Neurophysiological identification and characterization of thalamic neurons with single unit recording in essential tremor patients

Lee, Bae Hwan; Lee, K. H.; Chung, Sang Sup; Chang, Jin Woo

doi:10.1007/978-3-7091-6081-7_28

Cited by 7 publications

(7 citation statements)

References 14 publications

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“…Pathological single-unit bursting activity recorded in human thalamus has been implicated in the genesis of tremor in patients with ET [Hua and Lenz, 2005; Kobayashi et al, 2003; Lee et al, 2003; Lenz et al, 1994; Molnar et al, 2005]. Thalamic bursting in the computational model was driven by cerebellar inputs transmitting oscillatory burst activity at the predominant interburst frequency of Vim neurons in humans with ET [Hua and Lenz, 2005].…”

Section: Discussionmentioning

confidence: 99%

Short pauses in thalamic deep brain stimulation promote tremor and neuronal bursting

Swan

Brocker

Hilliard

et al. 2016

Clinical Neurophysiology

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Objective We conducted intraoperative measurements of tremor during DBS containing short pauses (≤50 ms) to determine if there is a minimum pause duration that preserves tremor suppression. Methods Nine subjects with ET and thalamic DBS participated during IPG replacement surgery. Patterns of DBS included regular 130 Hz stimulation interrupted by 0, 15, 25 or 50 ms pauses. The same patterns were applied to a model of the thalamic network to quantify effects of pauses on activity of model neurons. Results All patterns of DBS decreased tremor relative to ‘off’. Patterns with pauses generated less tremor reduction than regular high frequency DBS. The model revealed that rhythmic burst-driver inputs to thalamus were masked during DBS, but pauses in stimulation allowed propagation of bursting activity. The mean firing rate of bursting-type model neurons as well as the firing pattern entropy of model neurons were both strongly correlated with tremor power across stimulation conditions. Conclusion The temporal pattern of stimulation influences the efficacy of thalamic DBS. Pauses in stimulation resulted in decreased tremor suppression indicating that masking of pathological bursting is a mechanism of thalamic DBS for tremor. Significance Pauses in stimulation decreased the efficacy of open-loop DBS for suppression of tremor.

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Section: Discussionmentioning

confidence: 99%

Short pauses in thalamic deep brain stimulation promote tremor and neuronal bursting

Swan

Brocker

Hilliard

et al. 2016

Clinical Neurophysiology

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“…Thalamic neurons that burst in synchrony with tremor in ET and Parkinson’s disease are distributed throughout the Vim and ventralis oralis thalamic nuclei (Hua and Lenz, 2005, Kobayashi et al, 2003, Lee et al, 2003, Lenz et al, 1994, Molnar, Pilliar, 2005) and are thought to play a critical role in the generation and maintenance of tremor. Recordings in Vim in persons with ET demonstrated that 75% of neurons responding to active movements burst in synchrony with tremor (Hua and Lenz, 2005).…”

Section: Discussionmentioning

confidence: 99%

Tremor reduction and modeled neural activity during cycling thalamic deep brain stimulation

Kuncel¹,

Birdno²,

Swan³

et al. 2012

Clinical Neurophysiology

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Objective The effectiveness of deep brain stimulation (DBS) depends on both the frequency and the temporal pattern of stimulation. We quantified responses to cycling DBS with constant frequency to determine if there was a critical on and/or off time for alleviating tremor. Methods We measured postural tremor in 10 subjects with thalamic DBS and quantified neuronal entropy in a network model of Vim thalamic DBS. We tested 12 combinations of cycling on/off times that maintained the same average frequenc7y of 125 Hz, four constant frequency settings, and baseline. Results Tremor and neural firing pattern entropy decreased as the percent on time increased from 50% to 100%. Cycling with stimulation on for at least 60% of the time was as effective as regular stimulation. All cycling settings reduced the firing pattern entropy of model neurons from the no stimulation condition by regularizing pathological firing patterns, either through synaptically-mediated inhibition or axon excitation. Conclusions These results indicate that pauses present in cycling stimulation decreased its effectiveness in suppressing tremor, and that changes in the amount of tremor suppression were strongly correlated with changes in the firing pattern entropy of model neurons. Significance Cycling stimulation may reduce power consumption during clinical DBS, and thereby increase the battery life of the implanted pulse generator.

