Pathological synchronisation in the subthalamic nucleus of patients with Parkinson's disease relates to both bradykinesia and rigidity

Kühn, Andrea A.; Tsui, Alexander; Aziz, Tipu Z.; Ray, Nicola; Brücke, Christof; Kupsch, Andreas; Schneider, Gerd‐Helge; Brown, Peter

doi:10.1016/j.expneurol.2008.11.008

Cited by 529 publications

(462 citation statements)

References 28 publications

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“…However, the present results showed that the discharge rates, bursting, and oscillatory activity in Vim in SCA were not different from those in ET, suggesting that ataxia may occur independent of changes in rate, burst, or oscillatory activity in Vim. The present results are in contrast to the disrupting patterns of background neural activity underlying akinesia/bradykinesia of Parkinson's disease 45, 46. Coherent oscillation underlies movement‐related activities within the motor system including the basal ganglia and cerebellar systems in the normal condition 47.…”

Section: Discussioncontrasting

confidence: 80%

Neuronal activity and outcomes from thalamic surgery for spinocerebellar ataxia

Hashimoto

Muralidharan

Yoshida

et al. 2017

Ann Clin Transl Neurol

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ObjectivesWe investigated the effects of deep brain stimulation (DBS) or lesions of the ventral intermediate nucleus (Vim) of the thalamus for spinocerebellar ataxia (SCA) and examined the pathophysiological role of neuronal activity of the Vim underlying ataxia.MethodsFive patients with SCA with cortical atrophy (ages 60‐69 years; 2 sporadic and three familial SCA) and five patients with essential tremor (ET) (ages 57–71 years) were treated with Vim surgery. Intraoperatively, we recorded neuronal activity from single neurons in the Vim thalamus while patients were at rest and compared the physiological properties of those neurons between patients with SCA and those with ET.ResultsPostsurgery mean scores for the Fahn–Tolosa–Marin Tremor Scale were improved from 78 to 44 in SCA patients and from 54 to 21 in ET patients. Stronger stimulation was necessary to optimize outcomes in SCA as compared to ET patients. We analyzed 68 Vim neurons in SCA and 60 Vim neurons in ET. Mean discharge rates, burst characteristics, and oscillatory activity were similar for both patient groups, however, we observed that the ratio of cells responding to passive manipulation was significantly smaller (P = 0.0001) in SCA (22%) than in ET (71%).InterpretationThalamic surgery led to a significant improvement in tremor in SCA patients. One potential mechanism underlying ataxia in SCA may be disruption of cerebellar sensory feedback, which modulates motor commands in the cerebello‐thalamo‐cortical network.

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Section: Discussioncontrasting

confidence: 80%

Neuronal activity and outcomes from thalamic surgery for spinocerebellar ataxia

Hashimoto

Muralidharan

Yoshida

et al. 2017

Ann Clin Transl Neurol

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“…To further evaluate the changes at specific frequency bands, we calculated the normalized spectrum before, during, and after laser stimulation. We found that optogenetic stimulation of SChIs robustly increased oscillation power across higher frequency bands conventionally defined as alpha (8)(9)(10)(11)(12)(13)(14)(15), beta (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), low gamma (30-60 Hz), and high gamma (60-100 Hz), but not lower frequency bands of delta (1-4 Hz) or theta (4-8 Hz) (Fig. 2 E and F; n = 7 mice).…”

Section: Resultsmentioning

confidence: 85%

“…Using conventionally defined frequency bands, we find SChI stimulation increased alpha oscillations (8-15 Hz) in striatum but not in M1. Interestingly, the PD motor symptoms of bradykinesia and rigidity are correlated with elevated beta oscillations in basal ganglia that can extend down to 8 Hz and, thus, includes the alpha frequency range (4,28).…”

Section: M1 Superficialmentioning

confidence: 99%

“…When compromised, these circuits contribute to neurological and psychiatric disorders, such as Parkinson's disease (PD). In PD, motor deficits correlate with the emergence of exaggerated beta frequency (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) oscillations throughout the CBT network. However, little is known about how specific cell types within individual CBT brain regions support the generation, propagation, and interaction of oscillatory dynamics throughout the CBT circuit or how specific oscillatory dynamics are related to motor function.…”

mentioning

confidence: 99%

“…striatum | optogenetics | beta oscillations | coherence | cholinergic interneurons E xaggerated beta oscillations (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) within the cortico-basal ganglia-thalamic (CBT) neural network are putative electrophysiological correlates of bradykinesia and rigidity in Parkinson's disease (PD) (1)(2)(3)(4). Therapies that effectively manage PD motor symptoms, such as dopamine replacement therapy and deep brain stimulation, are associated with a suppression of the exaggerated beta oscillations (4,5).…”

