Band 6, Heft 1

A growing body of evidence demonstrates that human vision operates differently in the space near and on the hands; for example, early findings in this literature reported that rapid onsets are detected faster near the hands, and that objects are searched more thoroughly. These and many other effects were attributed to enhanced attention via the recruitment of bimodal visual-tactile neurons representing the hand and near-hand space. However, recent research supports an alternative account: stimuli near the hands are preferentially processed by the action-oriented magnocellular visual pathway at the expense of processing in the parvocellular pathway. This Modulated Visual Pathways (MVP) account of altered vision near the hands describes a hand position-dependent trade-off between the two main retinal-cortical visual pathways between the eye and brain. The MVP account explains past findings and makes new predictions regarding near-hand vision supported by new research.

This mini-review briefly documents the phenomenon of blindsight and investigates evidence for a comparable state in olfaction. Blindsight evokes an appropriate response to a visual stimulus without any conscious visual experience or awareness of that event. For olfaction, we describe many routine aspects of perception that may occur without conscious awareness, arguably paralleling key aspects of blindsight. We then describe the limited neuropsychological evidence suggesting that people can apparently respond appropriately to odours that they cannot subjectively smell – what we would term “blindsmell”.

It has been argued that cognitive training may be effective in improving cognitive performance in healthy older adults. However, inappropriate active control groups often hinder the validity of these claims. Additionally there are relatively few independent empirical studies on popular commercially available cognitive training programs. The current research extends on previous work to explore cognitive training employing a more robust control group. Twenty-eight healthy older adults (age: M = 64.18, SD = 6.9) completed either a multi-faceted online computerised cognitive training program or trained on a simple reaction time task for 20 minutes a day over a 28 day period. Both groups significantly improved performance in multiple measures of processing speed. Only the treatment group displayed improved performance for measures of memory accuracy. These results suggest improvements in processing speed and visual working memory may be obtained over a short period of computerized cognitive training. However, gains over this time appear only to show near transfer. The use of similar active control groups in future research are needed in order to better understand changes in cognition after cognitive training.

Emerging research on the long-term impact of concussions on athletes has allowed public recognition of the potentially devastating effects of these and other mild head injuries. Mild traumatic brain injury (mTBI) is a multifaceted disease for which management remains a clinical challenge. Recent pre-clinical and clinical data strongly suggest a destructive synergism between brain temperature elevation and mTBI; conversely, brain hypothermia, with its broader, pleiotropic effects, represents the most potent neuro-protectant in laboratory studies to date. Although well-established in selected clinical conditions, a systemic approach to accomplish regional hypothermia has failed to yield an effective treatment strategy in traumatic brain injury (TBI). Furthermore, although systemic hypothermia remains a potentially valid treatment strategy for moderate to severe TBIs, it is neither practical nor safe for mTBIs. Therefore, selective head-neck cooling may represent an ideal strategy to provide therapeutic benefits to the brain. Optimizing brain temperature management using a National Aeronautics and Space Administration (NASA) spacesuit spinoff head-neck cooling technology before and/or after mTBI in contact sports may represent a sensible, practical, and effective method to potentially enhance recover and minimize post-injury deficits. In this paper, we discuss and summarize the anatomical, physiological, preclinical, and clinical data concerning NASA spinoff head-neck cooling technology as a potential treatment for mTBIs, particularly in the context of contact sports.

Background: An increase in the EEG upper/low a power ratio has been associated with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and to the atrophy of temporoparietal brain areas. Subjects with a higher α3/α2 frequency power ratio showed lower brain perfusion than in the low α3/α2 group. The two groups show significantly different hippocampal volumes and correlation with q frequency activity. Methods: Seventy-four adult subjects with MCI underwent clinical and neuropsychological evaluation, electroencephalogram (EEG) recording, and high resolution 3D magnetic resonance imaging (MRI). Twenty-seven of them underwent EEG recording and perfusion single-photon emission computed tomography (SPECT) evaluation. The α3/α2 power ratio and cortical thickness were computed for each subject. The difference in cortical thickness between the groups was estimated. Results: In the higher upper/low a group, memory impairment was more pronounced in both the MRI group and the SPECT MCI groups. An increase in the production of q oscillations was associated with greater interhemisperic coupling between temporal areas. It also correlated with greater cortical atrophy and lower perfusional rate in the temporoparietal cortex. Conclusion: High EEG upper/low α power ratio was associated with cortical thinning and lower perfusion in temporoparietal areas. Moreover, both atrophy and lower perfusion rate significantly correlated with memory impairment in MCI subjects. Therefore, the increase in the EEG upper/low α frequency power ratio could be useful in identifying individuals at risk for progression to AD dementia in a clinical context.

