bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging the effects of rTMS-induced cortical plasticity
Authors: Stagg Charlotte J. , O'Shea Jacinta , Johansen-Berg Heidi
Published: December 2019

Repetitive Transcranial Magnetic Stimulation (rTMS) paradigms are showing increasing promise as tools for neurorehabilitation in a variety of chronic neurological and psychiatric conditions. However, the mechanisms by which they modulate cortical activation are still not completely understood. In this review we summarize what non-invasive magnetic resonance imaging techniques can tell us about the cortical effects of rTMS – from changes at a cellular level within the stimulated motor cortex, to modulating activation patterns within the wider motor network. We discuss how variation in these effects in stroke patients may inform our understanding of how rTMS could improve function in these patients.
The modulation of cortical motor circuits and spinal reflexes	using theta burst stimulation in healthy and dystonic subjects
Authors: Huang Ying-Zu
Published: December 2019

Repetitive electrical stimulation has been applied to induce long-term changes in synaptic strength in animal preparations. It is generally believed that such changes in synapses form the basis of neural plasticity. Recently, several techniques, including repetitive transcranial magnetic stimulation (rTMS), have been developed to attempt to replicate similar plasticity effects in the brains of conscious humans. However, traditional paradigms of rTMS usually require lengthy stimulation and relatively high stimulus intensity. In light of these problems, a novel rTMS paradigm- theta burst stimulation (TBS) – was developed. TBS is able to produce plasticity-like effects more efficiently and powerfully than traditional protocols. The excitability of circuits within the motor cortex can be modified not only by TBS over the primary motor cortex but also when it is delivered to the premotor area. Moreover, TBS over the premotor cortex modifies aspects of spinal reflexes. Studies using TBS over the motor and premotor cortices provide further understanding of dystonia, and the results also distinguish the different mechanisms of the effects of TBS given to the primary motor and premotor cortices. In addition, some data also support the hypothesis that TBS is a potential candidate technique to help restore damaged motor functions through brain stimulation.
Effects of transcranial theta-burst stimulation on acute pain	perception
Authors: Antal Andrea , Paulus Walter
Published: December 2019

Transcranial stimulation of the primary motor cortex (M1) for the treatment of pain has attracted much interest in recent years. Non-invasive low frequency and high frequency repetitive transcranial magnetic stimulation (rTMS) over the M1 was reported to reduce both experimentally induced acute and chronic pain. In this paper we summarize the results of several studies from our laboratory and report the antinociceptive effects of a special rTMS paradigm, theta-burst stimulation (TBS). We have applied excitatory (iTBS) and inhibitory (cTBS) paradigms over two cortical locations (M1 and the primary somatosensory cortex (S1)). As evaluation criteria a pain rating scale and the recording of laser evoked potentials (LEPs) were used. Reduced subjective pain perception after cTBS could be objectified by alterations of LEPs that reflect pain related activations in the pain processing in the operculo-insular and anterior cingulate cortex. The stimulation of S1 had physiological effects (LEPs), but did not induce significant reduction in acute pain perception. We believe that the application of cTBS over M1 in pain research has a great potential and as a method it can contribute to a more efficient manipulation of the brain plasticity for therapeutic purposes, for example in chronic pain. Nevertheless, the effectiveness of other types of TBS paradigms should also be tested.
Short- and long-term effect of rTMS on motor function recovery	after ischemic stroke
Authors: Khedr Eman M. , Fetoh Noha Abo-El
Published: December 2019

This review discusses the clinical results that were obtained by applying rTMS in acute and chronic ischemic stroke patients. These studies included only the recovery of motor disability and dysphagia. In summary, two approaches have been used when employing rTMS as a potential therapy for the treatment of stroke. The most direct approach involves applying rTMS directly over the affected hemisphere in an attempt to increase excitability and plasticity of damaged circuits to improve motor function. The second approach has taken advantage of the concept of interhemispheric balance in which damage to the stroke hemisphere is exacerbated by increased inhibition from the intact non-stroke hemisphere. In this case, inhibitory rTMS is applied to the non-stroke hemisphere with the intention of reducing interhemispheric inhibition and restoring the balance of excitation between the motor cortices.The overall procedure remains to be optimized, in particular regarding the number of rTMS sessions, frequency and intensity of stimulation and the exact timing of rTMS application after stroke. Cortical stimulation is an effective method for improving functional recovery of acute and chronic stroke.
Using non-invasive brain interference as a tool for mimicking	spatial neglect in healthy volunteers
Authors: Sack Alexander T.
Published: December 2019

