Biophysical modeling of VIM to assess contributions of oscillatory activity to essential tremor (original) (raw)
Related papers
Neuroscience, 2016
There is increasing evidence to suggest that essential tremor has a central origin. Different structures appear to be part of the central tremorogenic network, including the motor cortex, the thalamus and the cerebellum. Some studies using EEG and MEG show linear association in the tremor frequency between the motor cortex and the contralateral tremor EMG. Additionally, high thalamomuscular coherence is found with the use of thalamic local field potential (LFP) recordings and tremulous EMG in patients undergoing surgery for deep brain stimulation (DBS). Despite a well-established reciprocal anatomical connection between thalamus and cortex, the functional association between the two structures during "tremor-on" periods remains elusive. Coherence analysis shows strong linear association between thalamic LFPs and contralateral tremor EMG, but the relationship between the EEG and the thalamus is much less clear. Thalamic (Vim) LFPs, ipsilateral scalp EEG from the sensorimoto...
Cerebello-Thalamo-Cortical Network Dynamics in the Harmaline Rodent Model of Essential Tremor
Frontiers in Systems Neuroscience
Essential Tremor (ET) is a common movement disorder, characterised by a posture or movement-related tremor of the upper limbs. Abnormalities within cerebellar circuits are thought to underlie the pathogenesis of ET, resulting in aberrant synchronous oscillatory activity within the thalamo-cortical network leading to tremors. Harmaline produces pathological oscillations within the cerebellum, and a tremor that phenotypically resembles ET. However, the neural network dynamics in cerebellar-thalamo-cortical circuits in harmaline-induced tremor remains unclear, including the way circuit interactions may be influenced by behavioural state. Here, we examined the effect of harmaline on cerebello-thalamo-cortical oscillations during rest and movement. EEG recordings from the sensorimotor cortex and local field potentials (LFP) from thalamic and medial cerebellar nuclei were simultaneously recorded in awake behaving rats, alongside measures of tremor using EMG and accelerometery. Analyses co...
The cerebral oscillatory network of voluntary tremor
2004
It has recently been shown that resting tremor in Parkinson's disease is associated with oscillatory neural coupling in an extensive cerebral network comprising a cerebello-diencephalic-cortical loop and cortical motor, somatosensory and posterior parietal areas contralateral to the tremor hand. The aim of the present study was to investigate whether this oscillatory brain network exclusively reflects a pathophysiological state in parkinsonian resting tremor or whether it constitutes a fundamental feature of physiological motor control. We investigated cerebro-muscular and cerebro-cerebral coupling in 11 healthy subjects imitating typical antagonistic parkinsonian tremor. We recorded brain activity with a 122-channel whole-head neuromagnetometer and surface EMGs of the forearm extensor. Analysis of cerebro-muscular and cerebro-cerebral coherence revealed oscillatory coupling in the same brain structures that comprise the oscillatory network of parkinsonian resting tremor. Interestingly, similar to parkinsonian resting tremor, cerebro-cerebral coherences often showed a significant peak at twice the simulated tremor frequency. The most striking differences between parkinsonian patients, as investigated in a previous study and healthy subjects imitating the antagonistic resting tremor were a reduction of the coupling between primary sensorimotor cortex and a diencephalic structure-most likely the thalamus-and an enhancement of the coupling between premotor and primary sensorimotor cortex. Our results indicate that the coupling of oscillatory activity within a cerebello-diencephalic-cortical loop constitutes a basic feature of physiological motor control. Thus, our data are consistent with the hypothesis that parkinsonian resting tremor involves oscillatory cerebro-cerebral coupling in a physiologically pre-existing network.
Computational modeling to improve treatments for essential tremor
Drug Discovery Today: Disease Models, 2016
Essential tremor (ET) is a neurological disorder of unknown etiology that is typically characterized by an involuntary periodic movement of the upper limbs. No longer considered monosymptomatic, ET patients often have additional motor and even cognitive impairments. Although there are several pharmacological treatments, no drugs have been developed specifically for ET [1], and 30-70% of patients are medication-refractory [2]. A subset of medicationrefractory patients may benefit from electrical deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus (VIM), which receives cerebellar inputs. Abnormal cerebellar input to VIM is presumed to be a major contributor to tremor symptoms, which is alleviated by DBS. Computational modeling of the effects of DBS in VIM has been a powerful tool to design DBS protocols to reduce tremor activity. However, far less is known about how these therapies affect non-tremor symptoms, and more experimental and computational modeling work is required to address these growing considerations. Models capable of addressing multiple facets of ET will lead to novel, more efficient treatment.
Distinguishing the Central Drive to Tremor in Parkinson's Disease and Essential Tremor
Journal of Neuroscience, 2015
Parkinson's disease (PD) and essential tremor (ET) are the two most common movement disorders. Both have been associated with similar patterns of network activation leading to the suggestion that they may result from similar network dysfunction, specifically involving the cerebellum. Here, we demonstrate that parkinsonian tremors and ETs result from distinct patterns of interactions between neural oscillators. These patterns are reflected in the tremors' derived frequency tolerance, a novel measure readily attainable from bedside accelerometry. Frequency tolerance characterizes the temporal evolution of tremor by quantifying the range of frequencies over which the tremor may be considered stable. We found that patients with PD (N ϭ 24) and ET (N ϭ 21) were separable based on their frequency tolerance, with PD associated with a broad range of stable frequencies whereas ET displayed characteristics consistent with a more finely tuned oscillatory drive. Furthermore, tremor was selectively entrained by transcranial alternating current stimulation applied over cerebellum. Narrow frequency tolerances predicted stronger entrainment of tremor by stimulation, providing good evidence that the cerebellum plays an important role in pacing those tremors. The different patterns of frequency tolerance could be captured with a simple model based on a broadly coupled set of neural oscillators for PD, but a more finely tuned set of oscillators in ET. Together, these results reveal a potential organizational principle of the human motor system, whose disruption in PD and ET dictates how patients respond to empirical, and potentially therapeutic, interventions that interact with their underlying pathophysiology.
