Dataset Information

Tremor in the Degenerative Cerebellum: Towards the Understanding of Brain Circuitry for Tremor.

ABSTRACT: Cerebellar degenerative pathology has been identified in tremor patients; however, how the degenerative pathology could contribute to tremor remains unclear. If the cerebellar degenerative pathology can directly drive tremor, one would hypothesize that tremor is likely to occur in the diseases of cerebellar ataxia and follows the disease progression in such disorders. To further test this hypothesis, we studied the occurrence of tremor in different disease stages of classical cerebellar degenerative disorders: spinocerebellar ataxias (SCAs). We further separately analyzed postural tremor and rest tremor, two forms of tremor that both involve the cerebellum. We also explored tremor in different subtypes of SCAs. We found that 18.1% of SCA patients have tremor. Interestingly, SCA patients with tremor have worse ataxia than those without tremor. When stratifying patients into mild, moderate, and severe disease stages according to the severity of ataxia, moderate and severe SCA patients more commonly have tremor than those with mild ataxia, the effect most prominently observed in postural tremor of SCA3 and SCA6 patients. Finally, tremor can independently contribute to worse functional status in SCA2 patients, even after adjusting for ataxia severity. Tremor is more likely to occur in the severe stage of cerebellar degeneration when compared to mild stages. Our results partially support the cerebellar degenerative model of tremor.

SUBMITTER: Lai RY

PROVIDER: S-EPMC6520148 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Tremor in the Degenerative Cerebellum: Towards the Understanding of Brain Circuitry for Tremor.

Lai Ruo-Yah RY Tomishon Darya D Figueroa Karla P KP Pulst Stefan M SM Perlman Susan S Wilmot George G Gomez Christopher M CM Schmahmann Jeremy D JD Paulson Henry H Shakkottai Vikram G VG Ying Sarah H SH Zesiewicz Theresa T Bushara Khalaf K Geschwind Michael M Xia Guangbin G Subramony S H SH Ashizawa Tetsuo T Kuo Sheng-Han SH

Cerebellum (London, England) 20190601 3

Cerebellar degenerative pathology has been identified in tremor patients; however, how the degenerative pathology could contribute to tremor remains unclear. If the cerebellar degenerative pathology can directly drive tremor, one would hypothesize that tremor is likely to occur in the diseases of cerebellar ataxia and follows the disease progression in such disorders. To further test this hypothesis, we studied the occurrence of tremor in different disease stages of classical cerebellar degenera ...[more]

PMID: 30830673

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Project description:There is a clinically unmet need for a neuropsychological tool that reflects the pathophysiology of cognitive dysfunction in cerebellar degeneration. We investigated cognitive flexibility in degenerative cerebellar ataxia patients and aim to identify the pathophysiological correlates of cognitive dysfunction in relation to cerebellar cognitive circuits. We prospectively enrolled degenerative cerebellar ataxia patients with age-matched healthy controls who underwent 3 T 3D and resting-state functional MRI. All 56 participants were evaluated with the Scale for Assessment and Rating of Ataxia and neuropsychological tests including the Wisconsin Card Sorting Test, Trail Making Test, Montreal Cognitive Assessment and Mini-Mental State Examination. From MRI scans, we analysed the correlation of whole-brain volume and cortico-cerebellar functional connectivity with the Wisconsin Card Sorting Test performances. A total of 52 participants (29 ataxia patients and 23 healthy controls) were enrolled in this study. The Wisconsin Card Sorting Test scores (total error percentage, perseverative error percentage, non-perseverative error percentage and categories completed), Trail Making Test A and Montreal Cognitive Assessment were significantly impaired in ataxia patients (P < 0.05) compared to age-matched healthy controls. The Wisconsin Card Sorting Test error scores showed a significant correlation with the ataxia score (P < 0.05) controlling for age and sex. In volumetric analysis, the cerebellar right crus I, II, VIIb and VIII atrophy correlated with non-perseverative error percentage in the ataxia group. In functional connectivity analysis, the connectivity between crus I, II and VIIb of the cerebellum and bilateral superior parietal and superior temporal gyrus was significantly altered in ataxia patients. The functional connectivity between left crus II and VIIb of the cerebellum and dorsolateral prefrontal and superior frontal/parietal cortices showed a positive correlation with perseverative error percentage. The connectivity between left crus VIIb and pontine nucleus/middle cerebellar peduncle showed a significant negative correlation with non-perseverative error percentage in the ataxia group. The impaired cognitive flexibility represented by the Wisconsin Card Sorting Test was significantly impaired in degenerative cerebellar ataxia patients and correlated with disease severity. The Wisconsin Card Sorting Test performance reflects hypoactivity of the cognitive cerebellum and disrupted cortico-cerebellar connectivity in non-demented patients with degenerative cerebellar ataxia.

Project description:This work presents the first simulation of a large-scale, bio-physically constrained cerebellum model performed on neuromorphic hardware. A model containing 97,000 neurons and 4.2 million synapses is simulated on the SpiNNaker neuromorphic system. Results are validated against a baseline simulation of the same model executed with NEST, a popular spiking neural network simulator using generic computational resources and double precision floating point arithmetic. Individual cell and network-level spiking activity is validated in terms of average spike rates, relative lead or lag of spike times, and membrane potential dynamics of individual neurons, and SpiNNaker is shown to produce results in agreement with NEST. Once validated, the model is used to investigate how to accelerate the simulation speed of the network on the SpiNNaker system, with the future goal of creating a real-time neuromorphic cerebellum. Through detailed communication profiling, peak network activity is identified as one of the main challenges for simulation speed-up. Propagation of spiking activity through the network is measured, and will inform the future development of accelerated execution strategies for cerebellum models on neuromorphic hardware. The large ratio of granule cells to other cell types in the model results in high levels of activity converging onto few cells, with those cells having relatively larger time costs associated with the processing of communication. Organizing cells on SpiNNaker in accordance with their spatial position is shown to reduce the peak communication load by 41%. It is hoped that these insights, together with alternative parallelization strategies, will pave the way for real-time execution of large-scale, bio-physically constrained cerebellum models on SpiNNaker. This in turn will enable exploration of cerebellum-inspired controllers for neurorobotic applications, and execution of extended duration simulations over timescales that would currently be prohibitive using conventional computational platforms.

Dataset Information

Tremor in the Degenerative Cerebellum: Towards the Understanding of Brain Circuitry for Tremor.

Publications

Tremor in the Degenerative Cerebellum: Towards the Understanding of Brain Circuitry for Tremor.

Similar Datasets

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