Tremor Frequency Band Research Articles

Wearable sensor-driven responsive deep brain stimulation for essential tremor

BackgroundDeep brain stimulation (DBS) is an effective surgical therapy for individuals with essential tremor (ET). However, DBS operates continuously, resulting in adverse effects such as postural instability or dysarthria. Continuous DBS (cDBS) also presents important practical issues including limited battery life of the implantable neurostimulator (INS). Collectively, these shortcomings impact optimal therapeutic benefit in ET. ObjectiveThe goal of the study was to establish a physiology-driven responsive DBS (rDBS) system to provide targeted and personalized therapy based on electromyography (EMG) signals. MethodsTen participants with ET underwent rDBS using Nexus-D, a Medtronic telemetry wand that acts as a direct conduit to the INS by modulating stimulation voltage. Two different rDBS paradigms were tested: one driven by one EMG (single-sensor) and another driven by two or more EMGs (multi-sensor). The feature(s) used in the rDBS algorithms was the pow2er in the participant's tremor frequency band derived from the sensors controlling stimulation. Both algorithms were trained on kinetic and postural data collected during DBS off and cDBS states. ResultsUsing established clinical scales and objective measurements of tremor severity, we confirm that both rDBS paradigms deliver equivalent clinical benefit as cDBS. Moreover, both EMG-driven rDBS paradigms delivered less total electrical energy translating to an increase in the battery life of the INS. ConclusionsThe results of this study verify that EMG-driven rDBS provides clinically equivalent tremor suppression compared to cDBS, while delivering less total electrical energy. Controlling stimulation using a dynamic rDBS paradigm can mitigate limitations of traditional cDBS systems.

<p>Asymmetry of Subthalamic Neuronal Firing Rate and Oscillatory Characteristics in Parkinson’s Disease</p>

PurposeThe aim of this study was to compare the neuronal firing rate and oscillatory activity of the subthalamic nucleus (STN) between the more affected (MA) and the less affected (LA) hemispheres in Parkinson’s disease (PD).Patients and MethodsWe recorded and analyzed the intra-operative microelectrode recordings (MER) from the STN of 24 PD subjects. Lateralized Unified Parkinson’s Disease Rating Scale (UPDRS) III sub-scores (item 20–26) were calculated. The STN corresponding to the MA side was designated as the MA STN while the other side as the LA STN. Single unit characteristics including interspike intervals were identified and spectral analyses were assessed. Further, the mean spontaneous firing rate (MSFR) of neurons was calculated. The correlations between clinical symptoms and neuronal activity were analyzed.ResultsThe firing rate in the MA and LA sides were 43.18 ± 0.74 Hz and 36.94 ± 1.32 Hz, respectively, with an increase of 16.9% in the MA group. The number of neurons that oscillated in the Tremor-Frequency Band (TFB), β-Frequency Band (βFB), and the non-oscillatory cells in the MA group were 43, 115, and 62 versus 78, 68, and 54 in the LA group, respectively. The proportions of the three types of neurons were different between both groups. The firing rate of the STN neurons and the UPDRS III sub-scores were positively correlated. Additionally, we observed a positive correlation between the percentage of βFB oscillatory neurons and bradykinesia score.ConclusionThe firing rate of the STN in the MA hemisphere is higher than in the LA side, following disease progression and there seems to be an increase in firing rate. The βFB oscillatory neurons are at a larger proportion in the MA group while there were larger percentage of TFB oscillatory cells in the LA group. The proportion of βFB oscillatory neurons is selectively correlated with the severity of bradykinesia.

Voluntary and tremorogenic inputs to motor neuron pools of agonist/antagonist muscles in essential tremor patients.

