The role of electrical stimulation for rehabilitation and regeneration after spinal cord injury

Electrical stimulation is used to elicit muscle contraction and can be utilized for neurorehabilitation following spinal cord injury when paired with voluntary motor training. This technology is now an important therapeutic intervention that results in improvement in motor function in patients with spinal cord injuries. The purpose of this review is to summarize the various forms of electrical stimulation technology that exist and their applications. Furthermore, this paper addresses the potential future of the technology

Potential Mechanisms of Sensory Augmentation Systems on Human Balance Control

Numerous studies have demonstrated the real-time use of visual, vibrotactile, auditory, and multimodal sensory augmentation technologies for reducing postural sway during static tasks and improving balance during dynamic tasks. The mechanism by which sensory augmentation information is processed and used by the CNS is not well understood. The dominant hypothesis, which has not been supported by rigorous experimental evidence, posits that observed reductions in postural sway are due to sensory reweighting: feedback of body motion provides the CNS with a correlate to the inputs from its intact sensory channels (e.g., vision, proprioception), so individuals receiving sensory augmentation learn to increasingly depend on these intact systems. Other possible mechanisms for observed postural sway reductions include: cognition (processing of sensory augmentation information is solely cognitive with no selective adjustment of sensory weights by the CNS), “sixth” sense (CNS interprets sensory augmentation information as a new and distinct sensory channel), context-specific adaptation (new sensorimotor program is developed through repeated interaction with the device and accessible only when the device is used), and combined volitional and non-volitional responses. This critical review summarizes the reported sensory augmentation findings spanning postural control models, clinical rehabilitation, laboratory-based real-time usage, and neuroimaging to critically evaluate each of the aforementioned mechanistic theories. Cognition and sensory re-weighting are identified as two mechanisms supported by the existing literature

Objective evaluation of Parkinson's disease bradykinesia

Bradykinesia is the fundamental motor feature of Parkinson’s disease - obligatory for diagnosis and central to monitoring. It is a complex clinicalsign that describes movements with slow speed, small amplitude, irregular rhythm, brief pauses and progressive decrements. Clinical ascertainment of the presence and severity of bradykinesia relies on subjective interpretation of these components, with considerable variability amongst clinicians, and this may contribute to diagnostic error and inaccurate monitoring in Parkinson’s disease. The primary aim of this thesis was to assess whether a novel non-invasive device could objectively measure bradykinesia and predict diagnostic classification of movement data from Parkinson’s disease patients and healthy controls. The second aim was to evaluate how objective measures of bradykinesia correlate with clinical measures of bradykinesia severity. The third aim was to investigate the characteristic kinematic features of bradykinesia. Forty-nine patients with Parkinson’s disease and 41 healthy controls were recruited in Leeds. They performed a repetitive finger-tapping task for 30 seconds whilst wearing small electromagnetic tracking sensors on their finger and thumb. Movement data was analysed using two different methods - statistical measures of the separable components of bradykinesia and a computer science technique called evolutionary algorithms. Validation data collected independently from 13 patients and nine healthy controls in San Francisco was used to assess whether the results generalised. The evolutionary algorithm technique was slightly superior at classifying the movement data into the correct diagnostic groups, especially for the mildest clinical grades of bradykinesia, and they generalised to the independent group data. The objective measures of finger tapping correlated well with clinical grades of bradykinesia severity. Detailed analysis of the data suggests that a defining feature of Parkinson’s disease bradykinesia called the sequence effect may be a physiological rather than a pathological phenomenon. The results inform the development of a device that may support clinical diagnosis and monitoring of Parkinson’s disease and also be used to investigate bradykinesia

Activation of the pro-resolving receptor Fpr2 attenuates inflammatory microglial activation

