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Sample records for 18f-flt human brain

  1. [18F]FDG and [18F]FLT positron emission tomography imaging following treatment with belinostat in human ovary cancer xenografts in mice

    Belinostat is a histone deacetylase inhibitor with anti-tumor effect in several pre-clinical tumor models and clinical trials. The aim of the study was to evaluate changes in cell proliferation and glucose uptake by use of 3’-deoxy-3’-[18F]fluorothymidine ([18F]FLT) and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) following treatment with belinostat in ovarian cancer in vivo models. In vivo uptake of [18F]FLT and [18F]FDG in human ovary cancer xenografts in mice (A2780) were studied after treatment with belinostat. Mice were divided in 2 groups receiving either belinostat (40 mg/kg ip twice daily Day 0–4 and 6–10) or vehicle. Baseline [18F]FLT or [18F]FDG scans were made before treatment (Day 0) and repeated at Day 3, 6 and 10. Tracer uptake was quantified using small animal PET/CT. Tumors in the belinostat group had volumes that were 462 ± 62% (640 mm3) at Day 10 relative to baseline which was significantly different (P = 0.011) from the control group 769 ± 74% (926 mm3). [18F]FLT SUVmax increased from baseline to Day 10 (+30 ± 9%; P = 0.048) in the control group. No increase was observed in the treatment group. [18F]FDG SUVmean was significantly different in the treatment group compared to the control group (P = 0.0023) at Day 10. Within treatment groups [18F]FDG uptake and to a lesser extent [18F]FLT uptake at Day 3 were significantly correlated with tumor growth at Day 10. [18F]FDG uptake early following treatment initiation predicted tumor sizes at Day 10, suggesting that [18F]FDG may be a valuable biomarker for non-invasive assessment of anti-tumor activity of belinostat

  2. 18F-FLT and 18F-FDOPA PET kinetics in recurrent brain tumors

    In this study, kinetic parameters of the cellular proliferation tracer 18F-3'-deoxy-3'-fluoro-l-thymidine (FLT) and the amino acid probe 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine (FDOPA) were measured before and early after the start of therapy, and were used to predict the overall survival (OS) of patients with recurrent malignant glioma using multiple linear regression (MLR) analysis. High-grade recurrent brain tumors in 21 patients (11 men and 10 women, age range 26 - 76 years) were investigated. Each patient had three dynamic PET studies with each probe: at baseline and after 2 and 6 weeks from the start of treatment. Treatment consisted of biweekly cycles of bevacizumab (an angiogenesis inhibitor) and irinotecan (a chemotherapeutic agent). For each study, about 3.5 mCi of FLT (or FDOPA) was administered intravenously and dynamic PET images were acquired for 1 h (or 35 min for FDOPA). A total of 126 PET scans were analyzed. A three-compartment, two-tissue model was applied to estimate tumor FLT and FDOPA kinetic rate constants using a metabolite- and partial volume-corrected input function. MLR analysis was used to model OS as a function of FLT and FDOPA kinetic parameters for each of the three studies as well as their relative changes between studies. An exhaustive search of MLR models using three or fewer predictor variables was performed to find the best models. Kinetic parameters from FLT were more predictive of OS than those from FDOPA. The three-predictor MLR model derived using information from both probes (adjusted R2 = 0.83) fitted the OS data better than that derived using information from FDOPA alone (adjusted R2 = 0.41), but was only marginally different from that derived using information from FLT alone (adjusted R2 = 0.82). Standardized uptake values (either from FLT alone, FDOPA alone, or both together) gave inferior predictive results (best adjusted R2 = 0.25). For recurrent malignant glioma treated with bevacizumab and irinotecan, FLT kinetic

  3. [18F]FLT PET for Non-Invasive Assessment of Tumor Sensitivity to Chemotherapy: Studies with Experimental Chemotherapy TP202377 in Human Cancer Xenografts in Mice

    Jensen, Mette Munk; Erichsen, Kamille Dumong; Björkling, Fredrik;

    2012-01-01

    3'-deoxy-3'-[¹⁸F]fluorothymidine ([18F]FLT) is a tracer used to assess cell proliferation in vivo. The aim of the study was to use [18F]FLT positron emission tomography (PET) to study non-invasively early anti-proliferative effects of the experimental chemotherapeutic agent TP202377 in both sensi...

  4. Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses

    18F-FLT is a novel PET radiotracer which has demonstrated a strong potential utility for imaging cellular proliferation in human tumors in vivo. To facilitate future regulatory approval of 18F-FLT for clinical use, we wished to demonstrate the safety of radiotracer doses of 18F-FLT administered to human subjects, by: 1) performing an evaluation of the toxicity of 18F-FLT administered in radiotracer amounts for PET imaging, 2) comparing a radiotracer dose of FLT to clinical trial doses of FLT. Twenty patients gave consent to a 18F-FLT injection, subsequent PET imaging, and blood draws. For each patient, blood samples were collected at multiple times before and after 18F-FLT PET. These samples were assayed for a comprehensive metabolic panel, total bilirubin, complete blood and platelet counts. 18F-FLT doses of 2.59 MBq/Kg with a maximal dose of 185 MBq (5 mCi) were used. Blood time-activity curves were generated for each patient from dynamic PET data, providing a measure of the area under the FLT concentration curve for 12 hours (AUC12). No side effects were reported. Only albumin, red blood cell count, hematocrit and hemoglobin showed a statistically significant decrease over time. These changes are attributed to IV hydration during PET imaging and to subsequent blood loss at surgery. The AUC12 values estimated from imaging data are not significantly different from those found from serial measures of FLT blood concentrations (p = 0.66). The blood samples-derived AUC12 values range from 0.232 ng*h/mL to 1.339 ng*h/mL with a mean of 0.802 ± 0.303 ng*h/mL. This corresponds to 0.46% to 2.68% of the lowest and least toxic clinical trial AUC12 of 50 ng*h/mL reported by Flexner et al (1994). This single injection also corresponds to a nearly 3,000-fold lower cumulative dose than in Flexner's twice daily trial. This study shows no evidence of toxicity or complications attributable to 18F-FLT injected intravenously

  5. 18F-FDG and 18F-FLT-PET imaging for monitoring everolimus effect on tumor-growth in neuroendocrine tumors: studies in human tumor xenografts in mice.

    Camilla Bardram Johnbeck

    Full Text Available The mTOR inhibitor everolimus has shown promising results in some but not all neuroendocrine tumors. Therefore, early assessment of treatment response would be beneficial. In this study, we investigated the in vivo and in vitro treatment effect of everolimus in neuroendocrine tumors and evaluated the performance of 18F-FDG and the proliferation tracer 18F-FLT for treatment response assessment by PET imaging.The effect of everolimus on the human carcinoid cell line H727 was examined in vitro with the MTT assay and in vivo on H727 xenograft tumors. The mice were scanned at baseline with 18F-FDG or 18F-FLT and then treated with either placebo or everolimus (5 mg/kg daily for 10 days. PET/CT scans were repeated at day 1,3 and 10.Everolimus showed significant inhibition of H727 cell proliferation in vitro at concentrations above 1 nM. In vivo tumor volumes measured relative to baseline were significantly lower in the everolimus group compared to the control group at day 3 (126±6% vs. 152±6%; p = 0.016, day 7 (164±7% vs. 226±13%; p<0.001 and at day 10 (194±10% vs. 281±18%; p<0.001. Uptake of 18F-FDG and 18F-FLT showed little differences between control and treatment groups, but individual mean uptake of 18F-FDG at day 3 correlated with tumor growth day 10 (r2 = 0.45; P = 0.034, 18F-FLT mean uptake at day 1 correlated with tumor growth day 7 (r2 = 0.63; P = 0.019 and at day 3 18F-FLT correlated with tumor growth day 7 (r2 = 0.87; P<0.001 and day 10 (r2 = 0.58; P = 0.027.Everolimus was effective in vitro and in vivo in human xenografts lung carcinoid NETs and especially early 18F-FLT uptake predicted subsequent tumor growth. We suggest that 18F-FLT PET can be used for tailoring therapy for neuroendocrine tumor patients through early identification of responders and non-responders.

  6. Histopathologic validation of 3′-deoxy-3′-18F-fluorothymidine PET for detecting tumor repopulation during fractionated radiotherapy of human FaDu squamous cell carcinoma in nude mice18F-FLT PET repopulation -->

    Background and purpose: FaDu human squamous cell carcinoma (FaDu-hSCC) demonstrates accelerated tumor repopulation during fractionated irradiation with pathological validation (Ki-67 and BrdUrd makers) in a xenograft model system. However, these and other functional assays must be performed ex vivo and post hoc. We propose a novel, in vivo, real-time assay utilizing 18F-FLT PET. Material and methods: Nude mice with FaDu-hSCC were irradiated with 12 or 18 fractions of 1.8 Gy ([Dm] = 3.0 Gy), either daily or every second day. 18F-FLT micro-PET scans were performed at different time points, FLT parameters (SUVmax, SUVmean, and T/NT) were measured. Tumor sections were stained for Ki-67 and BrdUrd, a labeling index (LI) was calculated. Imaging-pathology correlation was determined by comparing FLT parameters and immunohistochemical results. Results: Measured SUVmax, SUVmean and T/NT decreased significantly after daily irradiation with 12 fractions in 12 days (P < 0.05) and 18 fractions in 18 days (P < 0.05). In contrast, these parameters increased in mice treated with 12 fractions in 24 days (P > 0.05) and 18 fractions in 36 days (P > 0.05), suggesting accelerated repopulation. Similarly, Ki-67 and BrdUrd LIs demonstrated significant decreases with daily irradiation (P < 0.05), and increases with every-second-day irradiation (P > 0.05). 18F-FLT parameters correlated strongly with proliferation markers (r2: 0.679–0.879, P < 0.001). Conclusions: 18F-FLT parameters were in good agreement with Ki-67 and BrdUrd Li. These results may support a potential role for 18F-FLT PET in real-time detection of tumor repopulation during fractionated radiotherapy

  7. {sup 18}F-FLT and {sup 18}F-FDOPA PET kinetics in recurrent brain tumors

    Wardak, Mirwais; Schiepers, Christiaan; Dahlbom, Magnus; Phelps, Michael E.; Huang, Sung-Cheng [David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States); Cloughesy, Timothy F. [David Geffen School of Medicine at UCLA, Department of Neurology, Los Angeles, CA (United States)

    2014-06-15

    In this study, kinetic parameters of the cellular proliferation tracer {sup 18}F-3'-deoxy-3'-fluoro-l-thymidine (FLT) and the amino acid probe 3,4-dihydroxy-6-{sup 18}F-fluoro-l-phenylalanine (FDOPA) were measured before and early after the start of therapy, and were used to predict the overall survival (OS) of patients with recurrent malignant glioma using multiple linear regression (MLR) analysis. High-grade recurrent brain tumors in 21 patients (11 men and 10 women, age range 26 - 76 years) were investigated. Each patient had three dynamic PET studies with each probe: at baseline and after 2 and 6 weeks from the start of treatment. Treatment consisted of biweekly cycles of bevacizumab (an angiogenesis inhibitor) and irinotecan (a chemotherapeutic agent). For each study, about 3.5 mCi of FLT (or FDOPA) was administered intravenously and dynamic PET images were acquired for 1 h (or 35 min for FDOPA). A total of 126 PET scans were analyzed. A three-compartment, two-tissue model was applied to estimate tumor FLT and FDOPA kinetic rate constants using a metabolite- and partial volume-corrected input function. MLR analysis was used to model OS as a function of FLT and FDOPA kinetic parameters for each of the three studies as well as their relative changes between studies. An exhaustive search of MLR models using three or fewer predictor variables was performed to find the best models. Kinetic parameters from FLT were more predictive of OS than those from FDOPA. The three-predictor MLR model derived using information from both probes (adjusted R{sup 2} = 0.83) fitted the OS data better than that derived using information from FDOPA alone (adjusted R{sup 2} = 0.41), but was only marginally different from that derived using information from FLT alone (adjusted R{sup 2} = 0.82). Standardized uptake values (either from FLT alone, FDOPA alone, or both together) gave inferior predictive results (best adjusted R{sup 2} = 0.25). For recurrent malignant glioma treated

  8. [18F]FDG and [18F]FLT positron emission tomography imaging following treatment with belinostat in human ovary cancer xenografts in mice

    Jensen, Mette Munk; Erichsen, Kamille Dumong; Johnbeck, Camilla Bardram;

    2013-01-01

    Belinostat is a histone deacetylase inhibitor with anti-tumor effect in several pre-clinical tumor models and clinical trials. The aim of the study was to evaluate changes in cell proliferation and glucose uptake by use of 3'-deoxy-3'-[(18)F]fluorothymidine ([18F]FLT) and 2-deoxy-2-[(18)F]fluoro-...

  9. [18F]FLT and [18F]FDG PET for non-invasive treatment monitoring of the nicotinamide phosphoribosyltransferase inhibitor APO866 in human xenografts

    Erichsen, Kamille Dumong; Johnbeck, Camilla Bardram; Björkling, Fredrik;

    2013-01-01

    APO866 is a new anti-tumor compound inhibiting nicotinamide phosphoribosyltransferase (NAMPT). APO866 has an anti-tumor effect in several pre-clinical tumor models and is currently in several clinical phase II studies. 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) is a tracer used to assess cell pr...

  10. Evaluation of 3'-deoxy-3'-[18F]-fluorothymidine (18F-FLT) kinetics correlated with thymidine kinase-1 expression and cell proliferation in newly diagnosed gliomas

    The thymidine analog 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) has been developed as a positron emission tomography (PET) tracer to assess the proliferation activity of tumors in vivo. The present study investigated the relationship between the kinetic parameters of 18F-FLT in vivo and thymidine kinase-1 (TK-1) expression and cell proliferation rate in vitro, and blood-brain barrier (BBB) breakdown in human brain gliomas. A total of 21 patients with newly diagnosed gliomas were examined by 18F-FLT PET kinetic analysis. Maximum standardized uptake value (SUVmax) and tumor-to-normal (T/N) ratio of 18F-FLT in the tumor and 18F-FLT kinetic parameters in the corresponding contralateral region were determined. The expression levels of TK-1 protein and mRNA were determined by immunohistochemistry (IHC) and real-time polymerase chain reaction (PCR), respectively, using surgical specimens. The cell proliferation rate of the tumor was determined in terms of the Ki-67 labeling index. BBB breakdown was evaluated on MR images with contrast enhancement. 18F-FLT SUVmax and T/N ratio were significantly correlated with the influx rate constant (K1; P = 0.001 and P 3). IHC and real-time PCR studies demonstrated a significant correlation between K1 and TK-1 mRNA expression (P = 0.001), but not between k3 and TK-1 protein and mRNA expression. Linear regression analysis revealed a significant correlation between K1 and the Ki-67 index (P = 0.003), but not between k3 and the Ki-67 index. TK-1 mRNA expression was significantly correlated with the Ki-67 index (P = 0.009). 18F-FLT SUVmax and T/N ratio were significantly correlated with BBB breakdown evaluated by contrast enhancement in MR images (P = 0.003 and P = 0.011, respectively). These results indicate that 18F-FLT uptake in the tumor is significantly related to transport through the disrupted BBB, but not through phosphorylation activity. Although the tissue TK-1 expression reflects tumor proliferation activity, the phosphorylation

  11. A Pilot Study of 18F-FLT PET/CT in Pediatric Lymphoma.

    Costantini, Danny L; Vali, Reza; McQuattie, Susan; Chan, Jeffrey; Punnett, Angela; Weitzman, Shiela; Shammas, Amer; Charron, Martin

    2016-01-01

    We performed an observational pilot study of 18F-FLT PET/CT in pediatric lymphoma. Eight patients with equivocal 18F-FDG PET/CT underwent imaging with 18F-FLT PET/CT. No immediate adverse reactions to 18F-FLT were observed. Compared to 18F-FDG, 18F-FLT uptake was significantly higher in bone marrow and liver (18F-FLT SUV 8.6 ± 0.6 and 5.0 ± 0.3, versus 18F-FDG SUV 1.9 ± 0.1 and 3.4 ± 0.7, resp., p SUVs of 2.6 ± 0.1 and 2.0 ± 0.4, respectively. Nonspecific uptake in reactive lymph nodes and thymus was observed. Future studies to assess the clinical utility of 18F-FLT PET/CT in pediatric lymphoma are planned. PMID:27313888