Background: There are numerous potential treatments assessed for acute cerebral ischemia using animal models. This study aimed to assess the effect of these treatments in terms of infarct size and neurobehavioral change. This meta-analysis was conducted to determine if any of these treatments provide a superior benefit so that they might be used on humans. Methods: A systematic search was conducted using several electronic databases for controlled animal studies using only nonsurgical interventions for acute cerebral ischemia. A random-effects model was used. Results: After an extensive literature search, 145 studies were included in the analysis. These studies included 1408 treated animals and 1362 control animals. Treatments that had the most significant effect on neurobehavioral scales included insulin, various antagonists, including N-methyl-Daspartate (NMDA) receptor antagonist ACEA1021, calmodulin antagonist DY-9760e, and α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist YM872, and antiviral agents. Treatments providing the greatest effect on infarct size included statins, sphingosine-1-phosphate agonist (fingolimod), alcohol, angiotensin, and leukotrienes. Treatments offering the greatest reduction in brain water content included various agonists, including sphingosine-1-phosphate agonist fingolimod, statins, and peroxisome proliferator-activated receptor gamma (PPAR-γ). Treatment groups with more than one study all had high heterogeneity (I 2 > 80%), however, using meta-regression we determined several sources of heterogeneity including sample size of the treatment and control groups, the occlusion time, but not the year when the study was conducted. Conclusions: Some treatments stand out when compared to others for acute cerebral ischemia in animals. Greater replication of treatment studies is required before any treatments are selected for future human trials.

We describe an as yet unreported neocentric small supernumerary marker chromosome (sSMC) derived from chromosome 1p21.3p21.2. It was present in 80% of the lymphocytes in a male patient with intellectual disability, severe speech deficit, mild dysmorphic features, and hyperactivity with elements of autism spectrum disorder (ASD). Several important neurodevelopmental genes are affected by the 3.56 Mb copy number gain of 1p21.3p21.2, which may be considered reciprocal in gene content to the recently recognized 1p21.3 microdeletion syndrome. Both 1p21.3 deletions and the presented duplication display overlapping symptoms, fitting the same disorder category. Contribution of coding and non-coding genes to the phenotype is discussed in the light of cellular and intercellular homeostasis disequilibrium. In line with this the presented 1p21.3p21.2 copy number gain correlated to 1p21.3 microdeletion syndrome verifies the hypothesis of a cumulative effect of the number of deregulated genes - homeostasis disequilibrium leading to overlapping phenotypes between microdeletion and microduplication syndromes. Although miR-137 appears to be the major player in the 1p21.3p21.2 region, deregulation of the DPYD (dihydropyrimidine dehydrogenase) gene may potentially affect neighboring genes underlying the overlapping symptoms present in both the copy number loss and copy number gain of 1p21. Namely, the all-in approach revealed that DPYD is a complex gene whose expression is epigenetically regulated by long non-coding RNAs (lncRNAs) within the locus. Furthermore, the long interspersed nuclear element-1 (LINE-1) L1MC1 transposon inserted in DPYD intronic transcript 1 (DPYD-IT1) lncRNA with its parasites, TcMAR-Tigger5b and pair of Alu repeats appears to be the “weakest link” within the DPYD gene liable to break. Identification of the precise mechanism through which DPYD is epigenetically regulated, and underlying reasons why exactly the break (FRA1E) happens, will consequently pave the way toward preventing severe toxicity to the antineoplastic drug 5-fluorouracil (5-FU) and development of the causative therapy for the dihydropyrimidine dehydrogenase deficiency.

