Restorative Neurology and Neuroscience - Volume 30, issue 2

Authors: Borich, Michael R. | Kimberley, Teresa Jacobson

Article Type: Research Article

Abstract: Purpose: Sleep following training can enhance motor skill memory consolidation while chronic sleep disruption can have the converse effect. The aim of this investigation was to explore the relationship between sleep measured by wrist actigraphy, motor skill consolidation and primary motor cortex excitability in young, healthy individuals. Methods: Training was a visuospatial finger-tracking task. Dependent measures included tracking skill performance, cortical excitability, measures of sleep, and level of arousal. Assessments occurred pre-training, post-training and at 12 h and 24 h retention. An activity monitor was worn on the wrist during the nights preceding and following training. Results: Results indicate that …sleep during the night following training was predictive of 1) offline skill consolidation following training (R2 = 0.34) and 2) cortical excitability at 24 h follow-up (R2 = 0.35) with less time spent awake associated with better skill performance and lower cortical excitability at 24 h follow-up. No difference in measures of sleep was observed between nights of sleep (p > 0.05). Sleep the night before training did not influence skill performance, skill acquisition during training, nor measures of cortical excitability at pre-training assessment. Conclusions: These findings suggest a relationship between motor skill development, cortical excitability and sleep following training. These results invite further investigation into the utility of actigraphy as a low-cost, easy-to-administer alternative to polysomnography for short and long-term evaluation of the relationship between sleep, cortical excitability and motor skill learning in healthy and patient populations. Show more

Keywords: Actigraphy, sleep, motor learning, cortical excitability, TMS, memory, consolidation, enhancement

DOI: 10.3233/RNN-2011-0622

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 2, pp. 81-90, 2012

Authors: Nordblom, Jonathan | Persson, Jonas K.E. | Åberg, Jonas | Blom, Hans | Engqvist, Håkan | Brismar, Hjalmar | Sjödahl, Johan | Josephson, Anna | Frostell, Arvid | Thams, Sebastian | Brundin, Lou | Svensson, Mikael | Mattsson, Per

Article Type: Research Article

Abstract: Purpose: Repairing the spinal cord with peripheral nerve grafts (PNG) and adjuvant acidic fibroblast growth factor (FGF1) has previously resulted in partial functional recovery. To aid microsurgical placement of PNGs, a graft holder device was previously developed by our group. In hope for a translational development we now investigate a new biodegradable graft holder device containing PNGs with or without FGF1. Methods: Rats were subjected to a T11 spinal cord resection with subsequent repair using twelve white-to-grey matter oriented PNGs prepositioned in a biodegradable device with or without slow release of FGF1. Animals were evaluated with BBB-score, electrophysiology and immunohistochemistry …including anterograde BDA tracing. Results: Motor evoked potentials (MEP) in the lower limb reappeared at 20 weeks after grafting. MEP responses were further improved in the group treated with adjuvant FGF1. Reappearance of MEPs was paralleled by NF-positive fibers and anterogradely traced corticospinal fibers distal to the injury. BBB-scores improved in repaired animals. Conclusions: The results continue to support that the combination of PNGs and FGF1 may be a regeneration strategy to reinnervate the caudal spinal cord. The new device induced robust MEPs augmented by FGF1, and may be considered for translational research. Show more

Keywords: Spinal cord injuries, motor evoked potential, rats, peripheral nerves, fibroblast growth factor 1, tracing, neurophysiology, axonal regeneration

DOI: 10.3233/RNN-2011-0623

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 2, pp. 91-102, 2012

Authors: Allendorfer, Jane B. | Storrs, Judd M. | Szaflarski, Jerzy P.