Pathological tremor is an oscillation of body parts at 3–10 Hz, determined by the output of spinal motor neurons (MNs), which receive synaptic inputs from supraspinal centers and muscle afferents. The behavior of spinal MNs during tremor is not well understood, especially in relation to the activation of the multiple muscles involved. Recent studies on patients with essential tremor have shown that antagonist MN pools receive shared input at the tremor frequency. In this study, we investigated the synaptic inputs related to tremor and voluntary movement, and their coordination across antagonist muscles. We analyzed the spike trains of motor units (MUs) identified from high-density surface electromyography from the forearm extensor and flexor muscles in 15 patients with essential tremor during postural tremor. The shared synaptic input was quantified by coherence and phase difference analysis of the spike trains. All pairs of spike trains in each muscle showed coherence peaks at the voluntary drive frequency (1–3 Hz, 0.2 ± 0.2, mean ± SD) and tremor frequency (3–10 Hz, 0.6 ± 0.3) and were synchronized with small phase differences (3.3 ± 25.2° and 3.9 ± 22.0° for the voluntary drive and tremor frequencies, respectively). The coherence between MN spike trains of antagonist muscle groups at the tremor frequency was significantly smaller than intramuscular coherence. We predominantly observed in-phase activation of MUs between agonist/antagonist muscles at the voluntary frequency band (0.6 ± 48.8°) and out-of-phase activation at the tremor frequency band (126.9 ± 75.6°). Thus MNs innervating agonist/antagonist muscles concurrently receive synaptic inputs with different phase shifts in the voluntary and tremor frequency bands.NEW & NOTEWORTHY Although the mechanical characteristics of tremor have been widely studied, the activation of the affected muscles is still poorly understood. We analyzed the behavior of motor units of pairs of antagonistic wrist muscle groups in patients with essential tremor and studied their activity at voluntary movement- and tremor-related frequencies. We found that the phase relation between inputs to antagonistic muscles is different at the voluntary and tremor frequency bands.

Potentials and pitfalls of permafrost active layer monitoring using the HVSR method: a case study in Svalbard

Abstract. Time-lapse monitoring of the subsurface using ambient seismic noise is a popular method in environmental seismology. We assess the reliability of the horizontal-to-vertical spectral ratio (HVSR) method for monitoring seasonal permafrost active layer variability in northwest Svalbard. We observe complex HVSR variability between 1 and 50 Hz in the record of a temporary seismic deployment covering frozen and thawed soil conditions between April and August 2016. While strong variations are due to changing noise conditions, mainly affected by wind speed and degrading coupling of instruments during melt season, a seasonal trend is observed at some stations that has most likely a subsurface structural cause. A HVSR peak emerges close to the Nyquist frequency (50 Hz) in beginning of June which is then gradually gliding down, reaching frequencies of about 15–25 Hz in the end of August. This observation is consistent with HVSR forward modeling for a set of structural models that simulate different stages of active layer thawing. Our results reveal a number of potential pitfalls when interpreting HVSRs and suggest a careful analysis of temporal variations since HVSR seasonality is not necessarily related to changes in the subsurface. In addition, we investigate if effects of changing noise sources on HVSRs can be avoided by utilizing a directional, narrowband (4.5 Hz) repeating seismic tremor which is observed at the permanent seismic broadband station in the study area. A significant change of the radial component HVSR shape during summer months is observed for all tremors. We show that a thawed active layer with very low seismic velocities would affect Rayleigh wave ellipticities in the tremor frequency band. We compile a list of recommendations for future experiments, including comments on network layouts suitable for array beamforming and waveform correlation methods that can provide essential information on noise source variability.

Subthalamic oscillatory activity in parkinsonian patients with off-period dystonia.

The study was aimed to explore oscillatory activity in the subthalamic nucleus (STN) in Parkinson's disease (PD) with off-period dystonia, a type of levodopa-induced dyskinesias (LID). Eighteen patients with PD who underwent STN DBS were studied. Nine patients had dyskinesia defined as the LID group and nine patients who did not present any sign of dyskinesia were defined as the control group. Microelectrode recordings in the STN together with electromyogram (EMG) were recorded. Spectral and coherence analyses were performed to study the neuronal oscillations in relation to limb muscles. Two hundred and fifteen neurons were identified. There were 39 neurons with tremor-frequency band (4-7 Hz) oscillation, 57 neurons with β-frequency band (12-30 Hz, β-FB) oscillation and 100 neurons without oscillation, and 19 neurons with very low-frequency band oscillation at a mean peak power of 1.2 ± 0.5 Hz (LFB). These LFB oscillatory neurons (n = 15) were frequently significantly coherent with EMG of off-period dystonia. Notably, 89% (n = 17) neurons with LFB oscillation were found in the patients in the off-dystonia group. The age at onset of PD, duration of PD, and levodopa equivalent dose daily consumption were statistically different between two groups (P < 0.05). Subthalamic LFB oscillatory neurons seem to play an important role in the genesis of off-period dystonia in advanced PD. Clinical and demographic analyses confirmed that the earlier age at onset of PD, longer duration of PD, and levodopa exposure are important risk factors in the development of the type of LID.

