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The dysfunction of subthalamic nucleus is the main cause of Parkinson's disease. Local field potentials in human subthalamic nucleus contain rich physiological information. The present study aimed to quantify the oscillatory and dynamic characteristics of local field potentials of subthalamic nucleus, and their modulation by the medication therapy for Parkinson's disease. The subthalamic nucleus local field potentials were recorded from patients with Parkinson's disease at the states of on and off medication. The oscillatory features were characterised with the power spectral analysis. Furthermore, the dynamic features were characterised with time-frequency analysis and the coefficient of variation measure of the time-variant power at each frequency. There was a dominant peak at low beta-band with medication off. The medication significantly suppressed the low beta component and increased the theta component. The amplitude fluctuation of neural oscillations was measured by the coefficient of variation. The coefficient of variation in 4-7 Hz and 60-66 Hz was increased by medication. These effects proved that medication had significant modulation to subthalamic nucleus neural oscillatory synchronization and dynamic features. The subthalamic nucleus neural activities tend towards stable state under medication. The findings would provide quantitative biomarkers for studying the mechanisms of Parkinson's disease and clinical treatments of medication or deep brain stimulation.

Pathological neural activity in subthalamic nucleus (STN) is closely related to the symptoms of Parkinson' s disease. Local field potentials (LFPs) recordings from subthalamic nucleus show that power spectral peaks exist at tremor, double tremor and tripble tremor frequencies, respectively. The interaction between these components in the multi-frequency tremor may be related to the generation of tremor. To study the linear and nonlinear relationship between those components, we analyzed STN LFPs from 9 Parkinson's disease patients using time frequency, cross correlation, Granger casuality and bi-spectral analysis. Results of the time-frequency analysis and cross-frequency correlation analysis demonstrated that the power density of those components significantly decreased as the alleviation of tremor and cross-correlation (0.18-0.50) exists during tremor period. Granger causality of the time-variant amplitude showed stronger contribution from tremor to double tremor components, and contributions from both tremor and double tremor components to triple tremor component. Quadratic phase couplings among these three components were detected by the bispectral approaches. The linear and nonlinear relationships existed among the multi-components and certainly confirmed that the dependence cross those frequencies and neurological mechanism of tremor involved complicate neural processes.

A functioning thalamus is essential for treatment of patients with disorders of consciousness (DOC) using deep brain stimulation (DBS). This work aims to identify the potential biomarkers related to consciousness from the thalamic deep brain local field potentials (LFPs) in DOC patients. The frequency features of central thalamic LFPs were characterized with spectral analysis. The features were further compared to those of LFPs from the ventroposterior lateral nucleus of the thalamus (VPL) in patients with pain. There are several distinct characteristics of thalamic LFPs found in patients with DOC. The most important feature is the oscillation around 10Hz which could be relevant to the existence of residual consciousness, whereas high power below 8Hz seemed to be associated with loss of consciousness. The invasive deep brain recording tool opens a unique way to explore the brain function in consciousness, awareness and alertness and clarify the potential mechanisms of thalamic stimulation in DOC.

Pain perception can be altered by activity in the periaqueductal gray (PAG). The PAG can decrease the incoming nociceptive signals at the level of the spinal dorsal horn, but it is not clear whether the PAG can also affect the sensory thalamus, ventral posterolateral and ventral posteromedial thalamic nuclei, to modulate pain. However, the PAG and the thalamus have direct connections with each other; so we postulated that the PAG may also modulate pain by inhibiting the sensory nuclei in the thalamus, and that these may also reciprocally influence the PAG. Here, by analyzing the local field potentials recorded from the sensory thalamus and the PAG in chronic pain patients with deep brain stimulation electrodes, we show that PAG stimulation inhibited the sensory thalamus with decreasing thalamic delta, theta, alpha and beta power, and sensory thalamus stimulation excited the PAG with increasing PAG delta and theta power. We demonstrate that the PAG and the sensory thalamus interact reciprocally at short latency, which may be related to pain modulation.