Visuospatial processing refers to the spatial perception, recognition and analysis of visual input. Human functional brain imaging studies have consistently revealed the involvement of fronto-parietal brain areas during the execution of visuospatial tasks. Just as the execution of these tasks activates fronto-parietal regions in the healthy brain, lesions to those structures, e.g. after stroke or brain injury, cause specific spatial deficits. The most prominent of these is known as spatial neglect. There are several competing theories on the neural mechanisms underlying spatial neglect. Although each of these theories postulates different underlying physiological mechanisms, they all account in their own way for the fact that the prevalence of neglect is much higher following right hemisphere lesions. This makes it difficult to distinguish between the different models at a behavioural level. Until today, it was impossible to empirically address these matters and to provide direct and conclusive empirical evidence in favour of one of the competing theories of spatial neglect. This review article describes the neural correlates of intact visuospatial processing as revealed by non-invasive functional brain imaging studies. It subsequently focuses on the approach of using the non-invasive brain inference technique of transcranial magnetic brain stimulation (TMS) to transiently and reversibly disrupt neural activity in these visuospatial processing-related brain regions. Using this approach, we can now imitate specific spatial deficits and neglect-like symptoms in healthy volunteers. Mimicking and manipulating the spatial deficits following unilateral brain lesions, under controlled experimental conditions, may allow for the development of new therapeutic interventions for parietal stroke patients suffering from real spatial neglect. The perspective is to use non-invasive brain interference to guide and promote functional recovery on a brain-system level in stroke and neglect patients, based on knowledge directly derived from fundamental brain research in healthy volunteers.
Transcranial alternating current stimulation in the low kHz range increases motor cortex excitability
Authors: Chaieb Leila , Antal Andrea , Paulus Walter
Published: December 2019

Purpose: External transcranial electric and magnetic stimulation techniques allow for the fast induction of sustained and measurable changes in cortical excitability. Here we aim to develop a paradigm using transcranial alternating current (tACS) in a frequency range higher than 1 kHz, which potentially interferes with membrane excitation, to shape neuroplastic processes in the human primary motor cortex (M1). Methods: Transcranial alternating current stimulation was applied at 1, 2 and 5 kHz over the left primary motor cortex with a reference electrode over the contralateral orbit in 11 healthy volunteers for a duration of 10 min at an intensity of 1 mA. Monophasic single- pulse transcranial magnetic stimulation (TMS) was used to measure changes in corticospinal excitability, both during and after tACS in the low kHz range, in the right hand muscle. As a control inactive sham stimulation was performed. Results: All frequencies of tACS increased the amplitudes of motor- evoked potentials (MEPs) up to 30–60 min post stimulation, compared to the baseline. Two and 5 kHz stimulations were more efficacious in inducing sustained changes in cortical excitability than 1 kHz stimulation, compared to sham stimulation. Conclusions: Since tACS in the low kHz range appears too fast to interfere with network oscillations, this technique opens a new possibility to directly interfere with cortical excitability, probably via neuronal membrane activation. It may also potentially replace more conventional repetitive transcranial magnetic stimulation (rTMS) techniques for some applications in a clinical setting.
Treatment of an autoimmune encephalomyelitis mouse model with nonmyeloablative conditioning and syngeneic bone marrow transplantation
Authors: Meng Li , Ouyang Jian , Zhang Haitao , Wen Yanting , Chen Junhao , Zhou Jinyong
Published: December 2019

Purpose: Hematopoietic stem cell transplantation (HSCT) has been proposed as a novel therapy for multiple sclerosis (MS). CD4 + CD25 + regulatory T cells (Tregs) expressing Foxp3 play an important role in the maintenance of immune tolerance to self. Our study was conducted to confirm the efficiency of nonmyeloablative conditioning and syngeneic bone marrow transplantation (BMT) on experimental autoimmune encephalomyelitis (EAE) mice and to determine whether Tregs plays a role in the underlying mechanism. Methods: EAE were induced in C57BL/6 mice and were randomly divided into 4 groups: the Conditioning group received the conditioning regimen, the Normal-EAE BMT group received conditioning and bone marrow (BM) grafts from normal mice, the EAE-EAE BMT group received conditioning and BM grafts from EAE mice and the EAE control group received no further therapy. The cumulative clinical score was used to assess the efficacy of the different treatments, and the proportion of Tregs in the spleen was measured by flow cytometry on day 40, 80 and 120 after BMT. Foxp3 mRNA expression was assessed by real-time PCR, and the expression of Foxp3 protein was tested by western blot on day 120 after BMT. Results: Conditioning and conditioning with BMT led to a significant clinical improvement on day 80 after BMT compared with EAE without further treatment. On day 120 after BMT, the clinical score of the Conditioning group showed no significant difference from that of the EAE control group, whereas BMT led to a further amelioration of the disease score. On day 80 and day 120 after BMT, the proportions of Tregs of the two BMT groups were significantly higher than that in EAE control group, whereas no statistically significant difference was found between the Conditioning group and the EAE control group. On day 120 after BMT, the Foxp3 mRNA level and Foxp3 protein expression was higher in the two BMT groups than in EAE control group or Conditioning group. Conclusions: Nonmyeloablative conditioning could temporarily reverse already established EAE, but it was not sufficient for the induction of long-term EAE remission. Transplantation by BM cells from healthy or diseased donors was necessary and responsible for complete and long-time remission of EAE, and these beneficial effects may be the result of the induction of Tregs and the Treg-related factor Foxp3.
Cortical reorganization in Bell's palsy
Authors: Klingner Carsten M. , Volk Gerd F. , Maertin Antje , Brodoehl Stefan , Burmeister Hartmut P. , Guntinas-Lichius Orlando , Witte Otto W.
Published: December 2019

