Methods in Genomic Neuroscience (Frontiers in Neuroscience)

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The results for a range of cancerous cell lines and actual tumor samples both positive and negative for this mutation were very promising. The device was proven highly accurate, as confirmed by complete sequencing of the gene in question in each sample. The small sample size required for the device reduces the invasiveness of sample harvesting. In fact the process takes only 15 minutes, enabling completion during an operation.

The immuno-wall could markedly increase success of glioma treatment by rapidly providing data to inform the course of the operation and tissue to remove. The key to success in the immuno-wall assay is that we luckily have HMab-2, the highly-specific antibody to the mutant IDH1.

This means the immuno-wall can identify the margins of tumors where only low numbers of cancerous cells are present. Alternatively, sampling could even involve only obtaining blood or cerebrospinal fluid, rather than removing brain tissue, making the procedure even less invasive. Science and Technology of Advanced Materials, Oct. DOI: Establishment of a novel preoperative brain mapping system by navigated transcranial magnetic stimulation nTMS. We perform awake brain mapping for safe and maximum resection of tumors with the simultaneous preservation of brain functions, in the eloquent areas of language, motor and higher function, and in their vicinity.

The biggest advantage of awake brain mapping is direct functional evaluation of a certain area, making it possible to prevent post-operative language and higher brain function disorders. Although faster and safe awake surgical mapping would be possible if information on brain function before surgery could be obtained, a non-invasive high precision pre-operative brain function test as such is not available at present.

WKW Frontiers in Neuroscience Lecture: David Goldman, M.D. - Laureate Institute for Brain Research

There is no evidence that pre-operative brain mapping with functional MRI correctly predicts that a certain area of the brain is actually used to perform those certain tasks. That area of the brain might only be slightly associated with a certain task, thus making pre-operative assessment incomplete. Transcranial magnetic stimulation TMS is a magnetic method used to stimulate nerves and small regions of the brain. In Japan, reports of outcomes with TMS have increased, especially in the recent years after the first safety guidelines were published in In this study, we use a non-invasive next generation instrument called navigation TMS nTMS to accurately identify language, motor and higher brain function areas pre-operatively.

Moreover, with comparative analysis with the fMRI and the results of awake surgery, we plan to develop an accurate method to identify language, motor, higher brain functions and dominant hemisphere pre-operatively. Investigate the insular function associated with the emotional and interoceptive awareness and using a brain mapping study. There has been a lot of research on how the brain and the body functions to recognise one's feelings. It has been considered from the research so far that the insular cortex is responsible for somatesthesia, especially in processing visceral sensation.

Also, our research collaborators Terasawa, Umeda and others have analyzed brain functions in brain injury cases with neurophysiological methods and functional MRI to understand social and emotional cognitive mechanisms. They reported that the activities of the insular cortex increases in cases of interoceptive senses and in emotionally awake state of subjective senses. Therefore, to experience emotions, interoceptive senses play an important role and insular cortex may function as its nerve center. In this study, by directly stimulating insular cortex and white matter while employing recognition of facial expression tasks and monitoring heart rate during awake surgery for tumors of insular cortex and neighboring areas, we aim to define the roles and functions of the insular cortex in emotional cognition and interoceptive sensation.

We have previously published 2 original research papers on cerebrospinal fluid proteins of Moyamoya disease MMD patients. Araki et al. BMC Neurology , Maruwaka et al. Journal of Stroke and Cerebrovascular Diseases, Vol. We are currently investigating the functions of these peptides. We are also conducting genetic analysis of CSF of moyamoya patients and control groups to discover genes responsible for MMD pathology. Elucidation of nNOS phosphorylation regulating mechanism in the hippocampal neural cells during Subarachnoid hemorrhage.

Nitric oxide NO , produced from L-arginine by NOS nitric oxide synthase , not only functions as a neurotransmitter but is also produced in the endothelium and is known to increase local blood flow through vasodilation. Our research collaborator Prof.


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We want to explain the following by investigating changes in hippocampal p-nNOS caused by post SAH acute increase in intracranial pressure. This research aims to explain the neuroprotective mechanism of NOS phosphorylation in the hippocampus immediately after SAH. Hopefully it can be used to prevent post SAH higher cognitive function disorder by inhibiting early brain injury after SAH.

Makino et al. Brain Res. We aim to develop safer and more effective surgical procedures by utilizing the neural network information generated by latest modalities like resting state fMRI, DTI tractography and MEG. We introduced a novel EEG-f MRI simultaneous recording device, diagnosed the focus of epilepsy and performed network analysis. Resting fMRI network analysis shows increase in epileptic abnormal connections pic: up right.