  12. Evaluation of pyrimidine metabolising enzymes and in vitro uptake of 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) in pancreatic cancer cell lines

    Here we report the expression of major pyrimidine metabolising enzymes in pancreatic cancer cell lines, chronic pancreatitis tissue and human pancreatic cancer and the in vitro uptake of 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT). The expression of pyrimidine metabolising enzymes was evaluated with real-time PCR, Western blot and immunostaining. Thymidine kinase 1 (TK-1) activity was measured with a fluorocytometric assay. The cellular uptake and intracellular metabolism of [18F]FLT were evaluated in pancreatic lobules and in transformed cancer cell lines. TK-1 and thymidine synthetase mRNA were increased in six pancreatic cancer cell lines, while mRNA levels of thymidine kinase 2 and deoxycytidine kinase were down-regulated. High TK-1 activity was confirmed in all cell lines. Furthermore, TK-1 was overexpressed in human pancreatic cancer as compared with normal pancreatic tissue and samples from patients with chronic pancreatitis. The cellular uptake of [18F]FLT was 18.4%±3.6% and 5.2%±1.4% of the applied radioactivity after 240 min in SW-979 and BxPc-3 cells, respectively, while uptake of [18F]fluorodeoxyglucose ([18F]FDG) was only 0.6%±0.04% (SW-979) and 0.3%±0.13% (BxPc-3) after 240 min of incubation. In contrast, cellular uptake of [18F]FLT in isolated pancreatic lobules and growth-arrested HT1080 cells was lower as compared with the uptake of [18F]FDG and with the malignant pancreatic cancer cell lines. HPLC analysis of the perchloric acid-soluble cell fraction demonstrated the phosphorylation of [18F]FLT to the respective monophosphate in both cell lines. Furthermore, 0.8%±0.12% (BxPc-3) and 1.3%±0.38% (SW-979) of the applied radioactivity was detected in the perchloric acid-insoluble cell fraction, indicating the incorporation of [18F]FLT into the DNA. Our results demonstrate the cellular uptake, intracellular trapping and incorporation into the DNA of [18F]FLT in pancreatic cancer cells in vitro. TK-1, as the rate-limiting enzyme of [18F]FLT

  13. 18FDG, [18F]FLT, [18F]FAZA, and 11C-Methionine Are Suitable Tracers for the Diagnosis and In Vivo Follow-Up of the Efficacy of Chemotherapy by miniPET in Both Multidrug Resistant and Sensitive Human Gynecologic Tumor Xenografts

    György Trencsényi

    2014-01-01

    Full Text Available Expression of multidrug pumps including P-glycoprotein (MDR1, ABCB1 in the plasma membrane of tumor cells often results in decreased intracellular accumulation of anticancer drugs causing serious impediment to successful chemotherapy. It has been shown earlier that combined treatment with UIC2 anti-Pgp monoclonal antibody (mAb and cyclosporine A (CSA is an effective way of blocking Pgp function. In the present work we investigated the suitability of four PET tumor diagnostic radiotracers including 2-[18F]fluoro-2-deoxy-D-glucose (18FDG, 11C-methionine, 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT, and [18F]fluoroazomycin-arabinofuranoside (18FAZA for in vivo follow-up of the efficacy of chemotherapy in both Pgp positive (Pgp+ and negative (Pgp− human tumor xenograft pairs raised in CB-17 SCID mice. Pgp+ and Pgp− A2780AD/A2780 human ovarian carcinoma and KB-V1/KB-3-1 human epidermoid adenocarcinoma tumor xenografts were used to study the effect of the treatment with an anticancer drug doxorubicin combined with UIC2 and CSA. The combined treatment resulted in a significant decrease of both the tumor size and the accumulation of the tumor diagnostic tracers in the Pgp+ tumors. Our results demonstrate that 18FDG, 18F-FLT, 18FAZA, and 11C-methionine are suitable PET tracers for the diagnosis and in vivo follow-up of the efficacy of tumor chemotherapy in both Pgp+ and Pgp− human tumor xenografts by miniPET.

  14. A Pilot Study of 18F-FLT PET/CT in Pediatric Lymphoma

    Danny L. Costantini

    2016-01-01

    Full Text Available We performed an observational pilot study of 18F-FLT PET/CT in pediatric lymphoma. Eight patients with equivocal 18F-FDG PET/CT underwent imaging with 18F-FLT PET/CT. No immediate adverse reactions to 18F-FLT were observed. Compared to 18F-FDG, 18F-FLT uptake was significantly higher in bone marrow and liver (18F-FLT SUV 8.6±0.6 and 5.0±0.3, versus 18F-FDG SUV 1.9±0.1 and 3.4±0.7, resp., p<0.05. In total, 15 lesions were evaluated with average 18F-FDG and 18F-FLT SUVs of 2.6±0.1 and 2.0±0.4, respectively. Nonspecific uptake in reactive lymph nodes and thymus was observed. Future studies to assess the clinical utility of 18F-FLT PET/CT in pediatric lymphoma are planned.

  15. Early changes in [{sup 18}F]FLT uptake after chemotherapy: an experimental study

    Dittmann, Helmut; Dohmen, Bernhard Matthias; Bartusek, Gabi; Pritzkow, Maren; Bares, Roland [Department of Nuclear Medicine, Eberhard-Karls-University, Roentgenweg 13, 72076 Tuebingen (Germany); Kehlbach, Rainer [Department of Diagnostic Radiology, Eberhard-Karls-University, Tuebingen (Germany); Sarbia, Mario [Institute of Pathology, Heinrich-Heine-University, Duesseldorf (Germany)

    2002-11-01

    This study evaluated the use of 3'-deoxy-3'-[{sup 18}F]fluorothymidine ([{sup 18}F]FLT) for monitoring of the early effects of anticancer chemotherapy on tumour cell proliferation. Cells derived from human oesophageal squamous cell carcinoma (OSC-1) were grown for 2 days and incubated with cisplatin (CDDP), 5-fluorouracil (5-FU), methotrexate (MTX) or gemcitabine (GEM) for 4 h. Cultures were incubated with drug doses (CDDP: 0.67, 6.7, 67 {mu}M; 5-FU 15.4, 154, 1,540 {mu}M; MTX: 4.4, 44, 440 {mu}M; GEM: 0.0067, 0.067, 0.67 {mu}M) corresponding to approximately 10%-95% proliferation inhibition (MTX: 10%-75%). Treatment was stopped and cells were allowed to recover for 4, 24 or 72 h. [{sup 18}F]FLT was added for 10-180 min. Control cultures were incubated with [{sup 18}F]fluorodeoxyglucose (FDG). Cell counts, viability, clonogenic activity and cell cycle distribution estimated by flow cytometry were used to evaluate the cytotoxic effects of chemotherapy. Strikingly, FLT uptake per 10{sup 5} viable cells was increased seven- to tenfold 24 h after treatment with 5-FU or MTX irrespective of dose. Thus, total FLT uptake per tissue culture exceeded that of controls despite a considerable decrease in overall cell counts due to cytostasis up to 72 h after treatment. 5-FU-treated cells showed accumulation in early S phase (overall S phase: 88% vs 42%). GEM treatment resulted in a more moderate increase in total FLT accumulation, to a maximum of fivefold at the dose close to the IC{sub 50}. In contrast, FLT accumulation was significantly reduced at cytostatic concentrations of CDDP and was still decreasing in a dose-related manner at 72 h despite considerable S phase arrest. With 5-FU or CDDP, the uptake of FDG did not differ significantly from control values 24 h after treatment. These findings demonstrate that tumour cell uptake of FLT - in contrast to that of FDG - reveals specific changes depending on the cytostatic drug used for treatment. The antimetabolites 5

  16. Early assessment of therapy response in malignant lymphoma with the thymidine analogue [18F]FLT

    The aim of this study was to determine whether the thymidine analogue 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) is adequate for early evaluation of the response of malignant lymphoma to antiproliferative treatment in a mouse xenotransplant model. Immunodeficient mice bearing a follicular lymphoma xenotransplant were treated with high-dose chemotherapy (cyclophosphamide, n 10), immunotherapy (CD20 mAb, ibritumomab-tiuxetan, n = 10) or radioimmunotherapy ([90Y]CD20 mAb, Zevalin, n = 10). Forty-eight hours after treatment, antiproliferative effects were assessed with [18F]FLT. Ninety minutes after i.v. injection of 5-10 MBq [18F]FLT, mice were sacrificed and radioactivity within the tumour and normal organs was measured using a gamma counter and calculated as % ID/g. The proliferation fraction in tissue samples derived from treated and untreated tumours was evaluated by Ki-67 immunohistochemistry, which served as the reference for proliferative activity. In untreated lymphoma, the mean proliferation fraction was 83.6%. After chemotherapy, the mean proliferation fraction decreased to 39.3% (p = 0.0001), after immunotherapy to 77.6% (p = 0.0078) and after radioimmunotherapy to 78.8% (p = 0.014). In none of the animals was a significant change in tumour size observed. In untreated lymphoma, tumoural [18F]FLT uptake was 5.4% ID/g, after chemotherapy it was 1.5% (p = 0.0005), after immunotherapy, 3.9% (non-significant), and after radioimmunotherapy, 5.8% (non-significant). In a lymphoma xenotransplant model, [18F]FLT detects early antiproliferative drug activity before changes in tumour size are visible. These findings further support the use of [18F]FLT-PET for imaging early response to treatment in malignant lymphoma. (orig.)

  17. [{sup 18}F]FLT is superior to [{sup 18}F]FDG for predicting early response to antiproliferative treatment in high-grade lymphoma in a dose-dependent manner

    Graf, Nicolas [Technische Universitaet Muenchen, Department of Hematology/Oncology, Munich (Germany); Schoen Klinik Starnberger See, Department of Hematology and Oncology, Berg (Germany); Herrmann, Ken; Numberger, Barbara; Zwisler, Daniela; Wester, Hans-Juergen; Senekowitsch-Schmidtke, Reingard; Schwaiger, Markus [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Aichler, Michaela; Feuchtinger, Annette [Technische Universitaet Muenchen, Institute of Pathology (Helmholtz Zentrum Muenchen), Munich (Germany); Schuster, Tibor [Technische Universitaet Muenchen, Institute of Medical Statistics and Epidemiology, Munich (Germany); Peschel, Christian; Keller, Ulrich; Dechow, Tobias [Technische Universitaet Muenchen, Department of Hematology/Oncology, Munich (Germany); Buck, Andreas K. [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Universitaetsklinikum Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany)

    2013-01-15

    Positron emission tomography (PET) with the thymidine analogue [{sup 18}F]fluorothymidine ([{sup 18}F]FLT) has been shown to detect early response to chemotherapy in high-grade lymphoma. In this preclinical in vitro and in vivo study we compared [{sup 18}F]FLT to the glucose analogue [{sup 18}F]fluorodeoxyglucose ([{sup 18}F]FDG) regarding dose-dependent visualization and prediction of early therapy response. Immunodeficient mice bearing human diffuse large B-cell lymphoma (SUDHL-4) xenotransplants were treated intraperitoneally with increasing doses of the cytotoxic agent doxorubicin. Metabolic and antiproliferative effects were assessed 2 days after therapy by [{sup 18}F]FLT and [{sup 18}F]FDG PET. Explanted lymphomas were analysed histologically and by immunostaining against Ki67 and caspase 3. In vitro, lymphoma cells were incubated with increasing concentrations of doxorubicin and analysed using the tetrazolium assay, fluorescence-activated cell sorting, and [{sup 18}F]FLT and [{sup 18}F]FDG uptake 48 h later. In vivo, tumour growth was inhibited by doses of doxorubicin ranging from 25 {mu}g to 200 {mu}g. The mean tumour-to-background ratio (TBR) of [{sup 18}F]FLT on day +2 was significantly reduced in all dose groups compared to control and baseline values and preceded changes in tumour volume. Importantly, there was a significant inverse correlation between reduction in TBR and dose of chemotherapy (r = -0.54, p = 0.021). The mean TBR of [{sup 18}F]FDG, however, increased after therapy and differed considerably between groups (r = -0.13, p = 0.668). Explanted tumours showed a dose-dependent decrease in the proliferation marker Ki67, but no change in the apoptotic marker caspase 3. In vitro, doxorubicin led to a dose-dependent reduction in cell viability and a decrease in S phase. Lymphoma cells showed a dose-dependent reduction in [{sup 18}F]FLT uptake, in contrast to a variable and decelerated reduction in [{sup 18}F]FDG uptake. Thus, the increase in [{sup

  18. [18F]FLT is superior to [18F]FDG for predicting early response to antiproliferative treatment in high-grade lymphoma in a dose-dependent manner

    Positron emission tomography (PET) with the thymidine analogue [18F]fluorothymidine ([18F]FLT) has been shown to detect early response to chemotherapy in high-grade lymphoma. In this preclinical in vitro and in vivo study we compared [18F]FLT to the glucose analogue [18F]fluorodeoxyglucose ([18F]FDG) regarding dose-dependent visualization and prediction of early therapy response. Immunodeficient mice bearing human diffuse large B-cell lymphoma (SUDHL-4) xenotransplants were treated intraperitoneally with increasing doses of the cytotoxic agent doxorubicin. Metabolic and antiproliferative effects were assessed 2 days after therapy by [18F]FLT and [18F]FDG PET. Explanted lymphomas were analysed histologically and by immunostaining against Ki67 and caspase 3. In vitro, lymphoma cells were incubated with increasing concentrations of doxorubicin and analysed using the tetrazolium assay, fluorescence-activated cell sorting, and [18F]FLT and [18F]FDG uptake 48 h later. In vivo, tumour growth was inhibited by doses of doxorubicin ranging from 25 μg to 200 μg. The mean tumour-to-background ratio (TBR) of [18F]FLT on day +2 was significantly reduced in all dose groups compared to control and baseline values and preceded changes in tumour volume. Importantly, there was a significant inverse correlation between reduction in TBR and dose of chemotherapy (r = -0.54, p = 0.021). The mean TBR of [18F]FDG, however, increased after therapy and differed considerably between groups (r = -0.13, p = 0.668). Explanted tumours showed a dose-dependent decrease in the proliferation marker Ki67, but no change in the apoptotic marker caspase 3. In vitro, doxorubicin led to a dose-dependent reduction in cell viability and a decrease in S phase. Lymphoma cells showed a dose-dependent reduction in [18F]FLT uptake, in contrast to a variable and decelerated reduction in [18F]FDG uptake. Thus, the increase in [18F]FDG uptake in vivo presumably reflected nonspecific glucose metabolism of

  19. Early assessment of therapy response in malignant lymphoma with the thymidine analogue [{sup 18}F]FLT

    Buck, Andreas K. [University Hospital Ulm, Department of Nuclear Medicine, Ulm (Germany); Technical University Munich, Department of Nuclear Medicine, Munich (Germany); Kratochwil, Clemens; Glatting, Gerhard; Tepsic, Djurdja; Vogg, Andreas T.J.; Neumaier, Bernd; Reske, Sven N. [University Hospital Ulm, Department of Nuclear Medicine, Ulm (Germany); Juweid, Malik [University of Iowa, Department of Radiology and Holden Comprehensive Cancer Center, Iowa City, IA (United States); Bommer, Martin [University Hospital Ulm, Department of Haematology, Ulm (Germany); Mattfeldt, Torsten; Moeller, Peter [University Hospital Ulm, Institute of Pathology, Ulm (Germany)

    2007-11-15

    The aim of this study was to determine whether the thymidine analogue 3'-deoxy-3'-[{sup 18}F]fluorothymidine ([{sup 18}F]FLT) is adequate for early evaluation of the response of malignant lymphoma to antiproliferative treatment in a mouse xenotransplant model. Immunodeficient mice bearing a follicular lymphoma xenotransplant were treated with high-dose chemotherapy (cyclophosphamide, n = 10), immunotherapy (CD20 mAb, ibritumomab-tiuxetan, n = 10) or radioimmunotherapy ([{sup 90}Y]CD20 mAb, Zevalin, n = 10). Forty-eight hours after treatment, antiproliferative effects were assessed with [{sup 18}F]FLT. Ninety minutes after i.v. injection of 5-10 MBq [{sup 18}F]FLT, mice were sacrificed and radioactivity within the tumour and normal organs was measured using a gamma counter and calculated as % ID/g. The proliferation fraction in tissue samples derived from treated and untreated tumours was evaluated by Ki-67 immunohistochemistry, which served as the reference for proliferative activity. In untreated lymphoma, the mean proliferation fraction was 83.6%. After chemotherapy, the mean proliferation fraction decreased to 39.3% (p = 0.0001), after immunotherapy to 77.6% (p = 0.0078) and after radioimmunotherapy to 78.8% (p = 0.014). In none of the animals was a significant change in tumour size observed. In untreated lymphoma, tumoural [{sup 18}F]FLT uptake was 5.4% ID/g, after chemotherapy it was 1.5% (p = 0.0005), after immunotherapy, 3.9% (non-significant), and after radioimmunotherapy, 5.8% (non-significant). In a lymphoma xenotransplant model, [{sup 18}F]FLT detects early antiproliferative drug activity before changes in tumour size are visible. These findings further support the use of [{sup 18}F]FLT-PET for imaging early response to treatment in malignant lymphoma. (orig.)

