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  • Deep brain stimulation for chronic pain investigated with magnetoencephalography.

    28 January 2018

    Deep brain stimulation has shown remarkable potential in alleviating otherwise treatment-resistant chronic pain, but little is currently known about the underlying neural mechanisms. Here for the first time, we used noninvasive neuroimaging by magnetoencephalography to map changes in neural activity induced by deep brain stimulation in a patient with severe phantom limb pain. When the stimulator was turned off, the patient reported significant increases in subjective pain. Corresponding significant changes in neural activity were found in a network including the mid-anterior orbitofrontal and subgenual cingulate cortices; these areas are known to be involved in pain relief. Hence, they could potentially serve as future surgical targets to relieve chronic pain.

  • Chronic pedunculopontine nucleus stimulation restores functional connectivity.

    28 January 2018

    The mechanisms of deep brain stimulation (DBS) are poorly understood. Earlier, high-frequency DBS has been thought to represent a depolarization block of the target area and low-frequency stimulation has been thought to 'drive' neuronal activity. We investigated the long-term effect of low-frequency DBS in a longitudinal imaging study of a patient who received bilateral pedunculopontine nucleus stimulation. We used the diffusion tensor imaging techniques including probabilistic tractography and topographic mapping to analyze long-term changes in connectivity with low-frequency DBS. Post-DBS connectivity analysis suggested a normalization of pathological pedunculopontine nucleus connectivity with DBS therapy. These findings may help elucidate the mechanisms of DBS, suggesting neuroplasticity involving a reorganization of target connectivity long term. This is the first reported case showing neuroimaging evidence of neuroplasticity after low-frequency DBS.

  • Deep brain stimulation can regulate arterial blood pressure in awake humans.

    19 March 2018

    The periaqueductal grey matter is known to play a role in cardiovascular control in animals. Cardiovascular responses to electrical stimulation of the periventricular/periaqueductal grey matter were measured in 15 awake human study participants following implantation of deep brain stimulating electrodes for treatment of chronic pain. We found that stimulation of the ventral periventricular/periaqueductal grey matter caused a mean reduction in systolic blood pressure of 14.2+/-3.6 mmHg in seven patients and stimulation of the dorsal periventricular/periaqueductal grey matter caused a mean increase of 16.7+/-5.9 mmHg in six patients. A comparison between ventral and dorsal electrodes demonstrated significant differences (P<0.05). These changes were accompanied by analogous changes in diastolic blood pressure, pulse pressure, maximum dP/dt but not in the time interval between each R wave on the electrocardiogram.

  • Connectivity of the pedunculopontine nucleus in parkinsonian freezing of gait.

    15 March 2018

    Parkinson's disease (PD) may involve sudden unintended arrests in gait or failure to initiate gait, known as gait freezing. Deep brain stimulation of the pedunculopontine nucleus (PPN) has been found to be an effective therapy for this phenomenon. In this study, we characterized the connectivity of the PPN freezing of gait (FOG) patients, compared with non-FOG PD and healthy controls using diffusion tensor imaging techniques. Differences in PPN connectivity profiles of the study groups were shown in the cerebellum and pons. The PPN showed connectivity with the cerebellum in controls and non-FOG PD. FOG patients showed absence of cerebellar connectivity, and increased visibility of the decussation of corticopontine fibres in the anterior pons. The findings suggest that corticopontine projections, which cross at the pons are increased in gait freezing, highlighting the importance and role of corticopontine-cerebellar pathways in the pathophysiology of this phenomenon.

  • Depiction of the neuroscientific principles of human motion 2 millennia ago by Lucretius.

    12 December 2017

    Titus Lucretius Carus was an ancient Roman philosopher of the Epicurean school whose epic poem On the Nature of Things described numerous aspects of the natural world. In fact, much contemporary scientific understanding is consistent with or inspired by his work. Among Lucretius's contributions to neurology were his descriptions of epileptic seizures, sleep, and his theory of vision. This report identifies how Lucretius's description of human motion recognized the fundamental principles understood by contemporary neurologists and neuroscientists, namely the importance of the mind and intelligence in determining whether to move, in the initiation of motion and its effect on the rest of the body; the importance of mental imagery and perception of the motor task's nature and workload in addition to the necessary systemic changes occurring in parallel with the muscle activity. Lucretius was the first commentator to introduce into Epicurean poetry the concept of such a mechanism consisting of a logical order of processes which are still consistent with modern concepts.

