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An assessment of central-peripheral ventilatory chemoreflex interaction using acid and bicarbonate infusions in humans.

16 February 2018

1. The object of this study was to investigate the effect of central chemoreceptor stimulation on the ventilatory responses to peripheral chemoreceptor stimulation. 2. The level of central chemoreceptor stimulation was varied by performing experiments at two different levels of end-tidal CO2 pressure (PCO2). Variations in peripheral chemoreceptor stimulus were achieved by varying arterial pH (at constant end-tidal PCO2) and by varying end-tidal O2 pressure (PO2). 3. Two protocols were each performed on six human subjects. In one protocol ventilatory measurements were made during eucapnia, when the arterial pH was lowered from 7.4 to 7.3. The variation in pH was achieved by the progressive infusion of acid (0.1 M HCl). In the other protocol ventilatory measurements were made during hypercapnia, when the arterial pH was increased from 7.3 to 7.4. The variation in pH was achieved by the progressive infusion of 1.26% NaHCO3. In each protocol ventilatory responses were measured during euoxia (end-tidal PO2, 100 Torr), hypoxia (end-tidal PO2, 50 Torr) and hyperoxia (end-tidal PO2, 300 Torr), with end-tidal PCO2 held constant. 4. The increase in ventilatory sensitivity to arterial pH induced by hypoxia (50 Torr) was not significantly different between protocols (acid protocol, -104 +/- 31 l min-1 (pH unit)-1 vs. bicarbonate protocol, -60 +/- 44 l min-1 (pH unit)-1; mean +/- S.E.M.; not significant (n.s.)). The ventilatory sensitivity to hypoxia at an arterial pH of 7.35 was not significantly different between protocols (acid protocol, 14.7 +/- 3.3 l min-1 vs. bicarbonate protocol, 15.6 +/- 2.4 l min-1; mean +/- S.E.M.; n.s.). The results provide no evidence to suggest that peripheral chemoreflex ventilatory responses are modulated by central chemoreceptor stimulation.

On the origin of oscillopsia during pedunculopontine stimulation.

6 February 2018

We report a case of induced oscillopsia caused by deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN). Recent reports have described involuntary oscillopsia during DBS of the PPN that patients have described as trembling vision. Here we substantiate this observation using infra-red eye tracking. It has been suggested that this phenomenon might be used as an indicator of accurate targeting of the PPN with DBS. Our observations suggest that this phenomenon may not be related to a constricted anatomical structure and therefore such practise may be unwise. Scrutiny has led us to believe that the oscillopsia in our patient is not caused by direct stimulation of the oculomotor nerve as suggested in a previous report, but by stimulation of fibres in the uncinate fasciculus of the cerebellum and the superior cerebellar peduncle, which in turn stimulate the saccadic pre-motor neurones in the brainstem.

Driving oscillatory activity in the human cortex enhances motor performance

19 February 2018

Voluntary movement is accompanied by changes in the degree to which neurons in the brain synchronize their activity within discrete frequency ranges. Two patterns of movement-related oscillatory activity stand out in human cortical motor areas. Activity in the beta frequency (15-30 Hz) band is prominent during tonic contractions but is attenuated prior to and during voluntary movement [1]. Without such attenuation, movement may be slowed, leading to the suggestion that beta activity promotes postural and tonic contraction, possibly at a cost to the generation of new movements [2, 3] . In contrast, activity in the gamma (60-90 Hz) band increases during movement [4]. The direction of change suggests that gamma activity might facilitate motor processing. In correspondence with this, increased frontal gamma activity is related with reduced reaction times [5] . Yet the possibility remains that these functional correlations reflect an epiphenomenal rather than causal relationship. Here we provide strong evidence that oscillatory activities at the cortical level are mechanistically involved in determining motor behavior and can even improve performance. By driving cortical oscillations using noninvasive electrical stimulation, we show opposing effects at beta and gamma frequencies and interactions with motor task that reveal the potential quantitative importance of oscillations in motor behavior. © 2012 Elsevier Ltd.

Parkinson's Disease tremor classification - A comparison between Support Vector Machines and neural networks

12 December 2017

A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation

3 April 2018

Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps. Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing, even where refractory to medication. However, the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established. The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral. Here, in a double-blinded study using objective spatiotemporal gait analysis, we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson's disease. Under experimental conditions, while OFF medication, Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions; off stimulation, unilateral stimulation and bilateral stimulation. Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls. Pedunculopontine nucleus stimulation improved objective measures of gait freezing, with bilateral stimulation more effective than unilateral. During unconstrained walking, Parkinsonian patients who experience gait freezing had reduced step length and increased step length variability compared to patients without gait freezing; however, these deficits were unchanged by pedunculopontine nucleus stimulation. Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Questionnaire scores, reflecting a reduction of the freezing encountered in patients' usual environments and medication states. This study provides objective, double-blinded evidence that in a specific subgroup of Parkinsonian patients, stimulation of a caudal pedunculopontine nucleus region selectively improves gait freezing but not background deficits in step length. Bilateral stimulation was more effective than unilateral. © 2012 The Author.

Parkinson's Disease tremor classification - A comparison between Support Vector Machines and neural networks

27 October 2017

Deep Brain Stimulation has been used in the study of and for treating Parkinson's Disease (PD) tremor symptoms since the 1980s. In the research reported here we have carried out a comparative analysis to classify tremor onset based on intraoperative microelectrode recordings of a PD patient's brain Local Field Potential (LFP) signals. In particular, we compared the performance of a Support Vector Machine (SVM) with two well known artificial neural network classifiers, namely a Multiple Layer Perceptron (MLP) and a Radial Basis Function Network (RBN). The results show that in this study, using specifically PD data, the SVM provided an overall better classification rate achieving an accuracy of 81% recognition. © 2012 Elsevier Ltd. All rights reserved.

