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Bo Fu,1 Shao-Nan Wen,1 Bin Wang,1 Kun Wang,2 Ji-Yan Zhang,3 Xie-Chuan Weng,1 Shao-Jun Liu1 1State Key Laboratory of Proteomics, Department of Neurobiology, Institute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing 100850, China; 2Department of Occupational Medicine, Tianjin Institute of Environmental and Occupational Medicine, Tianjin 300050, China; 3Department of Molecular Immunology, Institute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing 100850, China Purpose: Ventral tegmental area (VTA) dopamine system plays an important role in depression and is also involved in pain experience. In this study, we investigated the VTA dopaminergic (DA) neuron firing and local field potential (LFP) in pain-related depression, and we try to explore the underlying relationship between pain and depression.Materials and methods: We used neuropathic pain model [spare nerve injury (SNI)] to induce pain-related depression. The Dixon up–down method was used to test mechanical hypersensitivity. Behavioral changes like open field test, sucrose preference test, and forced swim test were used to test depression-like behaviors. Gabapentin (GBP) was used to explore the chronic analgesic treatment that could reverse pain-related depression. To investigate the in vivo variations of VTA DA neuron firing and LFP, multichannel acquisition processor system was used.Results: We used SNI to induce depression-like behaviors. Repeated GBP treatment reversed these behaviors after 14 days of injection. An in vivo electrophysiological analysis of the firing characteristics of VTA DA neurons and LFP revealed that SNI increased the firing rate of DA neurons, but not the burst firing activity. Surprisingly, chronic GBP reversed the firing rate of DA neurons and reduced the burst firing activity. Moreover, SNI increased the LFP power in delta and theta oscillation and decreased it in beta oscillation. Repeated administration of GBP significantly suppressed theta oscillation. Above all, chronic GBP altered these characteristics to reverse depression-like behaviors.Conclusion: The present study confirmed that the tonic firing activity of VTA DA neurons, but not the burst firing activity, was the key factor in peripheral neuropathy–induced depression. Chronic GBP regulated the firing pattern of DA neurons and decreased theta oscillation in VTA to treat pain-related depression. This variation tendency of electrophysiological characteristics of VTA DA neurons and theta oscillation in VTA might represent an attempt to cope with pain-related negative mood disorder. Keywords: chronic neuropathic pain, depression, dopaminergic neuron, LFP, VTA

In this work, novel monoclinic tungsten oxide (WO 3 )-encapsulated phosphate-rich porous sodium alginate (PASA) microspherical hydrogel beads were prepared for efficient U(VI) capture. These macroporous and hollow beads were systematically characterized through XRD, FTIR, EDX-mapping, and SEM-EDS techniques. The O and P atoms in the PO and monoclinic WO 3 offered inner-spherical complexation with U(VI). The in situ growth of WO 3 played a significant role inside the phosphate-rich biopolymeric network to improve its chemical stability, specific surface area, adsorption capacity, and sorption rate. The phytic acid (PA) served for heteroatom doping and crosslinking. The encapsulated WO 3 mass ratio was optimized in different composites, and WO 3 /PASA 3 (the microspherical beads with a mass ratio of 30.0 % w/w) exhibited remarkable maximum sorption capacity q m (336.42 mg/g) computed through the best-fit Langmuir model (R 2  ≈ 0.99) and rapid sorption equilibrium, t eq (150 min). The isothermal sorption studies were conducted at different temperatures (298, 303, and 308 K) and thermodynamic parameters concluded that the process of U(VI) sorption using WO 3 /PASA 3 is endothermic and feasible having ΔH o (8.19 kJ/mol), ΔG o (-20.75, -21.38, and - 21.86 kJ/mol) and proceeds with a minute increase in randomness ΔS o (0.09 kJ/mol.K). Tungsten oxide (WO 3 )-encapsulated phosphate-rich porous microspherical beads could be promising material for uranium removal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by cognitive deficits and dementia. AD entails predominant pathological characteristics including amyloid beta (Aβ) plaque formation, neurofibrillary entanglements, and brain atrophy, which gradually result in cognitive dysfunctions. Studies showed that these pathological changes are found in a myriad of brain structures, including the claustrum (CLA), a nucleus that penetrates deeply into the brain and is extensively interconnected to various brain structures. The CLA modulates many aspects of cognitive functions, with attention, executive function, visuospatial ability, language, and memory in particular. It is also implicated in multiple neuropsychiatric disorders, of which one worthy of particular attention is AD-related cognitive impairments. To inspire novel AD treatment strategies, this review has summarized the CLA functionality in discriminative cognitive dysfunctions in AD. And then propose an array of potential mechanisms that might contribute to the cognitive impairments caused by an abnormal CLA physiology. We advocate that the CLA might be a new promising therapeutic target in combination with existing anti-AD drugs and brain stimulation approaches for future AD treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Yang, Tu, Weng, Hu and Geng.)

Background: Developmental dyslexia (DD) is a specific impairment during the acquisition of reading skills and may have a lifelong negative impact on individuals. Reliable estimates of the prevalence of DD serve as the basis for evidence-based health resource allocation and policy making. However, the prevalence of DD in primary school children varies largely across studies. Moreover, it is unclear whether there are differences in prevalence in different genders and writing systems. Hence, the present study aims to conduct a systematic review and meta-analysis to assess the global prevalence of DD and to explore related factors., Methods: We will undertake a comprehensive literature search in 14 databases, including EMBASE, PubMed, Web of Science, China National Knowledge Infrastructure and Cochrane, from their inception to June 2021. Cross-sectional and longitudinal studies that describe the prevalence of DD will be eligible. The quality of the included observational studies will be assessed using the Strengthening the Reporting of Observational Studies in Epidemiology statement. The risk of bias will be determined by sensitivity analysis to identify publication bias., Results: One meta-analysis will be conducted to estimate the prevalence of DD in primary school children. Heterogeneity will be assessed in terms of the properties of subjects (e.g., gender, grade and writing system) and method of diagnosis in the included primary studies. Subgroup analyses will also be performed for population and secondary outcomes., Conclusion: The results will synthesize the prevalence of DD and provide information for policy-makers and public health specialists., (© 2022. Children's Hospital, Zhejiang University School of Medicine.)