  20. Comparative study of 18F-FLT PET and 18F-FDG PET of lung cancer

    Xi LIU

    2011-12-01

    Full Text Available Objective The current paper aims to investigate the value of 18F-FLT PET in the diagnosis of lung cancer and the monitoring of tumor proliferation.Methods A total of 36 patients received and cured by the General Hospital of Chinese PLA from September 2005 to October 2008(27 males and 9 females,aged 38 years to 74 years with chest CT suspected lung cancer were examined with 18F-FLT PET.Up to 42 patients(29 males and 13 females,aged 37 years to 75 years received and cured at the same time also underwent 18F-FDG PET.The current experimental results were compared with that of the tumor pathology.Immunohistochemistry was used to measure the expression of cell nuclear antigen of excisional disease tissues Ki-67.Results The 18F-FDG PET standardize uptake value(SUV of lung cancer(SUV,5.2±2.9 was higher than that of the 18F-FLT PET SUV(3.2±1.3(P < 0.05.The sensitivity of 18F-FLT PET for the detection of primary lung cancer was 77%,the specificity was 86%,and the accuracy was 78%.The sensitivity,specificity,and accuracy of 18F-FDG PET were 88%,50%,and 79%,respectively.The sensitivity,specificity,and accuracy for the lymph node staging with 18F-FLT PET were 47%,88% and 75%,respectively,compared with the 68%,84%,and 79% for 18F-FDG PET,respectively.18F-FLT SUV of lung cancer was positively correlated with the Ki-67 index(r=0.8278,P < 0.001 than that of 18F-FDG SUV(r=0.0079,P=0.968.Conclusions 18F-FLT can be made to uptake by specificity of lung cancer tissue,and its uptake value is correlated significantly with the proliferation of lung cancer.Therefore,18F-FLT PET can be applied to assist the diagnosis of lung tumor,and is expected to be a tool to determine the proliferation activity of tumor cells.

  1. Evaluation of 18F-FDG and 18F-FLT for monitoring therapeutic responses of colorectal cancer cells to radiotherapy

    In order to compare the efficacy of 18F-fluorothymidine (FLT) and 18F-fluorodeoxyglucose (FDG) for monitoring early responses to irradiation, two human colorectal cancer (CRC) cell lines SW480 and SW620, which were derived from the primary lesions and the metastatic lymph node, underwent X-ray irradiation of 0, 10, or 20 Gy and were examined at 0, 24 and 72 h After irradiation, reduced proliferation of both SW480 and SW620 cells was observed in a dose-dependent manner (P < 0.001), G0-G1 arrest was also noted in both cell types after 72 h in the 20 Gy group (P < 0.001). Although increased apoptosis was observed in both cell lines after irradiation (P < 0.001), a greater percentage of SW480 cells underwent apoptosis in response to irradiation than SW620 cells. Increased Hsp27 and decreased integrin β3, Ki67 and VEGFR2 expression was observed over time via immunocytochemistry and Western blot analysis (P < 0.001), however, no significant changes were noted in response to irradiation. Finally, reduced uptake of 18F-FLT by SW480 or SW620 cells was observed at 24-h post-irradiation, however, reduced 18F-FDG uptake was only observed after 72 h. Therefore, we conclude that 18F-FLT is a more suitable positron emission tomography (PET) tracer for monitoring early responses to irradiation in primary and metastatic lymph node CRC cells

  2. Monitoring of anti-cancer treatment with (18)F-FDG and (18)F-FLT PET

    Jensen, Mette Munk; Kjaer, Andreas

    2015-01-01

    treatment effect early in a treatment course and by that to stratify patients into responders and non-responders. With 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine((18)F-FLT) two of the cancer hallmarks, altered energy metabolism and increased cell proliferation, can...... be visualized and quantified non-invasively by PET. With (18)F-FDG and (18)F-FLT PET changes in energy metabolism and cell proliferation can thereby be determined after initiation of cancer treatment in both clinical and pre-clinical studies in order to predict, at an early time-point, treatment...... response. It is hypothesized that decreases in glycolysis and cell proliferation may occur in tumors that are sensitive to theapplied cancer therapeutics and that tumors that are resistant to treatment will show unchanged glucose metabolism and cell proliferation. Whether (18)F-FDG and/or (18)F-FLT PET can...

  3. Study of the production of the radiopharmaceutical 18F-FLT in automated system: contribution for process validation

    Radiopharmaceutical 18F-FLT is a thymidine nucleoside analogue and a promising tumor proliferation marker for PET images. The synthesis of this radiopharmaceutical is not simple, and often has low yields. This radiopharmaceutical has already been studied for some years; however, there is no production, nor are there clinical studies in Brazil. The study of the production process and its compliance with the guidelines of Good Manufacturing Practices (ANVISA) are of extreme importance. This study aimed to investigate the synthesis of this radiopharmaceutical, evaluate methods of quality control that will be used in future production routines, perform cytotoxicity studies, biodistribution studies and PET imaging in animals, thereby contributing to the development and elaboration of the process validation protocol and to the establishment of analytical methods to be used during production routines. Initially, we studied the synthesis and production of 18F-FLT, with the evaluation of three different temperatures of radiolabeling to check the behavior of the radiochemical yield and stability of the nal product. Studies of analytical methodology comprised the analysis of radionuclide identification, determination of chromatographic profiles, radiochemical purity, residual solvents, and pH. In vitro studies of internalization and cytotoxicity were also carried out. In in vivo studies, we evaluated the pharmacokinetics, biodistribution in healthy animals and in animals with tumor models, in addition to PET/CT images in animals with melanomas. The final product had high radiochemical purity and was stable for up to 10 hours after the synthesis, but got a relatively low radiochemical yield, as described in the literature. The tested analytical methods proved suitable for use in the quality control of 18F-FLT. In in vitro studies, 18F-FLT showed a significant percentage of binding to tumor cells, and the nonradiolabeled molecule was not considered toxic for these studied cells

  4. Evaluation of the radiochemical impurities arising during the competitive fluorination of nosyl group during the synthesis of 3'-deoxy-3'-fluorothymidine, [18F]FLT

    The study is aimed at the analysis and identification of radiochemical and chemical impurities present in [18F]FLT synthesized by a simplified combination-column purification procedure, instead of the currently used HPLC purification. HPLC analysis of the final product showed an anionic radioactive byproduct, which was established as [18F]4-FBSA. The identity of the product was also confirmed by the radiofluorination of nosyl chloride. Mass spectrum analysis of both a decayed sample of [18F]FLT and fluorinated nosyl chloride showed a major peak at 242. We have also investigated the possible interference of this byproduct during PET-imaging in rabbits. (author)

  5. SU-E-J-250: A Methodology for Active Bone Marrow Protection for Cervical Cancer Intensity-Modulated Radiotherapy Using 18F-FLT PET/CT Image

    Purpose: The purpose of this study was to compare a radiation therapy treatment planning that would spare active bone marrow and whole pelvic bone marrow using 18F FLT PET/CT image. Methods: We have developed an IMRT planning methodology to incorporate functional PET imaging using 18F FLT/CT scans. Plans were generated for two cervical cancer patients, where pelvicactive bone marrow region was incorporated as avoidance regions based on the range: SUV>2., another region was whole pelvic bone marrow. Dose objectives were set to reduce the volume of active bone marrow and whole bone marraw. The volumes of received 10 (V10) and 20 (V20) Gy for active bone marrow were evaluated. Results: Active bone marrow regions identified by 18F FLT with an SUV>2 represented an average of 48.0% of the total osseous pelvis for the two cases studied. Improved dose volume histograms for identified bone marrow SUV volumes and decreases in V10(average 18%), and V20(average 14%) were achieved without clinically significant changes to PTV or OAR doses. Conclusion: Incorporation of 18F FLT/CT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in cervical cancer

  6. [{sup 18}F]FLT PET for diagnosis and staging of thoracic tumours

    Dittmann, Helmut; Dohmen, Bernhard Matthias; Eichhorn, Kai; Eschmann, Susanne Martina; Machulla, Hans Juergen; Bares, Roland [Department of Nuclear Medicine, Eberhard-Karls-University Tuebingen, Otfried-Mueller-Strasse 14, 72076, Tuebingen (Germany); Paulsen, Frank [Department of Radiotherapy, Eberhard-Karls-University Tuebingen (Germany); Horger, Marius [Department of Diagnostic Radiology, Eberhard-Karls-University Tuebingen (Germany); Wehrmann, Manfred [Department of Pathology, Eberhard-Karls-University Tuebingen (Germany)

    2003-10-01

    The nucleoside analogue 3'-deoxy-3'-[{sup 18}F]fluorothymidine (FLT) has been introduced for imaging of tumour cell proliferation by positron emission tomography (PET). This study evaluated the use of FLT in patients with thoracic tumours prior to treatment. Whole-body FLT PET was performed in 16 patients with 18 tumours [17 thoracic tumours (nine non-small cell lung cancers, five oesophageal carcinomas, two sarcomas, one Hodgkin's lymphoma) and one renal carcinoma] before treatment. Fluorine-18 fluorodeoxyglucose (FDG) PET was performed for comparison except in those patients with oesophageal carcinoma. For semi-quantitative analysis, the average and maximum standardised uptake values (avgSUV and maxSUV, respectively) (FLT, 114{+-}20 min p.i.; FDG, 87{+-}8 min p.i.; 50% isocontour region of interest) was calculated. All 17 thoracic tumours and 19/20 metastases revealed significant FLT accumulation, resulting in easy delineation from surrounding tissue. The additional small grade 1 renal carcinoma was not detected with either FLT or FDG. In most lung tumours (avgSUV 1.5-8.2) and metastases, FLT showed intense uptake. However, one of two spinal bone metastases was missed owing to the high physiological FLT uptake in the surrounding bone marrow. Oesophageal carcinoma primaries (avgSUV 2.7-10.0) and occasional metastases showed particularly favourable tumour/non-tumour contrast. Compared with FDG, tumour uptake of FLT was lower (avgSUV, P=0.0006; maxSUV, P=0.0001), with a significant linear correlation (avgSUV, r{sup 2}=0.45; maxSUV, r{sup 2}=0.49) between FLT and FDG. It is concluded that FLT PET accurately visualises thoracic tumour lesions. In the liver and the bone marrow, high physiological FLT uptake hampers detection of metastases. On the other hand, FLT may be favourable for imaging of brain metastases owing to the low physiological uptake. (orig.)

  7. 18F-FLT uptake kinetics in head and neck squamous cell carcinoma: A PET imaging study

    Purpose: To analyze the kinetics of 3′-deoxy-3′-[F-18]-fluorothymidine (18F-FLT) uptake by head and neck squamous cell carcinomas and involved nodes imaged using positron emission tomography (PET). Methods: Two- and three-tissue compartment models were fitted to 12 tumor time-activity-curves (TACs) obtained for 6 structures (tumors or involved nodes) imaged in ten dynamic PET studies of 1 h duration, carried out for five patients. The ability of the models to describe the data was assessed using a runs test, the Akaike information criterion (AIC) and leave-one-out cross-validation. To generate parametric maps the models were also fitted to TACs of individual voxels. Correlations between maps of different parameters were characterized using Pearson'sr coefficient; in particular the phosphorylation rate-constants k3-2tiss and k5 of the two- and three-tissue models were studied alongside the flux parameters KFLT-2tiss and KFLT of these models, and standardized uptake values (SUV). A methodology based on expectation-maximization clustering and the Bayesian information criterion (“EM-BIC clustering”) was used to distil the information from noisy parametric images. Results: Fits of two-tissue models 2C3K and 2C4K and three-tissue models 3C5K and 3C6K comprising three, four, five, and six rate-constants, respectively, pass the runs test for 4, 8, 10, and 11 of 12 tumor TACs. The three-tissue models have lower AIC and cross-validation scores for nine of the 12 tumors. Overall the 3C6K model has the lowest AIC and cross-validation scores and its fitted parameter values are of the same orders of magnitude as literature estimates. Maps ofKFLT and KFLT-2tiss are strongly correlated (r = 0.85) and also correlate closely with SUV maps (r = 0.72 for KFLT-2tiss, 0.64 for KFLT). Phosphorylation rate-constant maps are moderately correlated with flux maps (r = 0.48 for k3-2tiss vs KFLT-2tiss and r = 0.68 for k5 vs KFLT); however, neither phosphorylation rate

  8. Multimodal imaging based on MRI and PET reveals [{sup 18}F]FLT PET as a specific and early indicator of treatment efficacy in a preclinical model of recurrent glioblastoma

    Corroyer-Dulmont, Aurelien; Peres, Elodie A.; Gerault, Aurelie N.; Divoux, Didier; Toutain, Jerome; Ibazizene, Meziane; MacKenzie, Eric T.; Barre, Louisa; Bernaudin, Myriam; Petit, Edwige; Valable, Samuel [CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Caen (France); CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy et LDM-TEP Groups, GIP CYCERON, Caen (France); UNICAEN, UMR 6301 ISTCT, CERVOxy et LDM-TEP Groups, GIP CYCERON, Caen (France); Normandie Univ., Caen(France); Savina, Ariel; Bouquet, Fanny [Roche SAS, Boulogne-Billancourt (France)

    2016-04-15

    The primary objective of this study was to compare the ability of PET and MRI biomarkers to predict treatment efficacy in a preclinical model of recurrent glioblastoma multiforme. MRI (anatomical, diffusion, vasculature and oxygenation) and PET ([{sup 18}F]FDG and [{sup 18}F]FLT) parameters were obtained 3 days after the end of treatment and compared with late tumour growth and survival. Early after tumour recurrence, no effect of treatment with temozolomide combined with bevacizumab was observed on tumour volume as assessed by T2-W MRI. At later times, the treatment decreased tumour volume and increased survival. Interestingly, at the earlier time, temozolomide + bevacizumab decreased [{sup 18}F]FLT uptake, cerebral blood volume and oedema. [{sup 18}F]FLT uptake, oedema and cerebral blood volume were correlated with overall survival but [{sup 18}F]FLT uptake had the highest specificity and sensitivity for the early prediction of treatment efficacy. The present investigation in a preclinical model of glioblastoma recurrence underscores the importance of multimodal imaging in the assessment of oedema, tumour vascular status and cell proliferation. Finally, [{sup 18}F]FLT holds the greatest promise for the early assessment of treatment efficacy. These findings may translate clinically in that individualized treatment for recurrent glioma could be prescribed for patients selected after PET/MRI examinations. (orig.)

  9. Multimodal imaging based on MRI and PET reveals [18F]FLT PET as a specific and early indicator of treatment efficacy in a preclinical model of recurrent glioblastoma

    The primary objective of this study was to compare the ability of PET and MRI biomarkers to predict treatment efficacy in a preclinical model of recurrent glioblastoma multiforme. MRI (anatomical, diffusion, vasculature and oxygenation) and PET ([18F]FDG and [18F]FLT) parameters were obtained 3 days after the end of treatment and compared with late tumour growth and survival. Early after tumour recurrence, no effect of treatment with temozolomide combined with bevacizumab was observed on tumour volume as assessed by T2-W MRI. At later times, the treatment decreased tumour volume and increased survival. Interestingly, at the earlier time, temozolomide + bevacizumab decreased [18F]FLT uptake, cerebral blood volume and oedema. [18F]FLT uptake, oedema and cerebral blood volume were correlated with overall survival but [18F]FLT uptake had the highest specificity and sensitivity for the early prediction of treatment efficacy. The present investigation in a preclinical model of glioblastoma recurrence underscores the importance of multimodal imaging in the assessment of oedema, tumour vascular status and cell proliferation. Finally, [18F]FLT holds the greatest promise for the early assessment of treatment efficacy. These findings may translate clinically in that individualized treatment for recurrent glioma could be prescribed for patients selected after PET/MRI examinations. (orig.)

