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@#Introduction: Studies show that adolescents are more reward sensitive compared to other age groups. The nucleus accumbens (NAcc) has been identified as a key brain area involved in reward through its connectivity to other reward-related brain areas. Our study aimed to characterise the white matter structural connectivity of nucleus accumbens with brain areas that are most often associated with reward in female adolescents. Methods: Fifteen healthy female Malay adolescents were recruited and underwent diffusion-weighted brain scanning. Two behaviour scales were also given to verify typical reward responsiveness. Then, probabilistic tractography and NAcc segmentation were performed on the data using FMRIB Software Library (FSL). Probabilistic tractography was performed to determine the relative connection probability of nucleus accumbens (NAcc) to areas shown to be associated with reward, namely amygdala, anterior cingulate cortex (ACC), medial orbitofrontal cortex (mOFC), hippocampus, ventrolateral prefrontal cortex (vlPFC) and dorsolateral prefrontal cortex (dlPFC). Connectivity-based segmentation of NAcc was performed to determine the spatial distribution of its connectivity with the target brain areas according to the highest connection probability. Results: The highest relative connection probability was found between NAcc to mOFC, while the NAcc parcellation showed the widest distribution of connection to mOFC compared to the other five targets on both sides of the brain. Conclusion: Our findings demonstrated the strongest structural connectivity and widest distribution between NAcc and mOFC compared with other brain areas related to reward. This study’s findings could be used as baseline to compare with people with atypical reward circuit problems.
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@#mesodermal origin and is commonly associated withsyringomyelia. Foramen magnum decompression is thefirst-line of standard treatment in symptomatic patients witha confirmed radiographic diagnosis. Magnetic resonance(MR) cine allows accurate evaluation of cerebrospinal fluid(CSF) physiology at the craniovertebral junction but oftenthis is under-utilised in Malaysia. Methods: In this series, we looked into nine cases of CM withsyringomyelia from clinical and radiological perspectivebefore and after surgery. The radiological parameters wereherniated tonsillar length, syrinx: cord ratio, syrinx lengthand diameter. Flow velocity and morphologic changes inChiari were illustrated. Results: Seven patients showed either reduction in syrinxlength, syrinx: cord ratio or both postoperatively. Clinicalrecovery somewhat varied in motor and sensory symptoms.Four patients gained better functional grade in modifiedRankin scale (MRS) while the rest remained similar. Thestudy highlighted the advantage of CSF flow dynamicsinformation over MR anatomical radiographic improvementin addressing the neurologic and functional recovery. Wealso discussed the practicality of cine sequence inpreoperative patient selection, syrinx analysis andpostoperative flow evaluation in anticipation of clinicaloutcome. Conclusion: Phase-contrast cine MRI is a useful tooldictated by resource availability. We recommend its routineuse in preoperative analysis and subsequent observationalfollow-up after surgery.
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@#Although the precise etiology of Glioblastoma multiforme (GBM, WHO grade IV) remains unknown, its progression is believed to be driven by the accumulation of multiple genetic alterations. Here, we report a case of a patient who developed GBM, and associated with dual alterations, particularly 4977-bp deletion in mtDNA (mtDNA4977) and p.Arg132His (R132H) mutation in IDH1. A 35-year old Malaysian woman patient who primary diagnosed with astrocytoma WHO grade I and subsequently after four years developed a GBM, was detected with a mtDNA4977. This deletion appears to be a sporadic mutation. Additionally, analysis of patient’s tumor tissue also found to harbor a heterozygous IDH1 R132H mutation. This represents the first case report of coexisting mtDNA4977 together with IDH1 R132H mutation in a Malaysian patient of GBM. The findings of dual alterations could be of therapeutic benefit if these alterations were justified to be contributing to GBM growth and aggressiveness.