It is commonly believed that alertness and attention decrease after sleep deprivation (SD). However, there are not enough studies on the changes in psychomotor vigilance testing (PVT) during SD and the corresponding changes in brain function and brain structure after SD. Therefore, we recruited 30 healthy adult men to perform a 36 h acute SD experiment, including the measurement of five indicators of PVT every 2 h, and analysis of cerebral blood flow (CBF) and grey matter volume (GMV) changes, before and after SD by magnetic resonance imaging (MRI). The PVT measurement found that the mean reaction time (RT), fastest 10% RT, minor lapses, and false starts all increased progressively within 20 h of SD, except for major lapses. Subsequently, all indexes showed a significant lengthening or increasing trend, and the peak value was in the range of 24 h-32 h and decreased at 36 h, in which the number of major lapses returned to normal. MRI showed that CBF decreased in the left orbital part of the superior frontal gyrus, the left of the rolandic operculum, the left triangular part, and the right opercular part of the inferior frontal gyrus, and CBF increased in the left lingual gyrus and the right superior gyrus after 36 h SD. The left lingual gyrus was negatively correlated with the major lapses, and both the inferior frontal gyrus and the superior frontal gyrus were positively correlated with the false starts. Still, there was no significant change in GMV. Therefore, we believe that 36 h of acute SD causes alterations in brain function and reduces alert attention, whereas short-term acute SD does not cause changes in brain structure.

Sleep deprivation critically affects vigilant attention. Previous neuroimaging studies have revealed altered inter-regional functional connectivity after sleep deprivation, which may disrupt topological properties of brain functional networks. However, little is known about alterations in the topology of intrinsic connectivity and its involvement in attention performance after sleep deprivation. In the current study, we investigated the topological properties of brain networks derived from resting-state functional magnetic resonance imaging of 26 healthy men in rested wakefulness (RW) state and after 36 h of total sleep deprivation (TSD). In the predefined sparsity threshold range, both global and nodal network properties were evaluated based on graph theory analysis. Vigilant attention was assessed using the psychomotor vigilance test (PVT) before and after TSD. Furthermore, Pearson's correlation analyses were conducted to explore the association between altered network properties and changed PVT performance after TSD. At the global level, the brain functional networks in the TSD state showed a significantly lower small-world coefficient than RW, with decreased global efficiency. At the nodal level, the altered regions were selectively distributed in frontoparietal networks, sensorimotor networks, temporal regions, and salience networks. More specifically, the altered clustering coefficient in the posterior superior temporal sulcus (pSTS) and insula, and altered local efficiency in pSTS were further associated with PVT performance after TSD. Our results suggest that the topological properties of brain functional networks are disrupted, and aberrant topology of temporal networks and salience networks may act as neural signatures underlying the vigilant attention impairments after TSD., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

RNA contains diverse modifications that exert an important influence in a variety of cellular processes. So far, more than 150 modifications have been identified in various RNA species, mainly in ribosomal RNA (rRNA), transfer RNA (tRNA), and messenger RNA (mRNA). In contrast to rRNA, tRNA, and mRNA, the known modifications in small RNA species have been primarily limited to 2'-O-ribose methylation in plants and inosine in mammals. The methylation of small RNAs in mammals is still unclear. Current methods widely used in the characterization of small RNAs are mainly based on the strategy of nucleic acid hybridization and sequencing, which cannot characterize modifications in small RNAs. Herein, we have systematically investigated modifications in small RNAs composed of 16-28 nucleotides (nt) by establishing an effective isolation and neutral enzymatic digestion of small RNAs in combination with liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). This method allowed us to simultaneously detect 57 different types of nucleoside modification. By using this approach, we revealed 24 modifications in small RNAs comprising 16-28 nt from human cells. In addition, we found that the obesity-associated protein (FTO) may demethylate N 6 -methyladenosine (m 6 A) and N 6 ,2'-O-dimethyladenosine (m 6 Am) in small RNAs of 16-28 nt. Our study demonstrates the existence of diverse modifications in small RNAs composed of 16-28 nt, which may promote in-depth understanding of the regulatory roles of noncoding RNAs., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To explore the effects of hyperpolarization-activated cyclic nucleotide-gated channels 2(HCN2) in the formation of peripheral neuropathic pain in rats., Methods: Twenty-four healthy adult rats were divided into two groups randomly( n =12):the sham group rats were only isolated the left L4, L5 spinal nerve, the spinal nerve ligation(SNL) group was separated the spinal nerve and performed the corresponding ligation. The behavioral experiments were tested 7 days after operation; The model rats were randomly divided into 3 groups( n =6):① negative group(Saline), intra-plantar injection of saline in left hindpaws; ② positive group(gabapentin, GBPT), intraperitoneal injection of gabapentin; ③ experimental group(ZD7288), intra-plantar injection of ZD7288 in left hindpaws. The behavioral experiments were tested before injection and 1 h, 4 h, 24 h and 48 h after injection; Obtaining the dorsal root ganglion(DRG) of the control group (before operation), sham group and the SNL group( n =6), using qPCR and Western blot to analyze the mRNA and protein of HCN2 in rats' DRG., Results: The rat model of neuropathic pain was successfully established. Compared with saline group, GBPT group and ZD7288 group could significantly reduce the symptoms of neuropathic pain in rats after injection 1 h ( P <0.01), and there was no difference between GBPT group and ZD7288 group. Compared with control group and sham group, the expression of HCN2 mRNA in SNL group's DRG was significantly increased ( P <0.01), and the expression of HCN2 channel protein was also increased significantly ( P <0.05)., Conclusions: HCN2 is involved in the development of peripheral neuropathic pain and is likely to be a potential new target for the treatment of neuropathic pain.

Objective: To explore the underlying electrophysiological mechanism of depression induced by chronic pain in dopaminergic neurons in midbrain ventral tegmental area (VTA) of rats., Methods: Twenty-four healthy adult rats were divided into two groups randomly( n =12):12 rats formed the sham group by exposing the spared nerve, and another 12 rats were served as the spared nerve injury (SNI)group by branchedness sciatic nerve injury surgery. The mechanical allodynia test were detected on the day of 3, 7, 14, 28, 42 and 56 after surgery, and the depressive-like behaviors such as open-field test, sucrose preference and forcedswim test were detected at the same time. Then we used the Multichannel Acquisition Processor (MAP) system to record the firing activity of neurons in VTA in both Sham rats and SNI rats., Results: ①Comparing to sham rats, the paw withdrawalmechanical threshold of SNI rats was decreased significantly ( P < 0.01);② According to depression-related behavioral test, SNI rats showed significant difference in open field text, sucrose preference, focus swim text comparing with Sham rats ( P < 0.01);③ The firing rate and burst activity of dopaminergic neuronsin midbrain VTA are increased in depression rats compare to sham rats( P <0.05)., Conclusions: Chronic pain could induce depression, and the increase of spontaneous firing rate of dopaminergic neurons in midbrain VTA might be contribute to the depression induced by the chronic neuropathic pain.

