1,721,247 research outputs found
The direction of oscillation in spiral drawings can be used to differentiate distal and proximal arm tremor
No full textThe assessment of the extent of involvement of the distal and proximal joints in a complex arm tremor is important clinically, as tremor generated around the distal and proximal arm joints can be differentially alleviated by surgical intervention to the thalamic and subthalamic targets, respectively. We observed that the tremor present in spiral drawings shows a diagonal directional preference. We hypothesized that the directional preference of tremor within spiral drawings could be related to the involvement of different arm joints. In this study, we tested this hypothesis by: (1) studying simulated tremulous drawings performed by healthy subjects with the joints selectively restrained; (2) recording surface EMGs from the forearm extensor and deltoid muscles during drawing; and (3) mathematical modelling the kinematics of the arm in 2D drawings. Our data showed that a “main diagonal” axis of orientation of the tremor along the orientation of the forearm indicates a predominantly proximal tremor driven by the shoulder, and a “cross diagonal” axis of orientation of tremor (i.e. perpendicular to the forearm) indicates that the tremor is predominantly distal and driven by the elbow or wrist. We conclude that the spiral drawing task can be used as an objective and quantitative method for differentiating the involvement of the proximal and distal arm joints in complex arm tremors
Different mechanisms may generate sustained hypertonic and rhythmic bursting muscle activity in idiopathic dystonia
No full textDespite that deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favored intervention for patients with medically intractable dystonia, the pathophysiological mechanisms of dystonia are largely unclear. In eight patients with primary dystonia who were treated with bilateral chronic pallidal stimulation, we correlated symptom-related electromyogram (EMG) activity of the most affected muscles with the local field potentials (LFPs) recorded from the globus pallidus electrodes. In 5 dystonic patients with mobile involuntary movements, rhythmic EMG bursts in the contralateral muscles were coherent with the oscillations in the pallidal LFPs at the burst frequency. In contrast, no significant coherence was seen between EMG and LFPs either for the sustained activity separated out from the compound EMGs in those 5 cases, or in the EMGs in 3 other cases without mobile involuntary movements and rhythmic EMG bursts. In comparison with the resting condition, in both active and passive movements, significant modulation in the GPi LFPs was seen in the range of 8–16 Hz. The finding of significant coherence between GPi oscillations and rhythmic EMG bursts but not sustained tonic EMG activity suggests that the synchronized pallidal activity may be directly related to the rhythmic involuntary movements. In contrast, the sustained hypertonic muscle activity may be represented by less synchronized activity in the pallidum. Thus, the pallidum may play different roles in generating different components of the dystonic symptom complex
Time-frequency analysis of transient neuromuscular events: dynamic changes in activity of the subthalamic nucleus and forearm muscles related to the intermittent resting tremor
No full textIn 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 ceasing 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 - 30Hz) preceded the onset of resting tremor which was presented as the increases in the power at the tremor frequency (3.0 - 4.5Hz) 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 (PSTN = 16.8 + 62.3*exp(-PEMG/6270.7); R2 = 0.72; p < 0.05). Significant linear correlation in the power values at the tremor frequency appears between STN LFPs and sEMGs (PSTN = 65.1 + 2.1*10-4PEMG; R2 = 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
Physiological and harmonic components in neuromuscular coherence in Parkinsonian tremor
No full textObjective: To differentiate physiological from harmonic components in coherence analysis of the tremor-related neural and muscular signals by comparing power, cross-power and coherence spectra. Methods: Influences of waveform, burst-width and additional noise on generating harmonic peaks in the power, cross-power and coherence spectra were studied using simulated signals. The local field potentials of the subthalamic nucleus (STN) and the EMGs of the contralateral forearm muscles in PD patients with rest tremor were analysed.Results: (1) Waveform had significant effect on generating harmonics; (2) noise significantly decreased the coherence values in a frequency-dependent fashion; and (3) cross-spectrum showed high resistance to harmonics. Among six examples of paired LFP-EMG signals, significant coherence appeared at the tremor frequency only, both the tremor and double tremor frequencies and the double-tremor frequency only. Conclusions: In coherence analysis of neural and muscular signals, distortion in waveform generates significant harmonic peaks in the coherence spectra and the coherence values of both physiological and harmonic components are modulated by extra noise or non-tremor related activity. Significance: The physiological or harmonic nature of a coherence peak at the double tremor frequency may be differentiated when the coherence spectra are compared with the power spectra and in particular the cross-spectra