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confidence: 99%

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Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

Kondabolu

Roberts

Bucklin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cortico-basal ganglia-thalamic (CBT) neural circuits are critical modulators of cognitive and motor function. When compromised, these circuits contribute to neurological and psychiatric disorders, such as Parkinson's disease (PD). In PD, motor deficits correlate with the emergence of exaggerated beta frequency (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) oscillations throughout the CBT network. However, little is known about how specific cell types within individual CBT brain regions support the generation, propagation, and interaction of oscillatory dynamics throughout the CBT circuit or how specific oscillatory dynamics are related to motor function. Here, we investigated the role of striatal cholinergic interneurons (SChIs) in generating beta and gamma oscillations in cortical-striatal circuits and in influencing movement behavior. We found that selective stimulation of SChIs via optogenetics in normal mice robustly and reversibly amplified beta and gamma oscillations that are supported by distinct mechanisms within striatal-cortical circuits. Whereas beta oscillations are supported robustly in the striatum and all layers of primary motor cortex (M1) through a muscarinic-receptor mediated mechanism, gamma oscillations are largely restricted to the striatum and the deeper layers of M1. Finally, SChI activation led to parkinsonianlike motor deficits in otherwise normal mice. These results highlight the important role of striatal cholinergic interneurons in supporting oscillations in the CBT network that are closely related to movement and parkinsonian motor symptoms.E xaggerated beta oscillations (15-30 Hz) within the cortico-basal ganglia-thalamic (CBT) neural network are putative electrophysiological correlates of bradykinesia and rigidity in Parkinson's disease (PD) (1-4). Therapies that effectively manage PD motor symptoms, such as dopamine replacement therapy and deep brain stimulation, are associated with a suppression of the exaggerated beta oscillations (4, 5). Beta oscillations are also found in the CBT circuits of patients with other movement-related disorders, such as epilepsy and dystonia (6, 7), and in normal, nonhuman primates (8, 9) and normal rodents (10, 11). Moreover, brief elevations (≤200 ms) of beta oscillations are observed in the basal ganglia of task-performing nonhuman primates and rodents during specific phases of behavioral tasks (10, 12, 13), indicating that beta oscillations may be important for motor and nonmotor functions. In contrast to the regulated temporal variability of beta oscillations in normal motor functions, temporal stability is correlated with the parkinsonian motor symptoms of bradykinesia and rigidity (2). Together, these findings suggest that brief epochs of beta oscillations are a normal aspect of basal ganglia dynamics, their temporal modulation is important for movement regulation, and loss of regulation or uncontrolled expression of beta oscillations may contribute to movement deficits, such as those observed in PD.Despite the clear link bet...

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Lack of progression of beta dynamics after long‐term subthalamic neurostimulation

Anderson

Wilkins²,

Parker

et al. 2021

Ann Clin Transl Neurol

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Objective: To investigate the progression of neural and motor features of Parkinson's disease in a longitudinal study, after washout of medication and bilateral subthalamic nucleus deep brain stimulation (STN DBS). Methods: Participants with clinically established Parkinson's disease underwent bilateral implantation of DBS leads (18 participants, 13 male) within the STN using standard functional frameless stereotactic technique and multi-pass microelectrode recording. Both DBS leads were connected to an implanted investigative sensing neurostimulator (Activa TM PC + S, Medtronic, PLC). Resting state STN local field potentials (LFPs) were recorded and motor disability, (the Movement Disorder Society-Unified Parkinson's Disease Rating Scalemotor subscale, MDS-UPDRS III) was assessed off therapy at initial programming, and after 6 months, 1 year, and yearly out to 5 years of treatment. The primary endpoint was measured at 3 years. At each visit, medication had been held for over 12/ 24 h and DBS was turned off for at least 60 min, by which time LFP spectra reached a steady state. Results: After 3 years of chronic DBS, there were no increases in STN beta band dynamics (p = 0.98) but there were increases in alpha band dynamics (p = 0.0027, 25 STNs). Similar results were observed in a smaller cohort out to 5 years. There was no increase in the MDS-UPDRS III score. Interpretation: These findings provide evidence that the beta oscillopathy does not substantially progress following combined STN DBS plus medication in moderate to advanced Parkinson's disease.

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Pathological synchronisation in the subthalamic nucleus of patients with Parkinson's disease relates to both bradykinesia and rigidity

Cited by 529 publications

References 28 publications

Neuronal activity and outcomes from thalamic surgery for spinocerebellar ataxia

Neuronal activity and outcomes from thalamic surgery for spinocerebellar ataxia

Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

Lack of progression of beta dynamics after long‐term subthalamic neurostimulation

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