Background: The midbrain periaqueductal and periventricular gray (PAVG) region is important for pain and autonomic modulation. We have previously described changes in blood pressure dependent upon dorsal or ventral electrode positioning with PAVG deep brain stimulation (DBS), yet controversy exists about whether DBS acts via endogenous opioid release., Method and Results: We combined local field potential (LFP) recording from PAVG DBS electrodes in humans with naloxone and saline infusions to determine whether dorsal and ventral PAVG DBS act through opioidergic or other mechanisms. Four awake human subjects were investigated. DBS were implanted contralateral to the painful body part. Electrode contact positions were mapped using MRI and brain atlas information. Naloxone then saline were randomly administered to the blinded subjects and pain rated using a numeric pain rating scale at 30s intervals for 3 min. Two subjects received dorsal DBS electrodes and two had ventral placements. Significantly elevated gamma frequency band (30-90 Hz) power concomitant with pain exacerbation was found with naloxone versus both saline and rest in dorsal not ventral PAVG LFPs (p<0.005). Significantly elevated delta frequency band (0-4 Hz) power (p=0.001) was seen in one ventral PAVG subject with both naloxone and saline infusions., Conclusions: Dorsal PAVG DBS may reduce pain by augmenting endogenous opioid release. Elevated gamma oscillations enhance awareness of worsening pain with opioid blockade. Ventral PAVG DBS may act by separate possibly autonomic mechanisms. Increased delta oscillations indicate a survival rhythm involved in the initiation of passive coping responses to homeostatic changes., (Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.)

We report a novel post-loading approach for constructing a multifunctional biodegradable polyacrylamide (PAA) nanoplatform for tumor-imaging (fluorescence) and photodynamic therapy (PDT). This approach provides an opportunity to post-load the imaging and therapeutic agents at desired concentrations. Among the PAA nanoparticles, a formulation containing the photosensitizer, HPPH [3-(1'-hexyloxyethyl)pyropheophorbide-a], and the cyanine dye in a ratio of 2:1 minimized the undesirable quenching of the HPPH electronic excitation energy because of energy migration within the nanoparticles and/or Förster (fluorescence) resonance energy transfer (FRET) between HPPH and cyanine dye. An excellent tumor-imaging (NIR fluorescence) and phototherapeutic efficacy of the nanoconstruct formulation is demonstrated. Under similar treatment parameters the HPPH in 1% Tween 80/5% aqueous dextrose formulation was less effective than the nanoconstruct containing HPPH and cyanine dye in a ratio of 2 to 1. This is the first example showing the use of the post-loading approach in developing a nanoconstructs for tumor-imaging and therapy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In this paper we introduce a robust classification framework for tongue-movement ear pressure signals based around an ensemble voting methodology. The ensemble members are comprised of different combinations of sensor inputs i.e. two in-ear microphones and an acoustic gel sensor positioned under the chin of the individual and classification using three different base models. It is shown that by using all nine ensemble members when compared to the individual (base) models, the average misclassification rate can be reduced from 23% to 2.8% when using the majority voting strategy. The correct classification rate is improved from 76% to 92.4% when utilizing either the borda count or condorcet methods. This is achieved through a combination of rejection based on ambiguity in the ensemble and diversity in the misclassified instances across the ensemble members.

Introduction:   Deep brain stimulation applied to the periaqueductal grey matter (PAG) of the midbrain in humans has been shown to increase or decrease arterial blood pressure during rest and to resist the postural fall on standing. The mechanism by which this effect is elicited is unknown. We hypothesize that PAG stimulation modulates performance of the autonomic nervous system., Methods:   Five consecutive male patients of a mean age of 49.1 years underwent PAG stimulation for intractable pain syndromes. Intra-operatively, blood pressure and heart rate were recorded continuously while patients were awake (four patients) or under general anesthesia (one patient). Recordings were made for 100 sec before stimulation, 100 sec during stimulation at one or two electrode locations within the PAG, and for 100 sec after stimulation., Results:   Stimulation altered not only systolic and diastolic blood pressure but also heart rate. During stimulation, systolic blood pressure increased in three electrode positions by 7.2-10.2 mmHg, decreased in two electrode positions by 3.1-11.5 mmHg, and was unchanged in two electrode positions. Heart rate variability also changed during stimulation. Percentage systolic blood pressure change was positively correlated with change in high-frequency power (Pearson's r= 0.685, p= 0.09, N= 7), low-frequency : high-frequency power ratio (r= 0.667, p= 0.10, N= 7), and low-frequency power (r= 0.818, p= 0.02, N= 7), the latter of which was statistically significant. The percentages of the variance explained (r(2)) were 46.9, 44.5, and 66.9, respectively., Conclusions:   PAG stimulation modulates autonomic nervous system activity and thereby elicits changes in cardiovascular performance. Understanding of the mechanisms by which this therapy causes cardiovascular modulation will inform future innovation in this field with the aim of improving the efficacy and safety of patient treatment options., (© 2010 International Neuromodulation Society.)

