Posture-Related Oscillations in Human Cerebellar Thalamus in Essential Tremor Are Enabled by Voluntary Motor Circuits

2005 ◽  
Vol 93 (1) ◽  
pp. 117-127 ◽  
Author(s):  
Sherwin E. Hua ◽  
Frederick A. Lenz
Keyword(s):  
Essential Tremor ◽  
Thalamic Nucleus ◽  
Oscillatory Activity ◽  
Active Movement ◽  
Thalamic Nuclei ◽  
Motor Circuits ◽  
Cross Correlation Analysis ◽  
Tremor Frequency ◽  
Sensory Nucleus ◽  
Proprioceptive Inputs

The mechanism of essential tremor (ET) is unclear. Animal models of tremor and functional imaging studies in ET predict that the cerebellum and a cerebellar recipient thalamic nucleus ( ventral intermediate, Vim) should exhibit oscillatory activity during rest and during tremor due to abnormal olivo-cerebellar activity. Physiologic responses of 152 single neurons were recorded during awake mapping of the ventral thalamus in seven patients with ET prior to thalamotomy. During postural tremor, spectral cross-correlation analysis demonstrated that 51% of the neurons studied exhibited a concentration of power at tremor frequency that was correlated with electromyography, i.e., tremor neurons. During rest, thalamic neurons did not exhibit tremor-frequency activity. Among the three thalamic nuclei surveyed, Vim had a significantly higher proportion of tremor neurons than did the principal somatic sensory nucleus ( ventral caudal, Vc) or a pallidal recipient thalamic nucleus ( ventral oral posterior, Vop). Neurons related to active movement (voluntary neurons) had significantly greater tremor-related activity than did nonvoluntary neurons. These findings are not consistent with a model of continuous olivo-cerebellar driving of the motor cortex through thalamic connections. Instead ET may be facilitated by motor circuits that enable tremor-related thalamic activity during voluntary movement. Additionally, a subgroup of tremor neurons with proprioceptive inputs were identified that may allow sensory feedback to access the central tremor network.

scholarly journals Role of cerebellar GABAergic dysfunctions in the origins of essential tremor

2019 ◽  
Vol 116 (27) ◽  
pp. 13592-13601 ◽  
Author(s):  
Xu Zhang ◽  
Sabato Santaniello
Keyword(s):  
Essential Tremor ◽  
Dentate Nucleus ◽  
Oscillatory Activity ◽  
High Frequency Stimulation ◽  
Inferior Olivary Nucleus ◽  
Functional Changes ◽  
Decay Times ◽  
Tremor Frequency ◽  
Frequency Stimulation ◽  
Inferior Olivary

Essential tremor (ET) is among the most prevalent movement disorders, but its origins are elusive. The inferior olivary nucleus (ION) has been hypothesized as the prime generator of tremor because of the pacemaker properties of ION neurons, but structural and functional changes in ION are unlikely under ET. Abnormalities have instead been reported in the cerebello-thalamo-cortical network, including dysfunctions of the GABAergic projections from the cerebellar cortex to the dentate nucleus. It remains unclear, though, how tremor would relate to a dysfunction of cerebellar connectivity. To address this question, we built a computational model of the cortico-cerebello-thalamo-cortical loop. We simulated the effects of a progressive loss of GABAA α1-receptor subunits and up-regulation of α2/3-receptor subunits in the dentate nucleus, and correspondingly, we studied the evolution of the firing patterns along the loop. The model closely reproduced experimental evidence for each structure in the loop. It showed that an alteration of amplitudes and decay times of the GABAergic currents to the dentate nucleus can facilitate sustained oscillatory activity at tremor frequency throughout the network as well as a robust bursting activity in the thalamus, which is consistent with observations of thalamic tremor cells in ET patients. Tremor-related oscillations initiated in small neural populations and spread to a larger network as the synaptic dysfunction increased, while thalamic high-frequency stimulation suppressed tremor-related activity in thalamus but increased the oscillation frequency in the olivocerebellar loop. These results suggest a mechanism for tremor generation under cerebellar dysfunction, which may explain the origin of ET.

