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  • Frequency specific activity in subthalamic nucleus correlates with hand bradykinesia in Parkinson's disease.

    3 July 2018

    Local field potential recordings made from the basal ganglia of patients undergoing deep brain stimulation have suggested that frequency specific activity is involved in determining the rate of force development and the peak force at the outset of a movement. However, the extent to which the basal ganglia might be involved in motor performance later on in a sustained contraction is less clear. We therefore recorded from the subthalamic nucleus region (STNr) in patients with Parkinson's disease (PD) as they made maximal voluntary grips. Relative to age-matched controls they had more rapid force decrement when contraction was meant to be sustained and prolonged release reaction time and slower rate of force offset when they were supposed to release the grip. These impairments were independent from medication status. Increased STNr power over 5-12 Hz (in the theta/alpha band) independently predicted better performance-reduced force decrement, shortened release reaction time and faster rate of force offset. In contrast, lower mean levels and progressive reduction of STNr power over 55-375 Hz (high gamma/high frequency) over the period when contraction was meant to be sustained were both strongly associated with greater force decrement over time. Higher power over 13-23 Hz (low beta) was associated with more rapid force decrement during the period when grip should have been sustained, and with a paradoxical shortening of the release reaction time. These observations suggest that STNr activities at 5-12 Hz and 55-375 Hz are necessary for optimal grip performance and that deficiencies of such activities lead to motor impairments. In contrast, increased levels of 13-25 Hz activity both promote force decrement and shorten the release reaction time, consistent with a role in antagonising (and terminating) voluntary movement. Frequency specific oscillatory activities in the STNr impact on motor performance from the beginning to the end of a voluntary grip.

  • Persistent suppression of subthalamic beta-band activity during rhythmic finger tapping in Parkinson's disease.

    3 July 2018

    OBJECTIVE: The function of synchronous oscillatory activity at beta band (15-30Hz) frequencies within the basal ganglia is unclear. Here we sought support for the hypothesis that beta activity has a global function within the basal ganglia and is not directly involved in the coding of specific biomechanical parameters of movement. METHODS: We recorded local field potential activity from the subthalamic nuclei of 11 patients with Parkinson's disease during a synchronized tapping task at three different externally cued rates. RESULTS: Beta activity was suppressed during tapping, reaching a minimum that differed little across the different tapping rates despite an increase in velocity of finger movements. Thus beta power suppression was independent of specific motor parameters. Moreover, although beta oscillations remained suppressed during all tapping rates, periods of resynchronization between taps were markedly attenuated during high rate tapping. As such, a beta rebound above baseline between taps at the lower rates was absent at the high rate. CONCLUSION: Our results demonstrate that beta desynchronization in the region of the subthalamic nucleus is independent of motor parameters and that the beta resynchronization is differentially modulated by rate of finger tapping, SIGNIFICANCE: These findings implicate consistent beta suppression in the facilitation of continuous movement sequences.

  • Stimulation of the subthalamic nucleus improves velocity of ballistic movements in Parkinson's disease.

    3 July 2018

    High-frequency stimulation of the subthalamic nucleus can markedly improve motor function in patients with Parkinson's disease. However, the underlying mechanisms mediating these improvements are not well understood. In particular, whether motor function is differentially improved in distal or proximal movements is not fully determined. Also, whether reaction time is improved along with other motor parameters is still a matter of debate. Here, we test patients OFF and ON subthalamic nucleus stimulation by capturing simple ballistic movements across four joints using kinematic motion analysis. We show that velocity, but not reaction time, is significantly improved with stimulation. There was no strong differential effect between joints. These results add evidence that deep brain stimulation of the subthalamic nucleus can enhance performance of ballistic movements in Parkinson's disease, and demonstrate that the subthalamic nucleus may be important in driving parameters of motor control after the response has been initiated.

  • Deep brain stimulation for pain.

    3 July 2018

    Deep brain stimulation (DBS) is a neurosurgical intervention whose efficacy, safety, and utility have been shown in the treatment of movement disorders. For the treatment of chronic pain refractory to medical therapies, many prospective case series have been reported, but few have published findings from patients treated during the past decade using current standards of neuroimaging and stimulator technology. We summarize the history, science, selection, assessment, surgery, and personal clinical experience of DBS of the ventral posterior thalamus, periventricular/periaqueductal gray matter, and, latterly, the rostral anterior cingulate cortex (Cg24) in 100 patients treated now at two centers (John Radcliffe Hospital, Oxford, UK, and Hospital de São João, Porto, Portugal) over 12 years. Several experienced centers continue DBS for chronic pain with success in selected patients, in particular those with pain after amputation, brachial plexus injury, stroke, and cephalalgias including anesthesia dolorosa. Other successes include pain after multiple sclerosis and spine injury. Somatotopic coverage during awake surgery is important in our technique, with cingulate DBS considered for whole-body pain or after unsuccessful DBS of other targets. Findings discussed from neuroimaging modalities, invasive neurophysiological insights from local field potential recording, and autonomic assessments may translate into improved patient selection and enhanced efficacy, encouraging larger clinical trials.