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@#When the first report of COVID-19 appeared in December 2019 from Wuhan, China, the world unknowingly perceived this as another flu-like illness. Many were surprised at the extreme steps that China had subsequently taken to seal Wuhan from the rest of the world. However, by February 2020, the SARS-CoV-2 virus, which causes COVID-19, had spread so quickly across the globe that the World Health Organization officially declared COVID-19 a pandemic. COVID-19 is not the first pandemic the world has seen, so what makes it so unique in Malaysia, is discussed to avoid a future coronacoma.
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@#Background: There has been increasing evidence showing that stingless bee honey exhibits anti-oxidant, anti-inflammatory and anti-cancer properties. Pharmacologically-active components in honey such as flavonoids and phenolic constituents are known to contribute to its medicinal benefits. To the best of our knowledge, this is the first study on evaluating anticancer effects of locally-produced Malaysian stingless bee honey from Heterotrigona itama sp. on malignant glioma cells. Methods: Proliferation and apoptosis studies of U-87 MG cells following stingless bee honey treatment were carried out using MTS assay and acridine orange/propidium iodide dual staining, respectively. Results: Results demonstrated time and dose-dependent cytotoxicity using 0.625%, 1.25% and 10% stingless bee honey (P < 0.05). IC50 values were calculated using cells treated with 10% stingless bee honey. It was also observed that 10% stingless bee honey induced nuclear shrinkage, chromatin condensation and nucleus fragmentation, indicating that cellular changes were consistent with the apoptotic characteristics of the cells. Conclusion: These data provide a good basis for further evaluation of the medicinal properties of stingless bee honey from Heterotrigona itama sp. This source of honey may serve as a potential therapy for malignant glioma.
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@#The Malaysian Journal of Medical Sciences (MJMS) would like to present a brief report of its progress in 2018 with a purpose to provide a clear picture of how it has performed so far. This report may considered as a helpful information, especially, to future authors who wish to submit their articles to MJMS. This report summarised the information of the total of original manuscripts received based on manuscript type, authors' country of origin and total of original manuscripts received by month. It also reveals the statistics of the final decisions made based on manuscript type, the accept-reject ratio by the editor and the time taken from submission to decision for all manuscripts submitted throughout 2018.
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@#Background: Ventriculoperitoneal (VP) shunting is a permanent form of cerebrospinal fluid (CSF) diversion that can be performed for hydrocephalus. Sterility of the CSF is an important prerequisite for permanent shunt placement. It has been hypothesised that in early stage of meningitis, ventricular CSF remains sterile. A study is conducted on the first CSF sample taken from patients suspected to have meningitic hydrocephalus. Method: A retrospective review case records of patients who had undergone external ventricular drainage (EVD) for suspected meningitic hydropcephalus in Hospital Sultanah Aminah Johor Bahru (HSAJB), Johor, Malaysia. Results: Fifty-one cases were analysed. Mean age of patients was 37.27 years old, with 64.7% of them was male. Univariate analysis revealed that the main parameters to determine CSF sterility were CSF glucose (95% CI, 0.852, 10.290, P = 0.001), CSF protein (CI 95%, 0.722, 14.898, P < 0.001), CSF gram stain (95% CI, 16.437, 0.877, P < 0.001 ) and CSF appearance ( 0.611, 6.362, P = 0.012). Multivariate analysis had proven that gram stain was the main parameter in the CSF analysis (CI 95%, 16.437, 0.029, P = 0.016). No significant differences in CSF results were observed from EVD and lumbar puncture. Conclusion: The most significant parameter in CSF to determine infection was gram stain.
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@#The combined effort of the neuroscience and psychology cluster at the Universiti Sains Malaysia (USM)—fundamental, applied and clinical—has moved the institution to the number two position in the country, behind Universiti Malaya. The strategy to join the Global Brain Consortium (GBC) and put Malaysia on the map to address the GBC mission, vision, focus areas and outcomes began recently, in May 2019.