scholarly journals Biophysical modeling of VIM to assess contributions of oscillatory activity to essential tremor

2018 ◽  
Author(s):  
Shane Lee ◽  
David J Segar ◽  
Wael F Asaad ◽  
Stephanie R Jones
Keyword(s):  
Computational Model ◽  
Movement Disorder ◽  
Essential Tremor ◽  
Treatment Strategies ◽  
Thalamic Reticular Nucleus ◽  
Oscillatory Activity ◽  
Reticular Nucleus ◽  
Biophysical Modeling ◽  
Tremor Frequency ◽  
A Site

AbstractEssential tremor (ET) is the most common movement disorder, in which the primary symptom is a prominent, involuntary 4–10 Hz rhythmic movement. The presence of tremor frequency oscillations (TFOs) in the ventral intermediate nucleus of the thalamus (VIM) is well-established, but it is often assumed that it is driven by cerebellar tremor frequency activity, while the role of intrinsic oscillatory activity in VIM is not clear. An improved understanding of the mechanisms of tremor and non-tremor frequency activity in VIM is critical to the development of improved pharmacological and neuromodulatory therapies. Starting from a canonical model of thalamus, we developed a biophysically-principled computational model of tremor field activity in the VIM, coupled with the thalamic reticular nucleus (TRN). We simulated TFOs in the model generated either by extrinsic tremor-periodic drive or intrinsic VIM-TRN interaction to understand whether these networks exhibited distinct biophysical properties, which may impact the efficacy of pharmacological or stimulation treatment for TFOs. Extrinsic and intrinsic TFOs in the model depended on T-type Ca2+channels in different ways. Each also depended on GABA modulation in a site- and type-specific manner. These results suggested that efficacy of pharmacological manipulations may depend upon the mechanisms generating TFOs in VIM. Simulated non-tremor-related motor activity from cerebellum decreased extrinsic but increased intrinsic TFOs. Our results suggest that both mechanisms may be important to understand the emergence and cessation of TFOs in VIM and lead to experimentally testable predictions on how to modulate tremor frequency activity to improve treatment strategies for ET.Significance StatementEssential Tremor (ET) is a movement disorder in which the primary symptom is a prominent, involuntary, and rhythmic shaking, often of the hands. Electrical activity in many areas of the brain exhibit rhythmicity related to the patient’s tremor. One such area resides in a structure called the thalamus, but it is not fully known what gives rise to tremor-related activity. We created a computational model of this activity, which suggested how to differentiate tremor mechanisms and how these differences may contribute to other impairments in ET. Knowledge of the biophysical mechanisms contributing to tremor can ultimately lead to improvements in treatments to alleviate symptoms of ET.

scholarly journals Noninvasive neuromodulation and thalamic mapping with low-intensity focused ultrasound

2018 ◽  
Vol 128 (3) ◽  
pp. 875-884 ◽  
Author(s):  
Robert F. Dallapiazza ◽  
Kelsie F. Timbie ◽  
Stephen Holmberg ◽  
Jeremy Gatesman ◽  
M. Beatriz Lopes ◽  
...  
Keyword(s):  
Focused Ultrasound ◽  
Thalamic Nucleus ◽  
Acoustic Energy ◽  
Similar Degree ◽  
Thalamic Nuclei ◽  
Low Intensity ◽  
Tissue Heating ◽  
The Central Nervous System ◽  
Selective Mapping ◽  
Noninvasive Neuromodulation