The interplay of neural discharge patterns involved in “respiration”, “circulation”, “opening movements in the mandible”, and “locomotion” was investigated electrophysiologically in a decerebrate and arterially perfused in situ rat preparation. Sympathetic tone increased with increases in perfusion flow rate. All nerve discharges became clearly organized into discharge episodes of increasing frequency and duration punctuated by quiescent periods as the perfusion flow rate increased at 26ºC. The modulated sympathetic tone at 10× total blood volume/ min activated the forelimb pattern generator and spontaneously generated fictive forelimb movement during discharge episodes. The coupling rhythm of respiration and locomotion during motion occurred at frequency ratios ranges of 1:2 and 1:3. Small increases in systemic pressure were always generated after the initiation of motion. Opening movements in the mandible, occurring during the inspiratory phase at all tested flow rates, were generated in both the inspiratory and expiratory phases during motion. Although the central mechanism for the entrainment of respiratory and locomotor rhythms has not been identified, a spinal-feedback mechanism generating fictive locomotion in the upper spinal cord contributed to generating the opening movement in the mandible in the expiratory phase during motion. The existence of this mechanism implies that there is a reciprocal functional interaction between the brainstem and the spinal cord, whereby the intake and output of air by the lungs is efficiently improved during movement by both nasal and mouth breathing. These results suggest that this reciprocal functional interaction plays an important role in increasing oxygenated blood flow during locomotion.

Population aging is rapidly accelerating worldwide; however, longer life expectancy is not the only public health goal. Indeed, extended lifetime involves maintaining function and the capacity of living independently. Sarcopenia and physical frailty are both highly relevant entities with regards to functionality and autonomy of older adults. The concepts and definitions of frailty and sarcopenia have largely been revised over the years. Sarcopenia is an age-related progressive and generalized loss of skeletal muscle mass and strength. On the other hand, frailty is a state of increased vulnerability to stressors, responsible for exposing the older person to enhanced risk of adverse outcomes. Physical frailty and sarcopenia substantially overlap and several adverse outcomes of frailty are likely mediated by sarcopenia. Indeed, the concepts of sarcopenia and physical frailty can be perceived as related to the same target organ (i.e., skeletal muscle) and it may be possible to combine them into a unique definition. The biological background of such a close relationship needs to be explored and clarified as it can potentially provide novel and pivotal insights for the assessment and treatment of these conditions in old age. The aim of this paper is to indicate and discuss possible biological markers to be considered in the framing of physical frailty and sarcopenia.

Oxaliplatin (OXL) is a third-generation chemotherapeutic agent commonly used to treat metastatic digestive tumors; however, one of the main limiting complications of OXL is neuropathic pain. In this study, the underlying mechanisms responsible for OXL evoked-neuropathic pain were examined. Using a rat model, the results demonstrated that intraperitoneal (i.p.) injection of OXL significantly increased mechanical pain and cold sensitivity as compared with control animals (P < 0.05 vs. control rats). Blocking proteinase-activated receptor 2 (PAR2) significantly attenuated mechanical pain and cold sensitivity observed in control rats and OXL rats (P < 0.05 vs. vehicle control). The attenuating effect of PAR2 on mechanical pain and cold sensitivity were significantly smaller in OXL-rats than in control rats. The role played by PAR2 downstream signaling pathways [namely, transient receptor potential ankyrin 1 (TRPA1)] in regulating OXL evoked-neuropathic pain was also examined. The data shows that TRPA1 expression was upregulated in the lumbar dorsal root ganglion (DRG) of OXL rats and blocking TRPA1 inhibited mechanical pain and heightened cold sensitivity (P <0.05 vs. control rats). Blocking PAR2 also significantly decreased TRPA1expression in the DRG. Findings in this study show that OXL intervention amplifies mechanical hyperalgesia and cold hypersensitivity and PAR2 plays an important role in regulating OXLinduced neuropathic pain via TRPA1 pathways.

This review highlights relevant issues about applications and improvements of atomic force microscopy (AFM) toward a better understanding of neurodegenerative changes at the molecular level with the hope of contributing to the development of effective therapeutic strategies for neurodegenerative illnesses. The basic principles of AFM are briefly discussed in terms of evaluation of experimental data, including the newest PeakForce Quantitative Nanomechanical Mapping (QNM) and the evaluation of Young’s modulus as the crucial elasticity parameter. AFM topography, revealed in imaging mode, can be used to monitor changes in live neurons over time, representing a valuable tool for high-resolution detection and monitoring of neuronal morphology. The mechanical properties of living cells can be quantified by force spectroscopy as well as by new AFM. A variety of applications are described, and their relevance for specific research areas discussed. In addition, imaging as well as non-imaging modes can provide specific information, not only about the structural and mechanical properties of neuronal membranes, but also on the cytoplasm, cell nucleus, and particularly cytoskeletal components. Moreover, new AFM is able to provide detailed insight into physical structure and biochemical interactions in both physiological and pathophysiological conditions.