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“…Stimulation levels were defined as the current necessary to activate a given percentage of the model neurons (4 mA for 40%, 10 mA for 70%, and 10 -32 mA for 100%). We introduced synchronous bursting at 4 Hz to model the pathological activity present in thalamic neurons in persons with tremor (Hua and Lenz 2005;Kobayashi et al 2003;Lee et al 2003;Magnin et al 2000) (Figs. 1E and 2B).…”

Section: Computational Modelmentioning

confidence: 99%

“…Synchronous bursting in the thalamus has been associated with both essential tremor and Parkinson's disease (Hua and Lenz 2005;Lenz et al 1994). Recent studies identified tremor cells in thalamic neurons of essential tremor subjects, but reported that the incidence of tremor cells is lower in essential tremor than in Parkinson's disease (Brodkey et al 2004;Kobayashi et al 2003;Lee et al 2003). However, these studies were performed with the subject at rest and essential tremor symptoms are manifested primarily as postural tremor.…”

Section: Computational Model Considerationsmentioning

confidence: 99%

Pulse-to-Pulse Changes in the Frequency of Deep Brain Stimulation Affect Tremor and Modeled Neuronal Activity

Birdno

Cooper²,

Rezai

et al. 2007

Journal of Neurophysiology

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Birdno MJ, Cooper SE, Rezai AR, Grill WM. Pulse-to-pulse changes in the frequency of deep brain stimulation affect tremor and modeled neuronal activity. J Neurophysiol 98: [1675][1676][1677][1678][1679][1680][1681][1682][1683][1684] 2007. First published July 18, 2007; doi:10.1152/jn.00547.2007. The effectiveness of deep brain stimulation (DBS) in relieving the symptoms of movement disorders is dependent on the average frequency of stimulation. However, no one has yet examined whether the effectiveness of DBS in relieving tremor is dependent on the pulse-to-pulse (instantaneous) frequency of DBS. We examined the effects of pairedpulse thalamic DBS on tremor in subjects with essential tremor and on the firing of model neurons in a biophysically based computational model of DBS. DBS with an average rate of 130 Hz was more effective at reducing tremor when pulses were evenly spaced than when there were large differences between intrapair and interpair pulse intervals. Similar correlations were observed in the firing patterns of model neurons: increasing the difference between the intrapair and interpair intervals rendered model neurons more likely to fire synchronous bursts, more likely to fire irregularly, and less likely to entrain to the stimulus. The tremor responses provide evidence that the pulse-to-pulse frequency of DBS, not just its average rate, plays an important role in DBS function. Modeling results also suggest that effective DBS overrides oscillatory pathological activity and replaces it with more regularized neuronal firing patterns. I N T R O D U C T I O NChronic high-frequency stimulation of the brain, or deep brain stimulation (DBS), is an effective treatment for motor symptoms in Parkinson's disease, dystonia, and essential tremor (Benabid et al. 1991;Gross and Lozano 2000;Schuurman et al. 2000). DBS is also being investigated for treatment of epilepsy (Goodman 2004;Hodaie et al. 2002) and psychiatric disorders (Gross 2004), including obsessive-compulsive disorder (Nuttin et al. 2003) and depression (Carpenter 2006;Mayberg et al. 2005). Despite the clinical success of DBS, the underlying physiological mechanisms of action are unclear (Breit et al. 2004;Garcia et al. 2005;Grill and McIntyre 2001;McIntyre et al. 2004b). This lack of knowledge may limit the application of DBS for treating novel diseases; it also complicates the identification of optimal anatomical targets and the selection of appropriate stimulation parameters. The purposes of this investigation were to quantify the effects of paired-pulse DBS on tremor in subjects with essential tremor and to provide insight into the mechanisms responsible for these effects by analysis with a computational model.The effects of frequency of DBS within the ventral intermediate nucleus of the thalamus (Vim) on tremor in essential tremor subjects are well documented. Reductions in tremor are typically observed only when the frequency of stimulation is Ͼ90 Hz; conversely, low-frequency DBS (Ͻ50 Hz) often worsens symptoms (Benabid et al. 1991;Kuncel et ...

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Neurophysiological identification and characterization of thalamic neurons with single unit recording in essential tremor patients

Cited by 7 publications

References 14 publications

Short pauses in thalamic deep brain stimulation promote tremor and neuronal bursting

Short pauses in thalamic deep brain stimulation promote tremor and neuronal bursting

Tremor reduction and modeled neural activity during cycling thalamic deep brain stimulation

Pulse-to-Pulse Changes in the Frequency of Deep Brain Stimulation Affect Tremor and Modeled Neuronal Activity

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