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World-renowned neurosurgeon, Professor Saleem Abdulrauf, has been featured in several medical journals for his successful “Awake Brain Aneurysm Surgery”. Regarded as a “world first”, this surgery, involves clipping un-ruptured brain aneurysms while patients are awake. Only one or two neurosurgery centres worldwide are capable of this. Performing the surgery while the patient is awake lowers risks of brain ischemia with neurological deficits and ventilator associated morbidities. The technique has been viewed as the start of a new era in brain surgery. Physicians from the Universiti Sains Malaysia (USM) School of Medical Sciences, at the Health Campus in Kelantan, headed by Professor Dr Zamzuri Idris (neurosurgeon) and Dr Wan Mohd Nazaruddin Wan Hassan (neuroanaesthetist), recently performed a similar procedure, the first such surgery in Malaysia and Southeast Asia. The USM team can therefore be considered to be among the first few to have done this brain surgery and achieved successful patient outcomes.
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Background: Bamboo shoot has been used as a treatment for epilepsy in traditional Chinese medicine for generations to treat neuronal disorders such as convulsive, dizziness and headaches. 4-hydroxybenzoic acid (4-hba) is a non-flavonoid phenol found abundantly in Dendrocalamus asper shoots (bamboo), fruits (strawberries and apples) and flowers. Kv1.4 is a rapidly inactivating Shaker-related member of the voltage-gated potassium channels with two inactivation mechanisms; the fast N-type and slow C-type. It plays vital roles in repolarisation, hyperpolarisation and signaling the restoration of resting membrane potential through the regulation of the movement of K+ across the cellular membrane. Methods: Chemical compounds from Dendrocalamus asper bamboo shoots were purified and identified as major palmitic acids mixed with other minor fatty acids, palmitic acid, 4-hydroxybenzaldehyde, lauric acid, 4-hydroxybenzoic acid and cholest-4-ene-3-one. The response of synthetic 4-hydroxybenzoic acid was tested on Kv1.4 potassium channel which was injected into viable oocytes that was extracted from Xenopus laevis. The current were detected by the two-microelectrode voltage clamp, holding potential starting from −80 mV with 20 mV stepup until +80 mV. Readings of treatments with 0.1% DMSO, 4-hba concentrations and K channel blockers were taken at +60 mV. The ratio of tail/peak amplitude is the index of the activity of the Kv1.4 channels with n ≥ 6 (number of oocytes tested). The decreases of the ratios of five different concentrations (1 μM, 10 μM, 100 μM, 1 mM and 2.5 mM) were compared with 0.1% DMSO as the control. Results: All concentration showed statistically significant results with P < 0.05 except for 100 μM. The normalised current of the 4-hba concentrations were compared with potassium channel blockers (TEA and 4-AP) and all groups showed statistically significant results. This study also showed that time taken for each concentration to affect Kv1.4 does not play any significant roles. Conclusion: 4-hydroxybenzoic acid was found to be able to enhance the inactivation of Kv1.4 by lowering the membrane potential so that the abnormal neuronal firing can be inhibited. With IC50 slightly higher than 10 μM, increasing concentrations (100 μM, 1 mM and 2.5 mM) had shown to exhibit toxicity effects. The best concentration from this study is 10 μM with Hill slope of 0.1799.
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People can work wonders without a room. Rooms make people think within a box, and people who are not confined within a room can wonder while thinking and solve problems as they see them in the environment. The dearth in the growth of professionals trained in the neurosciences who will use neurotechnology in the future is a dire situation facing Malaysia, according to the Academy of Sciences Malaysia’s 2017 Emerging Science, Engineering and Technology (ESET) study. Further, this human resource needs to be fundamentally cultivated at schools from a very young age. The author describes the activities that have taken place in the country via a bottom-up approach over the last two years and hopes that eventually these endeavours will end with the creation of an ASEAN Brain, Mind, Behaviour and Neuroscience Institute for Creativity and Innovation being established with the full support of the Government of Malaysia or other local and international financial donors.