In general, brain temperatures are elevated during physical sporting activities; therefore, reducing brain temperature shortly after a sports-related concussion (SRC) could be a promising intervention technique. The main objective of this study was to examine the effects of head and neck cooling on physiological and cognitive function in normal healthy volunteers. Twelve healthy volunteers underwent two different sessions of combined head and neck cooling, one session with a cold pack and one session with a room temperature pack. Physiological measurements included: systolic/diastolic blood pressure, pulse oximetry, heart rate, and sublingual and tympanic temperature. Cognitive assessment included: processing speed, executive function, and working memory tasks. Physiological measurements were taken pre-, mid- and post-cooling, while cognitive assessments were done before and after cooling. The order of the sessions was randomized. There was a significant decrease in tympanic temperature across both sessions; however more cooling occurred when the cold pack was in the device. There was no significant decrease in sublingual temperature across either session. The observed heart rates, pulse oximetry, systolic and diastolic blood pressure during the sessions were all within range of a normal healthy adult. Cognitive assessment remained stable across each session for both pre- and post-cooling. We propose that optimizing brain temperature management after brain injury using head and neck cooling technology may represent a sensible, practical, and effective strategy to potentially enhance recovery and perhaps minimize the subsequent short and long term consequences from SRC.

Background: To provide a review of the literature on the perception of emotion in Alzheimer’s dementia (AD) and Mild cognitive impairment (MCI), and to evaluate if emotion intensity matters. Methodology: A systematic literature search of PubMed database was carried out using combinations or truncated versions of the keywords “MCI”, ”Alzheimer”, “emotion recognition”, “facial emotion recognition”, “social cognition” or “emotion perception”. Twenty-eight articles were found to meet the inclusion criteria. Results: Overall, AD patients performed worse on emotion perception than MCI patients and healthy controls. Half of the studies found an emotion-specific deficit for MCI patients on the emotions anger, sadness and fear. However, studies taking emotion intensity into account are still scarce. Conclusions: An emotion-intensity based approach may be more sensitive to detect subtle impairments in facial emotion recognition. Future studies need to take emotion intensity into account and also consider confounding factors such as overall cognition and mood.

Stroke is the loss of brain function due to a disturbance in the blood supply to the brain resulting from either ischemia or hemorrhage. Previous studies have evaluated the clinical importance of nutritional interventions such as vitamin B supplementation in the management of acute strokes. However, it is still inconclusive whether or not vitamin B supplementation will benefit patients with acute strokes. Therefore, a meta-analysis was performed to assess the efficacy of vitamin B supplementation in the treatment of stroke patients. Medline, Embase, Scopus, and Cochrane Library databases were searched (from 1960 to June 2015) and forest plots were generated to illustrate the treatment effects. A systemic review of the electronic databases yielded 12 eligible studies consisting of 7474 patients. Forest plots from the meta-analyses of the included studies illustrated that vitamin B supplementation significantly lowered the plasma concentration of total homocysteine (SMD = -0.82; 95% CI: -0.77; Z = -29.06, p < 0.0001) and resulted in significant reduction in stroke recurrence (OR = 0.86%; 95% CI: 0.76, 0.97; Z = -2.41; p = 0.016) as well as a combined incidence of vascular events, including recurrent strokes, myocardial infarctions and vascular deaths (OR = 0.87%; 95% CI: 0.79, 0.96; Z= -2.73; p = 0.0063). Additionally, the nearly-symmetrical funnel plot (Egger’s test, t = −1.705, p = 0.1224) indicated the absence of publication bias regarding the meta-analysis that examined the effect of vitamin B supplementation on the plasma levels of homocysteine in acute stroke patients. These findings suggested that vitamin B supplementation presents a potential addition to the armamentarium for the management of acute stroke patients.