Individual differences in mind and behavior are believed to reflect the functional variability of the human brain. Due to the lack of a large-scale longitudinal dataset, the full landscape of variability within and between individual functional connectomes is largely unknown. We collected 300 resting-state functional magnetic resonance imaging (rfMRI) datasets from 30 healthy participants who were scanned every three days for one month. With these data, both intra- and inter-individual variability of six common rfMRI metrics, as well as their test-retest reliability, were estimated across multiple spatial scales. Global metrics were more dynamic than local regional metrics. Cognitive components involving working memory, inhibition, attention, language and related neural networks exhibited high intra-individual variability. In contrast, inter-individual variability demonstrated a more complex picture across the multiple scales of metrics. Limbic, default, frontoparietal and visual networks and their related cognitive components were more differentiable than somatomotor and attention networks across the participants. Analyzing both intra- and inter-individual variability revealed a set of high-resolution maps on test-retest reliability of the multi-scale connectomic metrics. These findings represent the first collection of individual differences in multi-scale and multi-metric characterization of the human functional connectomes in-vivo, serving as normal references for the field to guide the use of common functional metrics in rfMRI-based applications.

Efforts to identify meaningful functional imaging-based biomarkers are limited by the ability to reliably characterize inter-individual differences in human brain function. Although a growing number of connectomics-based measures are reported to have moderate to high test-retest reliability, the variability in data acquisition, experimental designs, and analytic methods precludes the ability to generalize results. The Consortium for Reliability and Reproducibility (CoRR) is working to address this challenge and establish test-retest reliability as a minimum standard for methods development in functional connectomics. Specifically, CoRR has aggregated 1,629 typical individuals' resting state fMRI (rfMRI) data (5,093 rfMRI scans) from 18 international sites, and is openly sharing them via the International Data-sharing Neuroimaging Initiative (INDI). To allow researchers to generate various estimates of reliability and reproducibility, a variety of data acquisition procedures and experimental designs are included. Similarly, to enable users to assess the impact of commonly encountered artifacts (for example, motion) on characterizations of inter-individual variation, datasets of varying quality are included.

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels, distributing in a variety of tissues, especially in excitable cells such as heart cells and many kinds of neurons, have an important role in the modulation of heart rate and neuronal excitability. Different from typical voltage-gated sodium channels and potassium channels, HCN channels were evoked inward currents when the cell was hyperpolarized. More and more recent studies have disclosed that HCN channels play important roles in the nervous system, which were linked with its special electrophysiological features as well as its regulatory effect on the cellular membrane excitability. HCN channels could be modulated by many factors including both extracellular molecules and intracellular signaling cascades, which made its functions complicated in the different condition. Based on its role, HCN channels are presumed to be a promising target for chronic pain and brain disorders. In this paper, we will focus on the advancement of roles of HCN channels in the neural system as well as its complex modulator factors.

Pancreatic cancer has one of worst prognosis among all human malignancies around the world, the development of novel and more efficient anti-cancer agents against this disease is urgent. In the current study, we tested the potential effect of INK-128, a novel mammalian target of rapamycin (mTOR) complex 1 and 2 (mTORC1/2) dual inhibitor, against pancreatic cancer cells in vitro. Our results demonstrated that INK-128 concentration- and time-dependently inhibited the survival and growth of pancreatic cancer cells (both primary cells and transformed cells). INK-128 induced pancreatic cancer cell apoptosis and necrosis simultaneously. Further, INK-128 dramatically inhibited phosphorylation of 4E-binding protein 1 (4E-BP1), ribosomal S6 kinase 1 (S6K1) and Akt at Ser 473 in pancreatic cancer cells. Meanwhile, it downregulated cyclin D1 expression and caused cell cycle arrest. Finally, we found that a low concentration of INK-128 significantly increased the sensitivity of pancreatic cancer cells to gemcitabine. Together, our in vitro results suggest that INK-128 might be further investigated as a novel anti-cancer agent or chemo-adjuvant for pancreatic cancer treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The present study investigated the relationship between Chinese reading skills and metalinguistic awareness skills such as phonological, morphological, and orthographic awareness for 101 Preschool, 94 Grade-1, 98 Grade-2, and 98 Grade-3 children from two primary schools in Mainland China. The aim of the study was to examine how each of these metalinguistic awareness skills would exert their influence on the success of reading in Chinese with age. The results showed that all three metalinguistic awareness skills significantly predicted reading success. It further revealed that orthographic awareness played a dominant role in the early stages of reading acquisition, and its influence decreased with age, while the opposite was true for the contribution of morphological awareness. The results were in stark contrast with studies in English, where phonological awareness is typically shown as the single most potent metalinguistic awareness factor in literacy acquisition. In order to account for the current data, a three-stage model of reading acquisition in Chinese is discussed.

Temporal and spectral perspectives are two fundamental facets in deciphering fluctuating signals. In resting state, the dynamics of blood oxygen level-dependent (BOLD) signals recorded by functional magnetic resonance imaging (fMRI) have been proven to be strikingly informative (0.01-0.1 Hz). The distinction between slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) has been described, but the pertinent data have never been systematically investigated. This study used fMRI to measure spontaneous brain activity and to explore the different spectral characteristics of slow-4 and slow-5 at regional, interregional, and network levels, respectively assessed by regional homogeneity (ReHo) and mean amplitude of low-frequency fluctuation (mALFF), functional connectivity (FC) patterns, and graph theory. Results of paired t-tests supported/replicated recent research dividing low-frequency BOLD fluctuation into slow-4 and slow-5 for ReHo and mALFF. Interregional analyses showed that for brain regions reaching statistical significance, FC strengths at slow-4 were always weaker than those at slow-5. Community detection algorithm was applied to FC data and unveiled two modules sensitive to frequency effects: one comprised sensorimotor structure, and the other encompassed limbic/paralimbic system. Graph theoretical analysis verified that slow-4 and slow-5 differed in local segregation measures. Although the manifestation of frequency differences seemed complicated, the associated brain regions can be grossly categorized into limbic/paralimbic, midline, and sensorimotor systems. Our results suggest that future resting fMRI research addressing the three above systems either from neuropsychiatric or psychological perspectives may consider using spectrum-specific analytical strategies.

