and pulsed ultrasound reduce pathological oscillations by different mechanisms. High-frequency pulsed separated electrical and ultrasonic deep brain stimulation (DBS) reduce pathological α-β power by entraining STN-neurons. In contrast, continuous-wave ultrasound reduces pathological oscillations by silencing the STN. Compared to the separated stimulation modalities, temporally simultaneous or alternating electro-acoustic stimulation can achieve higher reductions in α-β power for the same safety contraints on electrical/ultrasonic intensity. Signiﬁcance. Focused ultrasound has the potential of becoming a non-invasive alternative of conventional DBS for the treatment of Parkinson’s disease. Here, we elaborate on proposed beneﬁts of combined electro-acoustic stimulation in terms of improved dynamic range, efﬁciency, spatial resolution, and neuronal selectivity.

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Improved alpha-beta power reduction via combined Electrical and Ultrasonic stimulation in a Parkinsonian Cortex-Basal Ganglia-Thalamus Computational Model

10.1101/2021.02.03.429377 ◽

2021 ◽

Author(s):

Thomas Tarnaud ◽

Wout Joseph ◽

Ruben Schoeters ◽

Luc Martens ◽

Emmeric Tanghe

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Neuronal Network ◽

Continuous Wave ◽

Dynamic Range ◽

Cortical Cell ◽

Acoustic Stimulation ◽

Isolated Neurons ◽

Beta Power

AbstractObjectiveTo investigate computationally the interaction of combined electrical and ultrasonic modulation of isolated neurons and of the Parkinsonian cortex-basal ganglia-thalamus loop.MethodsContinuous-wave or pulsed electrical and ultrasonic neuromodulation is applied to isolated Otsuka plateau-potential generating subthalamic nucleus (STN) and Pospischil regular, fast and low-threshold spiking cortical cells in a temporally-alternating or simultaneous manner. Similar combinations of electrical/ultrasonic waveforms are applied to a Parkinsonian biophysical cortex-basal ganglia-thalamus neuronal network. Ultrasound-neuron interaction is modelled respectively for isolated neurons and the neuronal network with the NICE and SONIC implementations of the bilayer sonophore underlying mechanism. Reduction in α—β spectral energy is used as a proxy to express improvement in Parkinson’s disease by insonication and electrostimulation.ResultsSimultaneous electro-acoustic stimulation achieves a given level of neuronal activity at lower intensities compared to the separate stimulation modalities. Conversely, temporally alternating stimulation with 50 Hz electrical and ultrasound pulses is capable of eliciting 100 Hz STN firing rates. Furthermore, combination of ultrasound with hyperpolarizing currents can alter cortical cell relative spiking regimes. In the Parkinsonian neuronal network, high-frequency pulsed separated electrical and ultrasonic deep brain stimulation (DBS) reduce pathological α — β power by entraining STN-neurons. In contrast, continuous-wave ultrasound reduces pathological oscillations by silencing the STN. Compared to the separated stimulation modalities, temporally simultaneous or alternating electro-acoustic stimulation can achieve higher reductions in α — β power for the same contraints on electrical/ultrasonic intensity.ConclusionContinuous-wave and pulsed ultrasound reduce pathological oscillations by different mechanisms. Electroacoustic stimulation further improves α— β power for given safety limits and is capable of altering cortical relative spiking regimes.Significancefocused ultrasound has the potential of becoming a non-invasive alternative of conventional DBS for the treatment of Parkinson’s disease. Here, we elaborate on proposed benefits of combined electro-acoustic stimulation in terms of improved dynamic range, efficiency, resolution, and neuronal selectivity.