Purpose: Bell's palsy, a unilateral, idiopathic facial nerve palsy, is a common disorder that is generally followed by a good recovery of function. The aim of this study was to investigate the impact of such a transiently decreased motor control (without deafferentation) on the functional reorganization of the brain. Methods: To address this issue, functional MRI was applied to 10 patients in the acute state of Bell's palsy and after their complete clinical recovery. The functional paradigm consisted of unilateral facial movements with the affected as well as the non-affected side. Results: We found an overactivity of several brain areas contralateral to the palsy that are related to error detection and sensory-motor integration in the acute stage and motor integration and control in the follow-up. Functional connectivity was disrupted in the affected cortical motor system during the acute stage of Bell's palsy compared to the follow-up. This altered connectivity was found mostly between motor areas in the hemisphere contralateral to the paretic side, whereas the interhemispherical connectivity remained largely stable. Conclusion: Our results indicate that a transient peripheral deefferentation causes functional reorganization in the brain that partly persists even after an apparently complete clinical recovery.
Treatment with nerve grafts and aFGF attenuates allodynia caused by cervical root transection injuries
Authors: Lin Yi-Lo , Kuo Huai-Sheng , Lo Ming-Jei , Tsai May-Jywan , Lee Meng-Jen , Huang Wen-Cheng , Kuo Wen-Chun , Shih Yang-Hsin , Cheng Henrich , Huang Ming-Chao
Published: December 2019

Purpose: Nerve root traction injuries induce spinal cord inflammation and lead to neuronal death within days. In the present study, we examined the inflammatory response one week after multiple cervical root transections. Methods: In the transection group, the left cervical roots (C6-8) of rats were cut at the spinal cord junction. In the repair group, transected roots were repaired with nerve grafts and the subsequent application of aFGF and fibrin glue. A sham group had nerve roots exposed without transection. Mechanical allodynia and spinal glial responses were evaluated. Results: Allodynia did not differ between the treatment groups on day 2. Rats with transected spinal nerve roots had significantly more allodynia by 7 days, which was associated with IL-1β expression in dorsal and ventral horn astrocytes, and microglia activation. Repair of nerve roots with autologous intercostal nerve grafts and FGF in fibrin glue attenuated the allodynia, reduced IL-1β expression in astroctyes and reduced microglia activation, along with a significant increase in arginase I expression. Conclusion: This study demonstrated a correlation between an increased number of IL-1β-positive astrocytes and the development of allodynia. Our treatment significantly decreased IL-1β-positive astrocytes, thus preventing the occurrence of neuropathic pain following multiple cervical root injuries.
Activation changes in sensorimotor cortex during improvement due to CIMT in chronic stroke
Authors: Rijntjes Michel , Hamzei Farsin , Glauche Volkmar , Saur Dorothee , Weiller Cornelius
Published: December 2019

Purpose: The integrity of the pyramidal tract (PT) does not seem to influence clinical improvement after two weeks of Constraint-Induced Movement Therapy (CIMT). However, when PT is intact, improvement is associated with a decrease of fMRI-activation in primary sensorimotor cortex (SMC) and when affected, with an increase of activation in SMC. The aim was to observe the long-term effect of CIMT, depending on the integrity of the PT, and to correlate improvement with changes in fMRI-activation. Subjects and methods: Twelve new chronic stroke patients were treated with CIMT and integrity of PT was measured with transcranial magnetic stimulation. Before therapy, after therapy, and after 6 months, changes in motor function were correlated with differential and percent fMRI signal changes. Results: All patients improved after two weeks of therapy, but only those with intact PT maintained improvement after 6 months. When PT was intact, improvement correlated with first a decrease of activation in SMC and after 6 months with an increase. When PT was affected, improvement consistently correlated with an increase in a lateral extension of SMC. Percent changes of activation were surrounded by differential changes. Conclusions: An intact PT might be advantageous for lasting improvement after CIMT and subregions in the SMC seem to behave differently during recovery.
Isometric contraction interferes with transcranial direct current stimulation (tDCS) induced plasticity – evidence of state-dependent neuromodulation in human motor cortex
Authors: Thirugnanasambandam Nivethida , Sparing Roland , Dafotakis Manuel , Meister Ingo G. , Paulus Walter , Nitsche Michael A. , Fink Gereon R.
Published: December 2019