SCIRR39 is an identified upregulated gene in rat primary neuron injury and/or regeneration process. However, roles of SCIRR39 in the regeneration of central nervous system (CNS) injury are still largely unexplored. Using real-time quantitative PCR and Western blotting, SCIRR39 expression was detected in oligodendrocyte precursor cells (OPCs) and oligodendrocytes. Moreover, the results from cell proliferation and cell cycle indicated that SCIRR39 inhibited OPCs proliferation and induced cell cycle arrest in G0/G1 and G2/M phases. Importantly, SCIRR39 positively regulated OPC differentiation and the expression of myelin basic protein. We also examined the effect of SCIRR39 on expression of myelin-associated inhibitory factors, including myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp), and Nogo A. Nogo A level was markedly regulated by SCIRR39 overexpression or knockdown in oligodendrocytes and cortical neurons co-cultures, while the expression of MAG and OMgp was not obviously changed by SCIRR39 overexpression or knockdown. Taken together, our results indicate the important role of SCIRR39 either in OPC differentiation or in axon myelination, and may provide a new therapeutic target for the treatment of CNS injury.

Objective: The left-lateralized N170, an event-related potential component consistently shown in response to alphabetic words, is a robust electrophysiological marker for reading expertise in an alphabetic language. In contrast, such a marker is lacking for expertise in reading Chinese, because the existing results about the lateralization of N170 for Chinese characters are mixed, reflecting complicated factors such as top-down modulation that contribute to the relative magnitudes of N170 in the left and right hemispheres. The present study aimed to explore a potential electrophysiological marker for reading expertise in Chinese with minimal top-down influence., Methods: We recorded N170 responses to Chinese characters and three kinds of control stimuli in a content-irrelevant task, minimizing potential top-down effects., Results: Direct comparison of the N170 amplitude in response to Chinese characters between the hemispheres showed a marginally significant left-lateralization effect. However, detailed analyses of N170 in each hemisphere revealed a more robust pattern of left-lateralization - the N170 in the left but not the right hemisphere differentiated Chinese characters from control stimuli., Conclusion: These results suggest that the selectivity of N170 (a greater N170 in response to Chinese characters than to control stimuli) within the left hemisphere rather than the hemispheric difference of N170 with regard to Chinese characters is an electrophysiological marker for expertise in reading Chinese.

Objective: To explore the reproducibility and stability of brain functional area in the response of language tasks during Chinese word processing with functional magnetic resonance imaging (fMRI) by follow-up scanning so as to provide rationales for clinical preoperative localization and the mechanisms of recovery from aphasia., Methods: The fMRI data were collected by scanning semantic and phonologic judgments in 15 healthy volunteers. Each subject was scanned twice by the same fMRI procedure of both language tasks with an interval of 1 month. By analyzing the effective overlapping average activation maps, the reproducibility of inter-subject imaging result for two language tasks were estimated by selecting the main language areas, such as Broca's area and Wernicke's area as the region of interest (ROI). By individually calculating the spatial distance of ROI centroid coordinates in the same activating range before and after test, the inter-subject stability in between-session was calculated quantitatively., Results: Both language tasks activated more than one language-related brain areas in cerebral hemispheres. Both language tasks induced significant BOLD response in Broca's and Wernicke's areas with a tendency of left lateralization. The number of subjects in terms of the activation of both language tasks in Broca's and Wernicke's areas accounted over a half of the total subjects. As compared with the phonologic judgment task, the semantic judgment task showed better reproducibility in Broca's area. In the same spatial distance of ROI centroid coordinates, the stability of Broca's area was higher than that of Wernicke's area while the stability of semantic judgment in Broca's area higher than that of phonologic judgment., Conclusion: Such main language domains as Broca's and Wernicke's areas can be effectively activated by both semantic and phonologic judgments. By comparison, semantic judgment in Broca's area shows a higher level of reproducibility and stability. Thus it is applicable for clinical preoperative localization and the mechanisms of recovery from aphasia.

A negative event-related potential (ERP) component, known as N170, can be readily recorded over the posterior left brain region when skilled readers are presented with visual words. This left-lateralized word-related N170 has been attributed either to linguistic processes, particularly phonological processing, or to the role of orthographic regularity, emphasizing a perceptual origin. This debate, however, is difficult to resolve in the context of alphabetic scripts because of the tight relations between orthography and phonology. In contrast, Chinese characters have arbitrary mappings between orthographic and sound forms, making it possible to tease apart these two properties of visual words. We therefore addressed this issue by examining ERP responses to Chinese characters and three types of structurally matched but unpronounceable stimuli: pseudo-characters, false-characters, and stroke combinations. A content-irrelevant color matching task was adopted to minimize potentially different top-down modulations across stimulus types. Results show that, relative to false-characters and stroke combinations, real- and pseudo-characters evoked greater N170 in the left posterior brain region. Critically, despite being unpronounceable, pseudo-characters produced the same amplitude and left-lateralized N170, just as real-characters. These results provide strong evidence that orthography rather than phonology serves as the main driver for the enhanced and left-lateralized N170 to visual words., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: Sui SG, Wu MX, King ME, Zhang Y, Ling L, Xu JM, Weng XC, Duan L, Shan BC, Li LJ. Abnormal grey matter in victims of rape with PTSD in Mainland China: a voxel-based morphometry study., Objective: This study examined changes in brain grey matter in victims of rape (VoR) with and without post-traumatic stress disorder (PTSD). Previous research has focused on PTSD caused by various traumatic events, such as war and disaster, among others. Although considerable research has focused on rape-related PTSD, limited studies have been carried out in the context of Mainland China., Methods: The study included 11 VoR with PTSD, 8 VoR without PTSD and 12 healthy comparison (HC) subjects. We used voxel-based morphometry to explore changes in brain grey-matter density (GMD) by applying statistical parametric mapping to high-resolution magnetic resonance images., Results: Compared with HC, VoR with PTSD showed significant GMD reductions in the bilateral medial frontal cortex, left middle frontal cortex, middle temporal gyrus and fusiform cortex and significant GMD increases in the right posterior cingulate cortex, postcentral cortex, bilateral precentral cortex and inferior parietal lobule. Compared to VoR without PTSD, VoR with PTSD showed significant GMD reductions in the right uncus, left middle temporal gyrus, and the fusiform cortex, and increases in the left precentral cortex, inferior parietal lobule and right post-central cortex., Conclusion: The findings of abnormal GMD in VoR with PTSD support the hypothesis that PTSD is associated with widespread anatomical changes in the brain. The medial frontal cortex, precentral cortex, posterior cingulate cortex, post-central cortex and inferior parietal lobule may play important roles in the neuropathology of PTSD.

Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon&#95;1000/.

DNA exhibits many attractive features in the development of drug design and disease treatment, and there are some successful events for drugs targeting to DNA in clinic use. Nowadays, the specific recognition of DNA by small molecules is the crucial factor of the sustainable development of DNA-target drugs, for the serious side-effects of existing drugs. In this review, we discussed the current efforts of DNA-drug specific interaction that concerned with various DNA recognition models, such as abasic, mismatch or bulge site recognition, specific sequence recognition, and secondary structure recognition. Some compounds are found to show a remarkable potential to be an ideal drug.

Aim: To investigate the underlying mechanism of acid-sensing ion channel (ASIC) 1a involved in the acidosis-induced cytotoxicity of rat C6 glioma cells., Methods: The stable ASIC1a-silenced C6 cells built with the RNA interference technology were confirmed by RT-PCR and Western blot analysis. Intracellular calcium ([Ca2+]i) in both the wild-type rat C6 glioma cells and the ASIC1a-silenced C6 cells were analyzed before and after acid application/exposure with the calcium imaging experiment., Results: The rapid extracellular pH drop induced the increase of [Ca2+]i in the wild-type C6 cells, but not in the ASIC1a-silenced C6 cells. During the prolonged acid exposure, [Ca2+]i was lower in the ASIC1a-silenced C6 cells than that in the control cells., Conclusion: The resultant toxicity of [Ca2+]i might contribute to the acidosis-induced cytotoxicity.

This event-related functional MRI study examined the neural correlates for Chinese writing, by comparing the writing of logographic characters and that of pinyin, a phonetic notation system for Chinese characters. The temporal profile of the activations indicated that the middle frontal gyrus, superior parietal lobule, and posterior inferior temporal gyrus reflected more central processes for writing. Although pinyin writing elicited greater activity overall than character writing, the critical finding is that the two types of symbols recruited essentially the same brain regions. The results were compared with studies in Japanese showing dissociation between logographic kanji and phonetic kana writing and frequency of use was suggested to be an important factor in accounting for result differences across the two writing systems.

Aim: To study the role of acid-sensing ion channel (ASIC) 1a in the cell death and apoptosis induced by extracellular acid in C6 glioma cells., Methods: The stable ASIC1a-silenced C6 cell line, built with RNA interference technology, were confirmed by RT-PCR and Western blot analysis. The cell viability following acid exposure was analyzed with lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The apoptotic cells dyed with Annexin-V and propidium iodide were measured with a flow cytometer, while the changes of cell cycle were also assayed., Results: The downregulation of ASIC1a proteins by stable transfection of short hairpin RNA decreased the cell death percentage and increased cell viability following acid exposure with LDH and the MTT assay. The rate of apoptosis was lower in the ASIC1a-silenced cell line than that in the wild-type C6 cell line. The percentage of sub-G0 cells was lower in the ASIC1a-silenced C6 cells than that in the wild-type cells., Conclusion: Extracellular acid induced cell death and apoptosis via ASIC1a mechanisms in the C6 glioma cells.

A series of dicationic porphyrins were found to specifically recognize loop structures of oligodeoxynucleotides, and to selectively oxidize guanine residues upon photo-irradiation at micromolar concentrations. These compounds could, thus, be employed as promising structural probes for specific secondary DNA structures. The production of singlet oxygen ((1)O2) is responsible for the DNA-modification profiles. Both UV-titration and thermal-melting experiments indicate that the strong affinity of the charged porphyrins towards DNA loops is responsible for these molecular-recognition phenomena.

A series of biphenol-derived quaternary ammonium salts, originally developed as DNA-cross-linking agents, and carrying either two (i.e., 1) or four (i.e., 2) net positive charges, were investigated for their in vitro DNA-transcription- and acetylcholinesterase (AChE)-inhibitory activities. The effects of charge and type of linker between the two phenolic residues were systematically investigated. Several compounds showed good activities in both tests, which makes them potential lead candidates for drug design.

Objective: To investigate the roles the different functional activation areas in whole human brain related to movement play during motor preparation (CUE) and execution (GO)., Methods: Event-related functional MRI technique was used on 12 right-handed healthy subjects to record the brain activation in a manner of delayed sequential finger movement. Activation maps and time-signal intensity curves were generated., Results: Bilateral anterior parts of supplementary motor area (Pre-SMA), bilateral posterior parietal cortex (PPC), and bilateral anterior premotor cortex (PMC) were strongly activated during the preparation period, while bilateral SMA proper, and contralateral primary motor cortex (M1) were strongly activated during the execution period, Cerebellar cortex was activated during both periods. The time-signal intensity curves based on single voxel indicated that above-mentioned brain areas were activated during both periods to different degrees; however, the characteristics of distribution in every area were different., Conclusion: The brain areas related to movement are activated differently during preparation period and execution period, areas close to M1 participate in the motor execution process mainly, and the areas away from M1 are concerned with motor preparation process chiefly.

Background: A challenge in the management of severely brain-damaged patients with altered states of consciousness is the differential diagnosis between the vegetative state (VS) and the minimally conscious state (MCS), especially for the gray zone separating these clinical entities., Objective: To evaluate the differences in brain activation in response to presentation of the patient's own name spoken by a familiar voice (SON-FV) in patients with VS and MCS., Methods: By using fMRI, we prospectively studied residual cerebral activation to SON-FV in seven patients with VS and four with MCS. Behavioral evaluation was performed by means of standardized testing up to 3 months post-fMRI., Results: Two patients with VS failed to show any significant cerebral activation. Three patients with VS showed SON-FV induced activation within the primary auditory cortex. Finally, two patients with VS and all four patients with MCS not only showed activation in primary auditory cortex but also in hierarchically higher order associative temporal areas. These two patients with VS showing the most widespread activation subsequently showed clinical improvement to MCS observed 3 months after their fMRI scan., Conclusion: The cerebral responses to patient's own name spoken by a familiar voice as measured by fMRI might be a useful tool to preclinically distinguish minimally conscious state-like cognitive processing in some patients behaviorally classified as vegetative.