From the findings of awake surgical mapping, we studied functional preservation from hodological point of view and observed basic network change and sub-cortical linguistic network of default mode network from resting network analysis. We compared resting fMRI of linguistic network and fMRI with task pic: up right and by comparative study of results of electric stimulation mapping during surgery, we are pursuing non-invasive and more accurate pre-operative evaluation of brain function by understanding neural foundation.

NeuroMate is a computer-controlled, robotic system for stereotactic functional brain surgeries. A highly precise and safe targeting by the application of robotics promises improvement in accuracy and effectiveness of stereotactic surgery. It has been modified to fit Japanese surgical techniques and we have applied it to deep brain stimulation DBS for parkinsons disease in a clinical trial of 8 cases. We have confirmed its efficacy and verified its precision with existing stereotactic frame system fig above. After its pharmaceutical approval, it has mostly been used in DBS. With Neuromate, it is possible to make detailed verification of neural activities of basal ganglia by microelectrode recording MER during surgery fig right below.

We also use Neuromate to place multiple electrodes for focal diagnosis. We plan to broaden its application by frameless system installation and workstation improvisation. Non-invasive temperature mapping is possible with MRI and can be used effectively with FUS that uses heat coagulation as its main mechanism of action thus making it possible to assess treatment efficacy and side effects during surgery. A helmet with probes is equipped in a bed specially designed for FUS. The patient wears the helmet and enters the MRI machine.

The ultrasound waves generated from the ultrasound probe are focused to the precise region of the brain and cause the temperature of that region to increase thus bringing the therapeutic effect. Insightec's neurosurgery solution, Exablate Neuro, is the first focused ultrasound device approved by the FDA in July Exablate Neuro is in the process of PMDA for approval in Japan to treat patients with essential tremors and parkinsons disease.

It has also been found to be effective in tremors in parkinsons disease by targeting PTT. Besides these, its application is expected in trigeminal neuralgia, malignant brain tumors, and cerebrovascular diseases. At present August , 5 such systems have been installed so far and it is soon going to be installed in a Nagoya University Department of Neurosurgery affiliated hospital too. We plan to proceed with the efficacy study of this non-invasive technology of MRgFUS for essential tremor and Parkinson disease. Less invasive spine surgery; We have been practicing and studying the clinical outcomes of less invasive surgery to minimize the injury to normal structures of skin and muscles.

Sometimes the intraoperative wave changes can be false positives. We have used animal models rats and mice to analyze and predict reasons behind the false positives and have already reported blood pressure as a significant factor. We are now studying the effects of blood pressure to MEP waves in detail. Surgical outcomes are improving and we are studying them in detail.

We coordinate with the tumor group of the orthopedic department of Aichi Cancer Centre and have removed complicated tumors with combined effort of different faculties. Basic research of spinal nerve regeneration We have reported the immensely significant role of microglia in central nerve immune-response Takeuchi et al.

Experimental Neurology Cell transplantation , Ito et al. J of Neurotrauma Motor function improvement can be obtained with microglial inhibition Umebayashi et al. J Neurotrauma. Now, we are focusing on autoimmune response after spinal cord injury and working towards spinal regeneration with this autoimmune inhibition. Secondary craniosynostosis is premature synostosis occurring during the course of some other disease and treatment, with most of it arising in cases of excessive shunting, causing growth arrest of cranium and subsequent deformity and decrease in intracranial volume.

Special consideration is required in brain tumor cases because of higher chances of shunt placement for hydrocephalus in these cases. Moreover, craniosynostosis after radiation therapy may cause complicated cranial deformation, and chiari malformation like changes have been reported in posterior fossa irradiation.

Surgical management is not always easy, so preventive strategy is very important. We are studying the relevant risk factors and diagnostic markers with special focus on serum ALP level because of its role in bone formation. Among pediatric patients admitted to our department since , we studied 40 brain tumor resection patients and found that 26 of them presented with hydrocephalus and 11 In contrast, 14 patients with no hydrocephalus didn not develop craniosynostosis. Among craniosynostosis cases, 5 patients All the craniosynostosis cases had high ALP level for a certain period of time and the course was compatible with synostosis progress during that time period.

We believe this proves that not only continuous CSF drainage shunt but also decrease in intracranial pressure with a single surgery may cause secondary craniosynostosis. Although there are also several reports on developmental retardation after radiation therapy in pediatric patients, knowledge of secondary microcephaly and cranisynostosis is scarce. Therefore, change in the shape of the cranium should also be noted during follow up after brain tumor removal surgery, especially in cases with initial presentation of hydrocephalus.