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The Basal Ganglia and Disorders of Movement: Pathophysiological Mechanisms

Physiology ◽

10.1152/nips.01363.2001 ◽

2002 ◽

Vol 17 (2) ◽

pp. 51-55 ◽

Cited By ~ 11

Author(s):

José A. Obeso ◽

María C. Rodríguez-Oroz ◽

Manuel Rodríguez ◽

Javier Arbizu ◽

José M. Giménez-Amaya

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Neuronal Network ◽

Motor Circuit ◽

Pathophysiological Mechanisms ◽

Parallel Circuits

The basal ganglia are part of a neuronal network organized in parallel circuits. The “motor circuit” is most relevant to the pathophysiology of movement. Abnormal increment or reduction in the inhibitory output activity of basal ganglia give rise, respectively, to poverty and slowness of movement (i.e., Parkinson's disease) or dyskinesias.

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Basal Ganglia Modeling in Healthy and Parkinson's Disease State. I. Isolated Neurons Activity

2007 American Control Conference ◽

10.1109/acc.2007.4282741 ◽

2007 ◽

Cited By ~ 9

Author(s):

Sabato Santaniello ◽

Giovanni Fiengo ◽

Luigi Glielmo ◽

Warren M. Grill

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Disease State ◽

Isolated Neurons

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Changes in metabotropic glutamate receptor expression in the basal ganglia of Parkinson's disease models

Neuroscience Research ◽

10.1016/s0168-0102(00)81571-0 ◽

2000 ◽

Vol 38 ◽

pp. S121

Author(s):

M Takada

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Glutamate Receptor ◽

Metabotropic Glutamate Receptor ◽

Receptor Expression ◽

Disease Models ◽

Metabotropic Glutamate

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SPECT-Befunde bei Hemiparkinson-Syndrom mit 99mTc-HMPAO

Nuklearmedizin ◽

10.1055/s-0038-1629476 ◽

1989 ◽

Vol 28 (03) ◽

pp. 92-94 ◽

Cited By ~ 1

Author(s):

C. Neumann ◽

H. Baas ◽

R. Hefner ◽

G. Hör

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Neuronal Activity ◽

Tracer Uptake ◽

The Body ◽

99Mtc Hmpao ◽

Do So

The symptoms of Parkinson’s disease often begin on one side of the body and continue to do so as the disease progresses. First SPECT results in 4 patients with hemiparkinsonism using 99mTc-HMPAO as perfusion marker are reported. Three patients exhibited reduced tracer uptake in the contralateral basal ganglia One patient who was under therapy for 1 year, showed a different perfusion pattern with reduced uptake in both basal ganglia. These results might indicate reduced perfusion secondary to reduced striatal neuronal activity.

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Potassium channels in the basal ganglia: Promising new targets for the treatment of Parkinson's disease

Frontiers in Bioscience ◽

10.2741/2959 ◽

2008 ◽

Vol Volume (13) ◽

pp. 3685 ◽

Cited By ~ 1

Author(s):

Gang Wang

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Potassium Channels ◽

New Targets

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Corticostriatal Plastic Changes in Experimental L-DOPA-Induced Dyskinesia

Parkinson s Disease ◽

10.1155/2012/358176 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Veronica Ghiglieri ◽

Vincenza Bagetta ◽

Valentina Pendolino ◽

Barbara Picconi ◽

Paolo Calabresi

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Experimental Models ◽

Striatal Neurons ◽

Da Receptors ◽

Electrophysiological Studies ◽

Plastic Changes ◽

Stimulation Of

In Parkinson’s disease (PD), alteration of dopamine- (DA-) dependent striatal functions and pulsatile stimulation of DA receptors caused by the discontinuous administration of levodopa (L-DOPA) lead to a complex cascade of events affecting the postsynaptic striatal neurons that might account for the appearance of L-DOPA-induced dyskinesia (LID). Experimental models of LID have been widely used and extensively characterized in rodents and electrophysiological studies provided remarkable insights into the inner mechanisms underlying L-DOPA-induced corticostriatal plastic changes. Here we provide an overview of recent findings that represent a further step into the comprehension of mechanisms underlying maladaptive changes of basal ganglia functions in response to L-DOPA and associated to development of LID.

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