Background and Purpose: Neuroplastic alterations of cortical excitability and activity represent the likely neurophysiological foundation of learning and memory formation. Beyond their induction, alterations of these processes by subsequent modification of cortical activity, termed metaplasticity, came into the focus of interest recently. Animal slice experiments demonstrated that neuroplastic excitability enhancements, or diminutions, can be abolished by consecutive subthreshold stimulation. These processes, termed de-potentiation, and de-depression, have so far not been explored in humans. Methods: We combined neuroplasticity induction by transcranial direct current stimulation (tDCS) applied to the hand area of primary motor cortex (M1), which can be used to induce long-lasting excitability enhancements or reductions, dependent on the polarity of stimulation, with short-lasting voluntary muscle contraction (VMC), which itself does not induce plastic cortical excitability changes. Corticospinal and intra-cortical M1 excitability were monitored by different transcranial magnetic stimulation (TMS) protocols. Results: VMC reduced or tended to reverse the anodal tDCS-driven motor cortical excitability enhancement and the cathodal tDCS-induced excitability diminution. Our findings thus demonstrate de-potentiation- and de-depression-like phenomena at the system level in the human motor cortex. Conclusion: This neurophysiological study may contribute to a better understanding of the balance between induction and reversal of plasticity associated with motor learning and rehabilitation processes.
Ibuprofen attenuates the inflammatory response and allows formation of migratory neuroblasts from grafted stem cells after traumatic brain injury
Authors: Wallenquist U. , Holmqvist K. , Hånell A. , Marklund N. , Hillered L. , Forsberg-Nilsson K.
Published: December 2019

Purpose: There is hope for neural stem and progenitor cells (NSPC) to enhance regeneration when transplanted to the injured brain after traumatic brain injury (TBI). So far, the therapeutic effects of NSPC transplantation have been hampered mainly by the notable death of the transplanted cells. Neuroinflammation may lead to additional cell death after TBI and we hypothesized that survival of grafted NSPC could be enhanced by anti-inflammatory treatment. Methods: Mice that were subjected to controlled cortical impact TBI and grafted with NSPC, were treated with the non-steroidal anti-inflammatory drug ibuprofen. Results: Ibuprofen was found to down-regulate the TBI-induced inflammatory response. In addition, migrating neuroblasts from transplanted cells were observed near the contusion and in the ipsilateral hippocampus in ibuprofen-treated animals only, suggesting that the anti-inflammatory treatment had beneficial effects on graft survival and/or differentiation. However, Morris Water Maze performance or TBI-induced tissue loss was not influenced by ibuprofen treatment. Conclusions: Our data suggests that anti-inflammatory strategies may be a complement to enhance the outcome for the cell transplants following TBI.
Noninvasive brain stimulation in the treatment of aphasia: Exploring interhemispheric relationships and their implications for neurorehabilitation
Authors: Chrysikou Evangelia G. , Hamilton Roy H.
Published: December 2019

Aphasia is a common consequence of unilateral stroke, typically involving perisylvian regions of the left hemisphere. The course of recovery from aphasia after stroke is variable, and relies on the emergence of neuroplastic changes in language networks. Recent evidence suggests that rehabilitation interventions may facilitate these changes. Functional reorganization of language networks following left-hemisphere stroke and aphasia has been proposed to involve multiple mechanisms, including intrahemispheric recruitment of perilesional left-hemisphere regions and transcallosal interhemispheric interactions between lesioned left-hemisphere language areas and homologous regions in the right hemisphere. Moreover, it is debated whether interhemispheric interactions are beneficial or deleterious to recovering language networks. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are two safe and noninvasive procedures that can be applied clinically to modulate cortical excitability during poststroke language recovery. Intervention with these noninvasive brain stimulation techniques also allows for inferences to be made regarding mechanisms of recovery, including the role of intrahemispheric and interhemispheric interactions. Here we review recent evidence that suggests that TMS and tDCS are promising tools for facilitating language recovery in aphasic patients, and examine evidence that indicates that both right and left hemisphere mechanisms of plasticity are instrumental in aphasia recovery.
Understanding and enhancing motor recovery after stroke using transcranial magnetic stimulation
Authors: Hoyer Erik H. , Celnik Pablo A.
Published: December 2019

Stroke is the leading cause of long-term disability. Understanding how people recover from stroke and other brain lesions remain one of the biggest conundrums in neuroscience. As a result, concerted efforts in recent years have focused on investigating the neurophysiological changes that occur in the brain after stroke, and in developing novel strategies to enhance motor recovery. In particular, transcranial magnetic stimulation (TMS) is a non-invasive tool that has been used to investigate the brain plasticity changes resulting from stroke and as a therapeutic modality to safely improve motor function. In this review, we discuss the contributions of TMS to understand how different motor areas, such as the ipsilesional hemisphere, secondary motor areas, and contralesional hemisphere are involved in motor recovery. We also consider recent studies using repetitive TMS (rTMS) in stroke patients to enhance upper extremity function. Although further studies are needed, these investigations provide an important starting point to understand the stimulation parameters and patient characteristics that may influence the optimal response to non-invasive brain stimulation. Future directions of rTMS are discussed in the context of post-stroke motor recovery.
Optimizing recovery potential through simultaneous occupational therapy and non-invasive brain-stimulation using tDCS
Authors: Nair Dinesh G. , Renga Vijay , Lindenberg Robert , Zhu Lin , Schlaug Gottfried
Published: December 2019