  • Removing ECG noise from surface EMG signals using adaptive filtering.

    23 March 2018

    Surface electromyograms (EMGs) are valuable in the pathophysiological study and clinical treatment for dystonia. These recordings are critically often contaminated by cardiac artefact. Our objective of this study was to evaluate the performance of an adaptive noise cancellation filter in removing electrocardiogram (ECG) interference from surface EMGs recorded from the trapezius muscles of patients with cervical dystonia. Performance of the proposed recursive-least-square adaptive filter was first quantified by coherence and signal-to-noise ratio measures in simulated noisy EMG signals. The influence of parameters such as the signal-to-noise ratio, forgetting factor, filter order and regularization factor were assessed. Fast convergence of the recursive-least-square algorithm enabled the filter to track complex dystonic EMGs and effectively remove ECG noise. This adaptive filter procedure proved a reliable and efficient tool to remove ECG artefact from surface EMGs with mixed and varied patterns of transient, short and long lasting dystonic contractions.

  • Polymeric carrier systems for siRNA delivery.

    15 February 2018

    RNA interference is a technique to induce sequence-specific gene silencing, but is hampered by inefficient delivery of its mediator, short interfering RNA, into target cells. This review describes recent advances in siRNA delivery using polymeric carrier systems. Structural variations that have been applied to these polymers for optimizing their intracellular trafficking are discussed, as well as strategies for stabilization and targeting to diseased tissues in vivo. Recent findings have highlighted safety issues that need to be taken into account in the design of nanoparticles for clinical application.

  • Microvesicles and exosomes: Opportunities for cell-derived membrane vesicles in drug delivery

    19 March 2018

    Cell-derived membrane vesicles (CMVs) are endogenous carriers transporting proteins and nucleic acids between cells. They appear to play an important role in many disease processes, most notably inflammation and cancer, where their efficient functional delivery of biological cargo seems to contribute to the disease progress. CMVs encompass a variety of submicron vesicular structures that include exosomes and shedding vesicles. The lipids, proteins, mRNA and microRNA (miRNA) delivered by these vesicles change the phenotype of the receiving cells. CMVs have created excitement in the drug delivery field, because they appear to have multiple advantages over current artificial drug delivery systems. Two approaches to exploit CMVs for delivery of exogenous therapeutic cargoes in vivo are currently considered. One approach is based on engineering of natural CMVs in order to target certain cell types using CMVs loaded with therapeutic compounds. In the second approach, essential characteristics of CMVs are being used to design nano-scaled drug delivery systems. Although a number of limiting factors in the clinical translation of the exciting research findings so far exist, both approaches are promising for the development of a potentially novel generation of drug carriers based on CMVs. © 2011 Elsevier B.V. All rights reserved.

  • Exosome mimetics: a novel class of drug delivery systems.

    19 March 2018

    The identification of extracellular phospholipid vesicles as conveyors of cellular information has created excitement in the field of drug delivery. Biological therapeutics, including short interfering RNA and recombinant proteins, are prone to degradation, have limited ability to cross biological membranes, and may elicit immune responses. Therefore, delivery systems for such drugs are under intensive investigation. Exploiting extracellular vesicles as carriers for biological therapeutics is a promising strategy to overcome these issues and to achieve efficient delivery to the cytosol of target cells. Exosomes are a well studied class of extracellular vesicles known to carry proteins and nucleic acids, making them especially suitable for such strategies. However, the considerable complexity and the related high chance of off-target effects of these carriers are major barriers for translation to the clinic. Given that it is well possible that not all components of exosomes are required for their proper functioning, an alternative strategy would be to mimic these vesicles synthetically. By assembly of liposomes harboring only crucial components of natural exosomes, functional exosome mimetics may be created. The low complexity and use of well characterized components strongly increase the pharmaceutical acceptability of such systems. However, exosomal components that would be required for the assembly of functional exosome mimetics remain to be identified. This review provides insights into the composition and functional properties of exosomes, and focuses on components which could be used to enhance the drug delivery properties of exosome mimetics.