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The differentiated networks related to essential tremor onset and its amplitude modulation after alcohol intake.

ABSTRACT: The dysregulation of endogenous rhythms within brain networks have been implicated in a broad range of motor and non-motor pathologies. Essential tremor (ET), classically the purview of a single aberrant pacemaker, has recently become associated with network-level dysfunction across multiple brain regions. Specifically, it has been suggested that motor cortex constitutes an important node in a tremor-generating network involving the cerebellum. Yet the mechanisms by which these regions relate to tremor remain a matter of considerable debate. We sought to discriminate the contributions of cerebral and cerebellar dysregulation by combining high-density electroencephalography with subject-specific structural MRI. For that, we contrasted ET with voluntary (mimicked) tremor before and after ingestion of alcohol to regulate the tremorgenic networks. Our results demonstrate distinct loci of cortical tremor coherence, most pronounced over the sensorimotor cortices in healthy controls, but more frontal motor areas in ET-patients consistent with a heightened involvement of the supplementary motor area. We further demonstrate that the reduction in tremor amplitude associated with alcohol intake is reflected in altered cerebellar - but not cerebral - coupling with movement. Taken together, these findings implicate tremor emergence as principally associated with increases in activity within frontal motor regions, whereas modulation of the amplitude of established tremor relates to changes in cerebellar activity. These findings progress a mechanistic understanding of ET and implicate network-level vulnerabilities in the rhythmic nature of communication throughout the brain.

SUBMITTER: Pedrosa DJ

PROVIDER: S-EPMC5584663 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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The differentiated networks related to essential tremor onset and its amplitude modulation after alcohol intake.

Pedrosa David J DJ Nelles Christian C Brown Peter P Volz Lukas J LJ Pelzer Esther A EA Tittgemeyer Marc M Brittain John-Stuart JS Timmermann Lars L

Experimental neurology 20170725

The dysregulation of endogenous rhythms within brain networks have been implicated in a broad range of motor and non-motor pathologies. Essential tremor (ET), classically the purview of a single aberrant pacemaker, has recently become associated with network-level dysfunction across multiple brain regions. Specifically, it has been suggested that motor cortex constitutes an important node in a tremor-generating network involving the cerebellum. Yet the mechanisms by which these regions relate to ...[more]

PMID: 28754506

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Project description:ObjectiveDeep brain stimulation is a treatment for medically refractory essential tremor. To improve the therapy, closed-loop approaches are designed to deliver stimulation according to the system's state, which is constantly monitored by recording a pathological signal associated with symptoms (e.g. brain signal or limb tremor). Since the space of possible closed-loop stimulation strategies is vast and cannot be fully explored experimentally, how to stimulate according to the state should be informed by modeling. A typical modeling goal is to design a stimulation strategy that aims to maximally reduce the Hilbert amplitude of the pathological signal in order to minimize symptoms. Isostables provide a notion of amplitude related to convergence time to the attractor, which can be beneficial in model-based control problems. However, how isostable and Hilbert amplitudes compare when optimizing the amplitude response to stimulation in models constrained by data is unknown.ApproachWe formulate a simple closed-loop stimulation strategy based on models previously fitted to phase-locked deep brain stimulation data from essential tremor patients. We compare the performance of this strategy in suppressing oscillatory power when based on Hilbert amplitude and when based on isostable amplitude. We also compare performance to phase-locked stimulation and open-loop high-frequency stimulation.Main resultsFor our closed-loop phase space stimulation strategy, stimulation based on isostable amplitude is significantly more effective than stimulation based on Hilbert amplitude when amplitude field computation time is limited to minutes. Performance is similar when there are no constraints, however constraints on computation time are expected in clinical applications. Even when computation time is limited to minutes, closed-loop phase space stimulation based on isostable amplitude is advantageous compared to phase-locked stimulation, and is more efficient than high-frequency stimulation.SignificanceOur results suggest a potential benefit to using isostable amplitude more broadly for model-based optimization of stimulation in neurological disorders.

Project description:Essential tremor (ET) is among the most common neurological diseases and it often runs in families. How knowledgeable ET patients and their families are about their disease has been the subject of surprisingly little scholarship.To fill this gap in knowledge, we administered a comprehensive 32-item survey (i.e., questions about etiology, pathophysiology, symptoms and signs, natural history, and treatments) to 427 participants, including 76 ET probands, 74 affected relatives (AFRs), 238 unaffected relatives, and 39 spouses of unaffected relatives, all of whom were participating in two ET family studies. We hypothesized that there would be gaps in knowledge about ET and furthermore, that probands and AFRs would be the most knowledgeable, followed by unaffected relatives and then spouses of unaffected relatives, who would be the least knowledgeable.Overall, ET patients lacked knowledge about their disease. Nearly one-third of probands answered "yes" or "do not know" to the question, "is ET the same or different from the type of tremor that many normal people can get when they become old and frail?" A similar proportion did not know whether children could get ET or they responded "no." Nearly one-fourth of affecteds (i.e., probands and AFRs) did not know whether or to what degree (e.g., very well, moderately well, not well) the symptoms of ET could be medically controlled, and 38.0% either reported that there was no brain surgery for ET or reported that they did not know. Nearly 17% of affecteds did not endorse genes as a cause for ET, which was surprising given the fact that this was a family study of ET. Probands and AFRs were the most knowledgeable, followed by unaffected relatives. Spouses of unaffected relatives were the least knowledgeable.We targeted a large group of ET patients and their families, as this group is perhaps most likely to be informed about the disease. ET patients and their AFRs were more knowledgeable about the features of ET than their family members without ET. Overall, however, knowledge of ET was very limited and this lack of knowledge encompassed all aspects of the disease including its underlying causes, the nature of the symptoms and signs, its natural history and its treatment. Further ET awareness education and programs targeting both families of ET patients and the public would help alleviate this gap in knowledge.

Dataset Information

The differentiated networks related to essential tremor onset and its amplitude modulation after alcohol intake.

Publications

The differentiated networks related to essential tremor onset and its amplitude modulation after alcohol intake.

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