Pedunculopontine nucleus stimulation for gait and postural disorders in Parkinson's disease
Full text linkThe pedunculopontine nucleus (PPN) is a reticular collection of neurons at the junction of midbrain and pons. The PPN in animal models appears topographically organised and functionally related to locomotion and arousal. In Parkinson’s disease, the PPN degenerates and is susceptible to abnormal basal ganglia output. In patients with Parkinson’s disease, low frequency PPN stimulation is proposed to improve gait freezing and postural instability. However, the therapeutic mechanisms, optimal clinical application and precise effects on gait and posture of PPN stimulation are unclear.Here, a topographic arrangement of the PPN was supported by local field potential recordings in parkinsonian patients. In the PPN region, beta oscillations were recorded rostrally and alpha oscillations caudally. Alpha oscillations, consistent with their putative role in allocating attention, correlated with gait performance and attenuated with gait freezing. Thus the caudal PPN subregion may be the most relevant target for gait disorders.Accordingly, an unblinded clinical study suggested that stimulation of the caudal PPN subregion was beneficial for gait freezing, postural instability and falls. In a double-blinded study using spatiotemporal gait analysis, caudal PPN stimulation reduced triggered gait freezing, with bilateral stimulation more effective than unilateral. However, akinesia including akinetic gait did not improve with PPN stimulation. Accordingly, dopaminergic medication requirements did not change.Mechanisms underlying gait freezing and PPN stimulation were explored with reaction time experiments. Parkinsonian patients with severe gait freezing and postural instability demonstrated a ‘block’ to pre-programmed movement. This was evidenced by prolonged simple reaction times and the absence of ‘StartReact’, whereby pre-prepared responses are normally accelerated by loud acoustic stimuli. PPN stimulation improved simple reaction time and restored Startreact. The relief of this ‘motor block’ with PPN stimulation may therefore explain the associated improvement in gait freezing and postural instability, as these tend to occur in circumstances requiring triggered, pre-prepared adjustments
Probing and modulating brain circuits by deep brain stimulation: Functional connectivity between the sensory nuclei of thalamus and the periaqueductal grey in pain modulation
Full text linkBackgrounds. The periaqueductal grey(PAG) plays an important role in the descending pain modulation systems, which has been known to inhibit incoming nociceptive signals at the level of the spinal dorsal horn. But pain mechanism involves the brain and the spinal cord to maintain homeostasis, so theoretically pain modulation mechanism should involve both direction: ascending and descending pathways to the brain and spinal cord dorsal horn. However, literature addressing this question is limited. The sensory thalamus is the most important brain area receiving sensory signals. Moreover, with the fact that evidence indicates the PAG and the thalamus have functional connections, therefore we wanted to test if there is a functional connection between the PAG and the sensory thalamus related to pain modulation. Aims. To investigate the functional connectivity between the periaqueductal grey and the sensory nuclei of the thalamus in pain modulation Methods. Three experiments have been conducted. The first experiment is to investigate the effect of PAG DBS on the sensory thalamus, and vice versa, in chronic neuropathic pain patients. The second experiment is to estimate the change of spectral coherence between the sensory thalamus and the PAG during various pain states, when chronic neuropathic pain patients were being peripheral stimulated by ice to evoke pain. The third experiment is to test whether the functional connectivity between the two areas would be affected by general anaesthetics propofol. Results. PAG DBS inhibited the sensory thalamus with decreasing thalamic delta, theta, alpha and beta power, and sensory thalamus DBS excited the PAG with increasing PAG delta and theta power. The PAG and the sensory thalamus interact reciprocally at short latency, which may be related to pain modulation. The sensory thalamus and the periaqueductal grey also have high gamma coherence which would be inhibited by pain. This high-gamma coherence was increased during propofol induction period which is compatible with the hypothesis that propofol induces loss of consciousness via its GABAergic activity. Conclusions. This thesis suggests that the sensory thalamus and the periaqueductal grey have a reciprocal connection. Functionally this connectivity might be related to pain modulation. Also this functional connectivity might represent the fact that the transmission and processing of pain signals is always monitored and modified by central pain modulation systems so that organisms can respond properly to the incoming signals