Purpose: It is thought that following a stroke the contralesional motor region exerts an undue inhibitory influence on the lesional motor region which might limit recovery. Pilot studies have shown that suppressing the contralesional motor region with cathodal transcranial Direct Current Stimulation (tDCS) can induce a short lasting functional benefit; greater and longer lasting effects might be achieved with combining tDCS with simultaneous occupational therapy (OT) and applying this intervention for multiple sessions. Methods: We carried out a randomized, double blind, sham controlled study of chronic stroke patients receiving either 5 consecutive days of cathodal tDCS (for 30 minutes) applied to the contralesional motor region and simultaneous OT, or sham tDCS+OT. Results: we showed that cathodal tDCS+OT resulted in significantly more improvement in Range-Of-Motion in multiple joints of the paretic upper extremity and in the Upper-Extremity Fugl-Meyer scores than sham tDCS+OT, and that the effects lasted at least one week post-stimulation. Improvement in motor outcome scores was correlated with decrease in fMRI activation in the contralesional motor region exposed to cathodal stimulation. Conclusions: This suggests that cathodal tDCS combined with OT leads to significant motor improvement after stroke due to a decrease in the inhibitory effect that the contralesional hemisphere exerts onto the lesional hemisphere.
Third trimester amniotic fluid cells with the capacity to develop neural phenotypes and with heterogeneity among sub-populations
Authors: Bottai Daniele , Cigognini Daniela , Nicora Emanuela , Moro Monica , Grimoldi Maria Grazia , Adami Raffaella , Abrignani Sergio , Marconi Anna Maria , Di Giulio Anna Maria , Gorio Alfredo
Published: December 2019

Purpose: Our aim was the search for new sources of cells potentially useful for central nervous system regenerative medicine. Extra-embryonic tissues are promising sources of pluripotent stem cells. Among these, human second-trimester amniotic fluid (AF) contains cell populations exhibiting self-renewal capacity, multipotency and the expression of embryonic cell markers. Methods: Here we report the properties of the easily available third-trimester AF cells (AFCs). Different cell types from 6 of 9 AF samples were separated, expanded, and characterized by assessing their morphological, proliferative, and differentiative properties. Results: All isolated cultures presented CD105, CD90 and CD73 mesenchymal markers, whereas they differed among themselves in CD117, CD146, CD31, NG2 and CD133 expression. Their doubling time and telomere length were conserved throughout many passages. Importantly, immunofluorescence and Real-time PCR showed that, during their proliferative state and differentiation, several cultures expressed neuronal and glial markers such as nestin, GFAP, β-tubulin III and neurofilament H indicating their potential attitude towards a neural fate. Indeed, these cells showed a rather poor capacity to differentiate in adipogenic and osteogenic lineages. Conclusions: In this work we report that cells with neural differentiation capability can be isolated from third-trimester AF, such properties could be useful for neuro-regenerative purposes.
Non-viral gene delivery of the GDNF, either alone or fused to the C-fragment of tetanus toxin protein, prolongs survival in a mouse ALS model
Authors: Moreno-Igoa María , Calvo Ana Cristina , Ciriza Jesús , Muñoz María Jesús , Zaragoza Pilar , Osta Rosario
Published: December 2019

Purpose and background: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease with no effective therapy. Glial-cell line derived neurotrophic factor (GDNF) has been translated to clinical trials for treatment of ALS and its selective delivery to the motoneurons could improve its therapeutic abilities. Methods: To test this idea, we genetically fused GDNF to the C-fragment of tetanus toxin (TTC), a peptide able to specifically deliver molecules to motoneurons. Results: Single intramuscular administration of naked-DNA encoding GDNF or GDNF-TTC significantly delayed the onset of symptoms and functional deficits into the SODG93A mouse model of ALS, prolonging their lifespan. Conclusions: We have demonstrated a neuroprotective effect of GDNF-TTC as shown by the activation of survival pathways and inhibition of apoptotic proteins, such as Akt phosphorylation, or reduced caspase-3 activation respectively. However, the GDNF fusion with TTC did not improve the therapeutic effects when compared to GDNF alone.
Using actigraphy and transcranial magnetic stimulation to assess the relationship between sleep and visuomotor skill learning
Authors: Borich Michael R. , Kimberley Teresa Jacobson
Published: December 2019

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.
Non-invasive alternating current stimulation improves vision in optic neuropathy
Authors: Sabel Bernhard A. , Fedorov Anton B. , Naue Nicole , Borrmann Antonia , Herrmann Christoph , Gall Carolin
Published: December 2019