  • Deep Brain Stimulation for Blood Pressure Control

    3 July 2018

    This chapter focuses on the use of deep brain stimulation (DBS) for controlling blood pressure. Hypertension and orthostatic hypotension refractory to medical treatment present a considerable disease burden, with high associated morbidity and mortality. The periaqueductal gray area (PAG) is an important region for the modulation of pain targeted by DBS electrodes during the treatment of chronic, intractable neuropathic pain. The electrical stimulation of the PAG in animals elicits defence reactions, where dorsal regions are associated with active coping and hypertensive effects and ventral regions with passive coping and hypotensive effects. Thus PAG DBS has been related to hypertensive and chronotropic cardiovascular effects. In a study of 15 chronic neuropathic pain patients (two patients having bilateral implants), blood pressure and heart rate were continuously measured while DBS parameters were altered from 10 to 50 Hz. Cardiovascular responses to stimulation were consistent, as measured on at least three occasions, for any pair of electrode contacts used. Arterial blood pressure reduced significantly overall in seven pairs of electrode contacts in seven patients. Conversely, blood pressure increased significantly in six pairs of contacts in six patients. The demonstration that PAG DBS can increase as well as decrease blood pressure raises the possibility that orthostatic or postural hypotension might be treatable by neurosurgery. © 2009 Elsevier Ltd All rights reserved.

  • Deep brain stimulation for chronic pain

    3 July 2018

    As a clinical intervention, deep brain stimulation (DBS) has provided remarkable therapeutic benefits for otherwise treatment-resistant movement and affective disorders including chronic pain. In this review, we concentrate on the experience of using DBS to treat chronic pain in Oxford. We provide a brief historical background as well as details of our methods for patient selection, surgical techniques and assessment. While the precise mechanisms of action for DBS remain uncertain, we describe how DBS can help for treatment-resistant chronic pain and have great potential to advance our general understanding of the human brain. In particular, we show how DBS can be used in conjunction with methods such as local field potentials and magnetoencephalography to map the underlying mechanisms of normal and abnormal oscillatory synchronization in the brain related to the pleasure of pain relief. © 2010 by Nova Science Publishers, Inc. All rights reserved.

  • The effect of exercise on the development of respiratory depression during sustained isocapnic hypoxia in humans.

    3 July 2018

    The purpose of this study was to examine whether sustained hypoxia during exercise attenuates the degree of decline in hypoxic ventilatory sensitivity which occurs during sustained hypoxia at rest. The acute ventilatory response to hypoxia (AHVR) was used as a measure of the hypoxic ventilatory chemoreflex sensitivity. Seven subjects undertook three protocols. Protocol A was designed to assess the reduction in AHVR as a result of 20 min of isocapnic hypoxia (end-tidal PO2 50 mm Hg) at rest. The first AHVR (control) was measured on exposure to the hypoxia, and the second AHVR (test) measured 6 min after the end of the hypoxic period. Protocols B and C were designed to assess the reduction in AHVR as a result of 20 min of isocapnic hypoxic exercise (70 W). In protocol B, the AHVR (test) was measured at rest, 6 min after the end of 20 min of isocapnic hypoxic (end-tidal PO2 55 mm Hg) exercise. In protocol C, the AHVR (control) as measured at rest, 6 min after the end of 20 min of euoxic (end-tidal PO2 100 mm Hg) isocapnic exercise. There was a 30 +/- 5% decline (mean +/- SEM) in the magnitude of the AHVR after the period of sustained hypoxia at rest. There was an 11 +/- 7% decline in the magnitude of the resting AHVR after the period of sustained hypoxic exercise. The percentage change in AHVR following hypoxic exercise was significantly less than following hypoxia at rest (p < 0.05; paired t test). We conclude that the decline in hypoxic chemoreflex sensitivity which occurs during sustained hypoxia at rest is genuinely attenuated as a result of exercise.

  • Effect of pain and audiovisual stimulation on the depression of acute hypoxic ventilatory response by low-dose halothane in humans.

    3 July 2018

    BACKGROUND: The effects of different low-dose volatile agents in blunting the acute hypoxic ventilatory response (AHVR) are variable. Arousal (due to audiovisual stimulation) may prevent isoflurane-induced blunting of AHVR. The purpose of this study was to assess whether this was also the case for halothane. The authors also assessed the effects of pain on the interaction of halothane and AHVR. METHODS: Step decreases in end-tidal partial pressure of oxygen using dynamic end-tidal forcing were performed from normoxia to hypoxia (50 mmHg) in 10 healthy volunteers, with end-tidal partial pressure of carbon dioxide held 1-2 mmHg above normal, in six protocols: (1) control conditions (darkened, quiet room, eyes closed) without halothane and (2) with 0.1 minimum alveolar concentration (MAC) halothane; (3) audiovisual stimulation (bright room, loud television) without halothane and (4) with 0.1 MAC halothane; (5) pain (electrical stimulation of skin over the tibia to produce a visual analog pain score of 5-6 out of 10) without halothane and (6) with 0.1 MAC halothane. The Bispectral Index of the electroencephalogram was also monitored. RESULTS: Halothane did not affect normoxic minute ventilation in any arousal state but significantly reduced the magnitude of AHVR by 50% regardless of the background arousal state (P < 0.001). Bispectral Index values were reduced by halothane only in the absence of arousal (P < 0.003). Both pain and audiovisual stimulation modestly increased normoxic minute ventilation (P < 0.002) and AHVR (P < 0.003). CONCLUSIONS: Audiovisual stimulation does not prevent the blunting of AHVR by low-dose halothane. This result with halothane differs from previous results with isoflurane. Therefore, different anesthetics interact in different ways with arousal states. This finding raises the possibility that different anesthetics might differentially affect the hypoxic chemoreflex loop or that they might act in the brain at sites separate from the chemoreflex loop, differently to influence the wakefulness drive to ventilation.

  • Sparrow Group

    22 October 2015

    Investigating the Genetic and Environmental Causes of Congenital Heart Disease

  • Hens Group

    16 September 2013

  • Patton Group

    28 April 2014

    Nanodiamond as a sensor for biologically generated electric and magnetic fields

  • Garcia-Moreno Group

    19 December 2013

    Forebrain Evolution Research laboratory

  • Zifarelli Group

    5 February 2015

    CLC chloride channels and transporters

  • Packer Group

    21 May 2018