Background: Neuropsychiatric deficits can induce marked disability in patients with dementia and increase caregiver distress. Several studies have found that neuropsychiatric symptoms are common both in patients with Alzheimer’s disease (AD) and patients with vascular dementia (VaD). However, there are few studies of the neuropsychiatric disturbances in large clinical samples of patients with mixed (cortical - subcortical) VaD from mainland China. This study aimed to investigate the neuropsychiatric symptoms in VaD patients in mainland China. Methods: Eighty patients with mixed VaD for over 6 months duration, and their caregivers (VaD group), were recruited for interview in Zhongnan Hospital of Wuhan University, from June 2010 to June 2012. Eighty age- and sex-matched normal volunteers (control group) were interviewed at the same time. The Mini Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI) were administered to the VaD patients, their caregivers, and normal volunteers. Group differences were analyzed using the unpaired t-test. Results: The total mean scores of the NPI in the VaD group were higher than in the control group (P < 0.01). The subscale scores of NPI, including delusions, hallucinations, depression, apathy, irritability, agitation, aberrant motor behavior, and change in appetite were significantly higher in the VaD group than in the control group (P < 0.05-0.01). Compared with the mild VaD subgroup, the NPI subscale scores of apathy, irritability and total scores were significantly higher in the moderate VaD subgroup (P < 0.05-0.01); the NPI subscale scores of anxiety, apathy, irritability, and total scores were significantly higher in the severe VaD subgroup (P < 0.01). Compared with the moderate VaD subgroup, the NPI subscale scores of anxiety and apathy were significantly higher in the severe VaD subgroup (P < 0.05-0.01). Conclusions: Neuropsychiatric symptoms, such as hallucination, anxiety, apathy, irritability and aberrant action behavior, are common in patients with mixed VaD from mainland China; anxiety and apathy were more pronounced in the subgroup of severe VaD patients.

Neural progenitor transplantation is a promising therapeutic option for several neurological diseases and injuries. In nearly all human clinical trials and animal models that have tested this strategy, the low survival rate of progenitors after engraftment remains a significant challenge to overcome. Developing methods to improve the survival rate will reduce the number of cells required for transplant and will likely enhance functional improvements produced by the procedure. Here we briefly review the close relationship between the blood vasculature and neural progenitors in both the embryo and adult nervous system. We also discuss previous studies that have explored the role of the vasculature and hypoxic pre-conditioning in neural transplants. From these studies, we suggest that hypoxic pre-conditioning of a progenitor pool containing both neural and endothelial cells will improve engrafted transplanted neuronal survival rates.

The Five Digits Test (FDT) is a Stroop paradigm test that aims to evaluate executive functions. It is composed of four parts, two of which are related to automatic and two of which are related to controlled processes. It is known that pupillary diameter increases as the task’s cognitive demand increases. In the present study, we evaluated whether the pupillary diameter could distinguish cognitive effort between automated and controlled cognitive processing during the FDT as the task progressed. As a control task, we used a simple reading paradigm with a similar visual aspect as the FDT. We then divided each of the four parts into two blocks in order to evaluate the differences between the first and second half of the task. Results indicated that, compared to a control task, the FDT required higher cognitive effort for each consecutive part. Moreover, the first half of every part of the FDT induced dilation more than the second. The differences in pupil dilation during the first half of the four FDT parts were statistically significant between the parts 2 and 4 (p=0.023), and between the parts 3 and 4 (p=0.006). These results provide further evidence that cognitive effort and pupil diameter can distinguish controlled from automatic processes.

Background: The goal of the present study was to evaluate the color preferences of patients with schizophrenia and their correlations with personality traits. Methodology: Sixty-three patients with schizophrenia and 59 healthy volunteers were asked to undertake the color preference and the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) tests. Results: The healthy volunteers showed a greater preference for green but a lesser one for brown compared to the patients with schizophrenia. Patients scored higher than the healthy volunteers on the ZKPQ Neuroticism-Anxiety and Activity scales. Moreover, in patients, black preference ranking was associated with the Neuroticism-Anxiety, whereas pink and orange preferences were negatively associated with Activity; white preference correlated negatively with Sociability. Conclusions: Patients with schizophrenia preferred green less but brown more, and displayed their personality correlates of these color preferences. These findings are suggesting that patients with schizophrenia should be encouraged to be more exposed to bright colors such as green and white, and less to dark colors such as black, during therapy and rehabilitation sessions.