This study was designed to test the hypothesis that postsuspension cardiovascular manifestation in conscious rats after a medium-term (28-day) tail suspension (SUS) is hypertensive and tachycardiac and can be prevented by a countermeasure of daily 1-h dorsoventral (-G(x)) gravitation provided by standing (STD). To assess associated changes in cardiovascular regulation, blood pressure (BP) and heart rate (HR) variability were analyzed by spectral analysis computed by parametric autoregressive (AR) method and by nonlinear recurrence quantification analysis (RQA) and approximate entropy (ApEn) measure. The results showed that conscious SUS rats manifested hypertensive and tachycardiac response before and after being released from suspension compared with the controls, and the countermeasure of 1 h/day -G(x) prevented the hypertensive response. Auto- and cross-spectral analysis and transfer function analysis did not show significant changes in cardiovascular variability. However, SUS decreased the three RQA indexes [recurrence percentage (RC%), determinism percentage (DT%), and the longest diagonal line (L(max))] of systolic BP, whereas STD alleviated these changes. ApEn values of HR data sets were significantly higher in the SUS and SUS + STD groups compared with those of the control group before and after release from suspension. The present study has demonstrated that daily -G(x) for as short as 1 h is sufficient to prevent postsuspension cardiovascular alteration in conscious rats after a medium-term SUS. Nonlinear measures, but not spectral analysis, might provide promising data to estimate the overall changes in cardiovascular autonomic regulation due to microgravity exposure.

The goal of this work was to develop and implement a new filtering strategy to denoise acoustic signals in the ear canal resulting from voluntary movement of the tongue (as a method of generating control input), as well as from other active actions, (speech, eating, drinking, smoking), and passive actions (swallowing, adjusting the jaw, physiological activity). The strategy is based on a denoising wavelet shrinkage approach that separates rhythmic bursting activity and white noise representing sustained tonic activity. While past work has addressed the discrimination of voluntary TMEP signals from one-another, no work has addressed acoustic artefact rejection within the ear. The results described here, combined with our past work in isolating critical components of tongue movement ear pressure (TMEP) signals, provide a basis for discriminating voluntary and involuntary actions of the tongue by monitoring pressure in the ear. At this time, the system has worked in real-time for assistive device control.

We aimed to identify neural oscillations in the time-frequency representation of local field potentials recorded from the subthalamic nucleus. The time-frequency representation was normalised over the global mean and standard deviation global normalisation, or against the baseline period at each frequency, local normalisation. The cross-correlation between beta and gamma oscillations was enhanced by global normalisation. Furthermore, voluntary movement related amplitude changes in the gamma band and frequency modulation in the beta band were revealed by local normalisation. Thus global or local normalisation of time-frequency representation provides a reliable and effective way to identify oscillatory rhythms in subthalamic neural activity by reducing noise and increasing frequency discrimination. It can be used to enhance the detection of obscure or hidden neural oscillations and improve the sensitivity of post-hoc analysis.

In a patient of generalised dystonia treated with bilateral pallidal stimulation, serial surface EMGs recorded from the neck muscles during alternating head movements revealed progressive reduction in hypertonic activity and reversal of co-contraction to reciprocal contraction, which preceded clinical improvement., (Copyright 2003 Movement Disorder Society)