Parkinsonian tremor identification with multiple local field potential feature classification.

3 April 2018

This paper explores the development of multi-feature classification techniques used to identify tremor-related characteristics in the Parkinsonian patient. Local field potentials were recorded from the subthalamic nucleus and the globus pallidus internus of eight Parkinsonian patients through the implanted electrodes of a Deep brain stimulation (DBS) device prior to device internalization. A range of signal processing techniques were evaluated with respect to their tremor detection capability and used as inputs in a multi-feature neural network classifier to identify the activity of Parkinsonian tremor. The results of this study show that a trained multi-feature neural network is able, under certain conditions, to achieve excellent detection accuracy on patients unseen during training. Overall the tremor detection accuracy was mixed, although an accuracy of over 86% was achieved in four out of the eight patients.

A robust strategy for decoding movements from deep brain local field potentials to facilitate brain machine interfaces

19 March 2018

A major thrust in brain machine interface (BMI) is to establish a robust, bi-directional direct link between the central nervous system (CNS) and artificial devices (e.g. medical implants, artificial organs, neural stimulators, robotic hands, etc.) for cybernetic interface and treatment of a range of neurodegenerative conditions. Significant effort has centered on support of motor control through external devices and direct stimulation through implanted electrodes in the brain, ideally supporting paralyzed or neurally damaged patients by bypassing damaged regions of the brain. The majority of neural decoding studies have focused on cortical areas for BMIs; however deep brain structures have also been involved in motor control. The subthalamic nucleus (STN) in the basal ganglia, for example, is involved in the preparation, execution and imagining of movements, and represents an unexplored alternative source with great potential for driving BMIs. The goal of this study is to establish this potential through decoding of deep brain local field potentials (LFPs) related to movement execution and laterality of visually cued movements. LFPs were recorded bilaterally from the STN through deep brain stimulation electrodes surgically implanted in patients with Parkinson's disease. The frequency dependent components of the LFPs were extracted using the wavelet packet transform. In each frequency component, signal features were extracted as the instantaneous power computed using the Hilbert transform. Based on these extracted features, a new feature selection strategy was developed to efficiently select the optimal feature subset. Two classifiers, the Bayesian and support vector machine (SVM) were implemented alongside this novel feature selection strategy, and evaluated using a cross-validation procedure. With optimised feature subset, average correct decoding of movement achieved 99.6±0.2% and 99.8±0.2% and subsequent laterality (left or right) classification reached 77.9±2.7% and 82.7±2.8% using the Bayesian and SVM classifier respectively. The work suggests that the neural activity in the basal ganglia can be used for controlling BMIs and holds great promise for a future generation of interfaces based in the STN. © 2012 IEEE.

The pathophysiology of brain swelling associated with subdural hemorrhage: the role of the trigeminovascular system.

28 March 2018

INTRODUCTION: This paper reviews the evidence in support of the hypothesis that the trigeminal system mediates brain swelling associated with subdural bleeding. The trigeminovascular system has been extensively studied in migraine; it may play an important but under-recognized role in the response to head trauma. Nerve fibers originating in trigeminal ganglion cells are the primary sensors of head trauma and, through their collateral innervation of the intracranial and dural blood vessels, are capable of inciting a cascade of vascular responses and brain swelling. The extensive trigeminal representation in the brainstem initiates and augments autonomic responses. Blood and tissue injury in the dura incite neurogenic inflammatory responses capable of sensitizing dural nerves and potentiating the response to trauma. DISCUSSION: The trigeminal system may provide the anatomo-physiological link between small-volume, thin subdural bleeds and swelling of the underlying brain. This physiology may help to explain the poorly understood phenomena of "second-impact syndrome," the infant response to subdural bleeding (the "big black brain"), as well as post-traumatic subdural effusions. Considerable age-specific differences in the density of dural innervation exist; age-specific responses of this innervation may explain differences in the brain's response to trauma in the young. An understanding of this pathophysiology is crucial to the development of intervention and treatment of these conditions. Antagonists to specific neuropeptides of the trigeminal system modify brain swelling after trauma and should be further explored as potential therapy in brain trauma and subdural bleeding.

Fusion of magnetometer and gradiometer sensors of MEG in the presence of multiplicative error.

9 January 2018

Novel neuroimaging techniques have provided unprecedented information on the structure and function of the living human brain. Multimodal fusion of data from different sensors promises to radically improve this understanding, yet optimal methods have not been developed. Here, we demonstrate a novel method for combining multichannel signals. We show how this method can be used to fuse signals from the magnetometer and gradiometer sensors used in magnetoencephalography (MEG), and through extensive experiments using simulation, head phantom and real MEG data, show that it is both robust and accurate. This new approach works by assuming that the lead fields have multiplicative error. The criterion to estimate the error is given within a spatial filter framework such that the estimated power is minimized in the worst case scenario. The method is compared to, and found better than, existing approaches. The closed-form solution and the conditions under which the multiplicative error can be optimally estimated are provided. This novel approach can also be employed for multimodal fusion of other multichannel signals such as MEG and EEG. Although the multiplicative error is estimated based on beamforming, other methods for source analysis can equally be used after the lead-field modification.