OBJECTIVEUltrasound can be precisely focused through the intact human skull to target deep regions of the brain for stereotactic ablations. Acoustic energy at much lower intensities is capable of both exciting and inhibiting neural tissues without causing tissue heating or damage. The objective of this study was to demonstrate the effects of low-intensity focused ultrasound (LIFU) for neuromodulation and selective mapping in the thalamus of a large-brain animal.METHODSTen Yorkshire swine (Sus scrofa domesticus) were used in this study. In the first neuromodulation experiment, the lemniscal sensory thalamus was stereotactically targeted with LIFU, and somatosensory evoked potentials (SSEPs) were monitored. In a second mapping experiment, the ventromedial and ventroposterolateral sensory thalamic nuclei were alternately targeted with LIFU, while both trigeminal and tibial evoked SSEPs were recorded. Temperature at the acoustic focus was assessed using MR thermography. At the end of the experiments, all tissues were assessed histologically for damage.RESULTSLIFU targeted to the ventroposterolateral thalamic nucleus suppressed SSEP amplitude to 71.6% ± 11.4% (mean ± SD) compared with baseline recordings. Second, we found a similar degree of inhibition with a high spatial resolution (∼ 2 mm) since adjacent thalamic nuclei could be selectively inhibited. The ventromedial thalamic nucleus could be inhibited without affecting the ventrolateral nucleus. During MR thermography imaging, there was no observed tissue heating during LIFU sonications and no histological evidence of tissue damage.CONCLUSIONSThese results suggest that LIFU can be safely used to modulate neuronal circuits in the central nervous system and that noninvasive brain mapping with focused ultrasound may be feasible in humans.

Cortical Involvement in the Generation of Essential Tremor

2007 ◽  
Vol 97 (5) ◽  
pp. 3219-3228 ◽  
Author(s):  
Jan Raethjen ◽  
R. B. Govindan ◽  
Florian Kopper ◽  
M. Muthuraman ◽  
Günther Deuschl
Keyword(s):  
Essential Tremor ◽  
Hot Spot ◽  
Power Spectra ◽  
Emg Activity ◽  
Cortical Circuits ◽  
Coherent Signals ◽  
Cortical Motor ◽  
Tremor Frequency ◽  
Cortical Involvement

Conflicting results on the existence of tremor-related cortical activity in essential tremor (ET) have raised questions on the role of the cortex in tremor generation. Here we attempt to address these issues. We recorded 64 channel surface EEGs and EMGs from forearm muscles in 15 patients with definite ET. EEG and EMG power spectra, relative power of the rhythmic EMG activity, relative EEG power at the tremor frequency, and EEG–EMG and EEG–EEG coherence were calculated and their dynamics over time explored. Corticomuscular delay was studied using a new method for narrow-band coherent signals. Corticomuscular coherence in the contralateral central region at the tremor frequency was present in all patients in recordings with a relative tremor EMG power exceeding a certain level. However, the coherence was lost intermittently even with tremors far above this level. Physiological 15- to 30-Hz coherence was found consistently in 11 patients with significantly weaker EMG activity in this frequency range. A more frontal (mesial) hot spot was also intermittently coupled with the tremor and the central hot spot in five patients. Corticomuscular delays were compatible with transmission in fast corticospinal pathways and feedback of the tremor signal. Thus the tremor rhythm is intermittently relayed only in different cortical motor areas. We hypothesize that tremor oscillations build up in different subcortical and subcortico-cortical circuits only temporarily entraining each other.

scholarly journals Mechanisms of deep brain stimulation

2016 ◽  
Vol 115 (1) ◽  
pp. 19-38 ◽  
Author(s):  
Todd M. Herrington ◽  
Jennifer J. Cheng ◽  
Emad N. Eskandar
Keyword(s):  
Synaptic Plasticity ◽  
Deep Brain Stimulation ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Movement Disorders ◽  
Oscillatory Activity ◽  
Treatment Resistant ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Deep Brain

Deep brain stimulation (DBS) is widely used for the treatment of movement disorders including Parkinson's disease, essential tremor, and dystonia and, to a lesser extent, certain treatment-resistant neuropsychiatric disorders including obsessive-compulsive disorder. Rather than a single unifying mechanism, DBS likely acts via several, nonexclusive mechanisms including local and network-wide electrical and neurochemical effects of stimulation, modulation of oscillatory activity, synaptic plasticity, and, potentially, neuroprotection and neurogenesis. These different mechanisms vary in importance depending on the condition being treated and the target being stimulated. Here we review each of these in turn and illustrate how an understanding of these mechanisms is inspiring next-generation approaches to DBS.