Poster number: P-T099 Theme: Neurodegenerative disorders & ageing Activation of the pro-resolving receptor Fpr2 reverses inflammatory microglial activation Authors: Edward S Wickstead - Life Science & Technology University of Westminster/Queen Mary University of London Inflammation is a major contributor to many neurodegenerative disease (Heneka et al. 2015). Microglia, as the resident immune cells of the brain and spinal cord, provide the first line of immunological defence, but can become deleterious when chronically activated, triggering extensive neuronal damage (Cunningham, 2013). Dampening or even reversing this activation may provide neuronal protection against chronic inflammatory damage. The aim of this study was to determine whether lipopolysaccharide (LPS)-induced inflammation could be abrogated through activation of the receptor Fpr2, known to play an important role in peripheral inflammatory resolution. Immortalised murine microglia (BV2 cell line) were stimulated with LPS (50ng/ml) for 1 hour prior to the treatment with one of two Fpr2 ligands, either Cpd43 or Quin-C1 (both 100nM), and production of nitric oxide (NO), tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) were monitored after 24h and 48h. Treatment with either Fpr2 ligand significantly suppressed LPS-induced production of NO or TNFα after both 24h and 48h exposure, moreover Fpr2 ligand treatment significantly enhanced production of IL-10 48h post-LPS treatment. As we have previously shown Fpr2 to be coupled to a number of intracellular signaling pathways (Cooray et al. 2013), we investigated potential signaling responses. Western blot analysis revealed no activation of ERK1/2, but identified a rapid and potent activation of p38 MAP kinase in BV2 microglia following stimulation with Fpr2 ligands. Together, these data indicate the possibility of exploiting immunomodulatory strategies for the treatment of neurological diseases, and highlight in particular the important potential of resolution mechanisms as novel therapeutic targets in neuroinflammation. References Cooray SN et al. (2013). Proc Natl Acad Sci U S A 110: 18232-7. Cunningham C (2013). Glia 61: 71-90. Heneka MT et al. (2015). Lancet Neurol 14: 388-40

Functional network correlates of language and semiology in epilepsy

Epilepsy surgery is appropriate for 2-3% of all epilepsy diagnoses. The goal of the presurgical workup is to delineate the seizure network and to identify the risks associated with surgery. While interpretation of functional MRI and results in EEG-fMRI studies have largely focused on anatomical parameters, the focus of this thesis was to investigate canonical intrinsic connectivity networks in language function and seizure semiology. Epilepsy surgery aims to remove brain areas that generate seizures. Language dysfunction is frequently observed after anterior temporal lobe resection (ATLR), and the presurgical workup seeks to identify the risks associated with surgical outcome. The principal aim of experimental studies was to elaborate understanding of language function as expressed in the recruitment of relevant connectivity networks and to evaluate whether it has value in the prediction of language decline after anterior temporal lobe resection. Using cognitive fMRI, we assessed brain areas defined by parameters of anatomy and canonical intrinsic connectivity networks (ICN) that are involved in language function, specifically word retrieval as expressed in naming and fluency. fMRI data was quantified by lateralisation indices and by ICN_atlas metrics in a priori defined ICN and anatomical regions of interest. Reliability of language ICN recruitment was studied in 59 patients and 30 healthy controls who were included in our language experiments. New and established language fMRI paradigms were employed on a three Tesla scanner, while intellectual ability, language performance and emotional status were established for all subjects with standard psychometric assessment. Patients who had surgery were reinvestigated at an early postoperative stage of four months after anterior temporal lobe resection. A major part of the work sought to elucidate the association between fMRI patterns and disease characteristics including features of anxiety and depression, and prediction of postoperative language outcome. We studied the efficiency of reorganisation of language function associated with disease features prior to and following surgery. A further aim of experimental work was to use EEG-fMRI data to investigate the relationship between canonical intrinsic connectivity networks and seizure semiology, potentially providing an avenue for characterising the seizure network in the presurgical workup. The association of clinical signs with the EEG-fMRI informed activation patterns were studied using the data from eighteen patients’ whose seizures and simultaneous EEG-fMRI activations were reported in a previous study. The accuracy of ICN_atlas was validated and the ICN construct upheld in the language maps of TLE patients. The ICN construct was not evident in ictal fMRI maps and simulated ICN_atlas data. Intrinsic connectivity network recruitment was stable between sessions in controls. Amodal linguistic processing and the relevance of temporal intrinsic connectivity networks for naming and that of frontal intrinsic connectivity networks for word retrieval in the context of fluency was evident in intrinsic connectivity networks regions. The relevance of intrinsic connectivity networks in the study of language was further reiterated by significant association between some disease features and language performance, and disease features and activation in intrinsic connectivity networks. However, the anterior temporal lobe (ATL) showed significantly greater activation compared to intrinsic connectivity networks – a result which indicated that ATL functional language networks are better studied in the context of the anatomically demarked ATL, rather than its functionally connected intrinsic connectivity networks. Activation in temporal lobe networks served as a predictor for naming and fluency impairment after ATLR and an increasing likelihood of significant decline with greater magnitude of left lateralisation. Impairment of awareness served as a significant classifying feature of clinical expression and was significantly associated with the inhibition of normal brain functions. Canonical intrinsic connectivity networks including the default mode network were recruited along an anterior-posterior anatomical axis and were not significantly associated with clinical signs

