Objective: This study aimed to better understand the mechanism underlying the pathological brain activity observed in essential tremor (ET) and the effect of thalamic deep brain stimulation (DBS) on such activity. 

Background: ET is the most common movement disorder and affects up to one percent of adults over 40 years. While the mechanisms underlying ET are unknown, some malfunction of the cerebellar-thalamocortical network, such as pathological oscillations, has been implicated. DBS is an effective clinical therapy used to alleviate the symptoms of ET, with the most common region targeted being the ventralis intermedius (Vim) nucleus of the thalamus. However, despite the benefits of DBS, the neurophysiological changes which are induced to lead to the therapeutic effect remains to be understood. In addition, during the procedure, the pathological neural activity can be recorded to better understand the pathology and the effect of stimulation. 

Methods: The pathological brain activity was recorded intra-operatively via implanted DBS electrodes in the form of local field potentials (LFP), whilst simultaneously recording muscle activity in the corresponding limbs using EMG during three behavioural epochs: rest, maintained posture and movement. We then modelled the cerebellar-thalamocortical network using the Wilson-Cowan approach. This framework models each brain region as a single population of neurons and allows the weights between populations to be altered.

Results: The electrophysiological data showed that the LFP-EMG coherence peaked in the tremor range, and that this was more pronounced during epochs where the patients maintained a posture. Furthermore, our computational model exhibited oscillatory behaviour in the same frequency range, and applying an input to thalamus to mimic DBS, we were able to suppress such oscillations by switching the big amplitude pathological activity to small amplitude high frequency activity.

Conclusions: Our study demonstrates that the cerebellar-thalamocortical network has the dynamics to support large amplitude tremor-band oscillations and that high, but not low-frequency DBS changes this network activity, which may be one of the mechanisms through which DBS is effective.

This work has been previously presented at  MecBioeng 2014, the 2015 Computational Neuroscience Meeting and Neuroinformatics 2016 resulting in a published abstract [1]. The work has been accepted for publication [2]. 

References: Yousif N, Mace M, Pavese N, Nandi D, Borisyuk R and Bain P (2016). A Wilson-Cowan model of oscillatory activity in essential tremor. Front. Neuroinform. Conference Abstract: Neuroinformatics 2016.

N Yousif, M Mace, N Pavese, R Borisyuk, D Nandi, P Bain^. A Network Model of Local Field Potential Activity in Essential Tremor and the Impact of Deep Brain Stimulation. PLOS Computational Biology (In Press) 2017.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-effect-of-deep-brain-stimulation-in-a-computational-model-of-essential-tremor/