Comparison of Oculomotor Neuronal Activity in Paralaminar and Mediodorsal Thalamus in the Rhesus Monkey

2005 ◽  
Vol 93 (1) ◽  
pp. 614-619 ◽  
Author(s):  
Ikuo Tanibuchi ◽  
Patricia S. Goldman-Rakic
Keyword(s):  
Thalamic Nucleus ◽  
Delayed Response ◽  
Thalamic Nuclei ◽  
Related Activity ◽  
Dorsal Thalamus ◽  
Mediodorsal Thalamic Nucleus ◽  
Picture Stimuli ◽  
Fixation Task ◽  
Response Task ◽  
Lateral Nucleus

We previously reported that neurons in the mediodorsal thalamic nucleus (MD) are topographically organized and express spatial and nonspatial coding properties similar to those of the prefrontal areas with which they are connected. In the course of mapping the dorsal thalamus, we also studied neurons in a subset of thalamic nuclei (the caudal part of the ventral lateral nucleus (VLc), the oral part of the ventral posterior lateral nucleus (VPLo), the parvocellular part of the ventral anterior nucleus (VApc)) lateral to the MD and just across the internal medullary lamina. We compared these “paralaminar” neurons to MD neurons by having monkeys perform the same spatial and nonspatial cognitive tasks as those used to investigate the MD; these included two saccadic tasks—one requiring delayed and the other immediate responses—and one picture fixation task. Of the paralaminar thalamic neurons modulated by the saccadic tasks, a majority had saccade-related activity, and this was nearly always spatially tuned. Also, for about half of these neurons, the saccade-related activity occurred exclusively during the delayed-response task. No neurons with event-related activity in the saccadic tasks were preferentially modulated by specific picture stimuli, although other neurons were. All of these results were similar to what we had found for MD neurons. However, in contrast to the high proportion of presaccadic responses observed in the MD, the majority of saccade-related neurons in paralaminar thalamus exhibited mid- or postsaccadic activity, i.e., that started during or after the saccade. Our findings suggest that neurons in the paralaminar thalamus may be possible conduits of oculomotor feedback signals, especially during memory-guided saccades.

Essential tremor frequency decreases with time

Neurology ◽  
2000 ◽  
Vol 55 (10) ◽  
pp. 1547-1551 ◽  
Author(s):  
R. J. Elble
Keyword(s):  
Essential Tremor ◽  
Tremor Frequency

scholarly journals Prediction of Clinical Deep Brain Stimulation Target for Essential Tremor From 1.5 Tesla MRI Anatomical Landmarks

2021 ◽  
Vol 12 ◽  
Author(s):  
Julien Engelhardt ◽  
Emmanuel Cuny ◽  
Dominique Guehl ◽  
Pierre Burbaud ◽  
Nathalie Damon-Perrière ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Essential Tremor ◽  
Clinical Outcomes ◽  
Brain Stimulation ◽  
Prediction Models ◽  
External Validation ◽  
Support Vector ◽  
Anatomical Landmarks ◽  
Thalamic Nuclei ◽  
Deep Brain

Background: Deep brain stimulation is an efficacious treatment for refractory essential tremor, though targeting the intra-thalamic nuclei remains challenging.Objectives: We sought to develop an inverse approach to retrieve the position of the leads in a cohort of patients operated on with optimal clinical outcomes from anatomical landmarks identifiable by 1.5 Tesla magnetic resonance imaging.Methods: The learning database included clinical outcomes and post-operative imaging from which the coordinates of the active contacts and those of anatomical landmarks were extracted. We used machine learning regression methods to build three different prediction models. External validation was performed according to a leave-one-out cross-validation.Results: Fifteen patients (29 leads) were included, with a median tremor improvement of 72% on the Fahn–Tolosa–Marin scale. Kernel ridge regression, deep neural networks, and support vector regression (SVR) were used. SVR gave the best results with a mean error of 1.33 ± 1.64 mm between the predicted target and the active contact position.Conclusion: We report an original method for the targeting in deep brain stimulation for essential tremor based on patients' radio-anatomical features. This approach will be tested in a prospective clinical trial.

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