Extracting burst and tonic components from surface electromyograms in dystonia using adaptive wavelet shrinkage
No full textThe compound surface EMGs recorded from patients with dystonia commonly contains superimposed bursting and tonic activity representing various motor symptoms. It is desirable to differentially extract them from the compound EMGs so that different symptoms can be more specifically investigated and different mechanisms revealed. A non-linear denoising approach based on wavelet transformation was investigated by applying soft thresholding to the wavelet coefficients. Thresholds were determined according to three different principles and two models. Different techniques for wavelet shrinkage were investigated for separating burst and tonic activity in the compound EMGs. The combination of Stein’s unbiased risk estimate principle with a non-white noise model proved optimal for separating burst and tonic activity. These turned out to be exponentially related; and the temporal relationships between antagonist muscle contractions could now be seen clearly. We conclude that adaptive soft-thresholding wavelet shrinkage provides effective separation of burst and tonic activity in the compound EMG in dystonia. This separation should improve our understanding of the pathophysiology of dystonia
Neuromodulation for Intractable Pain
Full text linkOver 7% of the Western population suffers from intractable pain. Despite pharmacotherapy, many patients (1.5%) suffer from refractory pain. In addition to the pain, patients continue to be highly debilitated and suffer from depression and anxiety, poor quality of life and loss of employment. An ever enlarging global problem concerns the use of opiates which have risen to dangerous levels. Neuromodulation of the nervous system—where the function of the nervous system is altered by a device—has, over time, emerged as an effective alternative to pharmacotherapy in the management of these patients. In this Special Issue, we discussed the indications, safety, efficacy, mechanisms of action and other aspects of neurmodulation therapies for pain relief. These include peripheral nerve stimulation, peripheral field stimulation, spinal cord stimulation, dorsal root ganglion stimulation, motor cortex stimulation and deep brain stimulation. We do not intend this Special Issue to be a comprehensive study of pain but a guide to help clinicians to refer patients appropriately and to decide which procedure would best be offered in certain situations
Approach to study the brain: towards the early detection of neurodegenerative disease
Full text linkNeurodegeneration is a progressive loss of neuron function or structure, including death of neurons, and occurs at many different levels of neuronal circuitry. In this thesis I discuss Parkinson’s Disease (PD), the second most common neurodegenerative disease (NDD). PD is a devastating progressive NDD often with delayed diagnosis due to detection methods that depend on the appearance of visible motor symptoms. By the time cardinal symptoms manifest, 60 to 80 percent or more of the dopamine-producing cells in the substantia nigra are irreversibly lost. Although there is currently no cure, earlier detection would be highly beneficial to manage treatment and track disease progression. However, today’s clinical diagnosis methods are limited to subjective evaluations and observation. Onset, symptoms and progression significantly vary from patient to patient across stages and subtypes that exceed the scope of a standardized diagnosis. The goal of this thesis is to provide the basis of a more general approach to study the brain, investigating early detection method for NDD with focus on PD. It details the preliminary development, testing and validation of tools and methods to objectively quantify and extrapolate motor and non-motor features of PD from behavioral and cognitive output during everyday life. Measures of interest are categorized within three domains: the motor system, cognitive function, and brain activity. This thesis describes the initial development of non-intrusive tools and methods to obtain high-resolution movement and speech data from everyday life and feasibility analysis of facial feature extraction and EEG for future integration. I tested and validated a body sensor system and wavelet analysis to measure complex movements and object interaction in everyday living situations. The sensor system was also tested for differentiating between healthy and impaired