The interaction between CT-DNA and the zinc phthalocyanine ZnPc (1) was studied by UV/VIS and fluorescence titration, as well as by thermal denaturation. ZnPc was found to strongly bind to CT-DNA (K(app)=7.35 x 10(5) M(-1)) in a non-intercalative mode. The photosensitized cleavage of pBR322 DNA was found to efficiently proceed via singlet-oxygen ((1)O(2)) production. Further, ZnPc (1) caused site-specific scission of guanine (G) bases around the bulge of the hairpin oligonucleotides OD1-OD3, as clearly shown by gel-electrophoresis experiments.

In this study, 4 male Qigong masters (aged 60 +/- 12) who had Qigong practicing experience for more than 30 years were tested. By using the technique of fMRI, the change of brain function under the state of Qigong was observed through the peripheral pain stimulation generated by potassium penetrating method. The fMRI examination was running on a GE signa VH/3.0 T MRI machine and block design was used. The test was repeated several times, which was carried out before and 15 min after Qigong practicing. The heart and respiration rate of these 4 Qigong masters were monitored during the whole test. SPM2 was used for the data analysis, and the result showed that before Qigong practicing, besides SI and SII-insula regions, many other Brodmann areas, the cigulate cortex, the thalamus, and the cerebellum were all activated, while 15 min after that, the activated areas were decreased obviously, which were mainly at the SII-insula region and some other Brodmann areas. Since the SII-insula region was activated in both of these two states, further analysis of the response curve was focused on it. Its response amplitude under the state of Qigong (3.5%) was greater than that before Qigong (1.2%). Our result indicated that the main manifestation of brain functional change under Qigong was functional suppressing, but in some particular regions such as SII-insula region in our study, the response amplitude was increased. Further study of the exact physiological mechanism of Qigong is needed.

Objective: To study the inhibitory effect of Ganoderma lucidum, the extract of chloroform, the extract of ethyl acetate and the remains after two-time extraction on BEL-7402 and MGC-803 cells and their protective effects on HL-7702 cells pre-and post-exposed to cisplatin (DDP) and various doses of 60Co gamma irradiation., Method: The antitumor activity and protective effects on damaged HL-7702 cells induced by radiotherapy and chemotherapy of ganoderma lucidum were determined by MTT technique., Result: The anticancer activity of the extract of chloroform Ganoderma lucidum was the best: at the concentration of 0.125 mg x mL(-1), the inhibitory rate was over 50%. To the HL-7702 cells damaged by DDP, four kinds of extracts didn't exert restoring effect, but the pretreatment with the extract of chloroform reduced the damaged degree significantly. To the 60Co gamma irradiated HL-7702 cells, only the extract of chloroform exerted restoring effect to some extent when exposed to middle or high dose of irradiation. The pre-administration of four kinds of extracts reduced the damaged degree by radiation., Conclusion: The extract of chloroform exerts notable antitumor effects on cancer cells and protective effects on damaged normal cells induced by radiotherapy and chemotherapy.

Objective: To detect the differences in subcortical structures between patients with paroxysmal kinesigenic dyskinesia (PKD) and normal subjects during movement preparation and execution., Methods: The PKD patients performed a movement task, in which a CUE signal (preparation) indicated the movement sequence prior to the appearance of an imperative GO signal (execution). Event-related functional magnetic resonance imaging (fMRI) and 3dDeconvolve program of AFNI were used to estimate the hemodynamic response function and to generate activation maps., Result: During movement preparation, the activated brain areas in PKD patients were less than those of normal subject, and there was no activation in basal ganglia in PKD patients. During execution, the activation was also less in PKD patients except in bilateral M1., Conclusion: During intermission, abnormalities of the brain still exist in PKD patients when during preparing or performing movement. The movement circuit in the brain displays an unusual state. The attack may be caused by reducing of inhibition in brain areas.

Using event-related functional magnetic resonance imaging to study the Stroop effect on both behavioral and brain activation of ADHD children off or on methylphenidate (MPH). Nine ADHD boys (aged 9.8-14.5 years) and 9 age-matched normal controls were included. A Stroop-like paradigm was used. AFNI (Analysis of Functional NeuroImaging) and its Deconvolution Analysis were used in a descriptive comparison between ADHD and control groups. (1) Both behavioral reaction time and brain activation showed Stroop effect in controls but neither was found in ADHD children off MPH. When MPH was administered, the Stroop effect tended to appear. (2) The activation volume (AV) of prefrontal cortex (PFC) in both the neutral (NC) and interference conditions (IC) in ADHD children off MPH was smaller than in controls. AV of anterior cingulate cortex in the IC in ADHD children off MPH was smaller than that in controls, but was similar in the NC to that in controls. AV of the basal ganglia, insula and cerebellum was also smaller in the IC, but was larger in the NC for ADHD children off MPH compared with controls. These findings are consistent with prior findings of hypofrontality in ADHD children and implicate a compensatory network including basal ganglia, insula and cerebellum for relative lower cognitive load tasks.

Objective: To explore the heterogeneity of aging brain., Methods: Blood oxygenation level dependent functional magnetic resonance imaging was performed on 10 subjects meeting the standards of successful aging (SA), 9 subjects meeting the standards of usual aging (UA), and 9 subjects meeting the criteria of mild cognitive impairment (MCI), all age, and sex-matched, under stimulation of verbal fluent test (VFT). The activation level of different regions of interest (ROI), laterality index, and the activation level of occipital lobe were analyzed., Results: The achievement in VFT of the SA group was greater than that of the UA group, and much greater than that of the MCI group with significant differences between any 2 groups (all P < 0.05) except in the task of "names of vegetables". The activation volume of the SA group was greater than that of the UA group, and much greater than that of the MCI group. The main activated regions of the SA and UA groups included left precuneus, anterior cingulate gyrus, middle frontal gyrus, superior frontal gyrus and inferior parietal lobule, and bilateral occipital lobes. The main activated regions of the MCI group included the bilateral prefrontal lobe. The intensity of activation was not significantly different between the SA and UA groups, however, was significantly different between the SA and MCI groups and between the UA and MCI groups. The laterality index (LI) was 0.46 in the SA group, significantly higher than those of the UA group (-0.12) and MCI group (-0.06) (both P < 0.01), however, without a significant difference between the UA group and MCI group. The activation of left prefrontal lobe in the SA group was more obvious than that in the UA group, and much more obvious than that in the MCI group with a significant difference between the UA and MCI groups as well (all P < 0.01). The activation volume of the left dorsal lateral prefrontal cortex (DLPFC) in the SA group was 787 voxels, significantly greater than that in the UA group (292 voxels) and MCI group (0 voxel) (all P < 0.01)., Conclusion: Heterogeneity exists in the course of aging, associated with complicated brain mechanism. The activation level of DLPFC and LI may be used as sensitive indexes in evaluation of the brain function of the elderly.