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Background: Previous studies from animal models have shown that pre-synapticNMDA receptors (preNMDARs) are present in the cortex, but the role of inhibition mediated bypreNMDARs during epileptogenesis remains unclear. In this study, we wanted to observe thechanges in GABAergic inhibition through preNMDARs in sensory-motor and visual corticalpyramidal neurons after pilocarpine-induced status epilepticus.Methods: Using a pilocarpine-induced epileptic mouse model, sensory-motor and visualcortical slices were prepared, and the whole-cell patch clamp technique was used to recordspontaneous inhibitory post-synaptic currents (sIPSCs).Results: The primary finding was that the mean amplitude of sIPSC from the sensorymotorcortex increased significantly in epileptic mice when the recording pipette contained MK-801 compared to control mice, whereas the mean sIPSC frequency was not significantly different,indicating that post-synaptic mechanisms are involved. However, there was no significant presynapticinhibition through preNMDARs in the acute brain slices from pilocarpine-inducedepileptic mice.Conclusion: In the acute case of epilepsy, a compensatory mechanism of post-synapticinhibition, possibly from ambient GABA, was observed through changes in the amplitude withoutsignificant changes in the frequency of sIPSC compared to control mice. The role of preNMDARmediatedinhibition in epileptogenesis during the chronic condition or in the juvenile stagewarrants further investigation.
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Background: Meningiomas are the most common intracranial tumours; they accountfor 13%–26% of all the primary intracranial tumours. Skull base meningiomas make up 25% of allmeningiomas and are one of the most difficult intracranial tumours to be managed surgically. Thisis due to the fact that it is difficult to approach the lesions which are also close to vital structuressuch as cranial nerves and major blood vessels. Despite the abundance of these cases in Malaysia,local data on meningiomas is scarce.Methods: This is a retrospective study consisting of 199 patients with meningiomaswho have been operated at the Kuala Lumpur General Hospital from January 2010–December2014. They were categorised into skull base and non-skull base groups. Demography, tumourcharacteristics, and patient outcomes were analysed. Kaplan-Meier survival curves as well asCox hazard univariable and multivariable regressions for the possible predictors of survival wereanalysed.Results: 97.5% of the patients (n = 194) had WHO grade I meningioma and only fivepatients had WHO grade II meningioma. There was a female predominance (n = 134; 67.3%), witha male-to-female ratio of 1:2. Some 27.1 % patients had skull base meningiomas. Patients with skullbase meningiomas had poorer outcomes and discharge conditions (n = 23; 42.6% P < 0.01), inaddition to higher risk of incomplete resections (n = 34; 63% P < 0.01). Multivariate cox hazardregressions showed that the skull base meningioma group had four times the risk of death of thenon-skull base group.Conclusions: Symptomatic meningiomas can be curative if the tumour is completelyremoved. Our study has revealed that skull base meningiomas which were operated locallyhad higher rates of incomplete resection and poorer surgical outcomes as compared to the nonskullbase group. Patients with skull base meningiomas had four times the risk of death vis-à-visnon-skull base ones. More local studies are needed to look into skull base meningiomas for theimprovement of its surgical outcomes.
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@#Neuroplasticity has been subjected to a great deal of research in the last century. Recently, significant emphasis has beenplaced on the global effect of localized plastic changes throughout the central nervous system, and on how these changesintegrate in a pathological context. The present study aimed to demonstrate the functional cortical reorganization beforeand after surgery using magnetoencephalography (MEG) in a participant with brain tumor. Results of Visual EvokedMagnetic Field (VEF) based on functional MEG study revealed significantly different of MEG N100 waveforms before andafter surgery. Larger and additional new locations for visual activation areas after the surgery were found suggestingneuroplasticity. The present study highlight a physiological plasticity in a teenage brain and the alterations regardingneural plasticity and network remodeling described in pathological contexts in higher-order visual association areas.
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@#The present study discussed functional reorganization and alteration in respond to the slow-growing tumour,hemangiopericytoma in the occipital cortex. Visual evoked field (VEF) and auditory evoked field (AEF) usingmagnetoencephalography (MEG) was used to evaluate the source localization and brain activity. Results of VEF sourcelocalization show a typical brain waves. Brain activity of the occipital lobe demonstrate low activation in the ipsilateralto the tumour. However, result shows the activation on the contralateral hemisphere was high and bigger in activationvolume. AEF result shows an identical source localization and both side of the temporal lobe are activated. This resultsuggests that there is a positive plasticity in auditory cortex and slow-growing tumour can induce functional reorganizationand alteration to the brain.