Article Type: Research Article

Abstract: Purpose: In this study, we examine whether an excitatory repetitive transcranial magnetic stimulation (rTMS) protocol called intermittent theta burst stimulation (iTBS) applied to the affected left hemisphere leads to changes in white matter fractional anisotropy (FA). Methods: Diffusion tensor imaging (DTI) data were collected in 8 aphasic stroke patients before and after 10 daily iTBS treatments. Alignment of structural and DTI data and derivation of diffusion index maps were performed using Analysis of Functional NeuroImages software followed by Tract-Based Spatial Statistics using FMRIB Software Library. Paired t-tests were performed to compare pre- to post-rTMS changes in FA. Results: There were …significant (p < 0.001) left-hemispheric FA increases near the inferior and superior frontal gyri and anterior corpus callosum. FA also increased in the right midbrain and bilaterally near temporal, parietal and posterior cingulate regions. FA decreased bilaterally near the fusiform gyrus and in left cerebellum. Conclusions: Overall, left-hemispheric regions that showed increased FA corresponded to areas previously shown to have increases in fMRI language activation after iTBS. The increased white matter integrity near the stimulation sites may reflect improvements in cortical function mediated by excitatory rTMS through its ability to facilitate synaptic connections. Show more

Keywords: DTI, fractional anisotropy, TBSS, white matter, excitatory rTMS, post-stroke aphasia

DOI: 10.3233/RNN-2011-0627

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 2, pp. 103-113, 2012

Authors: Cekic, Milos | Johnson, Sarah J. | Bhatt, Vinay H. | Stein, Donald G.

Article Type: Research Article

Abstract: Purpose: The neuroactive steroid progesterone (PROG) has been shown to be an effective treatment for traumatic brain injury (TBI) both in animal models and in humans, but the signaling pathways involved have not yet been fully described. Here we characterize the protein expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and their pro-proteins and receptors following PROG treatment for TBI. Methods: To evaluate whether PROG treatment given after TBI alters mature and proneurotrophin protein balance and the expression of receptors involved in apoptotic and cell survival signaling, we used Western blots in tissue obtained 24 h, 72 h, …and 7 days after injury from rats with bilateral frontal cortical contusions. Results: Compared to controls, PROG reduced levels of pro-apoptotic NGF precursor (proNGF) at 24 h and 7 days post-injury, reduced levels of pro-apoptotic BDNF precursor (proBDNF) and the BDNF receptor TrkB at all time points, and increased levels of mature NGF at 72 h. Levels of mature BDNF were decreased at 24 and 72 h. These observations were associated with reduced markers of apoptosis and improved behavioral parameters in PROG-treated rats. Conclusions: Some of PROG's protective effects after TBI are mediated, in part, by simultaneous induction of pro-survival neurotrophin signaling and inhibition of apoptotic proneurotrophin signaling. Show more

Keywords: Apoptosis, brain-derived growth factor (BDNF), frontal cortex, nerve growth factor (NGF), progesterone, proneurotrophins, recovery of function, traumatic brain injury, TrkA

DOI: 10.3233/RNN-2011-0628

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 2, pp. 115-126, 2012

Authors: Saito, Fukuki | Nakatani, Toshio | Iwase, Masaaki | Maeda, Yuji | Murao, Yoshinori | Suzuki, Yoshihisa | Fukushima, Masanori | Ide, Chizuka

Article Type: Research Article

Abstract: Purpose: To determine whether intrathecal administration of cultured autologous bone marrow stromal cells (BMSCs) is safe and feasible for treatment of subacute spinal injury. Methods: Five patients with complete tetraplegia due to cervical spinal injury on admission were included. A small amount of bone marrow was obtained during surgery for spinal fusion. BMSCs were cultured, reaching 107 –108 cells. The properties and functional efficacy of the BMSCs were verified with surface marker analysis and a neurite extension test. BMSCs were administered by lumbar puncture. The patients were closely observed for 6 months, and the Committee on Effectiveness and Safety …of Clinical Treatment (CESCT) evaluated safety. Results: No adverse responses were observed in biochemical and radiographic examinations. The CESCT did not recognize any harmful effects of the transplantation, and concluded it was safe for treatment. The patients were further followed up for 1 to 4 years with no adverse responses. The recovery of American Spinal Injury Association Impairment Scale (AIS) B and C patients at transplantation was rapid and remarkable, but gradual or limited in AIS A patients. Conclusion: This study demonstrated that intrathecal administration of cultured autologous BMSCs is safe and feasible for treatment of spinal cord injury. Show more