A network model of neural activity in essential tremor

Deep brain stimulation (DBS) is a surgical treatment used for a number of movement disorders, involving the chronic implantation of electrodes into disorder specific regions in the brain. For essential tremor (ET) the targeted brain structure is the ventralis intermedius (ViM) nucleus of the thalamus. ET is a common movement disorder, which affects as many as 4 out of 100 adults over 40 years of age. While the cause of this disorder is unknown, DBS works well, achieving up to 90% improvement in symptoms [1,2]. However, the mechanisms by which the therapeutic effect is obtained are not fully understood, which in turn slows the process of finding the optimal parameter settings which suppress symptoms and minimise unwanted side effects. DBS additionally provides an opportunity to record the pathological neural activity via intraoperative recordings from the implanted electrodes in the form of local field potentials (LFP) whilst simultaneously recording muscle activity from the affected limbs (EMG). Here, we present data which shows peaks in the EMG-LFP cross spectra within the tremor frequency band (4-12 Hz). To understand the effects of a DBS input on such pathological neural activity, we adopt a computational modelling approach using a population representation of the network hypothesised to underlie ET, namely cortex, cerebellum and thalamus (Figure 1 A) and is based on previous descriptions of the essential tremor network [3]. The model is implemented using the Wilson-Cowan approach [4], and was simulated by exploring the parameter space to uncover regions which produced oscillatory thalamic activity and we found that the network exhibited oscillatory behaviour within the tremor frequency range (Figure 1B). By applying an input to the thalamus simulating the effect of DBS (e.g. 150Hz square pulse), we found that these oscillations are suppressed. Therefore, this study shows that the dynamics of the ET network are able to support oscillations at the tremor frequency. Furthermore, the application of a DBS-like input to such a network disrupts synchronous activity, which could explain one mechanism by which DBS achieves therapeutic benefit. Figure 1 The structure of the model is shown schematically (A), and consists of the cortex, the ViM nucleus and the reticular nucleus (nRT) of the thalamus, and the deep cerebellar nuclei (DCN). The baseline oscillatory activity of the thalamic population is within ...

Experimental muscle pain increases variability of neural drive to muscle and decreases motor unit coherence in tremor frequency band.

It has been observed that muscle pain influences force variability and low-frequency (<3 Hz) oscillations in the neural drive to muscle. In this study, we aimed to investigate the effect of experimental muscle pain on the neural control of muscle force at higher frequency bands, associated with afferent feedback (alpha band, 5-13 Hz) and with descending cortical input (beta band, 15-30 Hz). Single-motor unit activity was recorded, in two separate experimental sessions, from the abductor digiti minimi (ADM) and tibialis anterior (TA) muscles with intramuscular wire electrodes, during isometric abductions of the fifth finger at 10% of maximal force [maximum voluntary contraction (MVC)] and ankle dorsiflexions at 25% MVC. The contractions were repeated under three conditions: no pain (baseline) and after intramuscular injection of isotonic (0.9%, control) and hypertonic (5.8%, painful) saline. The results showed an increase of the relative power of both the force signal and the neural drive at the tremor frequency band (alpha, 5-13 Hz) between the baseline and hypertonic (painful) conditions for both muscles (P < 0.05) but no effect on the beta band. Additionally, the strength of motor unit coherence was lower (P < 0.05) in the hypertonic condition in the alpha band for both muscles and in the beta band for the ADM. These results indicate that experimental muscle pain increases the amplitude of the tremor oscillations because of an increased variability of the neural control (common synaptic input) in the tremor band. Moreover, the concomitant decrease in coherence suggests an increase in independent input in the tremor band due to pain.

