Dynamic Activity Model of Movement Disorders: The Fundamental Role of the <i>Hyperdirect</i> Pathway

Nambu, Atsushi; Chiken, Satomi; Sano, Hiromi; Hatanaka, Nobuhiko; Obeso, José A.

doi:10.1002/mds.29646

Cited by 9 publications

(3 citation statements)

References 40 publications

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“…How do the results in the present study fit in with models of basal ganglia function? Both the ‘firing rate model’ (Albin et al, 1989) and the ‘dynamic activity model’ (Nambu et al, 2023) rely on an inhibition of basal ganglia output activity to facilitate movement. When solely considering the average population activity we did not find that movement periods exhibited a statistically significant lower activity ( Fig.…”

Section: Discussionmentioning

confidence: 99%

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Basal ganglia output coding - entopeduncular nucleus - of contextual kinematics and reward in the freely moving mouse

Verma-Rodríguez,

Ramírez-Jarquín,

Rossi-Pool

et al. 2024

Preprint

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The entopeduncular nucleus (EPN) is often termed as one of the output nuclei of the basal ganglia owing to their highly convergent anatomy. The rodent EPN has been implicated in reward and value coding whereas the primate analogue internal Globus Pallidus has been found to be modulated by some movements and in some circumstances. In this study we sought to understand how the rodent EPN might be coding kinematic, reward, and value parameters, particularly during locomotion. Furthermore, we aimed to understand the level of movement representation: whole-body or specific body parts. To this end, mice were trained in a freely moving two-alternative forced choice task with two periods of displacement (Return and Go trajectories) and performed electrophysiological recordings together with video-based tracking. We found 1) robust reward, but not value, coding. 2) Spatio-temporal variables better explain EPN activity during movement compared to kinematic variables, while both types of variables were more robustly represented in reward-related movement. 3) Reward sensitive units encode kinematics similarly to reward insensitive ones. 4) Population dynamics that best account for differences between these two periods of movement can be explained by allocentric references like distance to reward port. 5) The representation of paw and licks is not mutually exclusive, discarding a somatotopic muscle-level representation of movement in the EPN. Our data suggest that EPN activity represents movements and reward in a complex way: highly multiplexed, influenced by the objective of the displacement, where trajectories that lead to reward better represent spatial and kinematic variables. Interestingly, there are intertwining representations of whole-body movement kinematics with single paw and licking variables. Further, reward and kinematic coding are not mutually exclusive, challenging the notion of distinct pathways for reward and movement processing.

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Section: Discussionmentioning

confidence: 99%

“…On the other hand, current theories of the overall function of the basal ganglia, like the ‘rate theory’ (Albin et al, 1989)or the ‘dynamic activity model’ (Nambu et al, 2023), posit that the firing rate of the output nuclei is inversely related to movement facilitation.…”

Section: Introductionmentioning

confidence: 99%

Basal ganglia output coding - entopeduncular nucleus - of contextual kinematics and reward in the freely moving mouse

Verma-Rodríguez,

Ramírez-Jarquín,

Rossi-Pool

et al. 2024

Preprint

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show abstract

“…In conditions like Parkinson's disease, abnormal rhythms, particularly in the β-band frequency, disrupt the basal ganglia-thalamocortical circuits, leading to motor symptoms. Conversely, higher frequency oscillations may be associated with normal functions [12][13][14].…”

Section: Discussionmentioning

confidence: 99%

Hyperkinetic and Hypokinetic Movement Disorders in SSPE: A Systematic Review of Case Reports and Case Series

Garg,

Pandey,

Malhotra

et al. 2024

TOHM

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Background: Subacute Sclerosing Panencephalitis (SSPE) typically presents with periodic myoclonus; however, a spectrum of movement disorders including dystonia, chorea, tremor, and parkinsonism have also been described. This review aims to evaluate the array of movement disorders in SSPE, correlating them with neuroimaging findings, disease stages, and patient outcomes. Methods: A comprehensive review of published case reports and case series was conducted on patients with SSPE exhibiting movement disorders other than periodic myoclonus. PRISMA guidelines were followed, and the protocol was registered with PROSPERO (2023 CRD42023434650). A comprehensive search of multiple databases yielded 37 reports detailing 39 patients. Dyken’s criteria were used for SSPE diagnosis, and the International Movement Disorders Society definitions were applied to categorize movement disorders. Results: The majority of patients were male, with an average age of 13.8 years. Approximately, 80% lacked a reliable vaccination history, and 39% had prior measles infections. Dystonia was the most common movement disorder (49%), followed by parkinsonism and choreoathetosis. Rapid disease progression was noted in 64% of cases, with a disease duration of ≤6 months in 72%. Neuroimaging showed T2/FLAIR MR hyperintensities, primarily periventricular, with 26% affecting the basal ganglia/thalamus. Brain biopsies revealed inflammatory and neurodegenerative changes. Over half of the patients (56%) reached an akinetic mute state or died. Conclusion: SSPE is associated with diverse movement disorders, predominantly hyperkinetic. The prevalence of dystonia suggests basal ganglia dysfunction.

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Corticospinal excitability at rest outside of a task does not differ from task intertrial intervals in healthy adults

Bakken,

Horton,

Fisher

et al. 2024

Exp Brain Res

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Dynamic Activity Model of Movement Disorders: The Fundamental Role of the Hyperdirect Pathway

Cited by 9 publications

References 40 publications

Basal ganglia output coding - entopeduncular nucleus - of contextual kinematics and reward in the freely moving mouse

Basal ganglia output coding - entopeduncular nucleus - of contextual kinematics and reward in the freely moving mouse

Hyperkinetic and Hypokinetic Movement Disorders in SSPE: A Systematic Review of Case Reports and Case Series

Corticospinal excitability at rest outside of a task does not differ from task intertrial intervals in healthy adults

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