Evidence for the Central Oscillators in the Physiological Tremor Generation Process
2000
Physiological tremor is a complex signal resulting from interactions between several mechanical and neural factors. In this paper we bring into discussion only the neurogenic components that, first, have been mainly attributed to spinal interneuronal systems or subcortical oscillators but more recently, also to cortical rhythms. Here we investigated, using visual stimuli at different frequencies (5Hz, 10Hz, 15Hz), whether the
The cerebral oscillatory network of parkinsonian resting tremor
2003
Partial coherence analysis and the calculation of phase shifts revealed a strong bidirectional coupling between the EMG and diencephalic activity and a direct afferent coupling between the EMG and SII and the PPC. In contrast, the cerebellum, SMA/CMA and PM show little evidence for direct coupling with the peripheral EMG but seem to be connected with the periphery via other cerebral areas (e.g. M1). In summary, our results demonstrate tremor-related oscillatory activity within a cerebral network, with abnormal coupling in a cerebello-diencephalic±cortical loop and cortical motor (M1, SMA/CMA, PM) and sensory (SII, PPC) areas contralateral to the tremor hand. The main frequency of cerebro-cerebral coupling corresponds to double the tremor frequency. Abbreviations: CMA = cingulate motor area; DICS = Dynamic Imaging of Coherent Sources; EDC = extensor digitorum communis; EMG = electromyography; GPI = internal globus pallidus; M1 = primary motor cortex; MEG = magnetoencephalography; PM = premotor cortex; PPC = posterior parietal cortex; SII = secondary somatosensory cortex; SMA = supplementary motor areas; STN = subthalamic nucleus ã Guarantors of Brain 2003
European Journal of Neuroscience, 2003
The pathophysiology of parkinsonian tremor remains a matter of debate with two opposing hypotheses proposing a peripheral and a central origin, respectively. A central origin of tremor could arise either from a rhythmic activity of the internal segment of the globus pallidus (GPi) or from a structure such as the thalamus, outside the basal ganglia. In this study, single-unit recordings were performed in three 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys within the GPi and within three territories of the motor thalamus (delimited by their afferent inputs from the GPi, the substantia nigra and the cerebellum, respectively). For each recorded neuron, we compared the variations in ®ring rate and pattern in tremor and no tremor periods. Tremor either occurred spontaneously or was induced by external stimulation. When the animals entered into a tremor period we observed: (i) an increase in the mean ®ring rate in about half of the recorded neurons of the motor thalamus; and (ii), a change from an irregular to a rhythmic discharge within the range of tremor frequency (5±7 Hz) in about 10% of the recorded neurons of the motor thalamus (pallidal and cerebellar territories) and the GPi. Most of the thalamic neurons that exhibited a rhythmic discharge during tremor were found to be sensitive to external stimulation. Because the changes in ®ring rate occurred predominantly in the motor thalamus and not in the GPi, and because a fast rhythmic discharge of 10±15 Hz was frequently observed in the GPi and not in the motor thalamus, we conclude that thalamic activity is not a simple reproduction of basal ganglia output. Moreover, we suggest that thalamic processing of basal ganglia outputs could participate in the genesis of tremor, and that this thalamic processing could be in¯uenced by sensory inputs and/or changes in attentional level elicited by external stimulation.
A modelling study on transmission of the central oscillator in tremor by a motor neuron pool
2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2011
In spite of decades of intense research, pathological tremors still constitute unknown disorders. This study addresses, based on a multi-scale model, the behavior of an entire pool of motor neurons in tremor, under the hypothesis that tremor is an oscillation of central origin commonly projected to all motor neurons that innervate a muscle. Our results show that under such conditions both paired discharges and enhanced motor neuron synchronization, two of the characteristic landmarks of tremor, emerge. Moreover, coherence and correlation analyses suggest that the central tremor oscillator is transmitted linearly by the motor neuron pool given that a small set (7 or 8) of motor neurons are sampled.
The nature of tremor circuits in parkinsonian and essential tremor
Brain : a journal of neurology, 2014
Tremor is a cardinal feature of Parkinson's disease and essential tremor, the two most common movement disorders. Yet, the mechanisms underlying tremor generation remain largely unknown. We hypothesized that driving deep brain stimulation electrodes at a frequency closely matching the patient's own tremor frequency should interact with neural activity responsible for tremor, and that the effect of stimulation on tremor should reveal the role of different deep brain stimulation targets in tremor generation. Moreover, tremor responses to stimulation might reveal pathophysiological differences between parkinsonian and essential tremor circuits. Accordingly, we stimulated 15 patients with Parkinson's disease with either thalamic or subthalamic electrodes (13 male and two female patients, age: 50-77 years) and 10 patients with essential tremor with thalamic electrodes (nine male and one female patients, age: 34-74 years). Stimulation at near-to tremor frequency entrained trem...