Objective: To investigate the brain functional laterality in motor areas during motor execution systematically., Methods: Functional magnetic resonance imaging (fMRI) was employed combined with right hand sequential finger movement task to investigate brain activation pattern and laterality in 8 right-handed subjects. 3dDeconvolve program of AFNI was used to estimate the hemodynamic response function and to generate activation maps. Then the laterality index (LI) was calculated and tested statistically., Result: All motor areas including the areas which were previously considered to be engage in movement preparation only were activated in movement execution. In the activation map, it appeared left lateralization in cerebra and right lateralization in cerebella. After further statistical test, it was found that in primary motor area (M1), supplementary motor area (SMA) and posterior parietal cortex (PPC), there were left lateralization. While in premotor cortex (PMC), cingulate gyrus and basal ganglia (BG), the lateralization tendency was not obvious. The activation in cerebella is characterized with right lateralization., Conclusion: Though there are tiny differences among subjects, most of the motor areas appear lateralized activation. Past studies only observed laterality in several motor areas. It may be due to the difficulty of the task or the experimental design.

Objective: To compare the dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation (OLT) in humans., Methods: Twenty male patients undergoing liver transplantation were randomly assigned to two comparable groups of 10 patients each to receive a continuous infusion of rocuronium or atracurium under intravenous balanced anesthesia. The response of adductor pollicis to train-of-four (TOF) stimulation of unlar nerve was monitored. The infusion rates of rocuronium and atracurium were adjusted to maintain T1/Tc ratio of 2%~10%. The total dose of each drug given during each of the three phases of OLT was recorded., Results: Rocuronium requirement, which were (0.468+/-0.167) mg/(kg.h) during the paleohepatic phase, decreased significantly during the anhepatic phase to (0.303+/-0.134) mg/(kg.h) and returned to the initial values at the neohepatic period ((0.429+/-0.130) mg/(kg.h)); whereas atracuruim requirements remained unchanged during orthotopic liver transplantation., Conclusions: This study showed that the exclusion of the liver from the circulation results in the significantly reduced requirement of rocuronium while the requirement of atracurium was not changed, which suggests that the liver is of major importance in the clearance of rocuronium. A continuous infusion of atracurium with constant rate can provide stable neuromuscular blockade during the three stages of OLT.

Previous research has found heroin addicts to be impulsive. This study employed functional magnetic resonance imaging technology to investigate the differences between heroin addicts and normal controls in neural activity associated with cognitive regulation of behavior. Twenty-one Chinese men participated in this study, 11 of whom were newly admitted heroin-addicted patients and 10 of whom were healthy volunteers. In the experimental task, the subjects were required to first identify the correct directions of arrowheads and then give the opposite answers. Behaviorally, the heroin-dependent patients took a much shorter time to complete the more demanding second part of the task but committed more errors than the normal controls. This pattern of behavior, characteristic of people who are disinhibited and who tend to be impulsive, was consistent with previous reports of impulsivity observed in people who have abused heroin. The neural activity of the patients that was associated with performing the experimental task of cognitive regulation was different to that of the normal controls in terms of the pattern of prefrontal activation, the attenuation of activity in the anterior cingulate, and the additional recruitment of the right inferior parietal region. This study is the first that seeks to understand the neural activity associated with impulsive behavior in people who abuse heroin. The pattern of imaging data obtained resembled the pattern of data observed in immature brains attempting to exercise cognitive control of behavior. Further theoretical and clinical implications of the findings are discussed.

Objective: The aim of this study was to investigate the changes in plasma concentrations of propofol in three phases (the paleohepatic, anhepatic, and neohepatic phases) during orthotopic liver transplantation (OLT) using target-controlled infusion (TCI)., Methods: Ten patients undergoing OLT without venovenous bypass were studied (age 29-53 years, weight 56-79 kg). After intubation, a non-hypnotic target concentration of propofol 0.5 microg ml(-1) using a Diprifusor pump (Zeneca Pharmaceuticals, Macclesfield, UK) was administered as a supplement anesthesia throughout the procedure. Plasma samples were obtained in each phase for propofol assay, respectively. Performance parameters for the Diprifusor system in each phase, the percentage median performance error (MDPE), the percentage median absolute performance error (MDAPE), and the percentage median absolute constancy error (MDACE) were evaluated., Results: In all patients, measured plasma propofol concentrations were several times higher than Diprifusor values in each phase during the procedure. In nine patients, propofol concentrations in the anhepatic phase were higher than those in the paleohepatic or neohepatic phase (P < 0.05). There were no significant differences between the paleohepatic and neohepatic phases. Interindividual variation of the plasma propofol concentrations was significant (P < 0.05). Percentage median performance error of Diprifusor in each phase, as well as MDAPE, was large (>300%) and was significantly higher in the anhepatic phase (P < 0.01), whereas MDACE was relatively small and there was no significant difference between phases., Conclusions: Models used by Diprifusor are not suitable for liver transplantation patients. A further study should be performed in order to determine all pharmacokinetic parameters of propofol in these patients.

Objective: To explore the differences in brain activation between musicians and non-musicians by use of functional MRI., Methods: Twelve right-handed musicians and twelve right-handed non-musicians were recruited in the study. During a listening task, they were scanned on the Sigma 1.5T scanner (GE) while they were passively listening to several segments of music of "the Butterfly Love" and the white noise with same physical energy., Result: Both musicians and non-musicians demonstrated bilateral transverse gyrus weak activated while listening to the white noise. But when listening to music, they showed bilateral temporal areas strongly activated including superior temporal gyrus, transverse gyrus and some middle temporal areas. Moreover, musicians showed relative left dominance (10/12), whereas non-musicians demonstrated right dominance(11/12). Furthermore,besides bilateral temporal areas, more and stronger activated areas were found in musicians such as cuneus, precuneus,medial frontal and left middle occipital gyrus., Conclusion: There are different neuro-patterns between musicians and non-musicians.