Traumatic brain injury (TBI) is a multifaceted disease with intrinsically complex heterogeneity and remains a significant clinical challenge to manage. TBI model systems have demonstrated many mechanisms that contribute to brain parenchymal cell death, including glutamate and calcium toxicity, oxidative stress, inflammation, and mitochondrial dysfunction. Mitochondria are critically regulated by uncoupling proteins (UCP), which allow protons to leak back into the matrix and thus reduce the mitochondrial membrane potential by dissipating the proton motive force. This uncoupling of oxidative phosphorylation from adenosine triphosphate (ATP) synthesis is potentially critical for protection against cellular injury as a result of TBI and stroke. A greater understanding of the underlying mechanism or mechanisms by which uncoupling protein-2 (UCP2) functions to maintain or optimize mitochondrial function, and the conditions which precipitate the failure of these mechanisms, would inform future research and treatment strategies. We posit that UCP2-mediated function underlies the physiological response to neuronal stress associated with traumatic and ischemic injury and that clinical development of UCP2-targeted treatment would significantly impact these patient populations. With a focus on clinical relevance in TBI, we synthesize current knowledge concerning UCP2 and its potential neuroprotective role and apply this body of knowledge to current and potential treatment modalities.

Perceptual decision making depends on the choices available for the presented task. Most event-related potential (ERP) experiments are designed with two options, such as YES or NO. In some cases, however, subjects may become confused about the presented task in such a way that they cannot provide a behavioral response. This study aims to put subjects into such a puzzled state in order to address the following questions: How does the brain respond during puzzling moments? And what is the brain’s response to a non-answerable task? To address these questions, ERP were acquired from the brain during a scintillation grid illusion task. The subjects were required to count the number of illusory dots, a task that was impossible to perform. The results showed the presence of N130 over the parietal area during the puzzling task. Coherency among the brain hemispheres was enhanced with the complexity of the task. The neural generators’ source localizations were projected to a multimodal complex covering the left postcentral gyrus, supramarginal gyrus, and angular gyrus. This study concludes that the brain component N130 is strongly related to perception in a puzzling task network but not the visual processing network.

This review highlights the most important discovery in the reticular activating system (RAS) in the last 10 years, the manifestation of gamma (γ) band activity in cells of the RAS, especially in the pedunculopontine nucleus (PPN), which is in charge of the high frequency states of waking and rapid eye movement sleep. This discovery is critical to understanding the modulation of movement by the RAS and how it sets the background over which we generate voluntary and triggered movements. The presence of γ band activity in the RAS is proposed to participate in the process of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions. Early findings using stimulation of this region to induce arousal, and also to elicit stepping, are placed in this context. This finding also helps explain the novel use of PPN deep brain stimulation for the treatment of Parkinson’s disease, although considerable work remains to be done.

Purpose: To investigate the effect of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase (Trk) on potassium chloride cotransporter 2 (KCC2) in rats following nicotine withdrawal and the roles played by BDNF/Trk/KCC2 pathway in nicotine withdrawal-induced hyperalgesia. Methods: Seventy-eight rats were randomly assigned to five groups: control group (n = 12) without any treatment, normal saline group (NS group, n = 12) and nicotine withdrawal group (NW group, n = 30) receiving a subcutaneous injection of saline or nicotine for 7 days, respectively. The NW + dimethyl sulfoxide (DMSO) (n = 12) and NW+ Trk antagonist K252a groups (n = 12) received an intrathecal injection of DMSO (10 μl) and K252a (10 μg/10 μl) for 3 days after nicotine withdrawal, respectively. Nicotine withdrawal was precipitated by subcutaneous injection of nonselective and noncompetitive antagonist of nicotinic acetylcholine receptors mecamylamine. Pain was tested using thermal withdrawal latency (TWL). A Western blot was used to examine the expression of BDNF and KCC2. Results: The TWL was significantly decreased in NW group relative to control and NS groups (P < 0.01). Compared with the NW group, the NW+K252a group manifested a significantly higher latency (P < 0.01). The BDNF expression was increased and KCC2 was decreased in NW group compared with the control group (P < 0.01). K252a reduced KCC2 downregulation. Conclusion: BDNF/Trk signaling may contribute to nicotine withdrawal-induced hyperalgesia via downregulation of KCC2.