  10. {sup 18}F-FLT uptake kinetics in head and neck squamous cell carcinoma: A PET imaging study

    Liu, Dan, E-mail: dan.liu@oncology.ox.ac.uk; Fenwick, John D. [Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom); Chalkidou, Anastasia; Landau, David B.; Marsden, Paul K. [Division of Imaging Sciences and Biomedical Engineering, School of Medicine, King' s College London, St Thomas' Hospital, Westminster Bridge Road, London SE1 7EH (United Kingdom)

    2014-04-15

    Purpose: To analyze the kinetics of 3{sup ′}-deoxy-3{sup ′}-[F-18]-fluorothymidine (18F-FLT) uptake by head and neck squamous cell carcinomas and involved nodes imaged using positron emission tomography (PET). Methods: Two- and three-tissue compartment models were fitted to 12 tumor time-activity-curves (TACs) obtained for 6 structures (tumors or involved nodes) imaged in ten dynamic PET studies of 1 h duration, carried out for five patients. The ability of the models to describe the data was assessed using a runs test, the Akaike information criterion (AIC) and leave-one-out cross-validation. To generate parametric maps the models were also fitted to TACs of individual voxels. Correlations between maps of different parameters were characterized using Pearson'sr coefficient; in particular the phosphorylation rate-constants k{sub 3-2tiss} and k{sub 5} of the two- and three-tissue models were studied alongside the flux parameters K{sub FLT-2tiss} and K{sub FLT} of these models, and standardized uptake values (SUV). A methodology based on expectation-maximization clustering and the Bayesian information criterion (“EM-BIC clustering”) was used to distil the information from noisy parametric images. Results: Fits of two-tissue models 2C3K and 2C4K and three-tissue models 3C5K and 3C6K comprising three, four, five, and six rate-constants, respectively, pass the runs test for 4, 8, 10, and 11 of 12 tumor TACs. The three-tissue models have lower AIC and cross-validation scores for nine of the 12 tumors. Overall the 3C6K model has the lowest AIC and cross-validation scores and its fitted parameter values are of the same orders of magnitude as literature estimates. Maps ofK{sub FLT} and K{sub FLT-2tiss} are strongly correlated (r = 0.85) and also correlate closely with SUV maps (r = 0.72 for K{sub FLT-2tiss}, 0.64 for K{sub FLT}). Phosphorylation rate-constant maps are moderately correlated with flux maps (r = 0.48 for k{sub 3-2tiss} vs K{sub FLT-2tiss} and r

  11. Use of Molecular Imaging Markers of Glycolysis, Hypoxia and Proliferation (18F-FDG, 64Cu-ATSM and 18F-FLT in a Dog with Fibrosarcoma: The Importance of Individualized Treatment Planning and Monitoring

    Kamilla Westarp Zornhagen

    2015-09-01

    Full Text Available Glycolysis, hypoxia, and proliferation are important factors in the tumor microenvironment contributing to treatment-resistant aggressiveness. Imaging these factors using combined functional positron emission tomography and computed tomography can potentially guide diagnosis and management of cancer patients. A dog with fibrosarcoma was imaged using 18F-FDG, 64Cu-ATSM, and 18F-FLT before, during, and after 10 fractions of 4.5 Gy radiotherapy. Uptake of all tracers decreased during treatment. Fluctuations in 18F-FDG and 18F-FLT PET uptakes and a heterogeneous spatial distribution of the three tracers were seen. Tracer distributions partially overlapped. It appears that each tracer provides distinct information about tumor heterogeneity and treatment response.

  12. Imaging proliferation of 18F-FLT PET/CT correlated with the expression of microvessel density of tumour tissue in non-small-cell lung cancer

    The aim of this study was to analyse the correlation between 18F-labelled 3'-deoxy-3'-fluorothymidine (18F-FLT) PET/CT proliferation images and tumour angiogenesis as reflected by intratumoral microvessel density (MVD) in non-small-cell lung cancer (NSCLC) to provide a noninvasive method to predict the response to antiangiogenic therapy. A total of 68 patients with proven or suspected NSCLC underwent FLT PET/CT scans followed by surgery. PET/CT images were compared with pathology. Tumour proliferation was evaluated in terms of a Ki-67 labelling index (Ki-67 LI). MVD was determined using an anti-CD31 mAb (CD31-MVD), anti-CD34 mAb (CD34-MVD) and an anti-CD105 mAb (CD105-MVD) for each resected tumour. Tumour FLT maximum standardized uptake values (SUVmax) were significantly correlated with the Ki-67 LI and CD105-MVD (r = 0.550 and 0.633, P = 0.000 and 0.000, respectively), but were only marginally correlated with the CD31-MVD and CD34-MVD (r = 0.228 and 0.235, P = 0.062 and 0.054, respectively). The FLT PET false-negative patients had a longer median survival time than the FLT PET true-positive patients (log rank test, P = 0.012). The patients with a lower CD105-MVD had a longer median survival time than those with a higher CD105-MVD (P = 0.046), while patients with a lower CD31-MVD and CD34-MVD did not have a longer median survival time than those with a higher value (P = 0.438 and 0.187, respectively). FLT PET/CT imaging correlated with tumour angiogenesis as reflected by CD105-MVD and prognosis, and may be helpful in assessing antiangiogenic therapy of NSCLC. (orig.)

  13. The value of delayed PET/CT imaging using 18F-FDG and18 F-FLT in pulmonary nodules%18F-FDG与18F-FLT PET/CT延迟显像对肺结节诊断效能的评价

    杨小丰; 王爽; 吴文凯; 田嘉禾; 于丽娟; 陈萍; 辛军; 马黎明; 冯惠茹; 赵周社; 李宏利

    2008-01-01

    目的 通过对多中心、前瞻性研究中接受了18F-脱氧葡萄糖(FDG)与18F-脱氧胸腺嘧啶核苷(FLT)延迟显像病例的分析,探讨18F-FDG与18F-FLT延迟显像对肺结节诊断的效能.方法 6个PET/CT中心,从2006年1月至2007年6月,按照统一标准,采用同机型、同一扫描条件,开展了肺结节样病变18F-FLT和18F-FDG PET/CT显像的多中心临床研究.在经确诊的55例病例中,25例患者进行了18F-FLT显像和延迟显像,34例患者进行了18F-FDG延迟显像.按常规计算延迟显像时病灶最大标准摄取值(SUVmax)及与早期显像时SUVmax相比的变化率(△SUVmax).对照临床确诊结果分析其诊断效能.采用SPSS11.0软件进行统计学处理.结果 18F-FDG延迟显像患者中,6例肺癌中5例、12例结核中9例、16例炎症或其他良性结节中9例的SUVmax较早期相升高.18F-FLT延迟显像组中,7例肺癌中3例、8例结核中3例和10例其他良性病灶中2例的SUVmax上升.经分组统计分析,不同疾病组间18F-FDG延迟显像SUVmax和△SUVmax差异无统计学意义;18F-FLT延迟显像SUVmax和△SUVmax组间差异也无统计学意义.无论18F-FDG还是18F-FLT,延迟显像的诊断效能均不如早期相.无论早期还是延迟显像,单独18F-FDG或18F-FLT显像的诊断效能均不如二者联合应用.结论 18F-FDG和18F-FLT延迟显像的SUVmax变化规律性不强,不宜单独应用于肺结节的鉴别诊断.%Objective Based on a multicentre clinical trial, the value of dual-phase PET/CT imaging in differential diagnosis of pulmonary pathologies using "F-fluorodeoxyglucose (FDG) and 18F-fluorothymidine (FLT) was investigated. Methods The multicentre clinical trial about 18F-FLT and 18F-FDG PET/CT imaging in lung nodules was carried out in six medical centers from January 2006 to June 2007 following the standardized protocols. Among 55 subjects successfully passed the data verification, 25 had delayed 18F-FLT PET/CT scanning and 34 18F-FDG at 120min post

  14. Study of the production of the radiopharmaceutical {sup 18}F-FLT in automated system: contribution for process validation; Estudo da producao do radiofarmaco FLT-{sup 18}F em sistema automatizado: contribuicao para a validacao do processo

    Zanette, Camila

    2013-07-01

    Radiopharmaceutical {sup 18}F-FLT is a thymidine nucleoside analogue and a promising tumor proliferation marker for PET images. The synthesis of this radiopharmaceutical is not simple, and often has low yields. This radiopharmaceutical has already been studied for some years; however, there is no production, nor are there clinical studies in Brazil. The study of the production process and its compliance with the guidelines of Good Manufacturing Practices (ANVISA) are of extreme importance. This study aimed to investigate the synthesis of this radiopharmaceutical, evaluate methods of quality control that will be used in future production routines, perform cytotoxicity studies, biodistribution studies and PET imaging in animals, thereby contributing to the development and elaboration of the process validation protocol and to the establishment of analytical methods to be used during production routines. Initially, we studied the synthesis and production of {sup 18}F-FLT, with the evaluation of three different temperatures of radiolabeling to check the behavior of the radiochemical yield and stability of the nal product. Studies of analytical methodology comprised the analysis of radionuclide identification, determination of chromatographic profiles, radiochemical purity, residual solvents, and pH. In vitro studies of internalization and cytotoxicity were also carried out. In in vivo studies, we evaluated the pharmacokinetics, biodistribution in healthy animals and in animals with tumor models, in addition to PET/CT images in animals with melanomas. The final product had high radiochemical purity and was stable for up to 10 hours after the synthesis, but got a relatively low radiochemical yield, as described in the literature. The tested analytical methods proved suitable for use in the quality control of {sup 18}F-FLT. In in vitro studies, {sup 18}F-FLT showed a significant percentage of binding to tumor cells, and the nonradiolabeled molecule was not considered toxic

  15. Study of [18F]FLT and [123I]IaraU for cellular imaging in HSV1 tk-transfected murine fibrosarcoma cells: evaluation of the tracer uptake using 5-fluoro, 5-iodo and 5-iodovinyl arabinosyl uridines as competitive probes

    As one of the most intensively studied probes for imaging of the cellular proliferation, [18F]FLT was investigated whether the targeting specificity of thymidine kinase 1 (TK1) dependency could be enhanced through a synergistic effect mediated by herpes simplex type 1 virus (HSV1) tk gene in terms of the TK1 or TK2 expression. 5-[123I]Iodo arabinosyl uridine ([123I]IaraU) was prepared in a radiochemical yield of 8% and specific activity of 21 GBq/μmol, respectively. Inhibition of the cellular uptake of these two tracers was compared by using the arabinosyl uridine analogs such as 5-iodo, 5-fluoro and 5-(E)-iodovinyl arabinosyl uridine along with 2′-fluoro-5-iodo arabinosyl uridine (FIAU). Due to potential instability of the iodo group, accumulation index of 1.6 for [123I]IaraU by HSV1-TK vs. control cells could virtually be achieved at 1.5 h, but dropped to 0.2 compared to 2.0 for [18F]FLT at 5 h. The results from competitive inhibition by these nucleosides against the accumulation of [18F]FLT implied that FLT exerted a mixed TK1- and TK2-dependent inhibition with HSV1-tk gene transfection because of the shifting of thymidine kinase status. Taken together, the combination of [18F]FLT and HSV1-TK provides a synergistic imaging potency.

  16. The diagnostic accuracy of 18F-FLT, 18F-FDG for pulmonary neopalsms%18F-FLT与18F-FDG PET/CT不同判断方法鉴别肺良恶性肿瘤诊断效能的比较

    陈萍; 王爽; 吴文凯; 田嘉禾; 杨小丰; 于丽娟; 辛军; 马黎明; 冯惠茹; 赵周社; 李宏利

    2008-01-01

    Objective The purpose of this study was to compare the diagnostic accuracy of 18F-fluorothymidine (FLT), 18F-fluorodeoxyglucose (FDG) for pulmonary nodules. Methods This paired, open, prospective, randomized and semi-blind multicentre clinical trial was executed from January 2006 to June 2007. All the patients enrolled in this trial were imaged twice by 18F-FDG and 18F-FLT within 1 week. Histopathology and clinic results served as the reference standard. Statistically significant differences in pulmonary neoplasm diagnosis between 18F-FDG and 18F-FLT were determined with 95% interval obtained by using receiver operating characteristic (ROC) curve analysis. Results Fifty-five patients were enrolled. Sixteen patients with histopathology proved lung cancers, and others' final diagnosis included 16 tuberculoses, 23 other benign lesions (inflammation, pseudotumor, granuloma, firbrosis and others). The area under curve (AUC) of 18F-FDG maximum standardized uptake value (SUVmax) was 0.780±0.065, and the AUC of 18F-FLT SUVmax was 0.828±0.058. The diagnostic sensitivity, specificity, accuracy of, 18F-FDG (SUVmax≥6.0) and 18SF-FLT (SUVmax≥2.4) and combination them by eye-ball for pulmonary neoplasm were 75.0%(12/16),64.1%(25/39) and 67.3%(37/55);81.3%(13/16),82.1%(32/39) and 81.8%(45/55);81.3%(13/16),87.2%(34/39) and 85.5%(47/55), respectively. Conclusions The diagnostic accuracy for malignant pulmonary neoplasm between 18F-FLT and 18F-FDG was no difference. And it could improve significantly pulmonary neoplasm diagnosis value if we combine 18F-FLT and 18F-FDG imaging.%目的 通过分析多中心临床研究病例,比较18F-脱氧胸腺嘧啶核苷(FIT)、18F-脱氧葡萄糖(FDG)PET/CT显像诊断肺恶性肿瘤的效能.方法 通过随机、盲法、前瞻性的多中心研究,获得以病理检查或临床随访结果确定诊断的55例肺结节患者,均同时行18F-FDG和18F-FLT PET/CT检查.应用受试者工作特征(ROC)曲线分析方法,分别计算病灶

  17. Human brain imaging

    Just as there have been dramatic advances in the molecular biology of the human brain in recent years, there also have been remarkable advances in brain imaging. This paper reports on the development and broad application of microscopic imaging techniques which include the autoradiographic localization of receptors and the measurement of glucose utilization by autoradiography. These approaches provide great sensitivity and excellent anatomical resolution in exploring brain organization and function. The first noninvasive external imaging of receptor distributions in the living human brain was achieved by positron emission tomography (PET) scanning. Developments, techniques and applications continue to progress. Magnetic resonance imaging (MRI) is also becoming important. Its initial clinical applications were in examining the structure and anatomy of the brain. However, more recent uses, such as MRI spectroscopy, indicate the feasibility of exploring biochemical pathways in the brain, the metabolism of drugs in the brain, and also of examining some of these procedures at an anatomical resolution which is substantially greater than that obtainable by PET scanning. The issues will be discussed in greater detail

  18. 18F-Fluorothymidine-Pet Imaging of Glioblastoma Multiforme: Effects of Radiation Therapy on Radiotracer Uptake and Molecular Biomarker Patterns

    Sanjay Chandrasekaran

    2013-01-01

    Full Text Available Introduction. PET imaging is a useful clinical tool for studying tumor progression and treatment effects. Conventional 18F-FDG-PET imaging is of limited usefulness for imaging Glioblastoma Multiforme (GBM due to high levels of glucose uptake by normal brain and the resultant signal-to-noise intensity. 18F-Fluorothymidine (FLT in contrast has shown promise for imaging GBM, as thymidine is taken up preferentially by proliferating cells. These studies were undertaken to investigate the effectiveness of 18F-FLT-PET in a GBM mouse model, especially after radiation therapy (RT, and its correlation with useful biomarkers, including proliferation and DNA damage. Methods. Nude/athymic mice with human GBM orthografts were assessed by microPET imaging with 18F-FDG and 18F-FLT. Patterns of tumor PET imaging were then compared to immunohistochemistry and immunofluorescence for markers of proliferation (Ki-67, DNA damage and repair (γH2AX, hypoxia (HIF-1α, and angiogenesis (VEGF. Results. We confirmed that 18F-FLT-PET uptake is limited in healthy mice but enhanced in the intracranial tumors. Our data further demonstrate that 18F-FLT-PET imaging usefully reflects the inhibition of tumor by RT and correlates with changes in biomarker expression. Conclusions. 18F-FLT-PET imaging is a promising tumor imaging modality for GBM, including assessing RT effects and biologically relevant biomarkers.