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BACKGROUND: Mitochondria are major cellular sources of reactive oxygen species (ROS) generation which can induce mitochondrial DNA damage and lead to carcinogenesis. The mitochondrial 10398A>G alteration in NADH-dehydrogenase subunit 3 (ND3) can severely impair complex I, a key component of ROS production in the mitochondrial electron transport chain. Alteration in ND3 10398A>G has been reported to be linked with diverse neurodegenerative disorders and cancers. The aim of this study was to find out the association of mitochondrial ND3 10398A>G alteration in brain tumor of Malaysian patients. METHODS: Brain tumor tissues and corresponding blood specimens were obtained from 45 patients. The ND3 10398A>G alteration at target codon 114 was detected using the PCR-RFLP analysis and later was confirmed by DNA sequencing. RESULTS: Twenty-six (57.8%) patients showed ND3 10398A>G mutation in their tumor specimens, in which 26.9% of these mutations were heterozygous mutations. ND3 10398A>G mutation was not significantly correlated with age, gender, and histological tumor grade, however was found more frequently in intra-axial than in extra-axial tumors (62.5% vs. 46.2%, p G mutations in a Malaysian brain tumor population. It can be concluded that mitochondrial ND3 10398A>G alteration is frequently present in brain tumors among Malaysian population and it shows an impact on the intra-axial tumors.
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Humans , Brain Neoplasms , Brain , Carcinogenesis , Codon , DNA, Mitochondrial , Electron Transport , Malaysia , Mitochondria , Neurodegenerative Diseases , Reactive Oxygen Species , Sequence Analysis, DNAالملخص
Introduction: Symptomatic chronic subdural hematomas (CSDH) remain one of the most frequent diagnoses in current neurosurgical practice. Burr-hole craniostomy with irrigation and placement of close-system drainage is the current recommended surgery for symptomatic CSDH. The aim of this study is to perform a direct comparison between two surgical techniques in the treatment of symptomatic CSDH, which have been proven in previous studies to be efficient. Our main objective was to compare the efficacy of placement of a subperiosteal drain (SPD) and a subdural drain (SDD) following single burr-hole craniostomy and irrigation, and to demonstrate any significant differences in terms of overall surgical complications, functional outcome at three months and mortality rate. Materials and Methods: The study was carried out in two local neurosurgical centres. The SPD group was performed in Hospital Umum Sarawak (HUS) and the SDD group was performed in Hospital Sultanah Aminah Johor Bahru (HSAJB), from 1 January 2012 till 30 January 2014 with a total of 30 patients in both treatment groups. Results: Overall, there were no statistically significant difference in terms of patient general characteristics, pre-operative and post-operative symptoms, Markwalder grades, postoperative hematoma volume and recurrence, mortality and functional outcome at discharge and at three month follow-up between both groups. Albeit not achieving statistical significance, we observed a lower rate of surgical complication especially for post-operative intracranial hematoma with placement of the SPD system. Conclusions: Our study concludes that both treatment methods proved to be highly effective in the treatment of CSDH. However, with a lower overall surgical complication rate, treatment with single burr-hole craniostomy, irrigation and placement of the SPD system can be considered a treatment of choice for the management of symptomatic CSDH.