Synapses are the principal sites for chemical communication between neurons and are essential for performing the dynamic functions of the brain. In Alzheimer’s disease and related tauopathies, synapses are exposed to disease modified protein tau, which may cause the loss of synaptic contacts that culminate in dementia. In recent decades, structural, transcriptomic and proteomic studies suggest that Alzheimer’s disease represents a synaptic disorder. Tau neurofibrillary pathology and synaptic loss correlate well with cognitive impairment in these disorders. Moreover, regional distribution and the load of neurofibrillary lesions parallel the distribution of the synaptic loss. Several transgenic models of tauopathy expressing various forms of tau protein exhibit structural synaptic deficits. The pathological tau proteins cause the dysregulation of synaptic proteome and lead to the functional abnormalities of synaptic transmission. A large body of evidence suggests that tau protein plays a key role in the synaptic impairment of human tauopathies.

Objective: The aim of this study is to evaluate variations in cortical activation in early and late Uygur-Chinese bilinguals from the Xinjiang Uygur Autonomous Region of China. Methodology: During a semantic judgment task with visual stimulation by a single Chinese or Uygur word, functional magnetic resonance imaging (fMRI) was performed. The fMRI data regarding activated cortical areas and volumes by both languages were analyzed. Results: The first language (L1) and second language (L2) activated language-related hemispheric regions, including the left inferior frontal and parietal cortices, and L1 specifically activated the left middle temporal gyrus. For both L1 and L2, cortical activation was greater in the left hemisphere, and there was no significant difference in the lateralization index (LI) between the two languages (p > 0.05). Although the total activated cortical areas were larger in early than late bilinguals, the activation volumes were not significantly different. Conclusion: Activated brains areas in early and late fluent bilinguals largely overlapped. However, these areas were more scattered upon presentation of L2 than L1, and L1 had a more specific pattern of activation than L2. For both languages, the left hemisphere was dominant. We found that L2 proficiency level rather than age of acquisition had a greater influence on which brain areas were activated with semantic processing.

Background: Short-latency afferent inhibition (SAI) results when somatosensory afferent input inhibits the corticospinal output from primary motor cortex (M1). The present study examined SAI in the flexor carpi radialis (FCR) muscle in individuals with spinal cord injury (SCI) and uninjured controls. Methods: Short-latency afferent inhibition (SAI) was evoked by stimulating the median nerve at the elbow at intervals of 15, 20 and 25 ms in advance of a transcranial magnetic stimulation (TMS) pulse over M1. SAI was tested with the FCR at rest and also during ~20% of maximum voluntary contraction. Corticospinal output was assessed through measuring both motor thresholds and motor evoked potential (MEP) recruitment curves. The afferent volley was assessed via the N20-P25 amplitude of the somatosensory evoked potential (SEP) and the amplitude of sensory nerve action potentials (SNAP) recorded over the median nerve at the elbow. Results: SAI is reduced in SCI in both the contracted and non-contracted FCR muscle. MEP recruitment curves and thresholds were decreased in SCI only in the active state and not the resting state. N20-P25 amplitude was similar between groups in both the resting and active states although SNAP was significantly reduced in SCI at rest. Conclusions: We conclude that reduced SAI in SCI is likely attributed to neuroplasticity altering the intrinsic M1 circuitry mediating SAI and/or reduced afferent input traversing a direct thalamocortical route to M1. These data provide a new avenue of research aimed at identifying therapeutic approaches to alter SAI to improve upper limb function in individuals with SCI.

Glial-restricted precursor (GRP) cells, the earliest glial progenitors for both astrocytes and oligodendrocytes, have been derived from embryos and embryonic stem cells (ESC) in rodents. However, knowledge regarding the equivalent cell type in primates is limited due to restrictions imposed by ethics and resources. Here we report successful derivation and characterization of primate GRP cells from rhesus monkey ESC. The purified monkey GRP cells were A2B5-positive and FGF2-dependent for survival and proliferation. The differentiation assays indicated that they were tri-potential in vitro and bi-potential in vivo. These newly purified GRP cells will help to facilitate understanding of the molecular mechanism of glial development in primates as well as provide a source of therapeutic donor cells for use in neuroregenerative medicine.