  19. Analysis of the growth dynamics of angiogenesis dependent and independent experimental glioblastomas by multimodal small animal PET and MRI

    The hypothesis of this study was that distinct experimental glioblastoma phenotypes resembling human disease can be noninvasively distinguished at various disease stages by imaging in vivo. Cultured spheroids from 2 human glioblastomas were implanted into the brains of nude rats. Glioblastoma growth dynamics were followed by PET using 18F-FDG, 11C-methyl-L-methionine (11C-MET), and 39-deoxy- 39-18F-fluoro-thymidine (18F-FLT) and by MRI at 3-6 wk after implantation. For image validation, parameters were co-registered with immunohistochemical analysis. Two tumor phenotypes (angiogenic and infiltrative) were obtained. The angiogenic phenotype showed high uptake of 11C-MET and 18F-FLT and relatively low uptake of 18F-FDG. 11C-MET was an early indicator of vessel remodeling and tumor proliferation. 18F-FLT uptake correlated to positive Ki67 staining at 6 wk. T1- and T2-weighted MR images displayed clear tumor delineation with strong gadolinium enhancement at 6 wk. The infiltrative phenotype did not accumulate 11C-MET and 18F-FLT and impaired the 18F-FDG uptake. In contrast, the Ki67 index showed a high proliferation rate. The extent of the infiltrative tumors could be observed by MRI but with low contrast. For angiogenic glioblastomas, noninvasive assessment of tumor activity corresponds well to immunohistochemical markers, and 11C-MET was more sensitive than 18F-FLT at detecting early tumor development. In contrast, infiltrative glioblastoma growth in the absence of blood-brain barrier breakdown is difficult to noninvasively follow by existing imaging techniques, and a negative 18F-FLT PET result does not exclude the presence of proliferating glioma tissue. The angiogenic model may serve as an advanced system to study imaging-guided anti-angiogenic and antiproliferative therapies. (authors)

  20. Genes and human brain evolution

    Geschwind, Daniel H.; Konopka, Genevieve

    2012-01-01

    Several genes were duplicated during human evolution. It seems that one such duplication gave rise to a gene that may have helped to make human brains bigger and more adaptable than those of our ancestors.

  1. Educating the Human Brain. Human Brain Development Series

    Posner, Michael I.; Rothbart, Mary K.

    2006-01-01

    "Educating the Human Brain" is the product of a quarter century of research. This book provides an empirical account of the early development of attention and self regulation in infants and young children. It examines the brain areas involved in regulatory networks, their connectivity, and how their development is influenced by genes and…

  2. Human Brain and Its Size

    邹国如

    2006-01-01

    @@ Two studies suggest that the human brain continues to change through the process of evolution.The findings conflict with a common belief that the brain has evolved about as much as it ever will.Scientists say modern humans developed about two hundred thousand years ago.Bruce Lahn of the Howard Hughes Medical Institute and the University of Chicago led the studies.The findings appeared in Science magazine.

  3. Neural network plasticity in the human brain

    Rizk, Sviatlana

    2013-01-01

    The human brain is highly organized within networks. Functionally related neural-assemblies communicate by oscillating synchronously. Intrinsic brain activity contains information on healthy and damaged brain functioning. This thesis investigated the relationship between functional networks and behavior. Furthermore, we assessed functional network plasticity after brain damage and as a result of brain stimulation. In different groups of patients we observed reduced functional connectivity bet...

  4. Human Brain Reacts to Transcranial Extraocular Light

    Sun, Lihua; Peräkylä, Jari; Kovalainen, Anselmi; Ogawa, Keith H.; Karhunen, Pekka J.; Hartikainen, Kaisa M.

    2016-01-01

    Transcranial extraocular light affects the brains of birds and modulates their seasonal changes in physiology and behavior. However, whether the human brain is sensitive to extraocular light is unknown. To test whether extraocular light has any effect on human brain functioning, we measured brain electrophysiology of 18 young healthy subjects using event-related potentials while they performed a visual attention task embedded with emotional distractors. Extraocular light delivered via ear can...

  5. Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice

    Jensen, Mette Munk; Erichsen, Kamille Dumong; Björkling, Fredrik;

    2010-01-01

    3'-Deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) is a tracer used to assess cell proliferation in vivo. The aim of the study was to use (18)F-FLT positron emission tomography (PET) to study treatment responses to a new anti-cancer compound. To do so, we studied early anti-proliferative effects of t...

  6. Brain mechanisms underlying human communication

    Matthijs L Noordzij

    2009-07-01

    Full Text Available Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”. However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender and recognizing the communicative intention of the same actions (by a receiver relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus. The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities.

  7. Towards multimodal atlases of the human brain

    Toga, Arthur W.; Thompson, Paul M.; Mori, Susumu; Amunts, Katrin; Zilles, Karl

    2006-01-01

    Atlases of the human brain have an important impact on neuroscience. The emergence of ever more sophisticated imaging techniques, brain mapping methods and analytical strategies has the potential to revolutionize the concept of the brain atlas. Atlases can now combine data describing multiple aspects of brain structure or function at different scales from different subjects, yielding a truly integrative and comprehensive description of this organ. These integrative approaches have provided si...

  8. Brain Evolution and Human Neuropsychology: The Inferential Brain Hypothesis

    Koscik, Timothy R.; Tranel, Daniel

    2012-01-01

    Collaboration between human neuropsychology and comparative neuroscience has generated invaluable contributions to our understanding of human brain evolution and function. Further cross-talk between these disciplines has the potential to continue to revolutionize these fields. Modern neuroimaging methods could be applied in a comparative context, yielding exciting new data with the potential of providing insight into brain evolution. Conversely, incorporating an evolutionary base into the the...

  9. The human parental brain: In vivo neuroimaging

    Swain, James E.

    2010-01-01

    Interacting parenting thoughts and behaviors, supported by key brain circuits, critically shape human infants’ current and future behavior. Indeed, the parent–infant relationship provides infants with their first social environment, forming templates for what they can expect from others, how to interact with them and ultimately how they go on to themselves to be parents. This review concentrates on magnetic resonance imaging experiments of the human parent brain, which link brain physiology w...

  10. Modeling human brain development with cerebral organoids

    Muzio, Luca; Consalez, G. Giacomo

    2013-01-01

    The recent discovery of a new three-dimensional culture system for the derivation of cerebral organoids from human induced pluripotent stem cells provides developmental neurobiologists with the first example of a three-dimensional framework for the study of human brain development. This innovative approach permits the in vitro assembly of a human embryonic brain rudiment that recapitulates the developing human cerebrum. Organoids contain progenitor populations that develop to yield mature cor...

  11. Specialization of Functions in the Human Brain

    Parvizi, Josef

    2013-01-01

    The brain has fascinated us for ages. Some of the first serious discussions about the human brain started in ancient Egypt where the king of Alexandria allowed live dissections of criminals for the study of human anatomy [1]. Those who performed the dissections opened up the skull bone and saw the brain live. When they cut through the brain, they discovered large spaces inside it. These spaces were connected to each other like chambers in a house. They were also filled with a unique looking, ...

  12. New peptide receptor radionuclide therapy of invasive cancer cells: in vivo studies using 177Lu-DOTA-AE105 targeting uPAR in human colorectal cancer xenografts

    The proposition of uPAR as a potential target in cancer therapy is advanced by its predominant expression at the invasive front of colorectal cancer (CRC) and its value as prognostic biomarker for poor survival in this disease. In this study, we provide the first in vivo proof-of-concept for a theranostic approach as treatment modality in a human xenograft colorectal cancer model. Methods: A DOTA-conjugated 9-mer high affinity uPAR binding peptide (DOTA-AE105) was radiolabeled with 64Cu and 177Lu, for PET imaging and targeted radionuclide therapy study, respectively. Human uPAR-positive CRC HT-29 cells were inoculated in Nude mice and treated with 177Lu-DOTA-AE105 once a visible tumor had formed. To evaluate the true effect of the targeted radiotherapy, two controls groups were included in this study, one receiving a 177Lu-labeled non-binding control peptide and one receiving vehicle. All animals were treated day 0 and 7. A parallel 18F-FLT PET/CT study was performed on day 0, 1, 3 and 6. Dosimetry calculations were based on a biodistribution study, where organs and tissue of interest were collected 0.5, 1.0, 2.0, 4.0 and 24 h post injection of 177Lu-DOTA-AE105. Toxicity was assessed by recording mouse weight and by H and E staining of kidneys in each treatment group. Results: uPAR-positive HT-29 xenograft was clearly visualized by PET/CT imaging using 64Cu-DOTA-AE105. Subsequently, these xenograft transplants were locally irradiated using 177Lu-DOTA-AE105, where a significant effect on tumor size and the number of uPAR-positive cells in the tumor was found (p 18F-FLT PET/CT imaging study revealed a significant correlation between 18F-FLT tumor uptake and efficacy of the radionuclide therapy. A histological examination of the kidneys from one animal in each treatment group did not reveal any gross abnormalities and the general performance of all treated animals also showed no indications of radioactivity-induced toxicity. Conclusion: These findings document for the

  13. Male microchimerism in the human female brain.

    William F N Chan

    Full Text Available In humans, naturally acquired microchimerism has been observed in many tissues and organs. Fetal microchimerism, however, has not been investigated in the human brain. Microchimerism of fetal as well as maternal origin has recently been reported in the mouse brain. In this study, we quantified male DNA in the human female brain as a marker for microchimerism of fetal origin (i.e. acquisition of male DNA by a woman while bearing a male fetus. Targeting the Y-chromosome-specific DYS14 gene, we performed real-time quantitative PCR in autopsied brain from women without clinical or pathologic evidence of neurologic disease (n=26, or women who had Alzheimer's disease (n=33. We report that 63% of the females (37 of 59 tested harbored male microchimerism in the brain. Male microchimerism was present in multiple brain regions. Results also suggested lower prevalence (p=0.03 and concentration (p=0.06 of male microchimerism in the brains of women with Alzheimer's disease than the brains of women without neurologic disease. In conclusion, male microchimerism is frequent and widely distributed in the human female brain.

  14. Male Microchimerism in the Human Female Brain

    Chan, William F. N.; Gurnot, Cécile; Montine, Thomas J.; Sonnen, Joshua A.; Guthrie, Katherine A.; Nelson, J. Lee

    2012-01-01

    In humans, naturally acquired microchimerism has been observed in many tissues and organs. Fetal microchimerism, however, has not been investigated in the human brain. Microchimerism of fetal as well as maternal origin has recently been reported in the mouse brain. In this study, we quantified male DNA in the human female brain as a marker for microchimerism of fetal origin (i.e. acquisition of male DNA by a woman while bearing a male fetus). Targeting the Y-chromosome-specific DYS14 gene, we...

  15. 18F-FLT PET in hematologic disorders : A novel technique to analyze the bone marrow compartment

    Agool, Ali; Schot, Bart W.; Jager, Pieter L.; Vellenga, Edo

    2006-01-01

    Few diagnostic procedures are available to determine the degree of bone marrow cellularity and the numbers of cycling cells in patients with bone marrow disorders. Noninvasive imaging of the bone marrow compartment may be helpful. The PET tracer 3'-fluoro-3'-deoxy-L-thymidine (F-18-FLT) has been dev

  16. Analysis of a human brain transcriptome map

    Greene Jonathan R

    2002-04-01

    Full Text Available Abstract Background Genome wide transcriptome maps can provide tools to identify candidate genes that are over-expressed or silenced in certain disease tissue and increase our understanding of the structure and organization of the genome. Expressed Sequence Tags (ESTs from the public dbEST and proprietary Incyte LifeSeq databases were used to derive a transcript map in conjunction with the working draft assembly of the human genome sequence. Results Examination of ESTs derived from brain tissues (excluding brain tumor tissues suggests that these genes are distributed on chromosomes in a non-random fashion. Some regions on the genome are dense with brain-enriched genes while some regions lack brain-enriched genes, suggesting a significant correlation between distribution of genes along the chromosome and tissue type. ESTs from brain tumor tissues have also been mapped to the human genome working draft. We reveal that some regions enriched in brain genes show a significant decrease in gene expression in brain tumors, and, conversely that some regions lacking in brain genes show an increased level of gene expression in brain tumors. Conclusions This report demonstrates a novel approach for tissue specific transcriptome mapping using EST-based quantitative assessment.

  17. Lactate fuels the human brain during exercise

    Quistorff, Bjørn; Secher, Niels H; Van Lieshout, Johannes J

    2008-01-01

    The human brain releases a small amount of lactate at rest, and even an increase in arterial blood lactate during anesthesia does not provoke a net cerebral lactate uptake. However, during cerebral activation associated with exercise involving a marked increase in plasma lactate, the brain takes up...... suggests that lactate may partially replace glucose as a substrate for oxidation. Thus, the notion of the human brain as an obligatory glucose consumer is not without exceptions....... blockade but not with beta(1)-adrenergic blockade alone. Also, CMR decreases in response to epinephrine, suggesting that a beta(2)-adrenergic receptor mechanism enhances glucose and perhaps lactate transport across the blood-brain barrier. The pattern of CMR decrease under various forms of brain activation...

  18. Human brain mapping: Experimental and computational approaches

    Wood, C.C.; George, J.S.; Schmidt, D.M.; Aine, C.J. [Los Alamos National Lab., NM (US); Sanders, J. [Albuquerque VA Medical Center, NM (US); Belliveau, J. [Massachusetts General Hospital, Boston, MA (US)

    1998-11-01

    This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). This program developed project combined Los Alamos' and collaborators' strengths in noninvasive brain imaging and high performance computing to develop potential contributions to the multi-agency Human Brain Project led by the National Institute of Mental Health. The experimental component of the project emphasized the optimization of spatial and temporal resolution of functional brain imaging by combining: (a) structural MRI measurements of brain anatomy; (b) functional MRI measurements of blood flow and oxygenation; and (c) MEG measurements of time-resolved neuronal population currents. The computational component of the project emphasized development of a high-resolution 3-D volumetric model of the brain based on anatomical MRI, in which structural and functional information from multiple imaging modalities can be integrated into a single computational framework for modeling, visualization, and database representation.

  19. Multiple aldehyde reductases of human brain.

    Hoffman, P L; Wermuth, B; von Wartburg, J P

    1980-01-01

    Human brain contains four forms of aldehyde reducing enzymes. One major activity, designated AR3, has properties indicating its identity with the NADPH-dependent aldehyde reductase, EC 1.1.1.2. The other major form of human brain enzyme, AR1, which is also NADPH-dependent, reduces both aldehyde and ketone-containing substrates, including vitamin K3 (menadione) and daunorubicin, a cancer chemotherapeutic agent. This enzyme is very sensitive to inhibition by the flavonoids quercitrin and quercetine, and may be analogous to a daunorubicin reductase previously described in liver of other species. One minor form of human brain aldehyde reductase, AR2, demonstrates substrate specificity and inhibitor sensitivity which suggest its similarity to aldose reductases found in lens and other tissues of many species. This enzyme, which can also use NADH as cofactor to some extent, is the most active in reducing the aldehyde derivatives of the biogenic amines. The fourth human brain enzyme ("SSA reductase") differs from the other forms in its ability to use NADH as well as or better than NADPH as cofactor, and in its molecular weight, which is nearly twice that of the other forms. It is quite specific for succinic semialdehyde (SSA) as substrate, and was found to be significantly inhibited only by quercetine and quercitrin. AR3 can also reduce SSA, and both enzymes may contribute to the production of gamma-hydroxybutyric acid in vivo. These results indicate that the human brain aldehyde reductases can play relatively specific physiologic roles. PMID:7424738

  20. Imaging the Addicted Human Brain

    Fowler, Joanna S.; Volkow, Nora D.; Kassed, Cheryl A; Chang, Linda

    2007-01-01

    Modern imaging techniques enable researchers to observe drug actions and consequences as they occur and persist in the brains of abusing and addicted individuals. This article presents the five most commonly used techniques, explains how each produces images, and describes how researchers interpret them. The authors give examples of key findings illustrating how each technique has extended and deepened our knowledge of the neurobiological bases of drug abuse and addiction, and they address po...

  1. Human Nerual Stem Cells for Brain Repair

    Kim, Seung U.; Lee, Hong J.; In H Park; Chu, Kon; Lee, Soon T.; Kim, Manho; Roh, Jae K.; Kim, Seung K.; Wang, Kyu C.