Minimal radiological changes may be difficult to observe; but blood ALP levels could be useful diagnostic markers. We plan to continue our study by with more number of cases. Until now, treatment of recurrent medulloblastoma included Temozolomide Cefalo et. Aguilera et. At present we are studying the efficacy of this protocol as the possible standard treatment for recurrent medulloblastoma in our hospital.

We use immune-histological findings of cases treated in our hospital to comprehensively search for possible biomarkers including VEGF. Development of novel endoscopic surgical techniques and peripheral equipment for intracranial lesions. Surgical treatment using an endoscope is becoming more and more common in the neurosurgical field these days. Trans-nasal endoscopic pituitary tumor resection was first reported about 20 years ago and is an area that will further develop in the future.

To use this surgical technique in larger tumors less invasively, it is necessary to develop new surgical approaches and equipment. The goal of this project is as follows. Widening the indications of endoscopic trans-nasal trans-sphenoidal, approach and equipment development Trans-nasal trans-sphenoidal approach is already being used in different hospitals for pituitary tumors, tuberculum sella meningioma, craniopharyngioma, chordoma etc. With this surgical method, approach to the lesions is possible without touching the normal brain, thus is a very less invasive procedure.

However, because manipulating space is limited in the surgery through the nasal cavity, surgical manipulation becomes more difficult as you move lateral from the central axis. By deepening our knowledge of the nasal cavity and developing novel nasal cavity techniques, we are developing techniques and tools to make this surgical method even further less invasive and widen its indication for larger tumors.

Special equipment are necessary for this surgery, for example, it is necessary to develop forceps that can bend and rotate in deep seated locations. We have started surgical equipment development in cooperation with other universities and enterprises and have been successful in its partial productization. Application of endoscopic surgery for brain tumors and equipment development We are developing surgeries to remove brain lesions by applying endoscopic skull base techniques.

A mm small clear tube is inserted toward the lesion, thereby minimizing damage to the peritumoral normal brain parenchyma by to doing the complete tumor excision within the cylinder itself. Although it is possible to make brain tumor surgery less invasive, it is necessary to develop special device for the new surgical methods. We plan to develop these surgical techniques and tools and make them available for worldwide use in the future. Application of nasal surgery to brain stem lesion. Brain tumor surgery using clear sheath.

Head circumference is expanded. Expanded ventricles can be observed. Basic research To resolve the questions that arise from our daily clinical practice, we have been developing experimental systems that serve as a model to prove our clinical practice. The experimental models not only give us hints on solving our clinical questions but also serve to improve endovascular neurosurgery by helping us develop new treatment methods which we again apply in our clinical practice.

We are currently conducting the following clinically applicable basic research. Search Japanese. Introduction Neurosurgical operations: Nagoya University Department of Neurosurgery boasts a fully equipped and highly precise robotic-assisted "Neuronavigation" surgical support system, including intraoperative MRI, navigation system, Neuromate, etc. Research Projects 1. Project leader: Kazuya MOTOMURA MD, PhD We perform awake brain mapping for safe and maximum resection of tumors with the simultaneous preservation of brain functions, in the eloquent areas of language, motor and higher function, and in their vicinity.

Anterior cervical decompression We treat cervical radiculopathy with a 6 mm small hole drilled with the assistance of surgical microscope and without placing any artificial implants. With this technique, inter-vertebral mobility is preserved and risk of degenerative change to the adjacent vertebra is minimized. We have reported good clinical outcomes and vertebral stability using finite element method. At present we are studying post-operative change in the alignment of the vertebrae, stability of the operated vertebra through radio-imaging, and influence on the adjacent vertebra.

Posterior lumbar fixation with Wiltse approach In Wiltse approach, the lateral side of the facet is approached by dissecting between muscles causing minimal muscular damage. With this approach screw placement is possible with almost no muscular damage, and we have been studying the clinical outcome of its application in thoraco-lumbar posterior fixation. Compared to conventional methods, similar treatment effects have been achieved with less blood loss and less post-operative pain.

We are studying the results of further minimization of surgical invasion by combining it with oblique lumbar interbody fusion OLIF. Treatment of Vertebral and Spinal Tumor. Surgical outcomes of spinal intramedullary tumors We apply minimally invasive techniques to prevent post operative spine deformity, to minimize the risk of post operative palsy and sensory disorder.