Purpose: Partial blindness after visual system damage is considered irreversible, yet the brain has residual visual capacities and considerable plasticity potential. We now applied non-invasive alternating current stimulation (ACS) to the visual system of patients with optic nerve damage with the aim to induce recovery of visual functions. Methods: In a prospective, double-blind, randomized, placebo-controlled clinical trial patients with several year old partial optic nerve lesions were treated with ACS (n = 12) or placebo-stimulation (n = 10). ACS was delivered transorbitally for 40 minutes on 10 days. Visual outcome measures and EEG were measured before and after treatment. Results: ACS, but not placebo, led to significant improvement of a visual field detection deficit by 69%, and also significantly improved temporal processing of visual stimuli, detection performance in static perimetry, and visual acuity. These changes were associated with alpha-band changes in the EEG power spectra. Visual improvements were stable for at least 2-months. Conclusions: ACS can induce vision restoration many years after optic neuropathy. Though the mechanism is still unclear, EEG changes indicate increased synchronization in posterior brain regions. The present study provides Class Ib evidence that non-invasive transorbital ACS is well tolerated and improves visual function in optic neuropathy.
Progesterone treatment alters neurotrophin/proneurotrophin balance and receptor expression in rats with traumatic brain injury
Authors: Cekic Milos , Johnson Sarah J. , Bhatt Vinay H. , Stein Donald G.
Published: December 2019

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.
Neural correlates of somatosensory processing in patients with neglect
Authors: Hassa Thomas , Schoenfeld Mircea Ariel , Dettmers Christian , Stoppel Christian Michael , Weiller Cornelius , Lange Rüdiger
Published: December 2019

Purpose: Recent evidence from neuroimaging studies using visual tasks suggests that the right superior parietal cortex plays a pivotal role for the recovery of neglect. Importantly, neglect-related deficits are not limited to the visual system and have a rather multimodal nature. We employed somatosensory stimulation in patients with neglect in order to analyze activity changes in networks that are presumably associated with this condition. Methods: Eleven chronic neglect patients with right hemispherical stroke were investigated with a fMRI paradigm in which the affected and unaffected hand were passively moved. Results: Brain activation was correlated with the performance in clinical neglect tests. Significant positive correlations with brain activation were found for the lesion duration, the performance in bells and letter cancellation tests and the line bisection test. These activated areas formed a distributed pattern in the right superior parietal cortex. Conclusions: The results suggest a shared representation of visual and somatosensory networks in the right superior parietal cortex in patients with right hemispherical strokes and neglect. The spatial pattern of activity in the superior parietal cortex points out to a different representation of changes related to lesion duration and neglect.
Pharmacological enhancement of glutamate transport reduces excitotoxicity in vitro
Authors: Beller Justin A. , Gurkoff Gene G. , Berman Robert F. , Lyeth Bruce G.
Published: December 2019

Purpose: Glutamate transporters are responsible for removing glutamate from the extracellular space and have the potential to protect neurons from excitotoxicity. In the present study, the effects of ceftriaxone and (2R, 4R)-APDC (APDC) on the protein expression of GLAST and GLT-1, the rate of glutamate uptake, and neuroprotection were evaluated in a cell culture model of glutamate excitotoxicity. Methods: Mixed neuron/astrocyte cultures were prepared from 1 day old rat pups. Protein levels of GLAST and GLT-1 glutamate transporters were quantified using In-Cell Western techniques after acute or 5-day treatment with either ceftriaxone or APDC. Glutamate uptake was measured using Michaelis-Menten kinetics to evaluate the effects of 5-day treatment with ceftriaxone or APDC. Neuronal cell death in response to a 10-minute 1 mM glutamate challenge was measured following 5-day treatment with either ceftriaxone or APDC. Results: Five-day treatment with 100 μM ceftriaxone significantly increased both GLAST and GLT-1 protein levels 31.3% and 47.5% above control, respectively, increased the Vmax 29.3%, increased the Km of glutamate uptake 117.9%, and reduced neuronal death 22.0% after a 1 mM glutamate challenge. Five-day treatment with 1 mM APDC significantly increased GLAST protein levels 27.6%, increased the Vmax 92.4%, increased the Km of glutamate transport 118.9%, and decreased neuronal death 36.8% after a 1 mM glutamate challenge. Conclusions: Chronic treatment with ceftriaxone or APDC provided neuroprotection from glutamate excitotoxicity while increasing GLAST and GLT-1 protein levels and increasing glutamate uptake. These compounds may have therapeutic potential in chronic excitotoxic neurodegenerative diseases.
Modulating neuronal excitability in the motor cortex with tDCS shows moderate hemispheric asymmetry due to subjects' handedness: A pilot study
Authors: Schade Sebastian , Moliadze Vera , Paulus Walter , Antal Andrea
Published: December 2019