    2008-01-01

    Cell replacement therapy and gene transfer to the diseased or injured brain have provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of human neurological diseases including Parkinson disease, Huntington disease, amyotrophic lateral sclerosis (ALS), Alzheimer disease, multiple sclerosis (MS), stroke, spinal cord injury and brain cancer. In recent years, neurons and glial cells have successfully been generated from neural stem cells, a...

  2. Mapping human brain activity in vivo.

    Mazziotta, J.C.

    1994-01-01

    A wide range of structural and functional techniques now exists to map the human brain in health and disease. These approaches span the gamut from external tomographic imaging devices (positron-emission tomography, single photon-emission computed tomography, magnetic resonance imaging, computed tomography), to surface detectors (electroencephalography, magnetoencephalography, transcranial magnetic stimulation), to measurements made directly on the brain's surface or beneath it (intrinsic sign...

  3. Learning and memory in the human brain

    Petersson, Karl Magnus

    2005-01-01

    The first chapter of the thesis 'Learning and Memory in the Human Brain' provides a brief review of the brain as well as cognition from the point of view of information processing in physical systems. We include a brief outline of information processing as conceived of within the classical framework of cognitive science. We show how this perspective can be understood in terms of information processing in a certain class of dynamical systems and we indicate how this view of c...

  4. Structural Brain Correlates of Human Sleep Oscillations

    Saletin, Jared M.; van der Helm, Els; Walker, Matthew P.

    2013-01-01

    Sleep is strongly conserved within species, yet marked and perplexing inter-individual differences in sleep physiology are observed. Combining EEG sleep recordings and high-resolution structural brain imaging, here we demonstrate that the morphology of the human brain offers one explanatory factor of such inter-individual variability. Grey matter volume in interoceptive and exteroceptive cortices correlated with the expression of slower NREM sleep spindle frequencies, supporting their propose...

  5. Computed tomography studies of human brain movements

    Rhythmic brain movements have been revealed by sets of sequential computed tomography scans of human brains (seen retrospectively to be normal). These scans have shown that both (unenhanced) brain parenchymal density and the shapes of the elements of the supratentorial ventricular/cisternal system are subject to wave motions having similar periods - ranging from 26 s through 56 s, 77-96 s, 109 s and 224 s to 224 X 2 s (or even longer), with good correlation between peak values. These motions, as well as phase variations between the waves, suggest a peristaltic movement of cerebrospinal fluid through the ventricular/cisternal system with progressive axial damping

  6. The human brain. Prenatal development and structure

    Marin-Padilla, Miguel

    2011-07-01

    This book is unique among the current literature in that it systematically documents the prenatal structural development of the human brain. It is based on lifelong study using essentially a single staining procedure, the classic rapid Golgi procedure, which ensures an unusual and desirable uniformity in the observations. The book is amply illustrated with 81 large, high-quality color photomicrographs never previously reproduced. These photomicrographs, obtained at 6, 7, 11, 15, 18, 20, 25, 30, 35, and 40 weeks of gestation, offer a fascinating insight into the sequential prenatal development of neurons, blood vessels, and glia in the human brain. (orig.)

  7. Human intelligence and brain networks.

    Colom, Roberto; Karama, Sherif; Jung, Rex E; Haier, Richard J

    2010-01-01

    Intelligence can be defined as a general mental ability for reasoning, problem solving, and learning. Because of its general nature, intelligence integrates cognitive functions such as perception, attention, memory, language, or planning. On the basis of this definition, intelligence can be reliably measured by standardized tests with obtained scores predicting several broad social outcomes such as educational achievement, job performance, health, and longevity. A detailed understanding of the brain mechanisms underlying this general mental ability could provide significant individual and societal benefits. Structural and functional neuroimaging studies have generally supported a frontoparietal network relevant for intelligence. This same network has also been found to underlie cognitive functions related to perception, short-term memory storage, and language. The distributed nature of this network and its involvement in a wide range of cognitive functions fits well with the integrative nature of intelligence. A new key phase of research is beginning to investigate how functional networks relate to structural networks, with emphasis on how distributed brain areas communicate with each other. PMID:21319494

  8. Brain Mechanisms Underlying Human Communication

    Noordzij, Matthijs L.; Newman-Norlund, Sarah E.; Jan Peter De Ruiter; Peter Hagoort; Levinson, Stephen C.; Ivan Toni

    2009-01-01

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”). However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behaviora...

  9. Model human heart or brain signals

    Tuncay, Caglar

    2008-01-01

    A new model is suggested and used to mimic various spatial or temporal designs in biological or non biological formations where the focus is on the normal or irregular electrical signals coming from human heart (ECG) or brain (EEG). The electrical activities in several muscles (EMG) or neurons or other organs of human or various animals, such as lobster pyloric neuron, guinea pig inferior olivary neuron, sepia giant axon and mouse neocortical pyramidal neuron and some spatial formations are a...

  10. Zika virus impairs growth in human neurospheres and brain organoids.

    Garcez, Patricia P; Loiola, Erick Correia; Madeiro da Costa, Rodrigo; Higa, Luiza M; Trindade, Pablo; Delvecchio, Rodrigo; Nascimento, Juliana Minardi; Brindeiro, Rodrigo; Tanuri, Amilcar; Rehen, Stevens K

    2016-05-13

    Since the emergence of Zika virus (ZIKV), reports of microcephaly have increased considerably in Brazil; however, causality between the viral epidemic and malformations in fetal brains needs further confirmation. We examined the effects of ZIKV infection in human neural stem cells growing as neurospheres and brain organoids. Using immunocytochemistry and electron microscopy, we showed that ZIKV targets human brain cells, reducing their viability and growth as neurospheres and brain organoids. These results suggest that ZIKV abrogates neurogenesis during human brain development. PMID:27064148

  11. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    HuaHu; Wei-PingZhang; LeiZhang; ZhongChen; Er-QingWei

    2004-01-01

    Aquaporin-4 (AQP4) is one of the aquaporins (AQPs), a water channel family. In the brain, AQP4 is expressed in astroeyte foot processes, and plays an important role in water homeostasis and in the formation of brain edema. In our study, AQP4 expression in human brain specimens from patients with traumatic brain injury or different brain tumors was detected

  12. Imaging visual function of the human brain

    Imaging of human brain structure and activity with particular reference to visual function is reviewed along with methods of obtaining the data including computed tomographic (CT) scan, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET). The literature is reviewed and the potential for a new understanding of brain visual function is discussed. PET is reviewed from basic physical principles to the most recent visual brain findings with oxygen-15. It is shown that there is a potential for submillimeter localization of visual functions with sequentially different visual stimuli designed for the temporal separation of the responses. Single photon emission computed tomography (SPECT), a less expensive substitute for PET, is also discussed. MRS is covered from basic physical principles to the current state of the art of in vivo biochemical analysis. Future possible clinical applications are discussed. Improved understanding of the functional neural organization of vision and brain will open a window to maps and circuits of human brain function.119 references

  13. Epilepsy: Extreme Events in the Human Brain

    Lehnertz, Klaus

    The analysis of Xevents arising in dynamical systems with many degrees of freedom represents a challenge for many scientific fields. This is especially true for the open, dissipative, and adaptive system known as the human brain. Due to its complex structure, its immense functionality, and — as in the case of epilepsy — due to the coexistence of normal and abnormal functions, the brain can be regarded as one of the most complex and fascinating systems in nature. Data gathered so far show that the epileptic process exhibits a high spatial and temporal variability. Small, specific, regions of the brain are responsible for the generation of focal epileptic seizures, and the amount of time a patient spends actually having seizures is only a small fraction of his/her lifetime. In between these Xevents large parts of the brain exhibit normal functioning. Since the occurrence of seizures usually can not be explained by exogenous factors, and since the brain recovers its normal state after a seizure in the majority of cases, this might indicate that endogenous nonlinear (deterministic and/or stochastic) properties are involved in the control of these Xevents. In fact, converging evidence now indicates that (particularly) nonlinear approaches to the analysis of brain activity allow us to define precursors which, provided sufficient sensitivity and specificity can be obtained, might lead to the development of patient-specific seizure anticipation and seizure prevention strategies.

  14. Methylomic trajectories across human fetal brain development.

    Spiers, Helen; Hannon, Eilis; Schalkwyk, Leonard C; Smith, Rebecca; Wong, Chloe C Y; O'Donovan, Michael C; Bray, Nicholas J; Mill, Jonathan

    2015-03-01

    Epigenetic processes play a key role in orchestrating transcriptional regulation during development. The importance of DNA methylation in fetal brain development is highlighted by the dynamic expression of de novo DNA methyltransferases during the perinatal period and neurodevelopmental deficits associated with mutations in the methyl-CpG binding protein 2 (MECP2) gene. However, our knowledge about the temporal changes to the epigenome during fetal brain development has, to date, been limited. We quantified genome-wide patterns of DNA methylation at ∼ 400,000 sites in 179 human fetal brain samples (100 male, 79 female) spanning 23 to 184 d post-conception. We identified highly significant changes in DNA methylation across fetal brain development at >7% of sites, with an enrichment of loci becoming hypomethylated with fetal age. Sites associated with developmental changes in DNA methylation during fetal brain development were significantly underrepresented in promoter regulatory regions but significantly overrepresented in regions flanking CpG islands (shores and shelves) and gene bodies. Highly significant differences in DNA methylation were observed between males and females at a number of autosomal sites, with a small number of regions showing sex-specific DNA methylation trajectories across brain development. Weighted gene comethylation network analysis (WGCNA) revealed discrete modules of comethylated loci associated with fetal age that are significantly enriched for genes involved in neurodevelopmental processes. This is, to our knowledge, the most extensive study of DNA methylation across human fetal brain development to date, confirming the prenatal period as a time of considerable epigenomic plasticity. PMID:25650246

  15. Human freedom and the brain.

    Kornhuber, Hans Helmut

    2009-06-01

    Freedom of will does exist, it is self-leadership of man based on reason and ethos. Evidence comes from truth. Determinism cannot be proved since if you try, you mean to prove a truth; but there is no truth without freedom. By contrast for freedom there are many pieces of evidence e.g. science, arts, technology. Freedom utilizes creative abstract thinking with phantasy. Freedom is graded, limited, based on nature, but not developed without good will. We perceive reliably freedom by self-consciousness and in other persons as long as we are sober. Freedom needs intelligence, but is more, it is a creative and moral virtue. The basis for freedom is phylogenesis and culture, in the individual learning and experimenting. Factors in the becoming of freedom are not only genes and environment but also self-discipline. But the creativity of free will is dangerous. Man therefore needs morale. Drives and feelings become humanized, cultural interests are developed. There is a humane nobility from long good will. PMID:25384854

  16. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    HU Hua; YAO Hong-tian; ZHANG Wei-ping; ZHANG LEI; DING Wei; ZHANG Shi-hong; CHEN Zhong; WEI Er-qing

    2005-01-01

    Objective: To characterize the expression of aquaporin-4 (AQP4), one of the aquaporins (AQPs), in human brain specimens from patients with traumatic brain injury or brain tumors. Methods: Nineteen human brain specimens were obtained from the patients with traumatic brain injury, brain tumors, benign meningioma or early stage hemorrhagic stroke. MRI or CT imaging was used to assess brain edema. Hematoxylin and eosin staining were used to evaluate cell damage. Immunohistochemistry was used to detect the AQP4 expression. Results: AQP4 expression was increased from 15h to at least 8 d after injury. AQP4immunoreactivity was strong around astrocytomas, ganglioglioma and metastatic adenocarcinoma. However, AQP4 immunoreactivity was only found in the centers of astrocytomas and ganglioglioma, but not in metastatic adenocarcinoma derived from lung.Conclusion: AQP4 expression increases in human brains after traumatic brain injury, within brain-derived tumors, and around brain tumors.

  17. Hierarchical modularity in human brain functional networks

    Meunier, D; Fornito, A; Ersche, K D; Bullmore, E T; 10.3389/neuro.11.037.2009

    2010-01-01

    The idea that complex systems have a hierarchical modular organization originates in the early 1960s and has recently attracted fresh support from quantitative studies of large scale, real-life networks. Here we investigate the hierarchical modular (or "modules-within-modules") decomposition of human brain functional networks, measured using functional magnetic resonance imaging (fMRI) in 18 healthy volunteers under no-task or resting conditions. We used a customized template to extract networks with more than 1800 regional nodes, and we applied a fast algorithm to identify nested modular structure at several hierarchical levels. We used mutual information, 0 < I < 1, to estimate the similarity of community structure of networks in different subjects, and to identify the individual network that is most representative of the group. Results show that human brain functional networks have a hierarchical modular organization with a fair degree of similarity between subjects, I=0.63. The largest 5 modules at ...

  18. "Messing with the Mind”: Evolutionary Challenges to Human Brain Augmentation

    ARTHUR SANIOTIS

    2014-01-01

    The issue of brain augmentation has received considerable scientific attention over the last two decades. A key factor to brain augmentation that has been widely overlooked are the complex evolutionary processes which have taken place in evolving the human brain to its current state of functioning. Like other bodily organs, the human brain has been subject to the forces of biological adaptation. The structure and function of the brain, is very complex and only now we are beginning to underst...

  19. Sex beyond the genitalia: The human brain mosaic

    Joel, Daphna; Berman, Zohar; Tavor, Ido; Wexler, Nadav; Gaber, Olga; Stein, Yaniv; Shefi, Nisan; Pool, Jared; Urchs, Sebastian; Margulies, Daniel S.; Liem, Franziskus; Hänggi, Jürgen; Jäncke, Lutz; Assaf, Yaniv

    2015-01-01

    Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains ("female brain" or "male brain"). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features ...

  20. Imaging Monoamine Oxidase in the Human Brain

    Fowler, J. S.; Volkow, N. D.; Wang, G-J.; Logan, Jean

    1999-11-10

    Positron emission tomography (PET) studies mapping monoamine oxidase in the human brain have been used to measure the turnover rate for MAO B; to determine the minimum effective dose of a new MAO inhibitor drug lazabemide and to document MAO inhibition by cigarette smoke. These studies illustrate the power of PET and radiotracer chemistry to measure normal biochemical processes and to provide information on the effect of drug exposure on specific molecular targets.

  1. Physical biology of human brain development

    Silvia eBudday; Paul eSteinmann; Ellen eKuhl

    2015-01-01

    Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal different...

  2. Mouse Genetic Models of Human Brain Disorders

    Celeste eLeung; Zhengping eJia

    2016-01-01

    Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectua...

  3. Imaging Monoamine Oxidase in the Human Brain

    Positron emission tomography (PET) studies mapping monoamine oxidase in the human brain have been used to measure the turnover rate for MAO B; to determine the minimum effective dose of a new MAO inhibitor drug lazabemide and to document MAO inhibition by cigarette smoke. These studies illustrate the power of PET and radiotracer chemistry to measure normal biochemical processes and to provide information on the effect of drug exposure on specific molecular targets

  4. Neocortical glial cell numbers in human brains

    Pelvig, D.P.; Pakkenberg, H.; Stark, A.K.; Pakkenberg, B.

    2008-01-01

    Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18-93 years, 18 females (average age 65 years, range 18-93) and 13 males (average age 57 years, range 19-87). The cells were differentiated in astrocytes, oligodendrocytes, microglia...... males, a difference of 24% with a high biological variance. These numbers can serve as reference values in quantitative studies of the human neocortex. (C) 2007 Elsevier Inc. All rights reserved Udgivelsesdato: 2008/11...

  5. Toward Developmental Connectomics of the Human Brain

    Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

    2016-01-01

    Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and developmental

  6. Towards Developmental Connectomics of the Human Brain

    Miao eCao

    2016-03-01

    Full Text Available Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and

  7. Toward Developmental Connectomics of the Human Brain.

    Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

    2016-01-01

    Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and developmental

  8. Human brain networks function in connectome-specific harmonic waves

    Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

    2016-01-01

    A key characteristic of human brain activity is coherent, spatially distributed oscillations forming behaviour-dependent brain networks. However, a fundamental principle underlying these networks remains unknown. Here we report that functional networks of the human brain are predicted by harmonic patterns, ubiquitous throughout nature, steered by the anatomy of the human cerebral cortex, the human connectome. We introduce a new technique extending the Fourier basis to the human connectome. In...