Modern Developments in Transcranial Magnetic Stimulation (TMS) – Applications and Perspectives in Clinical Neuroscience

Transcranial magnetic stimulation (TMS) is being increasingly used in neuroscience and clinics. Modern advances include but are not limited to the combination of TMS with precise neuronavigation as well as the integration of TMS into a multimodal environment, e.g., by guiding the TMS application using complementary techniques such as functional magnetic resonance imaging (fMRI), electroencephalography (EEG), diffusion tensor imaging (DTI), or magnetoencephalography (MEG). Furthermore, the impact of stimulation can be identified and characterized by such multimodal approaches, helping to shed light on the basic neurophysiology and TMS effects in the human brain. Against this background, the aim of this Special Issue was to explore advancements in the field of TMS considering both investigations in healthy subjects as well as patients

Cervical dystonia : abnormal cerebral activation patterns related to preparation and execution of hand movement

Cervical dystonia (CD) is a movement disorder characterized by sustained involuntary muscular contractions which cause repetitive twisting movements and abnormal postures of the head. CD is primarily a brain disorder. Several studies show that CD patients have abnormal brain activity not only during movement execution but also movement preparation. An important area for movement preparation is the parietal cortex where sensory information is integrated in the movement preparation plan. In CD, this parietal cortex seems to function abnormally since extra sensory information (by touching the chin or cheek) can temporarily reduce dystonia. This thesis investigated execution and preparation of movement in CD and healthy controls by letting the subjects perform and imagine a flexion/ extension movement in a normal, non-dystonic hand. Imagination of movement activates specific brain areas which are related to preparation of movement. Both tasks showed lower parietal cortex activity in CD compared to healthy controls. Induced impairment of the parietal cortex by transcranial magnetic stimulation (TMS) in healthy controls showed specific brain activation changes that were similar to brain activation patterns in CD patients without TMS. Parietal cortex TMS in CD reduced the already low activity even further and increased activity in other brain regions. These results confirm that the parietal cortex is impaired in CD. This functional impairment seems to be compensated by other brain regions during movement in normal, non-dystonic body parts. However, the electromyography study in this thesis showed that full compensation is not reached, although visually the movement looked normal. Execution of a flexion/ extension movement of a normal, non-dystonic hand in CD patients demonstrated lower muscle strength during wrist flexion and longer muscle activation during wrist extension. Nevertheless, in CD other factors besides impaired compensation mechanisms may be in play to undermine the neck movements in CD patients in such a way that it becomes dystonic.

Applications of EMG in Clinical and Sports Medicine

This second of two volumes on EMG (Electromyography) covers a wide range of clinical applications, as a complement to the methods discussed in volume 1. Topics range from gait and vibration analysis, through posture and falls prevention, to biofeedback in the treatment of neurologic swallowing impairment. The volume includes sections on back care, sports and performance medicine, gynecology/urology and orofacial function. Authors describe the procedures for their experimental studies with detailed and clear illustrations and references to the literature. The limitations of SEMG measures and methods for careful analysis are discussed. This broad compilation of articles discussing the use of EMG in both clinical and research applications demonstrates the utility of the method as a tool in a wide variety of disciplines and clinical fields