In this study we investigated the potential anti-epileptogenic effect of neuronal connexin Cx36 gap junction blockage via inhibition of microtubule-associated protein 2 (MAP-2) and synaptophysin (SYP) overexpression. Thirty adult male Wistar rats were divided into five groups (six animals per group): control, sham, carbenoxolone (CBX), quinine (QN), and quinidine (QND). An epilepsy model was produced by injecting kainic acid (KA) into the rat amygdala. Broad-spectrum and selective blockers of the Cx36 channel (CBX, QN, and QND) were administered via intraperitoneal injection. Expression of MAP-2 and SYP was assessed by immunofluorescent and immunohistochemical examination. Expression of MAP-2 and SYP was significantly increased after KA administration in the sham group compared with the control group. Expression of MAP-2 and SYP was significantly decreased in the CBX, QN, and QND groups compared with the sham group. The results provide new evidence regarding the key role of MAP-2 and SYP overexpression in three important mechanisms: the modulation of neuronal plasticity, hyperexcitability of the hippocampal neuronal network, and persistent seizure discharge. Furthermore, the reversal of MAP-2 and SYP overexpression following administration of Cx36 channel blockers indicates a potential role for Cx36 channel blockers in anti-epileptogenic treatment and in doing so, highlights a critical need for further investigation of these compounds.

The aim of this study was to examine the role played by substance P and calcitonin gene-related peptide (CGRP) within the dorsal horn of the spinal cord in engagement of antinociception evoked by dexmedetomidine (DEX). Paw withdrawal threshold (PWT) to mechanical stimulation was determined after chronic intrathecal infusion of DEX and enzyme-linked immunosorbent assay (ELISA) was employed to examine the levels of spinal substance P and CGRP. Our results show that PWT was significantly increased by intrathecal administration of DEX in rats (P < 0.05 vs. vehicle control, n = 20 in each group). Also, intrathecal infusion of DEX significantly decreased the concentrations of substance P and CGRP as compared with vehicle control (P < 0.05 DEX vs. vehicle control, n = 20 in each group). Blocking α2-adrenoreceptors (α2-AR) blunted the decreases of substance P and CGRP levels and the enhancement of PWT evoked by DEX. Additionally, a linear relationship was observed between PWT and the levels of spinal substance P (r = 0.87; P < 0.005) and CGRP (r = 0.85; P < 0.005). Moreover, blocking individual substance P and CGRP receptors amplified PWT without altering substance P and CGRP levels. Thus, DEX plays a role in stimulating α2-AR receptors, which thereby decreases substance P and CGRP levels within the dorsal horn. This contributes to DEX-evoked antinociception.

The purpose of this study was to analyze if there is a significant correlation between the results of diffusionweighted imaging (DWI) and the expression of proliferating cell nuclear antigen (PCNA) in astrocytomas. The DWI scans of 19 different-grade astrocytomas were obtained on a 3 T magnetic resonance scanner. The average regional apparent diffusion coefficients (ADC) were measured. The positive expression of PCNA was determined immunohistochemically by using streptavidin-peroxidase complex staining, and was quantified by calculating its calibrated opacity density (COD) using an image analysis system. The average regional ADC and PCNA COD of low grade and high grade astrocytomas were compared. Correlations between regional ADC and PCNA COD were analyzed. The average regional ADC of high grade astrocytomas was significantly (t = 10.169, P = 0.000) less (0.687 ± 0.225 x 10-3 mm2/s) than that of low grade astrocytomas (1.572 ± 0.333 x 10-3 mm2/s). The PCNA COD (0.343 ± 0.052) of high grade astrocytomas was significantly (t=-7.858, P=0.000) greater than that (0.194 ± 0.012) of low grade astrocytomas. There were strong negative correlations between regional ADC and PCNA COD (r = -0.801, P = 0.000). The results demonstrated that DWI is helpful in evaluating cell proliferation and preoperatively grading astrocytomas by measuring regional ADC.

Background: Palatal myoclonus (PM) is the hallmark of hypertrophic olivary degeneration (HOD); however, little is known regarding the association of thalamic lesions and PM. Case presentation: Here, we report a case of deteriorative PM after an acute small ventrolateral thalamic hemorrhage in a female Chinese patient with HOD. The sudden and severe deterioration of PM was preceded by at least 10 days of an occasionally occurring PM, which was related to an acute cerebellar hemorrhage 8 months earlier. A computed tomography scan upon admission showed a small intracerebral hematoma in the left ventrolateral thalamus, and a magnetic resonance imaging scan revealed the typical signs of HOD as well as a remote lesion in the dentate nucleus. Symptoms of PM were controlled by carbamazepine and clonazepam. Conclusion: These findings indicated that the damaged dentatothalamic tract might be due to a unique pathogenic mechanism involving a lesion of the ventrolateral thalamus and Guillain-Mollaret triangle.