Deep brain stimulation for movement disorder treatment: exploring frequency-dependent efficacy in a computational network model

AbstractA large-scale computational model of the basal ganglia network and thalamus is proposed to describe movement disorders and treatment effects of deep brain stimulation (DBS). The model of this complex network considers three areas of the basal ganglia region: the subthalamic nucleus (STN) as target area of DBS, the globus pallidus, both pars externa and pars interna (GPe-GPi), and the thalamus. Parkinsonian conditions are simulated by assuming reduced dopaminergic input and corresponding pronounced inhibitory or disinhibited projections to GPe and GPi. Macroscopic quantities are derived which correlate closely to thalamic responses and hence motor programme fidelity. It can be demonstrated that depending on different levels of striatal projections to the GPe and GPi, the dynamics of these macroscopic quantities (synchronisation index, mean synaptic activity and response efficacy) switch from normal to Parkinsonian conditions. Simulating DBS of the STN affects the dynamics of the entire network, increasing the thalamic activity to levels close to normal, while differing from both normal and Parkinsonian dynamics. Using the mentioned macroscopic quantities, the model proposes optimal DBS frequency ranges above 130 Hz.

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Deep Brain Stimulation rescues memory and synaptic activity in a rat model of global ischemia

Journal of Neuroscience ◽

10.1523/jneurosci.1222-18.2019 ◽

2019 ◽

pp. 1222-18 ◽

Cited By ~ 1

Author(s):

Elise Gondard ◽

Lucy Teves ◽

Lihua Wang ◽

Chris McKinnon ◽

Clement Hamani ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Rat Model ◽

Global Ischemia ◽

Synaptic Activity ◽

Deep Brain

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Deep brain stimulation of the subthalamic nucleus reestablishes neuronal information transmission in the 6-OHDA rat model of parkinsonism

Journal of Neurophysiology ◽

10.1152/jn.00713.2013 ◽

2014 ◽

Vol 111 (10) ◽

pp. 1949-1959 ◽

Cited By ~ 29

Author(s):

Alan D. Dorval ◽

Warren M. Grill

Keyword(s):

Deep Brain Stimulation ◽

Basal Ganglia ◽

Information Transmission ◽

Brain Stimulation ◽

Rat Model ◽

Information Transfer ◽

Firing Pattern ◽

Signal Propagation ◽

Neuronal Firing ◽

Deep Brain

Pathophysiological activity of basal ganglia neurons accompanies the motor symptoms of Parkinson's disease. High-frequency (>90 Hz) deep brain stimulation (DBS) reduces parkinsonian symptoms, but the mechanisms remain unclear. We hypothesize that parkinsonism-associated electrophysiological changes constitute an increase in neuronal firing pattern disorder and a concomitant decrease in information transmission through the ventral basal ganglia, and that effective DBS alleviates symptoms by decreasing neuronal disorder while simultaneously increasing information transfer through the same regions. We tested these hypotheses in the freely behaving, 6-hydroxydopamine-lesioned rat model of hemiparkinsonism. Following the onset of parkinsonism, mean neuronal firing rates were unchanged, despite a significant increase in firing pattern disorder (i.e., neuronal entropy), in both the globus pallidus and substantia nigra pars reticulata. This increase in neuronal entropy was reversed by symptom-alleviating DBS. Whereas increases in signal entropy are most commonly indicative of similar increases in information transmission, directed information through both regions was substantially reduced (>70%) following the onset of parkinsonism. Again, this decrease in information transmission was partially reversed by DBS. Together, these results suggest that the parkinsonian basal ganglia are rife with entropic activity and incapable of functional information transmission. Furthermore, they indicate that symptom-alleviating DBS works by lowering the entropic noise floor, enabling more information-rich signal propagation. In this view, the symptoms of parkinsonism may be more a default mode, normally overridden by healthy basal ganglia information. When that information is abolished by parkinsonian pathophysiology, hypokinetic symptoms emerge.

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Deep-brain stimulation for basal ganglia disorders

Basal Ganglia ◽

10.1016/j.baga.2011.05.001 ◽

2011 ◽

Vol 1 (2) ◽

pp. 65-77 ◽

Cited By ~ 52

Author(s):

Thomas Wichmann ◽

Mahlon R. DeLong

Keyword(s):

Deep Brain Stimulation ◽

Basal Ganglia ◽

Brain Stimulation ◽

Basal Ganglia Disorders ◽

Deep Brain

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Basal ganglia local field potentials: applications in the development of new deep brain stimulation devices for movement disorders

Expert Review of Medical Devices ◽

10.1586/17434440.4.5.605 ◽

2007 ◽

Vol 4 (5) ◽

pp. 605-614 ◽

Cited By ~ 46

Author(s):

Sara Marceglia ◽

Lorenzo Rossi ◽

Guglielmo Foffani ◽

AnnaMaria Bianchi ◽

Sergio Cerutti ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Basal Ganglia ◽

Local Field ◽

Brain Stimulation ◽

Movement Disorders ◽

Local Field Potentials ◽

Field Potentials ◽

Deep Brain

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Pediatric Deep Brain Stimulation Using Awake Recording and Stimulation for Target Selection in an Inpatient Neuromodulation Monitoring Unit

Brain Sciences ◽

10.3390/brainsci8070135 ◽

2018 ◽

Vol 8 (7) ◽

pp. 135 ◽

Cited By ~ 9

Author(s):

Terence D. Sanger ◽

Mark Liker ◽

Enrique Arguelles ◽

Ruta Deshpande ◽

Arash Maskooki ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Basal Ganglia ◽

Brain Stimulation ◽

Rating Scale ◽

Target Selection ◽

Test Stimulation ◽

Depth Electrodes ◽

A New Technique ◽

High Degree ◽

Deep Brain

Deep brain stimulation (DBS) for secondary (acquired, combined) dystonia does not reach the high degree of efficacy achieved in primary (genetic, isolated) dystonia. We hypothesize that this may be due to variability in the underlying injury, so that different children may require placement of electrodes in different regions of basal ganglia and thalamus. We describe a new targeting procedure in which temporary depth electrodes are placed at multiple possible targets in basal ganglia and thalamus, and probing for efficacy is performed using test stimulation and recording while children remain for one week in an inpatient Neuromodulation Monitoring Unit (NMU). Nine Children with severe secondary dystonia underwent the NMU targeting procedure. In all cases, 4 electrodes were implanted. We compared the results to 6 children who had previously had 4 electrodes implanted using standard intraoperative microelectrode targeting techniques. Results showed a significant benefit, with 80% of children with NMU targeting achieving greater than 5-point improvement on the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), compared with 50% of children using intraoperative targeting. NMU targeting improved BFMDRS by an average of 17.1 whereas intraoperative targeting improved by an average of 10.3. These preliminary results support the use of test stimulation and recording in a Neuromodulation Monitoring Unit (NMU) as a new technique with the potential to improve outcomes following DBS in children with secondary (acquired) dystonia. A larger sample size will be needed to confirm these results.

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