Keywords: Spinal cord injury treatment, bone marrow stromal cell, spinal cord regeneration, cerebrospinal fluid

DOI: 10.3233/RNN-2011-0629

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 2, pp. 127-136, 2012

Authors: Tass, Peter A. | Adamchic, Ilya | Freund, Hans-Joachim | von Stackelberg, Tatjana | Hauptmann, Christian

Article Type: Research Article

Abstract: Purpose: Subjective tinnitus is associated with pathologic enhanced neuronal synchronization. We used a model based desynchronization technique, acoustic coordinated reset (CR) neuromodulation, to specifically counteract tinnitus-related neuronal synchrony thereby inducing an unlearning of pathological synaptic connectivity and neuronal synchrony. Methods: In a prospective, randomized, single blind, placebo-controlled trial in 63 patients with chronic tonal tinnitus and up to 50 dB hearing loss we studied safety and efficacy of different doses of acoustic CR neuromodulation. We measured visual analogue scale and tinnitus questionnaire (TQ) scores and spontaneous EEG. Results: CR treatment was safe, well-tolerated and caused a significant decrease of tinnitus …loudness and symptoms. Placebo treatment did not lead to any significant changes. Effects gained in 12 weeks of treatment persisted through a preplanned 4-week therapy pause and showed sustained long-term effects after 10 months of therapy: Response, i.e. a reduction of at least 6 TQ points, was obtained in 75% of patients with a mean TQ reduction of 50% among responders. CR therapy significantly lowered tinnitus frequency and reversed the tinnitus related EEG alterations. Conclusion: The CR-induced reduction of tinnitus and underlying neuronal characteristics indicates a new non-invasive therapy which might also be applicable to other conditions with neuronal hypersynchrony. Show more

Keywords: Tinnitus treatment, desynchronization, plasticity, non-invasive neuromodulation

DOI: 10.3233/RNN-2012-110218

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 2, pp. 137-159, 2012

Authors: Lehmann, Konrad | Schmidt, Karl-Friedrich | Löwel, Siegrid

Article Type: Research Article

Abstract: Purpose: Little is known about neuronal changes during ageing in the visual system of mice which are increasingly being used as animal models for human visual disorders. Methods and results: Measuring the optomotor response to moving gratings, visual acuity of C57BL/6-mice was 0.39 cycles/degree (cyc/deg) until 12 months of age and declined to 0.27 cyc/deg (by 30%) at 26 months. In the visual water task, a cortex-dependent task based on visual discrimination learning, visual acuity remained stable at 0.58 cyc/deg up to 21 months and then declined to 0.48 cyc/deg (by 19%) at 27 months. Visual cortical activity recorded by …optical imaging declined by 33% between seven and 23 months of age. After monocular deprivation and daily testing of the optomotor response, visual acuity of the open eye increased by 29% in 4 to 7-month-old animals, while the increase was only 13% in 23-month-old mice. Interestingly, interindividual variability generally increased with age, so that some 23-month-old mice retained visual acuity and interocular plasticity like 4 or 7-month-old animals. Conclusions: In summary, reduced visual function was accompanied by a reduction of both visual cortical responses and interocular plasticity indicating a central nervous system component in age-related vision loss in mice. Show more

Keywords: Visual cortex, optomotry, visual water task, optical imaging, sensory learning

DOI: 10.3233/RNN-2012-110192

Citation: Restorative Neurology and Neuroscience, vol. 30, no. 2, pp. 161-178, 2012