Oscillatory activity in ventrolateral thalamus of patients with Parkinson's disease

Objective To explore the neuronal oscillatory activity in the ventrolateral thalamus (the ventral oral posterior nucleus,Vop/the ventral intermediate nucleus,Vim) in relation to parkinsonian motor signs.Methods 23 patients (M:20,F:3 ; mean age:60.6-± 8.2 years,mean duration of disease:6.6± 3.4 years) with Parkinson's disease (PD) who underwent thalamotomy were studied.Their mean Hoehn & Yahr score was 2.2 ± 0.4,and the unified Parkinson's disease rating scale (UPDRS Ⅲ)during OFFstate was 42.4 ± 12.1.The average L-dopa daily dose was 551.7 ± 219.5 mg.Microelectrode records in Vop/Vim and electromyography (EMG) on contralateral limbs to surgery were simultaneously performed.Single unit analysis,interspike interval (ISI) was used to study neuronal firing rate and pattern.Power spectral analysis was carried out to evaluate neuronal oscillation.Coherence analysis was used to study neuronal activity in relation to limb EMG.Clinical outcome was calculated by (presurgery-postsurgery/presurgery) × 100.Results 190 neurons were identified.Power spectral analysis showed that 60％ (n =114) neurons had oscillatory activity.Of those oscillatory neurons,78％ (n =89) neurons had tremor frequency band (3.0 ～ 7.5 Hz) (TFB).Oscillation showing as same frequency as tremor (P ＜0.05) ; 22％ (n =25) neurons had β frequency band(8 ～ 30 Hz) (βFB) oscillation.Further analysis showed that majority of neurons with TFB oscillation localized in Vim,while majority of neurons with βFB oscillations localized in Vop (t =2.048,P ＜ 0.05).In addition,it was found that the mean firing rate of oscillatory neurons in Vop was significantly lower than those neurons in Vim (24.3 ±9.9 Hz vs 28.5 ± 12.4 Hz,t =1.988,P ＜ 0.05).UPDRS revealed that clinical improvement was 89.7％ for tremor,48.4％ for rigidity and 38.1％ for bradykinesia respectively.Conclusions The data support that neuronal oscillations in the Vop/Vim are involved in parkinsonian symptoms.Neurons with TFB oscillation high densely distributed in the Vim indicate that the Vim is the best target for tremor.Since neurons with βFB oscillation are associated with bradykinesia,and the Vop is presumed pallidal relay nucleus.It is likely that the Vop is effective for parkinsonian bradykinesia/rigidity. Key words: Parkinson' s disease; Ventral thalamic nuclei; Microelectrodes; Neurons ; Oscillation

Power spectral density analysis of physiological, rest and action tremor in Parkinson’s disease patients treated with deep brain stimulation

BackgroundObservation of the signals recorded from the extremities of Parkinson’s disease patients showing rest and/or action tremor reveal a distinct high power resonance peak in the frequency band corresponding to tremor. The aim of the study was to investigate, using quantitative measures, how clinically effective and less effective deep brain stimulation protocols redistribute movement power over the frequency bands associated with movement, pathological and physiological tremor, and whether normal physiological tremor may reappear during those periods that tremor is absent.MethodsThe power spectral density patterns of rest and action tremor were studied in 7 Parkinson’s disease patients treated with (bilateral) deep brain stimulation of the subthalamic nucleus. Two tests were carried out: 1) the patient was sitting at rest; 2) the patient performed a hand or foot tapping movement. Each test was repeated four times for each extremity with different stimulation settings applied during each repetition. Tremor intermittency was taken into account by classifying each 3-second window of the recorded angular velocity signals as a tremor or non-tremor window.ResultsThe distribution of power over the low frequency band (<3.5 Hz – voluntary movement), tremor band (3.5-7.5 Hz) and high frequency band (>7.5 Hz – normal physiological tremor) revealed that rest and action tremor show a similar power-frequency shift related to tremor absence and presence: when tremor is present most power is contained in the tremor frequency band; when tremor is absent lower frequencies dominate. Even under resting conditions a relatively large low frequency component became prominent, which seemed to compensate for tremor. Tremor absence did not result in the reappearance of normal physiological tremor.ConclusionParkinson’s disease patients continuously balance between tremor and tremor suppression or compensation expressed by power shifts between the low frequency band and the tremor frequency band during rest and voluntary motor actions. This balance shows that the pathological tremor is either on or off, with the latter state not resembling that of a healthy subject. Deep brain stimulation can reverse the balance thereby either switching tremor on or off.