  9. Structural brain correlates of human sleep oscillations.

    Saletin, Jared M; van der Helm, Els; Walker, Matthew P

    2013-12-01

    Sleep is strongly conserved within species, yet marked and perplexing inter-individual differences in sleep physiology are observed. Combining EEG sleep recordings and high-resolution structural brain imaging, here we demonstrate that the morphology of the human brain offers one explanatory factor of such inter-individual variability. Gray matter volume in interoceptive and exteroceptive cortices correlated with the expression of slower NREM sleep spindle frequencies, supporting their proposed role in sleep protection against conscious perception. Conversely, and consistent with an involvement in declarative memory processing, gray matter volume in bilateral hippocampus was associated with faster NREM sleep spindle frequencies. In contrast to spindles, gray matter volume in the homeostatic sleep-regulating center of the basal forebrain/hypothalamus, together with the medial prefrontal cortex, accounted for individual differences in NREM slow wave oscillations. Together, such findings indicate that the qualitative and quantitative expression of human sleep physiology is significantly related to anatomically specific differences in macroscopic brain structure. PMID:23770411

  10. Visualization of monoamine oxidase in human brain

    Fowler, J.S.; Volkow, N.D.; Wang, G.J.; Pappas, N.; Shea, C.; MacGregor, R.R.; Logan, J.

    1996-12-31

    Monoamine oxidase is a flavin enzyme which exists in two subtypes, MAO A and MAO B. In human brain MAO B predominates and is largely compartmentalized in cell bodies of serotonergic neurons and glia. Regional distribution of MAO B was determined by positron computed tomography with volunteers after the administration of deuterium substituted [11C]L-deprenyl. The basal ganglia and thalamus exhibited the greatest concentrations of MAO B with intermediate levels in the frontal cortex and cingulate gyrus while lowest levels were observed in the parietal and temporal cortices and cerebellum. We observed that brain MAO B increases with are in health normal subjects, however the increases were generally smaller than those revealed with post-mortem studies.

  11. Tracking White Matter Fiber in Human Brain

    KANGNing; ZHANGJun; EricSCarlson

    2004-01-01

    A new approach for noninvasively tracing brain white matter fiber tracts is presented using diffusion tensor magnetic resonance imaging (DT-MRI) data. This technique is based on successive anisotropic diffusion simulations over the human brain, which are utilized to construct three dimensional diffusion fronts. The fiber pathways are determined by evaluating the distance and orientation from fronts to their corresponding diffusion seeds. Real DT-MRI data are used to demonstrate the tracking scheme. It is shown that several major white matter fiber pathways can be reproduced noninvasively, with the tract branching being allowed. Since the diffusion simulation,which is a truly physical phenomenon reflecting the underlying architecture of cerebral tissues, makes full use of the entire diffusion tensor data, the proposed approach is expected to enhance robustness and reliability of the DT-MRI based fiber tracking techniques in white matter fiber reconstruction.

  12. High-yielding, automated production of 3′-deoxy-3′-[18F]fluorothymidine using a modified Bioscan Coincidence FDG reaction module

    Introduction: High-yielding, automated production of a PET tracer that reflects proliferation, 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT), is reported using a modified Bioscan Coincidence FDG reaction module. Methods: Production of [18F]FLT was implemented through: (1) modification of an original FDG manifold; (2) application of an alternate time sequence; and (3) altered solid-phase extraction (SPE) purification. Quality control testing, including standard radiochemical figures of merit and preclinical positron emission tomography (PET) imaging, was carried out. Results: High decay-corrected yields of [18F]FLT (16–39%) were reproducibly obtained. The product exhibited very high specific activity (4586.9 TBq/mmol; 123,969 Ci/mmol) and radiochemical purity (>99%). Overall, the [18F]FLT produced in this manner was superior to typical productions that utilized a GE TRACERlab FXF-N reaction module. Additionally, purification with SPE cartridges, followed by manual elution, accelerated overall run time and resulted in a two-fold increase in [18F]FLT concentration. PET imaging showed the [18F]FLT produced by this method was highly suitable for non-invasive tumor imaging in mice. Conclusions: The Bioscan Coincidence GE FDG Reaction Module was readily adapted to reproducibly provide [18F]FLT in high yield, specific activity, and radiochemical purity. The approach was suitable to provide sufficient amounts of material for preclinical studies. - Highlights: • Synthesis of [18F]FLT using a modified Bioscan Coincidence GE FDG reaction module. • Typical decay-corrected yields of 16–39% were obtained (n=12). • Very high specific activities and radiochemical purity. • High, preferential uptake of [18F]FLT uptake in human colon cancer xenografts

  13. Diffusion Based Modeling of Human Brain Response to External Stimuli

    Namazi, Hamidreza

    2012-01-01

    Human brain response is the overall ability of the brain in analyzing internal and external stimuli in the form of transferred energy to the mind/brain phase-space and thus, making the proper decisions. During the last decade scientists discovered about this phenomenon and proposed some models based on computational, biological, or neuropsychological methods. Despite some advances in studies related to this area of the brain research there was less effort which have been done on the mathematical modeling of the human brain response to external stimuli. This research is devoted to the modeling of human EEG signal, as an alert state of overall human brain activity monitoring, due to receiving external stimuli, based on fractional diffusion equation. The results of this modeling show very good agreement with the real human EEG signal and thus, this model can be used as a strong representative of the human brain activity.

  14. Positive selection on gene expression in the human brain

    Khaitovich, Philipp; Tang, Kun; Franz, Henriette;

    2006-01-01

    Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1] . However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain...... shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1] , [2] and [3] . There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed in...... the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other...

  15. Physical biology of human brain development

    Silvia eBudday

    2015-07-01

    Full Text Available Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view towards surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level towards form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.

  16. The proteome of human brain microdialysate

    Feldmann Robert E

    2003-12-01

    Full Text Available Abstract Background Cerebral microdialysis has been established as a monitoring tool in neurocritically ill patients suffering from severe stroke. The technique allows to sample small molecules in the brain tissue for subsequent biochemical analysis. In this study, we investigated the proteomic profile of human cerebral microdialysate and if the identified proteins might be useful predictors for disease characteristics in stroke for tissue at risk in the contralateral hemisphere. We analysed cerebral protein expression in microdialysate from three stroke patients sampled from the hemisphere contralateral to the lesion. Using a proteomic approach based on two-dimensional gel electrophoresis and subsequent mass spectrometry, we created a protein map for the global protein expression pattern of human microdialyste. Results We found an average of 158 ± 24 (N = 18 protein spots in the human cerebral microdialysate and could identify 95 spots, representing 27 individual proteins. Most of these have been detected in human cerebrospinal fluid before, but 10 additional proteins mainly of cerebral intracellular origin were identified exclusively in the microdialysate. Conclusions The 10 proteins found exclusively in human cerebral microdialysate, but not in cerebrospinal fluid, indicate the possibility to monitor the progression of the disease towards deterioration. The correlation of protein composition in the human cerebral microdialysate with the patients' clinical condition and results of cerebral imaging may be a useful approach to future applications for neurological stroke diagnosis, prognosis, and treatment.

  17. The Human Brain in Numbers: A Linearly Scaled-up Primate Brain

    Suzana Herculano-Houzel

    2009-01-01

    The human brain has often been viewed as outstanding among mammalian brains: the most cognitively able, the largest-than-expected from body size, endowed with an overdeveloped cerebral cortex that represents over 80% of brain mass, and purportedly containing 100 billion neurons and 10× more glial cells. Such uniqueness was seemingly necessary to justify the superior cognitive abilities of humans over larger-brained mammals such as elephants and whales. However, our recent studies using a nove...

  18. Human brain : biochemical lateralization in normal subjects.

    Jayasundar R

    2002-07-01

    Full Text Available Chemical asymmetries in normal human brain were studied using the non-invasive technique of volume localized proton magnetic resonance spectroscopy (MRS. The technique of STEAM was used to acquire water-suppressed proton spectra from 8 ml voxels placed in bilaterally symmetrical positions in the two hemispheres of the brain. One hundred and sixty eight right-handed male volunteers were studied for six different regions in the brain (n=28, for each region. Parietal, occipital, temporal, frontal, thalamus and cerebellum regions were studied. The focus was on metabolites such as N-acetyl aspartate (NAA, creatine/phosphocreatine (Cr/PCr and choline (Cho containing compounds. Ratios of the peak areas were calculated for them. Quantitation of the metabolites were carried for data on 18 volunteers. Significant interhemispheric differences in the distribution of metabolites were observed for all the regions studied. There were statistically significant differences on right and left side for the metabolite ratios in all the regions studied. The study has shown the existence of significant lateralization in the distribution of proton MR visible metabolites for all the regions studied.

  19. Fast optical imaging of human brain function

    Gabriele Gratton

    2010-06-01

    Full Text Available Great advancements in brain imaging during the last few decades have opened a large number of new possibilities for neuroscientists. The most dominant methodologies (electrophysiological and magnetic resonance-based methods emphasize temporal and spatial information, respectively. However, theorizing about brain function has recently emphasized the importance of rapid (within 100 ms or so interactions between different elements of complex neuronal networks. Fast optical imaging, and in particular the event-related optical signal (EROS, a technology that has emerged over the last 15 years may provide descriptions of localized (to sub-cm level brain activity with a temporal resolution of less than 100 ms. The main limitations of EROS are its limited penetration, which allows us to image cortical structures not deeper than 3 cm from the surface of the head, and its low signal-to-noise ratio. Advantages include the fact that EROS is compatible with most other imaging methods, including electrophysiological, magnetic resonance, and trans-cranial magnetic stimulation techniques, with which can be recorded concurrently. In this paper we present a summary of the research that has been conducted so far on fast optical imaging, including evidence for the possibility of recording neuronal signals with this method, the properties of the signals, and various examples of applications to the study of human cognitive neuroscience. Extant issues, controversies, and possible future developments are also discussed.

  20. Distribution of melatonin receptor in human fetal brain

    WANG Guo-quan; SHAO Fu-yuan; ZHAO Ying; LIU Zhi-min

    2001-01-01

    Objective: To study the distribution of 2 kinds of melatonin receptor subtypes (mtl and MT2) in human fetal brain. Methods: The fetal brain tissues were sliced and the distribution ofmelatonin receptors in human fetal brain were detected using immunohistochemistry and in situ hybridization. Results: Melatonin receptor mtl existed in the cerebellun and hypothalamus, melatonin receptor MT2 exists in hypothalamus, occipital and medulla. Conclusion: Two kinds of melatonin receptors, mtl and MT2 exist in the membrane and cytosol of brain cells, indicating that human fetal brain is a target organ of melatonin.

  1. Model human heart or brain signals

    Tuncay, Caglar

    2008-01-01

    A new model is suggested and used to mimic various spatial or temporal designs in biological or non biological formations where the focus is on the normal or irregular electrical signals coming from human heart (ECG) or brain (EEG). The electrical activities in several muscles (EMG) or neurons or other organs of human or various animals, such as lobster pyloric neuron, guinea pig inferior olivary neuron, sepia giant axon and mouse neocortical pyramidal neuron and some spatial formations are also considered (in Appendix). In the biological applications, several elements (cells or tissues) in an organ are taken as various entries in a representative lattice (mesh) where the entries are connected to each other in terms of some molecular diffusions or electrical potential differences. The biological elements evolve in time (with the given tissue or organ) in terms of the mentioned connections (interactions) besides some individual feedings. The anatomical diversity of the species (or organs) is handled in terms o...

  2. Hierarchical modularity in human brain functional networks

    Renaud Lambiotte

    2009-10-01

    Full Text Available The idea that complex systems have a hierarchical modular organization originates in the early 1960s and has recently attracted fresh support from quantitative studies of large scale, real-life networks. Here we investigate the hierarchical modular (or “modules-within-modules” decomposition of human brain functional networks, measured using functional magnetic resonance imaging (fMRI in 18 healthy volunteers under no-task or resting conditions. We used a customized template to extract networks with more than 1800 regional nodes, and we applied a fast algorithm to identify nested modular structure at several hierarchical levels. We used mutual information, 0 < I < 1, to estimate the similarity of community structure of networks in different subjects, and to identify the individual network that is most representative of the group. Results show that human brain functional networks have a hierarchical modular organization with a fair degree of similarity between subjects, I=0.63. The largest 5 modules at the highest level of the hierarchy were medial occipital, lateral occipital, central, parieto-frontal and fronto-temporal systems; occipital modules demonstrated less sub-modular organization than modules comprising regions of multimodal association cortex. Connector nodes and hubs, with a key role in inter-modular connectivity, were also concentrated in association cortical areas. We conclude that methods are available for hierarchical modular decomposition of large numbers of high resolution brain functional networks using computationally expedient algorithms. This could enable future investigations of Simon's original hypothesis that hierarchy or near-decomposability of physical symbol systems is a critical design feature for their fast adaptivity to changing environmental conditions.

  3. [Neuroethics: Ethical Endowments of Human Brain].

    López Moratalla, Natalia

    2015-01-01

    The neurobiological processes underlying moral judgement have been the focus of Neuroethics. Neurosciences demonstrate which cerebral areas are active and inactive whilst people decide how to act when facing a moral dilemma; in this way we know the correlation between determined cerebral areas and our human acts. We can explain how the ″ethical endowments″ of each person, common to all human beings, is ″embedded″ in the dynamic of cerebral flows. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion related areas of the brain contribute to moral judgement. The outcome of man's natural inclinations is on one hand linked to instinctive systems of animal survival and to basic emotions, and on the other, to the life of each individual human uninhibited by automatism of the biological laws, because he is governed by the laws of freedom. The capacity to formulate an ethical judgement is an innate asset of the human mind. PMID:26546796

  4. Left Brain to Right Brain: Notes from the Human Laboratory.

    Baumli, Francis

    1982-01-01

    Examines the implications of the left brain-right brain theory on communications styles in male-female relationships. The author contends that women tend to use the vagueness of their emotional responses manipulatively. Men need to apply rational approaches to increase clarity in communication. (AM)

  5. The Complex Functioning of the Human Brain: The Two Hemispheres

    Iulia Cristina Timofti

    2010-01-01

    The present study reveals just a glimpse of the possible functions and reactions that the human brain can have. I considered as good examples different situations characteristic both of a normal person and a split-brain one. These situations prove that the brain, although divided in two, works as a unit, as an amazing computer that has data processing as a main goal.

  6. Listeriolysin O mediates cytotoxicity against human brain microvascular

    Penetration of the brain microvascular endothelial layer is one of the routes L. monocytogenes use to breach the blood-brain barrier. Because host factors in the blood severely limit direct invasion of human brain microvascular endothelial cells (HBMECs) by L. monocytogenes, alternative mechanisms m...

  7. Brain-Computer Interfaces and Human-Computer Interaction

    Tan, Desney; Nijholt, Anton; Tan, Desney S.; Nijholt, Anton

    2010-01-01

    Advances in cognitive neuroscience and brain imaging technologies have started to provide us with the ability to interface directly with the human brain. This ability is made possible through the use of sensors that can monitor some of the physical processes that occur within the brain that correspo

  8. Thresholding magnetic resonance images of human brain

    Qing-mao HU; Wieslaw L NOWINSKI

    2005-01-01

    In this paper, methods are proposed and validated to determine low and high thresholds to segment out gray matter and white matter for MR images of different pulse sequences of human brain. First, a two-dimensional reference image is determined to represent the intensity characteristics of the original three-dimensional data. Then a region of interest of the reference image is determined where brain tissues are present. The non-supervised fuzzy c-means clustering is employed to determine: the threshold for obtaining head mask, the low threshold for T2-weighted and PD-weighted images, and the high threshold for T1-weighted, SPGR and FLAIR images. Supervised range-constrained thresholding is employed to determine the low threshold for T1-weighted, SPGR and FLAIR images. Thresholding based on pairs of boundary pixels is proposed to determine the high threshold for T2- and PD-weighted images. Quantification against public data sets with various noise and inhomogeneity levels shows that the proposed methods can yield segmentation robust to noise and intensity inhomogeneity. Qualitatively the proposed methods work well with real clinical data.

