| 1. |
- Fuentes, Romulo, et al.
(författare)
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Restoration of locomotive function in Parkinson's disease by spinal cord stimulation: mechanistic approach
- 2010
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 32:7, s. 1100-1108
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Tidskriftsartikel (refereegranskat)abstract
- Specific motor symptoms of Parkinson's disease (PD) can be treated effectively with direct electrical stimulation of deep nuclei in the brain. However, this is an invasive procedure, and the fraction of eligible patients is rather low according to currently used criteria. Spinal cord stimulation (SCS), a minimally invasive method, has more recently been proposed as a therapeutic approach to alleviate PD akinesia, in light of its proven ability to rescue locomotion in rodent models of PD. The mechanisms accounting for this effect are unknown but, from accumulated experience with the use of SCS in the management of chronic pain, it is known that the pathways most probably activated by SCS are the superficial fibers of the dorsal columns. We suggest that the prokinetic effect of SCS results from direct activation of ascending pathways reaching thalamic nuclei and the cerebral cortex. The afferent stimulation may, in addition, activate brainstem nuclei, contributing to the initiation of locomotion. On the basis of the striking change in the corticostriatal oscillatory mode of neuronal activity induced by SCS, we propose that, through activation of lemniscal and brainstem pathways, the locomotive increase is achieved by disruption of antikinetic low-frequency (< 30 Hz) oscillatory synchronization in the corticobasal ganglia circuits.
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| 2. |
- Fuentes, Romulo, et al.
(författare)
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Spinal Cord Stimulation Restores Locomotion in Animal Models of Parkinson's Disease
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 323:5921, s. 1578-1582
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine replacement therapy is useful for treating motor symptoms in the early phase of Parkinson's disease, but it is less effective in the long term. Electrical deep-brain stimulation is a valuable complement to pharmacological treatment but involves a highly invasive surgical procedure. We found that epidural electrical stimulation of the dorsal columns in the spinal cord restores locomotion in both acute pharmacologically induced dopamine-depleted mice and in chronic 6-hydroxydopamine-lesioned rats. The functional recovery was paralleled by a disruption of aberrant low-frequency synchronous corticostriatal oscillations, leading to the emergence of neuronal activity patterns that resemble the state normally preceding spontaneous initiation of locomotion. We propose that dorsal column stimulation might become an efficient and less invasive alternative for treatment of Parkinson's disease in the future.
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| 3. |
- Halje, Pär, et al.
(författare)
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Oscillations in cortico-basal ganglia circuits : implications for Parkinson's disease and other neurologic and psychiatric conditions
- 2019
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Ingår i: Journal of Neurophysiology. - : AMER PHYSIOLOGICAL SOC. - 0022-3077 .- 1522-1598. ; 122:1, s. 203-231
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Forskningsöversikt (refereegranskat)abstract
- Cortico-basal ganglia circuits are thought to play a crucial role in the selection and control of motor behaviors and have also been implicated in the processing of motivational content and in higher cognitive functions. During the last two decades, electro-physiological recordings in basal ganglia circuits have shown that several disease conditions are associated with specific changes in the temporal patterns of neuronal activity. In particular, synchronized oscillations have been a frequent finding suggesting that excessive synchronization of neuronal activity may be a pathophysiological mechanism involved in a wide range of neurologic and psychiatric conditions. We here review the experimental support for this hypothesis primarily in relation to Parkinson's disease but also in relation to dystonia, essential tremor, epilepsy, and psychosis/schizophrenia.
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| 4. |
- Moenne-Loccoz, Cristobal, et al.
