The Basal Ganglia and Disorders of Movement: Pathophysiological Mechanisms

Physiology ◽  
2002 ◽  
Vol 17 (2) ◽  
pp. 51-55 ◽  
Author(s):  
José A. Obeso ◽  
María C. Rodríguez-Oroz ◽  
Manuel Rodríguez ◽  
Javier Arbizu ◽  
José M. Giménez-Amaya

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.

2021 ◽  
Author(s):  
Thomas Tarnaud ◽  
Wout Joseph ◽  
Ruben Schoeters ◽  
Luc Martens ◽  
Emmeric Tanghe

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.


2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Clara Rodriguez-Sabate ◽  
Ingrid Morales ◽  
Ricardo Puertas-Avendaño ◽  
Manuel Rodriguez

Abstract The closed-loop cortico-subcortical pathways of basal ganglia have been extensively used to describe the physiology of these centres and to justify the functional disorders of basal ganglia diseases. This approach justifies some experimental and clinical data but not others, and furthermore, it does not include a number of subcortical circuits that may produce a more complex basal ganglia dynamic than that expected for closed-loop linear networks. This work studied the functional connectivity of the main regions of the basal ganglia motor circuit with magnetic resonance imaging and a new method (functional profile method), which can analyse the multiple covariant activity of human basal ganglia. The functional profile method identified the most frequent covariant functional status (profiles) of the basal ganglia motor circuit, ordering them according to their relative frequency and identifying the most frequent successions between profiles (profile transitions). The functional profile method classified profiles as input profiles that accept the information coming from other networks, output profiles involved in the output of processed information to other networks and highly interconnected internal profiles that accept transitions from input profiles and send transitions to output profiles. Profile transitions showed a previously unobserved functional dynamic of human basal ganglia, suggesting that the basal ganglia motor circuit may work as a dynamic multiple covariance network. The number of internal profiles and internal transitions showed a striking decrease in patients with Parkinson’s disease, a fact not observed for input and output profiles. This suggests that basal ganglia of patients with Parkinson’s disease respond to requirements coming from other neuronal networks, but because the internal processing of information is drastically weakened, its response will be insufficient and perhaps also self-defeating. These marked effects were found in patients with few motor disorders, suggesting that the functional profile method may be an early procedure to detect the first stages of the Parkinson’s disease when the motor disorders are not very evident. The multiple covariance activity found presents a complementary point of view to the cortico-subcortical closed-loop model of basal ganglia. The functional profile method may be easily applied to other brain networks, and it may provide additional explanations for the clinical manifestations of other basal ganglia disorders.


2017 ◽  
Vol 118 (5) ◽  
pp. 2654-2669 ◽  
Author(s):  
David Escobar Sanabria ◽  
Luke A. Johnson ◽  
Shane D. Nebeck ◽  
Jianyu Zhang ◽  
Matthew D. Johnson ◽  
...  

Oscillatory neural activity in different frequency bands and phase-amplitude coupling (PAC) are hypothesized to be biomarkers of Parkinson’s disease (PD) that could explain dysfunction in the motor circuit and be used for closed-loop deep brain stimulation (DBS). How these putative biomarkers change from the normal to the parkinsonian state across nodes in the motor circuit and within the same subject, however, remains unknown. In this study, we characterized how parkinsonism and vigilance altered oscillatory activity and PAC within the primary motor cortex (M1), subthalamic nucleus (STN), and globus pallidus (GP) in two nonhuman primates. Static and dynamic analyses of local field potential (LFP) recordings indicate that 1) after induction of parkinsonism using the neurotoxin MPTP, low-frequency power (8–30 Hz) increased in the STN and GP in both subjects, but increased in M1 in only one subject; 2) high-frequency power (~330 Hz) was present in the STN in both normal subjects but absent in the parkinsonian condition; 3) elevated PAC measurements emerged in the parkinsonian condition in both animals, but in different sites in each animal (M1 in one subject and GPe in the other); and 4) the state of vigilance significantly impacted how oscillatory activity and PAC were expressed in the motor circuit. These results support the hypothesis that changes in low- and high-frequency oscillatory activity and PAC are features of parkinsonian pathophysiology and provide evidence that closed-loop DBS systems based on these biomarkers may require subject-specific configurations as well as adaptation to changes in vigilance. NEW & NOTEWORTHY Chronically implanted electrodes were used to record neural activity across multiple nodes in the basal ganglia-thalamocortical circuit simultaneously in a nonhuman primate model of Parkinson’s disease, enabling within-subject comparisons of electrophysiological biomarkers between normal and parkinsonian conditions and different vigilance states. This study improves our understanding of the role of oscillatory activity and phase-amplitude coupling in the pathophysiology of Parkinson’s disease and supports the development of more effective DBS therapies based on pathophysiological biomarkers.


Author(s):  
Thomas Tarnaud ◽  
Wout Joseph ◽  
Ruben Schoeters ◽  
Luc Martens ◽  
Emmeric Tanghe

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.


2016 ◽  
Vol 23 (1) ◽  
pp. 76-86 ◽  
Author(s):  
Lin-Lin Gao ◽  
Jia-Rong Zhang ◽  
Piu Chan ◽  
Tao Wu

1989 ◽  
Vol 28 (03) ◽  
pp. 92-94 ◽  
Author(s):  
C. Neumann ◽  
H. Baas ◽  
R. Hefner ◽  
G. Hör

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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