Two types of acid-sensing ion channel (ASIC)-like currents in cultured rat hippocampal neurons were recorded and their characteristics were studied by using a whole-cell recording technique. The results revealed that the ASIC-like currents, induced by a quick drop of the extracellular pH, decayed with different time constants (tau) of 229 +/- 16 (Type I) and 1209 +/- 56 ms (Type II). The ASIC-like currents displayed different sensitivities to extracellular proton (pH0.5 was 6.17 +/- 0.04 for Type I and 5.70 +/- 0.07 for Type II) and amiloride, a specific ASIC channel blocker (IC50 was 1.19 +/- 0.37 microM for Type I and 0.14 +/- 0.02 microM for Type II). Among all the 360 recorded neurons, ASIC-like currents were induced in 314 neurons (87.2%). In the neurons expressing ASICs, Type I currents were evoked from 269 neurons (85.7%) and Type II currents were induced only from 45 neurons (14.3%). As these ASIC-like currents presented various electrophysiological and pharmacological properties, further experiments should be conducted to decipher the complex subunit composition of ASICs in the hippocampus.

Background: Functional magnetic resonance imaging (fMRI) has become a powerful tool for tracking human brain activity in vivo. This technique is mainly based on blood oxygenation level dependence (BOLD) contrast. In the present study, we employed this newly developed technique to characterize the neural representations of human portraits and natural sceneries in the human brain., Methods: Nine subjects were scanned with a 1.5 T magnetic resonance imaging (MRI) scanner using gradient-recalled echo and echo-planar imaging (GRE-EPI) pulse sequence while they were visually presented with 3 types of white-black photographs: natural scenery, human portraits, and scrambled nonsense pictures. Multiple linear regression was used to identify brain regions responding preferentially to each type of stimulus and common regions for both human portraits and natural scenery. The relative contributions of each type of stimulus to activation in these regions were examined using linear combinations of a general linear test., Results: Multiple linear regression analysis revealed two distinct but adjacent regions in both sides of the ventral temporal cortex. The medial region preferentially responded to natural scenery, whereas the lateral one preferentially responded to the human portraits. The general linear test further revealed a distribution gradient such that a change from portraits to scenes shifted areas of activation from lateral to medial., Conclusions: The boundary between portrait-associated and scenery-associated areas is not as clear as previously demonstrated. The representations of portraits and scenes in ventral temporal cortex appear to be continuous and overlap.

Background: Functional neuroimaging has been used in neurolinguistic research on normal subjects and on patients with brain damage. This study was designed to investigate the differences of the neural basis underlying language processing between normal subjects and aphasics., Methods: Functional magnetic resonance imaging (fMRI) was used to map the language network in 6 normal subjects and 3 patients with aphasia who were in the stage of recovery from acute stroke. The participants performed a word generation task during multi-slice functional scanning for the measurement of signal change associated with regional neural activity induced by the task., Results: In normal subjects, a distributed language network was activated. Activations were present in the frontal, temporal, parietal and occipital regions. In the patient group, however, no activation was detected in the left inferior frontal gyrus whether the patient had a lesion in the left frontal lobe or not. Two patients showed activations in some right hemisphere regions where no activation appeared in normal subjects., Conclusions: fMRI with word generation task is feasible for evaluating language function in aphasic patients. Remote effect of focal lesion and functional redistribution or reorganisation can be found in aphasic patients.

Aim: To investigate whether agmatine could selectively block a given type of the voltage-gated calcium channels (VGCC) and whether related receptors are involved in the blocking effect of agmatine on VGCC., Methods: The whole-cell patch recording technique was performed to record VGCC currents in the cultured neonatal rat hippocampal neurons., Results: Verapamil (100 micromol/L), a selective blocker of L-type calcium channel, significantly inhibited VGCC current by 80 %+/- 7 %. Agmatine (100 micromol/L) could further depress the remained currents by 25 %+/-6 %. The alpha 2-adrenoceptor antagonist yohimbine (10 micromol/L) and the I2 imidazoline receptor antagonist idazoxon (10 and 40 micromol/L) had no significant effect on VGCC currents when used respectively. When the mixture of yohimbine and agmatine was applied, VGCC currents were still depressed remarkably. However, the blocking effect of agmatine was decreased by 29 %+/- 8 % in the presence of idazoxon (10 micromol/L). The effect of idazoxon did not increase at a higher concentration (40 micromol/L)., Conclusion: Agmatine could block the L- and other types of VGCC currents in the cultured rat hippocampal neurons. Blocking effect of agmatine on VGCC was partially related to I2 imidazoline receptor and had no relationship with alpha 2-adrenoceptors.

Aim: To investigate the mechanism of agmatine by observing the effect of agmatine on the voltage-gated channels in rat hippocampal neurons., Methods: The whole-cell patch recording technique was performed to record the voltage-gated potassium, sodium, and calcium currents in cultured rat hippocampus. Agmatine was applied directly to the single neuron using a pressure injector with microtubules., Results: Agmatine (500 micromol/L) had no significant effect on the voltage-gated potassium and sodium channels. Agmatine reversibly blocked the voltage-gated calcium channel and the blockade was enhanced with the increasing concentration of agmatine. The inhibitory rates were 21%+/-4%, 35%+/-6%, 49%+/-6%, 67%+/-4%, 69%+/-6%, 86%+/-8%, and 87%+/- 9%, at the concentration of 0.1, 0.5, 1.0, 5.0, 10.0, 50.0, and 100 micromol/L, respectively. IC50 was (1.2+/-0.4) micromol/L. Two-way ANOVA revealed that change of membrane potential displayed a significant interaction with the blockade by agmatine., Conclusion: Agmatine reversibly blocked the voltage-gated calcium channel in rat hippocampal neurons in a concentration- and voltage-dependent way. Agmatine might perform its physiological and pharmacological effects partially by blocking the calcium channel.

Using an event-related fMRI procedure, we investigated the role of the human cerebellum in sequential finger movements. Subjects performed a delayed sequential finger movement task in which an instructive cue preceded the imperative signal by 16.5 s. Bilateral activation was observed in the cerebellum following both the cue and imperative signals. The activated regions overlapped within the cerebellum, extending across intermediate and lateral regions corresponding to lobules HV-HVII. In contrast, activation in primary motor cortex was primarily restricted to the execution phase and most prominent in the contralateral hemisphere. These results indicate that the cerebellum is bilaterally recruited for the preparation and execution of sequential movements.