(författare)
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Cortico-Striatal Oscillations Are Correlated to Motor Activity Levels in Both Physiological and Parkinsonian Conditions
- 2020
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Ingår i: Frontiers in Systems Neuroscience. - : Frontiers Media S.A.. - 1662-5137. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Oscillatory neural activity in the cortico-basal ganglia-thalamocortical (CBGTC) loop is associated with the motor state of a subject, but also with the availability of modulatory neurotransmitters. For example, increased low-frequency oscillations in Parkinson's disease (PD) are related to decreased levels of dopamine and have been proposed as biomarkers to adapt and optimize therapeutic interventions, such as deep brain stimulation. Using neural oscillations as biomarkers require differentiating between changes in oscillatory patterns associated with parkinsonism vs. those related to a subject's motor state. To address this point, we studied the correlation between neural oscillatory activity in the motor cortex and striatum and varying degrees of motor activity under normal and parkinsonian conditions. Using rats with bilateral or unilateral 6-hydroxydopamine lesions as PD models, we correlated the motion index (MI)-a measure based on the physical acceleration of the head of rats-to the local field potential (LFP) oscillatory power in the 1-80 Hz range. In motor cortices and striata, we observed a robust correlation between the motion index and the oscillatory power in two main broad frequency ranges: a low-frequency range [5.0-26.5 Hz] was negatively correlated to motor activity, whereas a high-frequency range [35.0-79.9 Hz] was positively correlated. We observed these correlations in both normal and parkinsonian conditions. In addition to these general changes in broad-band power, we observed a more restricted narrow-band oscillation [25-40 Hz] in dopamine-denervated hemispheres. This oscillation, which seems to be selective to the parkinsonian state, showed a linear frequency dependence on the concurrent motor activity level. We conclude that, independently of the parkinsonian condition, changes in broad-band oscillatory activities of cortico-basal ganglia networks (including changes in the relative power of low- and high-frequency bands) are closely correlated to ongoing motions, most likely reflecting he operations of these neural circuits to control motor activity. Hence, biomarkers based on neural oscillations should focus on specific features, such as narrow frequency bands, to allow differentiation between parkinsonian states and physiological movement-dependent circuit modulation.
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| 5. |
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| 6. |
- Petersson, Per, et al.
(författare)
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Basal ganglia oscillations as biomarkers for targeting circuit dysfunction in Parkinson's disease
- 2020
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Ingår i: Recent advances in Parkinson's disease. - : Elsevier. - 0079-6123 .- 1875-7855. - 9780444642608 ; , s. 525-557
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Bokkapitel (refereegranskat)abstract
- Oscillations are a naturally occurring phenomenon in highly interconnected dynamical systems. However, it is thought that excessive synchronized oscillations in brain circuits can be detrimental for many brain functions by disrupting neuronal information processing. Because synchronized basal ganglia oscillations are a hallmark of Parkinson's disease (PD), it has been suggested that aberrant rhythmic activity associated with symptoms of the disease could be used as a physiological biomarker to guide pharmacological and electrical neuromodulatory interventions. We here briefly review the various manifestations of basal ganglia oscillations observed in human subjects and in animal models of PD. In this context, we also review the evidence supporting a pathophysiological role of different oscillations for the suppression of voluntary movements as well as for the induction of excessive motor activity. In light of these findings, it is discussed how oscillations could be used to guide a more precise targeting of dysfunctional circuits to obtain improved symptomatic treatment of PD.
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| 7. |
- Santana, Maxwell B, et al.
(författare)
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Spinal cord stimulation alleviates motor deficits in a primate model of Parkinson disease.
- 2014
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273. ; 84:4, s. 716-722
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Tidskriftsartikel (refereegranskat)abstract
- Although deep brain electrical stimulation can alleviate the motor symptoms of Parkinson disease (PD), just a small fraction of patients with PD can take advantage of this procedure due to its invasive nature. A significantly less invasive method-epidural spinal cord stimulation (SCS)-has been suggested as an alternative approach for symptomatic treatment of PD. However, the mechanisms underlying motor improvements through SCS are unknown. Here, we show that SCS reproducibly alleviates motor deficits in a primate model of PD. Simultaneous neuronal recordings from multiple structures of the cortico-basal ganglia-thalamic loop in parkinsonian monkeys revealed abnormal highly synchronized neuronal activity within each of these structures and excessive functional coupling among them. SCS disrupted this pathological circuit behavior in a manner that mimics the effects caused by pharmacological dopamine replacement therapy or deep brain stimulation. These results suggest that SCS should be considered as an additional treatment option for patients with PD.
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