Beyond the Basal Ganglia

Miocinovic, Svjetlana

doi:10.1001/jamaneurol.2013.4643

Cited by 3 publications

(3 citation statements)

References 12 publications

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“…Although PD originates from dysfunction of the basal ganglia circuitry, the fact that in our study, delivery of randomized microcurrents directly onto the motor cortex could generate beneficial effect supports our speculation that the motor cortex is a potential therapeutic target [21,22]. Indeed, in our study, we mimicked the effects of stochastic antidromic spikes that our group identified in experimental DBS on PD rats [18].…”

Section: Discussionsupporting

confidence: 70%

“…Since these antidromic spikes are random, they can disrupt the synchronized firing of the motor cortical neurons and in principle could serve as a powerful means to relieve motor symptoms from the pathological rhythm [18][19][20]. Therefore, the motor cortex could be a potential target in the treatment of PD [21,22]. Here we conducted a proof-of-principle study of this notion.…”

Section: Introductionmentioning

confidence: 97%

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Randomized cortical stimulation could ameliorate locomotive inability in Parkinsonian rats: a pilot study

Peng

Liu

Yao

et al. 2020

Biomed. Phys. Eng. Express

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Objective: Parkinson's disease (PD) is a neurodegenerative disease for which there is no known cure. Deep brain stimulation (DBS) is a surgical treatment effective in reducing motor symptoms for PD patients. Previous work implicates DBS may directly influence motor cortex through stochastic antidromic spikes originating from the site of stimulation. Here we tested the hypothesis that direct randomized cortical stimulation is therapeutically effective in PD animal models. Approach: As a proof-of-principle study, we utilized a multi-channel stimulating system to mimic the effects of stochastic antidromic activation on the motor cortex of rat, by delivering microcurrents randomized temporally and spatially, and assessed the efficacy in ameliorating motor symptoms in a rat PD model. Main results: We found that different combinations of frequency, amplitude and pulse width of randomized electrical currents delivered to the motor cortex exerted different effects on Parkinsonian rats. Among these, some stimulus patterns, defined by specific ranges of pulse width and stimulation frequencies, were able to produce transient beneficial effect on locomotive ability assessed by openfield locomotor activities. These results indicate that, in principle, cortical stimulation could achieve therapeutic outcome in PD. Significance: Direct cortical simulation based on a randomized protocol could be a less invasive approach than standard DBS in treating Parkinsonism. More refined mode of stimulation to achieve long-lasting and more robust effect should be explored.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 97%

Randomized cortical stimulation could ameliorate locomotive inability in Parkinsonian rats: a pilot study

Peng

Liu

Yao

et al. 2020

Biomed. Phys. Eng. Express

View full text Add to dashboard Cite

show abstract

“…Recently, researchers have been looking at motor cortex activity when attempting to regulate motor function with DBS [ 35 ]. An emerging hypothesis is that the benefit of DBS is derived from direct modulation of primary motor cortex (M1) as observed in non-human primate, where STN DBS influenced both motor performance and M1 neuronal activity systematically according to stimulus intensity [ 36 ].…”

Section: Reviewmentioning

confidence: 99%

Update on deep brain stimulation in Parkinson’s disease

Martínez-Ramírez

Bona

et al. 2015

Transl Neurodegener

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Deep brain stimulation (DBS) is considered a safe and well tolerated surgical procedure to alleviate Parkinson’s disease (PD) and other movement disorders symptoms along with some psychiatric conditions. Over the last few decades DBS has been shown to provide remarkable therapeutic effect on carefully selected patients. Although its precise mechanism of action is still unknown, DBS improves motor functions and therefore quality of life. To date, two main targets have emerged in PD patients: the globus pallidus pars interna and the subthalamic nucleus. Two other targets, the ventralis intermedius and zona incerta have also been selectively used, especially in tremor-dominant PD patients. The main indications for PD DBS have traditionally been motor fluctuations, debilitating medication induced dyskinesias, unpredictable “off time” state, and medication refractory tremor. Medication refractory tremor and intolerable dyskinesia are potential palliative indications. Besides aforementioned targets, the brainstem pedunculopontine nucleus (PPN) is under investigation for the treatment of ON-state freezing of gait and postural instability. In this article, we will review the most recent literature on DBS therapy for PD, including cutting-edge advances and data supporting the role of DBS in advanced neural-network modulation.

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Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation

Kumaravelu

Oza

Behrend

et al. 2018

Journal of Neurophysiology

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Parkinson's disease is associated with altered neural activity in the motor cortex. Chronic high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in suppressing parkinsonian motor symptoms and modulates cortical activity. However, the anatomical pathways responsible for STN DBS-mediated cortical modulation remain unclear. Cortical evoked potentials (cEP) generated by STN DBS reflect the response of cortex to subcortical stimulation, and the goal of this study was to determine the neural origin of STN DBS-generated cEP using a two-step approach. First, we recorded cEP over ipsilateral primary motor cortex during different frequencies of STN DBS in awake healthy and unilateral 6-OHDA-lesioned parkinsonian rats. Second, we used a detailed, biophysically based model of the thalamocortical network to deconstruct the neural origin of the recorded cEP. The in vivo cEP included short (R1)-, intermediate (R2)-, and long-latency (R3) responses. Model-based cortical responses to simulated STN DBS matched remarkably well the in vivo responses. The short-latency response was generated by antidromic activation of layer 5 pyramidal neurons, whereas recurrent activation of layer 5 pyramidal neurons via excitatory axon collaterals reproduced the intermediate-latency response. The long-latency response was generated by polysynaptic activation of layer 2/3 pyramidal neurons via the cortico-thalamic-cortical pathway. Antidromic activation of the hyperdirect pathway and subsequent intracortical and cortico-thalamo-cortical synaptic interactions were sufficient to generate cortical potential evoked by STN DBS, and orthodromic activation through basal ganglia-thalamus-cortex pathways was not required. These results demonstrate the utility of cEP to determine the neural elements activated by STN DBS that might modulate cortical activity and contribute to the suppression of parkinsonian symptoms. NEW & NOTEWORTHY Subthalamic nucleus (STN) deep brain stimulation (DBS) is increasingly used to treat Parkinson's disease (PD). Cortical potentials evoked by STN DBS in patients with PD exhibit consistent short-latency (1-3 ms), intermediate-latency (5-15 ms), and long-latency (18-25 ms) responses. The short-latency response occurs as a result of antidromic activation of the hyperdirect pathway comprising corticosubthalamic axons. However, the neural origins of intermediate- and long-latency responses remain elusive, and the dominant view is that these are produced through the orthodromic pathway (basal ganglia-thalamus-cortex). By combining in vivo electrophysiology with computational modeling, we demonstrate that antidromic activation of the cortico-thalamic-cortical pathway is sufficient to generate the intermediate- and long-latency cortical responses to STN DBS.

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Beyond the Basal Ganglia

Cited by 3 publications

References 12 publications

Randomized cortical stimulation could ameliorate locomotive inability in Parkinsonian rats: a pilot study

Randomized cortical stimulation could ameliorate locomotive inability in Parkinsonian rats: a pilot study

Update on deep brain stimulation in Parkinson’s disease

Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation

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