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Background: The neuroprotective role of minocycline in the treatment of brachial plexus injury is controversial. Objective: To study the neuroprotective effect of minocycline via different routes in adult Sprague Dawley rats with brachial plexus injury. Methods: The C7 nerve roots of the animals were avulsed via an anterior extravertebral approach. Traction force was used to transect the ventral motor nerve roots at the preganglionic level. Intraperitoneal and intrathecal minocycline (50 mg/kg for the first week and 25 mg/kg for the second week) were administered to promote motor healing. The spinal cord was harvested six weeks after the injury, and structural changes following the avulsion injury and pharmacological intervention were analysed. Results: Motor neuron death and microglial proliferation were observed after the administration of minocycline via two different routes (intraperitoneal and intrathecal) following traumatic avulsion injury of the ventral nerve root. The administration of intraperitoneal minocycline reduced the microglia count but increased the motor neuron count. Intrathecal minocycline also reduced the microglial count, with a greater reduction than in the intraperitoneal group, but it decreased the motor neuron count. Conclusions: Intraperitoneal minocycline increased motor neuron survival by inhibiting microglial proliferation following traumatic avulsion injury of the nerve root. The inhibitory effect was augmented by the use of intrathecal minocycline, in which the targeted drug delivery method increased the bioavailability of the therapeutic agent. However, motor neuron survival was impaired at a higher concentration of minocycline via the intrathecal route due to the more efficient method of drug delivery. Microglial suppression via minocycline can have both beneficial and damaging effects, with a moderate dose being beneficial as regards motor neuron survival but a higher dose proving neurotoxic due to impairment of the glial response and Wallerian degeneration, which is a pre-requisite for regeneration.
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Background: Intraventricular haemorrhage (IVH) causes blockage of ventricular conduits leading to hydrocephalus, increased intracranial pressure (ICP), and a reduced level of consciousness. The current standard management of IVH is insertion of an external ventricular drainage (EVD) catheter. However, this procedure addresses only the problems of acute hydrocephalus and raised ICP. Endoscopic washout allows for a more complete removal of the intraventricular clot. This study compared these two types of treatment in terms of shunt dependency and relevant clinical outcomes. Methods: Patients who were 10–80 years old and presented with a Graeb score of more than six were randomised into endoscopic washout and EVD treatment groups. A CT brain was repeated on each patient within 24 hours after surgery, and if a patient’s Graeb score was still more than six, a repeat endoscopic washout was performed to clear the remaining clots. All patients were monitored for shunt dependency at two weeks and three months, and clinical outcomes were measured at six months after the procedure. Results: A total of 39 patients were recruited; 19 patients were randomised into the endoscopic washout group, and 20 were randomised into the EVD group. However, three patients in the endoscopic group refused that treatment and opted for EVD insertion. Patients treated with endoscopic washout had significantly less drainage dependency at two weeks (P < 0.005) and at three months (P < 0.004) as compared to patients in the external ventricular drainage group. The reduction in Graeb scores was also significantly greater in the endoscopic washout group (P < 0.001). However, the functional outcome at six months measured via a modified Rankin scale score was no different in the two groups of patients. The difference in the functional outcome of the patients was mainly dependent on the initial pathology, with those presenting with a thalamic bleed with IVH showing a poor functional outcome. This parameter was also influenced by the Glasgow Coma Scale (GCS) score on admission, with those patients with a score of 12 or less having a poor functional outcome (MRS 5–6) at three and six months after the surgery. Conclusions: The use of neuroendoscopy in patients with a massive IVH significantly reduced drainage dependency. However, it did not alter the final functional outcome.
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The Academy of Sciences Malaysia and the Malaysian Industry-Government group for High Technology has been working hard to project the future of big data and neurotechnology usage up to the year 2050. On the 19 September 2016, the International Brain Initiative was announced by US Under Secretary of State Thomas Shannon at a meeting that accompanied the United Nations’ General Assembly in New York City. This initiative was seen as an important effort but deemed costly for developing countries. At a concurrent meeting hosted by the US National Science Foundation at Rockefeller University, numerous countries discussed this massive project, which would require genuine collaboration between investigators in the realms of neuroethics. Malaysia’s readiness to embark on using big data in the field of brain, mind and neurosciences is to prepare for the 4th Industrial Revolution which is an important investment for the country’s future. The development of new strategies has also been encouraged by the involvement of the Society of Brain Mapping and Therapeutics, USA and the International Neuroinformatics Coordinating Facility.