A model for simulating Local Field Potential in the thalamus of Essential Tremor patient during deep brain stimulation

Local Field Potential (LFP) is simulated by adding the neuronal membrane potential of a group of model neurons surrounding a typical intra-operative micro-electrode used to localize the target for deep brain stimulation (DBS) in Essential Tremor (ET). Each neuronal membrane potential is modeled as an Ornstein Uhlenbeck Process (OUP) and the model parameters are extracted from real neuronal recording during DBS surgery following the method in [1]. Before any test stimulation through the macro ring of the microelectrode, the LFP is simulated according to: (1) Where, x is the membrane potential of each neuron and r is the distance from the recording tip. The simulated signal, lfp is then low pass filtered (1-40 Hz) to produce the final signal. With stimulation on, the LFP is simulated similarly but only over time intervals in between two stimulation pulse which is free of the stimulation voltage artifact caused by amplifier saturation. The stimulation artifact time duration is estimated as: (2) Where, l(r) is the stimulation intensity at distance r from the recording tip and follows a similar inverse square decay as in (1), τ is the membrane time constant (an OUP model parameter) and S is the neuronal firing threshold. Thus the LFP simulated during stimulation depends on the stimulation intensity, pulse width and frequency. The stimulation parameters used are: frequency: 160 Hz (125 samples/period), pulse width: 0.4 ms, intensity:1.5 mA It was found that the power in the (5-12) Hz band decreases by 26.4% during stimulation. There is increased synchronization in neuronal activity of the thalamus in the theta band (4-7 Hz) for patients with ET [2]. The suppression of tremor by DBS is reflected in the reduction of power in the tremor frequency band. Such a model , can potentially be used to find an optimal set of stimulation parameters that will produce the maximum suppression in the tremor power. Figure 1 Spectrum of LFP before stimulation (in red) and during stimulation (in blue).

Subthalamic nucleus functional organization revealed by parkinsonian neuronal oscillations and synchrony

The emergence of oscillations and synchrony among neurons of the basal ganglia is a well-known characteristic of Parkinson's disease. In this study we used intra-operative microelectrode recording to investigate this interrelationship between these two phenomena in the subthalamic nucleus (STN) neurons of 39 human Parkinson's disease patients undergoing deep brain stimulation surgery. From the recorded neuronal traces both neuronal spike trains and their background activity were extracted, and their spectral characteristics were evaluated. We have used the background oscillations as a marker for synchronized activity in the local population in the neuron vicinity and studied its relation to single neuron oscillations. Spike train background oscillations were evaluated using a procedure of background reconstruction that consisted of spikes removal from the original traces and full wave rectification followed by standard spectral analysis. Coherence and phase analysis between oscillatory spike trains and their oscillatory background were also conducted to study the phase relationship between the two. Of the 231 neuronal spike-trains which were sorted offline, 82 (35%) showed significant oscillatory activity. These neurons were found to oscillate mostly in two bands; 3-7 Hz, termed the Tremor Frequency Band (TFB), and 8-20 Hz, termed the High-Frequency Band (HFB). While HFB neurons oscillated for longer periods and always coherently with their background activity, TFB neurons oscillated more episodically and only a half were coherent with their background. These findings indicate that the two neuronal populations are the outcome of very different oscillatory drives deriving from different local functional neuronal organizations.

Ten Hertz thalamus stimulation increases tremor activity in the subthalamic nucleus in a patient with Parkinson’s disease

Objective In patients with Parkinson’s disease (PD) the effect of thalamic stimulation on tremor pathophysiology remains largely unclear. By recording local field potentials (LFPs) in the subthalamic nucleus (STN) while stimulating the nucleus ventralis intermedius thalami (VIM), information of the stimulation effects should be gained. Methods We had the unique opportunity to intraoperatively record LFPs of the STN in a patient with PD while stimulating the VIM. VIM electrodes had been implanted 9 years previously because of tremor. Due to worsening of clinical symptoms an implantation of STN electrodes had become necessary. Results High frequency stimulation in the VIM lowered the power of the tremor frequency band (4–7 Hz) in the STN. In contrast, 10 Hz VIM stimulation elevated the power of the tremor frequency band as well as STN–EMG coupling. Conclusions The effect of high frequency stimulation may explain the improvement of tremor in patients who are treated with VIM deep brain stimulation. The power elevation during 10 Hz stimulation suggests that the pathological cerebral and cerebral–muscular communication in PD is mainly driven at 10 Hz. Significance The direct cerebral recordings support the view that a 10 Hz network is a pathophysiological key mechanism in the generation of motor deficits in PD.