We also conduct genetic analysis of the pathological specimens with special consideration to the difference in the genetics of spinal and brain tumors. Basic research Study on hydrocephalus pathogenesis using ciliary dyskinesia mouse models. Congenital hydrocephalus is a group of diseases that is often encountered in pediatric neurological practice. Among congenital hydrocephalus, one with no obvious occlusion is called communicating hydrocephalus, one of the reasons for which is failure of ciliary movement present in the ependymal cells.

Cilia is present in cell surface of various tissues like bronchus, fallopian tube, ventricles, etc. It is possible to know the origins of hydrocephalus by using the pili movement disorder model mouse. Along with the site of impaired spinal fluid reflux by impairment of ciliary motion, we are also studying ciliary motility in normal mice to learn how cilia contributes to the formation of cerebrospinal fluid circulation. Endovascular Neurosurgery Research Projects: Project leader: Takakashi IZUMI Basic research To resolve the questions that arise from our daily clinical practice, we have been developing experimental systems that serve as a model to prove our clinical practice.

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Safety of intracranial stent occlusion in silicon and animal model. We confirmed the feasibility and safety of intracranial stent occlusion in a silicon model. To verify its safety in vivo, we placed the stent in a rabbit model and verified the safety of the stent occlusion when it was covered with neo-intima. Catheter traction comparative experiments in silicon model Micro-catheter, when injected with liquid embolic substance such as NBCA or ONYX, may result in adhesion and may be difficult to remove and break off on pulling. Additional surgical invasion for its removal might be required.

Only a small portion of the tractive force applied while pulling out the micro-catheter is transmitted to its distal end because of meandering of the blood vessel. There are also differences depending on the material of the micro-catheter. We are comparing and verifying these differences in silicon models. Observation of the coil behavior in aneurysm coil embolization There are various features in the coils used for embolization of aneurysm.

To understand the characteristics of the respective coils, we are doing observational experiment using various coil movement models, which would be difficult to observe during a normal endovascular surgery. We are studying the behavior and filling rate of filling and finishing coils in model case scenarios with varying aneurysm shape and size. Study of pressure on the vessel at the time of balloon expansion during endovascular treatment. In endovascular surgery, balloon assist may be used to prevent coil prolapse.

However, balloon expansion may also cause vascular damage.


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We use silicon vascular models to measure expanded balloon pressure and to choose safe balloons and develop safer expansion techniques. Fig: A portion of the balloon bulges after it is expanded inside a silicon tube. Clinical Research Correlation between spinal dural arteriovenous fistula and degenerative diseases. The comorbidity of the spinal cord dural arteriovenous fistula and spinal degenerative disease was analyzed, including the correlation with the vein occlusion. Concomitant ipsilateral hernia or osteophytes were found in high rates. Furthermore, high rates of concomitant vein occlusion was also observed.

We believe that these findings suggest a correlation with the genesis of spinal dural arteriovenous fistula. Study of recurrence factor of unruptured brain aneurysm. We are analyzing the factors like size and location of aneurysms in our vast number of cases of unruptured aneurysm treatment.

While the size coil density of the aneurysm was significantly correlated with recurrence, we did not find any advantages with thick primary coil diameter. Study of risk factors for stenting in cervical carotid artery stenosis Treatment of carotid artery stenosis includes carotid endarterectomy CEA: direct surgery and stenting CAS: an endovascular treatment.

On the basis of the accumulated data in our hospital, we are studying the high-risk factors of the cases treated with CAS to develop safer treatment policies. Study of the optimal antiplatelet therapy as observed from long-term results of stent assisted coil embolization of brain aneurysms. Stent assisted coil embolization for brain aneurysms is becoming the main stream treatment.

However, dual antiplatelet therapy is a must in these stent cases. During long term follow up, the optimal timing to reduce antiplatelet to a single tablet DAPT-ACE study in progress and whether antiplatelet can be stopped altogether is still a matter of debate. We are studying our cases to find out the right answer and also analyzing ischemic and hemorrhagic complications and their risk factors.

Study of puncture site bleeding after the cerebral endovascular treatment Puncture site bleeding prolongs bed rest time after endovascular surgery and is a major risk factor for longer hospital stay. Pseudo-aneurysm may occur and surgical intervention might also be required in some cases. We did a retrospective study on the risk factors and on how to shorten bed rest and hospital stay, and as a result, endovascular treatment became safer and hospital stay shortened.

Study of the position of the shunt pouch in dural arteriovenous fistula of the cavernous sinus. There is a need to accurately identify the shunt pouch in order to do a super-selective embolization of the dural arteriovenous fistula. We are retrospectively analyzing the distribution of the opening of shunt pouch of the sinus. Incidence and risk factors of subdural hematoma after intraoperative cerebrospinal fluid leakage during the transsphenoidal approach.