Purpose: Transcranial direct current stimulation (tDCS) has proven to be a useful tool for fundamental brain research as well as for attempts in therapy of neurological and psychiatric diseases by modulating neuronal plasticity. Little is understood about the effects of tDCS are influenced by hemispheric dominance, even less in terms of handedness. The aim of our pilot study was to investigate whether tDCS induced neuroplastic changes may be different in right- and left-handed individuals due to existing differences in hemispheric lateralisation. Methods: We measured changes in motor evoked potentials (MEPs) after application of tDCS in 8 right-handers, 8 left-handers and 8 mixed-handers according to the Edinburgh Handedness Inventory (EHI). In double-blind sessions, we applied either anodal or cathodal tDCS for 5 minutes for each hemisphere. Results: While motor thresholds (MT) seem to be not influenced by handedness significantly, in right-handed subjects we reproduced the well-known effects of tDCS: anodal stimulation increased while cathodal stimulation decreased MEP amplitudes. However, left-and mixed-handed subjects differed from right-handed subjects. After anodal stimulation of the left hemisphere the increase of the MEP amplitudes was stronger in right handed subjects than in left and mixed handed subjects. Interestingly, after cathodal stimulation of the left hemisphere this difference was less marked. The stimulation of the right hemisphere showed the same tendency, but results were not significant. Conclusions: For the first time, we are able to demonstrate that the modulating effects of tDCS on corticospinal excitability differ moderately in the left-and mixed-handed population compared to right-handed subjects. The shown differences according to handedness should be taken into account in further studies.
Changes in cortical plasticity after mild traumatic brain injury
Authors: Bashir Shahid , Vernet Marine , Yoo Woo-Kyoung , Mizrahi Ilan , Theoret Hugo , Pascual-Leone Alvaro
Published: December 2019

Purpose: Even after a mild traumatic brain injury (TBI) symptoms may be long lasting and never resolve completely. The neurophysiologic substrate for such lasting deficits remains unclear. There is a lack of objective measures of early brain abnormalities following mild TBI, which could shed light on the genesis of these lasting impairments. Methods: Here we report findings in a previously healthy man tested 2 and 6 weeks after a well-documented concussion. Findings were compared with 12 control subjects. All subjects underwent brain magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI). Testing included neuropsychological evaluation and physiological assessment with TMS and EEG, excitatory/inhibitory balance and brain plasticity. Results: While the MRI, DTI and neuropsychological evaluations showed no abnormalities, neurophysiologic tests revealed subclinical abnormalities in our patient: (1) Significantly higher intracortical facilitation than the control group at both time points; (2) Intracortical inhibition presumably mediated by GABAB receptors was absent at week 2, but returned to normal value at week 6; (3) Abnormal mechanisms of plasticity at week 2, that normalize at week 6. Conclusions: These findings demonstrate a transient alteration of brain cortical physiology following concussion independent of anatomical findings and neuropsychological function. This case study suggests that TMS measures may serve as sensitive biomarkers of physiologic brain abnormalities after concussion.
Cathodal stimulation of human MT+ leads to elevated fMRI signal: A tDCS-fMRI study
Authors: Antal Andrea , Kovács Gyula , Chaieb Leila , Cziraki Csaba , Paulus Walter , Greenlee Mark W.
Published: December 2019

Purpose: Transcranial direct current stimulation (tDCS) was reintroduced about a decade ago as a tool for inducing long-lasting changes in cortical excitability. Recently it has been shown that both motor and cognitive functions can be influenced by tDCS. Here, we tested the effect of tDCS on the blood-oxygen level dependent (BOLD) signal evoked by coherent visual motion using functional magnetic resonance imaging (fMRI). Methods: The subjects underwent 10 min of cathodal and sham tDCS, applied over the right MT+. Following stimulation, random dot kinomatograms (RDK) with different percentages (10%, 30%, 50%) of coherently moving dots were presented. Results: All motion stimuli activated MT+ in both stimulation conditions. However, cathodal stimulation led to an increase in fMRI signal in MT+ when compared to sham stimulation. This effect did not depend on the coherence level of the visual stimulus. Conclusions: Here, we show for the first time, that cathodal tDCS stimulation leads to elevated fMRI signal in the human visual cortex.
Brain parenchymal fraction predicts motor improvement following intensive task-oriented motor rehabilitation for chronic stroke
Authors: Rickards Tyler , Taub Edward , Sterling Chelsey , Graham Michael J. , Barghi Ameen , Uswatte Gitendra , Mark Victor W.
Published: December 2019