Time–frequency analysis of transient neuromuscular events: dynamic changes in activity of the subthalamic nucleus and forearm muscles related to the intermittent resting tremor

In order to investigate the dynamic change in transient neuromuscular events and the functional correlation between the neural and muscular activity, local field potentials (LFPs) of the subthalamic nucleus (STN) and surface electromyograms (sEMGs) over several episodes of transient resting tremor from a patient with Parkinson's disease were quantitatively characterised in time–frequency domain using short-time Fourier transform and continuous wavelet transform. Events of onset and cessation of the tremor-related activity in the STN and muscles were correlated to reveal the temporal relationship between the two signals. A significant suppression in the power of the STN LFPs in the beta band (10–30 Hz) preceded the onset of resting tremor, which was presented as the increases in the power at the tremor frequency (3.0–4.5 Hz) in both STN LFPs and surface EMGs. Over the episodes of the intermittent resting tremor, the power of the STN LFPs in the beta band and the power of sEMGs in the tremor frequency band change in an alternating pattern with a significant exponential correlation ( P STN = 16.8 + 62.3 × exp( −P EMG/6270.7); R 2 = 0.72; p < 0.05). Significant linear correlation in the power values at the tremor frequency appears between STN LFPs and sEMGs ( P STN = 65.1 + 2.1 × 10 −4 P EMG; R 2 = 0.41; p < 0.05). In comparison with short-time Fourier transform, similar results could be achieved using continuous wavelet transform of an appropriate wavelet with a higher temporal resolution but larger distortion in the high frequency.

The targeted force steps developed by a human wrist: Cyclic components in the motor program

The targeted flexor isometric force steps developed by a wrist and corresponding EMG activity of the flexor muscles were studied in healthy volunteers. In 82.3–97.5% of trials, the main component of the force trajectory (before the postcorrections of the force level) showed complex dynamics: several (from two to five)dF/dt peaks were observed at this section of the trajectory. The distribution of time intervals from the initiation of the force trajectory todF/dt peaks was polymodal in all cases. The mean interval between successivedF/dt peaks varied from 56.7 msec to 84.4 msec in different individuals (the average group value was 70.5 msec). All tested subjects exhibited amplitude modulation of integrated EMG at the section reflecting the force step development; the averaged interval between the successive first-order EMG peaks calculated for the group of five persons was 78.6 msec. Strict temporal correlation ofdF/dt peaks and EMG peaks was found (coefficient of correlation averaged 0.94). It is concluded that the motor command ensuring performance of isometric force step includes a cyclic component; this feature must be taken into account when mechanisms controlling such motor events are interpreted. The frequency of the component is near the upper limit of a normal tremor frequency band. At the same time, it is impossible to regard the cyclic component in the motor command as a result of simple superposition of tremor on the targeted force development because the cyclic component is clearly synchronized with the force step initiation.

Does tremor pace repetitive voluntary motor behavior in parkinson's disease?

In patients with Parkinson's disease and in normal subjects, the influence of tremor on repetitive voluntary movement was investigated in the index finger by comparing frequency of isometric force tremor with frequency of voluntary alternating isometric contractions. Tremor frequency, measured over the range from 0 to 70% maximum voluntary force, usually increased with force. The tremor frequency band was lower and more often overlapped with the upper voluntary frequency range in patients than in normal subjects. Normal subjects could accurately produce voluntary contractions at all cue frequencies from 1 to 5 Hz. Patients could produce auditory-paced frequencies of 1 and 2 Hz, but at higher cue frequencies, their voluntary contractions were often faster or slower than the cue. The faster or "hastened" voluntary frequencies were within the tremor frequency band, whereas the slowed voluntary frequencies were below it. Maximal voluntary frequency was often greater than the lowest but always less than the highest tremor frequency. It is concluded that parkinsonian tremor may pace voluntary repetitive movements to go faster than intended with the highest tremor frequency being an upper limit for voluntary frequency. Similar mechanisms may underlie the hastened repetitive vocal responses that were also observed in the parkinsonian patients.