Pituitary, The "steppingstone" phenomenon: a new endoscopic finding in slit-ventricle syndrome. Childs Nerv Syst, Lateral temporal encephaloceles: case-based review. Childs Nerv Syst, ; World Neurosurg, ; Neurol Med Chir Tokyo , ; Cancer Immunol Res, ; 4: Rapid sensitive analysis of IDH1 mutation in lower-grade gliomas by automated genetic typing involving a quenching probe. Cancer Invest, ; Bilateral occlusion of the foramina of Monro after endoscopic third ventriculostomy for aqueductal stenosis--a case report.

A case of secondary somatosensory epilepsy with a left deep parietal opercular lesion: successful tumor resection using a transsubcentral gyral approach during awake surgery. J Neurosurg, ; Relationship between low response to clopidogrel and periprocedural ischemic events with coil embolization for intracranial aneurysms. J Neurointerv Surg, ; 8: Motomura K, Chalise L. No Shinkei Geka, ; Surgical benefits of combined awake craniotomy and intraoperative magnetic resonance imaging for gliomas associated with eloquent areas.

J Neurosurg, ; in press. How I do it: shoelace watertight dural closure in extended transsphenoidal surgery.

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Acta Neurochir Wien , ; Antitumorigenic effect of interferon-beta by inhibition of undifferentiated glioblastoma cells. Int J Oncol, ; Primary peripheral T-cell lymphoma, not otherwise specified, of the central nervous system in a child. Brain Tumor Pathol, ; Characteristic laryngoscopic findings in Parkinson's disease patients after subthalamic nucleus deep brain stimulation and its correlation with voice disorder. J Neural Transm Vienna , ; Operative wound-related complications after cranial revascularization surgeries. Applicable advances in the molecular pathology of glioblastoma.

J Neuropathol Exp Neurol, ; Brain Res, ; J Biol Chem, ; Nat Genet, ; Intraoperative subcortical mapping of a language-associated deep frontal tract connecting the superior frontal gyrus to Broca's area in the dominant hemisphere of patients with glioma. J Stroke Cerebrovasc Dis, ; Rhabdoid glioblastoma: an aggressive variaty of astrocytic tumor.

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Nagoya J Med Sci, ; His main interest is the genetic architecture of complex traits, how they are wired, how they are regulated, and how they evolve. She is an elected member of the Young Academy of the Royal Dutch Academy of Sciences, and recipient of several national and international awards. In , and she was elected as one of the most successful women under the age of 38 in the Netherlands. Her current research focuses on understanding mechanisms underlying neuropsychiatric and cognitive traits. She co-founded the Dutch iPScenter, which aims to detect biological mechanisms of brain-related traits using human induced pluripotent cells.

In , he moved to the Montreal Neurological Institute at McGill where his research interests include multi-modal brain imaging with PET and MRI, structural network modeling and large-scale brain databasing. In , he was inducted as a Fellow of the Royal Society of Canada. In , he was awarded the Senate of Canada Medal. This project provides a web-accessible reference database of normal maturation. He is Founder and Director of Biospective Inc.

Cognitive genomics: decoding human brain transcriptional networks. Konopka completed her Ph. Her lab uses a combination of primary human neurons, animal models, and primate comparative genomics to uncover human-specific, disease-relevant patterns of gene expression. Konopka is particularly interested in the evolution of language and part of her research has focused on the FOXP family of transcription factors. Recent work in her lab integrates gene expression with signatures of neuronal activity in the human brain. His doctoral work employed a multidisciplinary approach, importing insights from genetics, neuroscience, and psychology to study questions of interest to economists, such as human capital formation, the determinants of economic outcomes, and the effect of cognitive biases on economic choices.

During his doctorate, Jonathan also spent a semester at Princeton University working on a project in neuroeconomics.

Genomics in Neuroscience: New Research Applications

The genetics of education: DNA in the social context. She studies the causes and consequences of individual differences in psychological and behavioral development across the life course. Specifically, Sophie focuses on three areas, including a the relationship of genome-wide polygenic scores and educational attainment, b the effects of early life environments on children's cognitive growth; and c the role of personality traits like curiosity and imagination for learning outcomes. She has published more than 50 peer-reviewed journal articles and book chapters and developed two psychological research smartphone apps.

She is recipient of a Jacobs Foundation Fellowship By investigating evolutionary history using high throughput genomic tools, Elinor works to identify genes, pathways, and functional variants underlying polygenic diseases, and translate these discoveries into advances in human health care.