movements. Engineering and design criteria of the sensor system were tested for usability during everyday life. Cognitive processing was quantified during everyday living tasks with varying loaded conditions to test methods for measuring cognitive function. Everyday speech was analyzed for motor and non-motor correlations related to the severity of the disease. A neural oscillation detection (NOD) algorithm was tested in pain patients and facial expression was analyzed to measure both motor and non-motor aspects of PD. Results showed that the wearable sensor system can measure complex movements during everyday living tasks and demonstrates sensitivity to detect physiological differences between patients and controls. Preliminary engineering design supports clothing integration and development of a smartphone sensor platform for everyday use. Early results from loaded conditions suggest that attentional processing is most affected by cognitive demands and could be developed as a method to detect cognitive decline. Analysis of speech symptoms demonstrates a need to collect higher resolution spontaneous speech from everyday living to measure speech motor and non-motor speech features such as language content. Facial expression classifiers and the NOD algorithm indicated feasibility for future integration with additional validation in PD patients. Thus this thesis describes the initial development of tools and methods towards a more general approach to detecting PD. Measuring speech and movement during everyday life could provide a link between motor and cognitive domains to characterize the earliest detectable features of PD. The approach represents a departure from the current state of detection methods that use single data entities (e.g.one-off imaging procedures), which cannot be easily integrated with other data streams, are time consuming and economically costly. The long-term vision is to develop a non-invasive system to measure and integrate behavioral and cognitive features enabling early detection and progression tracking of degenerative disease
Neuromodulation in pain
Full text linkBackground
Chronic pain is one of the most debilitating disorders afflicting a wide cross-section of the global population. Unfortunately, conventional treatments for chronic pain have proven ineffective for a large subsection of this patient population, prompting the development of new therapeutic paradigms such as neuromodulation. Deep brain stimulation, dorsal root ganglion stimulation and non-invasive brain stimulation have emerged as useful tools in the therapeutic armamentarium for these medically refractory chronic pain patients. We sought to interrogate how these treatments might work and what insights can be gained into the neurophysiology of the pain experience through neuromodulation.
Methods
This thesis describes three categories of experiments into the neurophysiology of chronic pain. The first explored the mechanisms of dorsal root ganglion stimulation in the sensory, cognitive and affective dimensions of pain, as well as its potential to modulate the autonomic nervous system. The second interrogated the utility of non-invasive brain stimulation, transcranial direct current stimulation, to augment the supraspinal effects of dorsal root ganglion stimulation. The final experiment involved a retrospective analysis regarding the effectiveness stimulation frequency in deep brain stimulation for chronic pain and whether these treatments are dependent on underlying neural activity.
Results
1. There were significant neurophysiologic markers of pain (cortical theta activity) and pain relief (cortical beta activity) among dorsal root ganglion stimulation patients, with efficacy in modulating sensory, cognitive and autonomic indicators in chronic pain patients. The affective dimension of 3 pain revealed mixed results, however demonstrated features consistent with differences of emotional processing in chronic pain compared to healthy controls.
2. Transcranial direct current stimulation significantly enhanced the therapeutic efficacy of dorsal root ganglion stimulation on chronic pain in the acute setting and demonstrated augmentation of predetermined neurophysiologic indicators (cortical beta activity) of pain relief.
3. The efficacy of deep brain stimulation did not appear to be dependent on stimulation frequency. However, baseline local field potential recordings appear to be predictive of the ideal stimulation frequency to optimise analgesic effect in chronic pain patients.
Conclusion
This thesis provides novel evidence of the mechanisms of dorsal root ganglion stimulation and provides preliminary evidence of a synergistic effect between invasive and non-invasive neuromodulation in the treatment of chronic pain. We have also provided supportive evidence for the utility of physiologic biomarkers of pain in evaluating neuromodulatory therapies as a framework for personalising chronic pain treatments
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