Background and purpose: Infarct volume and location have a weak relationship with motor deficit in patients with chronic stroke. Recent research has focused on the relationship between spared or seemingly “healthy” neural tissue and motor function. In this study we examined MRI scans of patients with chronic stroke to determine if characteristics of seemingly normal parenchyma could predict either response to different forms of upper extremity physical rehabilitation or to pre-treatment motor status. Methods: Individuals with chronic stroke (ages 60.6 ± 11.9 years) and mild/moderate upper extremity hemiparesis were administered either CI therapy (n = 14) or a comparison therapy (n = 29). The patients were assessed prior to and following therapy with MRI scans and the Wolf Motor Function Test (WMFT) Performance Time measure. Total voxels in combined grey matter (GM) and white matter (WM) segments (parenchymal volume) were divided by total voxels in GM, WM, and cerebrospinal fluid segments (intracranial volume) to obtain the brain parenchymal fraction (BPF). Results: BPF correlated with treatment gains on the WMFT (r(43) = −0.31, p = 0.04). Significant correlations between pre-treatment motor function and BPF were not observed. Conclusions: Individuals with greater BPFs after stroke show larger arm function gains after CI therapy, suggesting that reductions in volume of normal-appearing tissue may relate to ability to benefit from rehabilitation therapy in chronic stroke.
A neurally-interfaced hand prosthesis tuned inter-hemispheric communication
Authors: Di Pino G. , Porcaro C. , Tombini M. , Assenza G. , Pellegrino G. , Tecchio F. , Rossini P.M.
Published: December 2019

Purpose: This work investigates how a direct bidirectional connection between brain and hand prosthesis modifies the bi-hemispheric sensorimotor system devoted to the movement control of the lost limb. Hand prostheses are often unable to satisfy users' expectations, mostly due to the poor performance of their interfacing system. Neural Interfaces implanted inside nerves of the stump offer the advantage of using the bidirectional neural pathways ‘naturally’ dispatching signals to control proper hand actions and feed-back sensations. Learning to control a neurally-interfaced hand prosthesis and decode sensory information was previously observed to reduce the inter-hemispheric asymmetry of cortical motor maps and the clinical symptoms of phantom limb syndrome. Methods: Electroencephalographic (EEG) data was analysed using Functional Source Separation (FSS), a semi-blind method that incorporates prior knowledge about the signal of interest into data decomposition to give access to cortical patch activities. Results: Bi-hemispheric cortices showed normalization of their activity (topographical and spectral patterns) and of functional connectivity between homologous hand controlling areas, during the delivery of the motor command to the cybernetic prosthesis. Conclusions: The re-establishment of central-peripheral communication with the lost limb induced by a neurally-interfaced hand prosthesis produces beneficial plastic reorganization, not only restructuring contralateral directly-connected control areas, but also their functional balance within the bi-hemispheric system necessary for motor control.
Using metaphors to study occupational transitions: A case study of	an injured worker with multiple chemical sensitivity
Authors: Arnold Crystal , Shaw Lynn , Landry Gerald
Published: December 2019

Background: The aim of this case study was to explore transitions of an injured worker suffering from multiple chemical sensitivity (MCS), and his lived experiences in learning to function in everyday life with this injury. To date, little research exists about the transitions of a worker to an injured worker beyond the focus of strategies in returning to work and rehabilitation.

Methods: The injured worker's perspective was captured through the use of metaphors in understanding the transition processes of participating in daily life without work. Metaphors were used to facilitate this injured worker's expression of deep thoughts and feelings, and to allow for different and abstract ways of thinking about disability and illness.

Findings: Metaphors were identified within several transitions involved in the process of going from a worker to an injured worker functioning in daily life.

Conclusions: The findings from this case study can be shared with others as a means of increasing the awareness of the experiences in managing daily life when living with MCS. In addition, insights from this injured worker's case could act as a venue for distributing knowledge about chemical injuries to health care professionals to broaden their views of this injury and its treatment.
Three-dimensional spiral computed tomographic cysto-urethrography	for post-traumatic complex posterior urethral strictures associated with	urethral-rectal fistula
Authors: Sa Ying Long , Xu Yue Min , Feng Chao , Ye Xu Xiao , Song Lu Jie
Published: December 2019

To evaluate the value of three-dimensional spiral computed tomography/cysto-urethrography (CTCUG) in diagnosing posterior urethral strictures associated with urethrorectal fistulas (URF). Between June 2008 and March 2012, 38 patients with posterior urethral strictures associated with URFs were examined by CTCUG, retrograde urethrography (RUG) and cysto-urethrography (CUG). Urethral reconstruction was undertaken and URFs were surgically repaired in all patients. The length of the urethral defect, location and size of URFs were recorded. Data from radiological examinations were compared with surgical findings. No statistically significant difference was found in the length of stricture measured using CTCUG (4.31 ± 2.28 cm) or conventional urethrography (4.02 ± 3.12 cm; p > 0.05), However, the accuracy in determining the location of the stricture was higher with CTCUG (93.12%) than with conventional urethrography (70.59%; p < 0.05). CTCUG identified URFs in all 38 patients (100%), whereas URFs were only observed in 27 patients (71%) using conventional urethrography. In conclusion, CTCUG was more accurate, safer and provided more details of URFs and urethral defects than conventional urethrography in patients with posterior urethral strictures associated with URFs.