![]() Therefore, we hypothesized that DBS at the VL thalamus (VLT), which is a homolog of VIM in humans, may act through changing neuronal firing patterns in the primary motor cortex (M1). In the neurophysiological view, rhythmic firing patterns such as oscillations and bursts have been considered as a way to process information in the brain ( Varela et al., 2001 Izhikevich et al., 2003). Thus, there is evidence for alterations in cerebello-thalamo-cortical circuit activities directly influencing ET. In the study of connectivity for the cerebello-thalamo-cortical network in humans, when tremor is severed, M1 has reduced cerebellar functional connectivity, whereas the thalamus has increased cerebellar functional connectivity ( Lenka et al., 2017). Recently, several studies have suggested that cortical thickness could be used as an ET diagnosis with a high accuracy ( Chung et al., 2013 Cerasa et al., 2014 Serrano et al., 2017 Benito-León et al., 2019), which may partly reflect a decrease in the amount of corticothalamic connections. Corticothalamic feedback neurons reside in cortical layer 6 and give rise to axons that terminate both in the thalamus and in the layers of the cortex receiving thalamic input ( Sherman, 2005 Wearden et al., 2006). Thalamic neurons receive robust input from corticothalamic feedback neurons, thereby allowing the cortex to communicate continuously with the thalamus during sensory processing ( Briggs and Usrey, 2008). The corticothalamic anatomical connections are well established ( Raethjen et al., 2007 Raethjen and Deuschl, 2012). The cerebral cortex is also a part of the tremor-generating neuronal network ( Hellwig et al., 2001 Raethjen et al., 2007). ![]() The VIM shows abnormal neuronal discharges in humans with ET ( Deuschl and Bergman, 2002). Ventral intermediate nucleus of the thalamus (VIM) is a well-established DBS target for ET ( Deuschl and Bergman, 2002), because the VIM is a cerebellar relay nucleus in the ventrolateral (VL) part of the thalamus and is known to be involved in ET ( Benabid et al., 1991 Hua et al., 1998 Schuurman et al., 2000). Therefore, deep brain stimulation (DBS) becomes an alternative treatment option when medication is not effective or not tolerated in patients with disabling tremor ( Zhang et al., 2010 Crowell and Shah, 2016). It is estimated that pharmacological treatment can improve tremor in only 50% of patients ( Lyons et al., 2003). Although the preferred treatment for ET is pharmacology based, medications for ET may decrease in efficacy over time or not be efficacious ( Chopra et al., 2013). ET is characterized by a positional and/or volitional 4- to 12-Hz tremor that can affect all body parts ( Marshall, 1962) and affects nearly 1% of the world’s population, increasing to 4% of those over age 40 ( Müller et al., 2016). As specific neuronal firing patterns like oscillation or burst are considered important for information processing, our results suggest that VL thalamic DBS may modify pathophysiologic relay information rather than simply inhibit the information transmission.Įssential tremor (ET) is a neurological condition that causes shaking or rhythmic motion in body parts. Four activity patterns – including oscillatory burst, oscillatory non-burst, irregular burst, and irregular non-burst – were identified by harmaline administration and those firing patterns were differentially affected by VL thalamic DBS, which seems to drive pathologic cortical signals to signals in normal status. To examine this, we measured single-unit neuronal activities in the resting state in M1 during VL thalamic DBS in harmaline-induced tremor rats and analyzed neuronal activity patterns in the thalamo-cortical circuit. As the motor thalamus is the most popular DBS target for ET, and it is known that the thalamic nucleus plays a key role in relaying information about the external environment to the cerebral cortex, it is important to investigate mechanisms of thalamic DBS in the context of the cerebello-thalamo-cortical neuronal network. 2Department of Neurologic Surgery, Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, United StatesĪlthough deep brain stimulation (DBS) is a clinically effective surgical treatment for essential tremor (ET), and its neurophysiological mechanisms are not fully understood.1Laboratory of Brain & Cognitive Sciences for Convergence Medicine, College of Medicine, Hallym University, Anyang, South Korea.
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