  9. Changes in cognitive state alter human functional brain networks

    Malaak Nasser Moussa

    2011-08-01

    Full Text Available The study of the brain as a whole system can be accomplished using network theory principles. Research has shown that human functional brain networks during a resting state exhibit small-world properties and high degree nodes, or hubs, localized to brain areas consistent with the default mode network (DMN. However, the study of brain networks across different tasks and or cognitive states has been inconclusive. Research in this field is important because the underpinnings of behavioral output are inherently dependent on whether or not brain networks are dynamic. This is the first comprehensive study to evaluate multiple network metrics at a voxel-wise resolution in the human brain at both the whole brain and regional level under various conditions: resting state, visual stimulation, and multisensory (auditory and visual stimulation. Our results show that despite global network stability, functional brain networks exhibit considerable task-induced changes in connectivity, efficiency, and community structure at the regional level.

  10. "Messing with the Mind: Evolutionary Challenges to Human Brain Augmentation

    ARTHUR eSANIOTIS

    2014-09-01

    Full Text Available The issue of brain augmentation has received considerable scientific attention over the last two decades. A key factor to brain augmentation that has been widely overlooked are the complex evolutionary processes which have taken place in evolving the human brain to its current state of functioning. Like other bodily organs, the human brain has been subject to the forces of biological adaptation. The structure and function of the brain, is very complex and only now we are beginning to understand some of the basic concepts of cognition. Therefore, this article proposes that brain-machine interfacing and nootropics are not going to produce augmented brains because we do not understand enough about how evolutionary pressures have informed the neural networks which support human cognitive faculties.

  11. "Messing with the mind": evolutionary challenges to human brain augmentation.

    Saniotis, Arthur; Henneberg, Maciej; Kumaratilake, Jaliya; Grantham, James P

    2014-01-01

    The issue of brain augmentation has received considerable scientific attention over the last two decades. A key factor to brain augmentation that has been widely overlooked are the complex evolutionary processes which have taken place in evolving the human brain to its current state of functioning. Like other bodily organs, the human brain has been subject to the forces of biological adaptation. The structure and function of the brain, is very complex and only now we are beginning to understand some of the basic concepts of cognition. Therefore, this article proposes that brain-machine interfacing and nootropics are not going to produce "augmented" brains because we do not understand enough about how evolutionary pressures have informed the neural networks which support human cognitive faculties. PMID:25324734

  12. From reverse transcription to human brain tumors

    Dmitrenko V. V.

    2013-05-01

    Full Text Available Reverse transcriptase from avian myeloblastosis virus (AMV was the subject of the study, from which the investi- gations of the Department of biosynthesis of nucleic acids were started. Production of AMV in grams quantities and isolation of AMV reverse transcriptase were established in the laboratory during the seventies of the past cen- tury and this initiated research on the cDNA synthesis, cloning and investigation of the structure and functions of the eukaryotic genes. Structures of salmon insulin and insulin-like growth factor (IGF family genes and their transcripts were determined during long-term investigations. Results of two modern techniques, microarray-ba- sed hybridization and SAGE, were used for the identification of the genes differentially expressed in astrocytic gliomas and human normal brain. Comparison of SAGE results on the genes overexpressed in glioblastoma with the results of microarray analysis revealed a limited number of common genes. 105 differentially expressed genes, common to both methods, can be included in the list of candidates for the molecular typing of glioblastoma. The first experiments on the classification of glioblastomas based on the data of the 20 genes expression were conducted by using of artificial neural network analysis. The results of these experiments showed that the expression profiles of these genes in 224 glioblastoma samples and 74 normal brain samples could be according to the Koho- nen’s maps. The CHI3L1 and CHI3L2 genes of chitinase-like cartilage protein were revealed among the most overexpressed genes in glioblastoma, which could have prognostic and diagnostic potential. Results of in vitro experiments demonstrated that both proteins, CHI3L1 and CHI3L2, may initiate the phosphorylation of ERK1/ ERK2 and AKT kinases leading to the activation of MAPK/ERK1/2 and PI3K/AKT signaling cascades in human embryonic kidney 293 cells, human glioblastoma U87MG, and U373 cells. The new human cell line

  13. Neuronal connectivity, regional differentiation, and brain damage in humans.

    Zaidel, Dahlia W.

    1999-01-01

    When circumscribed brain regions are damaged in humans, highly specific iimpairments in language, memory, problem solving, and cognition are observed. Neurosurgery such as "split brain" or hemispherectomy, for example has shown that encompassing regions, the left and right cerebral hemispheres each control human behavior in unique ways. Observations stretching over 100 years of patients with unilateral focal brain damage have revealed, withouth the theoretical benefits of "cognitive neurosci...

  14. Macroscopic networks in the human brain: mapping connectivity in healthy and damaged brains

    Nijhuis, E.H.J.

    2013-01-01

    The human brain contains a network of interconnected neurons. Recent advances in functional and structural in-vivo magnetic resonance neuroimaging (MRI) techniques have provided opportunities to model the networks of the human brain on a macroscopic scale. This dissertation investigates the possibil

  15. Analysis of brain CT on 120 patients of human cysticercosis

    A study on brain CT was made in 120 patients of human cysticercosis, which is a rare disease in Japan and clinical symptoms and laboratory data for the diagnosis were also discussed. From the point of therapeutic view, we proposed a new differentiation on brain CT of human cysticercosis, which is divided into two groups according to the alve or dead parasite. Furthermore, we proposed a new type named multiple large and small cysts type on brain CT. The idea of diagnostic standard was made integrating brain CT image, clinical symptoms and labolatory data. (author)

  16. Analysis of brain CT on 120 patients of human cysticercosis

    Ma, J.; To, R.; Ri, T.; Ra, S. (Jiamusi Medical Coll. (China)); Inomata, Taiten; Ogawa, Yasuhiro; Maeda, Tomoo

    1990-08-01

    A study on brain CT was made in 120 patients of human cysticercosis, which is a rare disease in Japan and clinical symptoms and laboratory data for the diagnosis were also discussed. From the point of therapeutic view, we proposed a new differentiation on brain CT of human cysticercosis, which is divided into two groups according to the alve or dead parasite. Furthermore, we proposed a new type named multiple large and small cysts type on brain CT. The idea of diagnostic standard was made integrating brain CT image, clinical symptoms and labolatory data. (author).

  17. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

    Li, Guangye; Zhang, Dingguo

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain. PMID:26982717

  18. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain. PMID:26982717

  19. Two action systems in the human brain.

    Binkofski, Ferdinand; Buxbaum, Laurel J

    2013-11-01

    The distinction between dorsal and ventral visual processing streams, first proposed by Ungerleider and Mishkin (1982) and later refined by Milner and Goodale (1995) has been elaborated substantially in recent years, spurred by two developments. The first was proposed in large part by Rizzolatti and Matelli (2003) and is a more detailed description of the multiple neural circuits connecting the frontal, temporal, and parietal cortices. Secondly, there are a number of behavioral observations that the classic "two visual systems" hypothesis is unable to accommodate without additional assumptions. The notion that the Dorsal stream is specialized for "where" or "how" actions and the Ventral stream for "What" knowledge cannot account for two prominent disorders of action, limb apraxia and optic ataxia, that represent a double dissociation in terms of the types of actions that are preserved and impaired. A growing body of evidence, instead, suggests that there are at least two distinct Dorsal routes in the human brain, referred to as the "Grasp" and "Use" systems. Both of these may be differentiated from the Ventral route in terms of neuroanatomic localization, representational specificity, and time course of information processing. PMID:22889467

  20. Brain Prostheses as a Dynamic System (Immortalizing the Human Brain?)

    Astakhov, Vadim

    2007-01-01

    Interest in development of brain prostheses, which might be proposed to recover mental functions lost due to neuron-degenerative disease or trauma, requires new methods in molecular engineering and nanotechnology to build artificial brain tissues. We develop a Dynamic Core model to analyze complexity of damaged biological neural network as well as transition and recovery of the system functionality due to changes in the system environment. We provide a method to model complexity of physical systems which might be proposed as an artificial tissue or prosthesis. Delocalization of Dynamic Core model is developed to analyze migration of mental functions in dynamic bio-systems which undergo architecture transition induced by trauma. Term Dynamic Core is used to define a set of causally related functions and Delocalization is used to describe the process of migration. Information geometry and topological formalisms are proposed to analyze information processes. A holographic model is proposed to construct dynamic e...

  1. New Heuristics for Interfacing Human Motor System using Brain Waves

    Mohammed El-Dosuky

    2012-09-01

    Full Text Available There are many new forms of interfacing human users to machines. We persevere here electric-mechanical form of interaction between human and machine. The emergence of brain-computer interface allows mind-to-movement systems. The story of the Pied Piper inspired us to devise some new heuristics for interfacing human motor system using brain waves, by combining head helmet and LumbarMotionMonitor. For the simulation we use java GridGain. Brain responses of classified subjects during training indicates that Probe can be the best stimulus to rely on in distinguishing between knowledgeable and not knowledgeable

  2. New Heuristics for Interfacing Human Motor System using Brain Waves

    Mohammed El-Dosuky; Ahmed El-Bassiouny; Taher Hamza; Magdy Rashad

    2012-01-01

    There are many new forms of interfacing human users to machines. We persevere here electric-mechanical form of interaction between human and machine. The emergence of brain-computer interface allows mind-to-movement systems. The story of the Pied Piper inspired us to devise some new heuristics for interfacing human motor system using brain waves, by combining head helmet and LumbarMotionMonitor. For the simulation we use java GridGain. Brain responses of classified subjects during training in...

  3. Common genetic variants influence human subcortical brain structures

    Hibar, Derrek P.; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from...

  4. Common genetic variants influence human subcortical brain structures

    Hibar, Derrek P.; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magn...

  5. Canonical Genetic Signatures of the Adult Human Brain

    Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Anil G. Jegga; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L; Menche, Jörge; Szafer, Aaron; Collman, Forrest

    2015-01-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological ann...

  6. Moment-to-moment brain signal variability: A next frontier in human brain mapping?

    Garrett, D.; Samanez-Larkin, G.; MacDonald, S; Lindenberger, U; McIntosh, A.; Grady, C.

    2013-01-01

    Neuroscientists have long observed that brain activity is naturally variable from moment-to-moment, but neuroimaging research has largely ignored the potential importance of this phenomenon. An emerging research focus on within-person brain signal variability is providing novel insights, and offering highly predictive, complementary, and even orthogonal views of brain function in relation to human life-span development, cognitive performance, and various clinical conditions. As a result, brai...

  7. Neuroglobin and Cytoglobin expression in the human brain

    Hundahl, Christian Ansgar; Kelsen, Jesper; Hay-Schmidt, Anders

    2013-01-01

    Neuroglobin and Cytoglobin are new members of the heme-globin family. Both globins are primarily expressed in neurons of the brain and retina. Neuroglobin and Cytoglobin have been suggested as novel therapeutic targets in various neurodegenerative diseases based on their oxygen binding and cell...... protecting properties. However, findings in Neuroglobin-deficient mice question the endogenous neuroprotective properties. The expression pattern of Neuroglobin and Cytoglobin in the rodent brain is also in contradiction to a major role of neuronal protection. In a recent study, Neuroglobin was ubiquitously...... expressed and up-regulated following stroke in the human brain. The present study aimed at confirming our previous observations in rodents using two post-mortem human brains. The anatomical localization of Neuroglobin and Cytoglobin in the human brain is much like what has been described for the rodent...

  8. Towards Developmental Connectomics of the Human Brain

    Miao eCao; Hao eHuang; Yun ePeng; Qi eDong; Yong eHe

    2016-01-01

    Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders...

  9. Common genetic variants influence human subcortical brain structures

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivieres, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Loohuis, Loes M. Olde; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santianez, Roberto; Rose, Emma J.; Salami, Alireza; Saemann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Puetz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Goering, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzah, Eva; Melle, Ingrid; Mahnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Muehleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Noethen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdes Hernandez, Maria C.; van't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffman, Wolfgang; Hosten, Norbert; Kahn, Rene S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Mueller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Voelzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernandez, Guillen; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Pol, Hilleke E. Hulshoff; Joensson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigat

  10. An anatomically comprehensive atlas of the adult human brain transcriptome

    Hawrylycz, M.J.; Beckmann, C.F.; et al., et al.

    2012-01-01

    Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising

  11. Alcohol-related brain damage in humans.

    Amaia M Erdozain

    Full Text Available Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann's area (BA 9 from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin β II, and α- and β-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in α-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in β-spectrin protein levels, and a significant increase in transmembranous α3 (catalytic subunit of the Na+,K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of α-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic α- and β-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics.

  12. Artificial Brain Based on Credible Neural Circuits in a Human Brain

    Burger, John Robert

    2010-01-01

    Neurons are individually translated into simple gates to plan a brain with human psychology and intelligence. State machines, assumed previously learned in subconscious associative memory are shown to enable equation solving and rudimentary thinking using nanoprocessing within short term memory.

  13. Decoding the visual and subjective contents of the human brain

    Kamitani, Yukiyasu; Tong, Frank

    2005-01-01

    The potential for human neuroimaging to read-out the detailed contents of a person’s mental state has yet to be fully explored. We investigated whether the perception of edge orientation, a fundamental visual feature, can be decoded from human brain activity measured with functional magnetic resonance imaging (fMRI). Using statistical algorithms to classify brain states, we found that ensemble fMRI signals in early visual areas could reliably predict on individual trials which of eight stimul...

  14. Optogenetic control of human neurons in organotypic brain cultures

    Andersson, My; Avaliani, Natalia; Svensson, Andreas;

    2016-01-01

    Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof......-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies....

  15. Quantitation of glial fibrillary acidic protein in human brain tumours

    Rasmussen, S; Bock, E; Warecka, K;

    1980-01-01

    The glial fibrillary acidic protein (GFA) content of 58 human brain tumours was determined by quantitative immunoelectrophoresis, using monospecific antibody against GFA. Astrocytomas, glioblastomas, oligodendrogliomas, spongioblastomas, ependymomas and medulloblastomas contained relatively high...... amounts of GFA, up to 85 times the concentration in parietal grey substance of normal human brain. GFA was not found in neurinomas, meningiomas, adenomas of the hypophysis, or in a single case of metastasis of adenocarcinoma. Non-glial tumours of craniopharyngioma and haemangioblastoma were infiltrated by...

  16. Optogenetic control of human neurons in organotypic brain cultures.

    Andersson, My; Avaliani, Natalia; Svensson, Andreas; Wickham, Jenny; Pinborg, Lars H; Jespersen, Bo; Christiansen, Søren H; Bengzon, Johan; Woldbye, David P D; Kokaia, Merab

    2016-01-01

    Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies. PMID:27098488

  17. Brain tumour stem cells: the undercurrents of human brain cancer and their relationship to neural stem cells

    Dirks, Peter B.

    2007-01-01

    Conceptual and technical advances in neural stem cell biology are being applied to the study of human brain tumours. These studies suggest that human brain tumours are organized as a hierarchy and are maintained by a small number of tumour cells that have stem cell properties. Most of the bulk population of human brain tumours comprise cells that have lost the ability to initiate and maintain tumour growth. Although the cell of origin for human brain tumours is uncertain, recent evidence poin...

  18. Functional network organization of the human brain

    Power, Jonathan D.; Cohen, Alexander L.; Nelson, Steven M.; Wig, Gagan S.; Barnes, Kelly Anne; Church, Jessica A.; Vogel, Alecia C.; Laumann, Timothy O.; Miezin, Fran M.; Schlaggar, Bradley L.; Petersen, Steven E.

    2011-01-01

    Real-world complex systems may be mathematically modeled as graphs, revealing properties of the system. Here we study graphs of functional brain organization in healthy adults using resting state functional connectivity MRI. We propose two novel brain-wide graphs, one of 264 putative functional areas, the other a modification of voxelwise networks that eliminates potentially artificial short-distance relationships. These graphs contain many subgraphs in good agreement with known functional br...

  19. Methylomic trajectories across human fetal brain development

    Spiers, Helen; Hannon, Eilis; Schalkwyk, Leonard C; Smith, Rebecca; Wong, Chloe C. Y.; Michael C. O’Donovan; Bray, Nicholas J.; Mill, Jonathan

    2015-01-01

    Epigenetic processes play a key role in orchestrating transcriptional regulation during development. The importance of DNA methylation in fetal brain development is highlighted by the dynamic expression of de novo DNA methyltransferases during the perinatal period and neurodevelopmental deficits associated with mutations in the methyl-CpG binding protein 2 (MECP2) gene. However, our knowledge about the temporal changes to the epigenome during fetal brain development has, to date, been limited...

  20. Estimating Neural Signal Dynamics in the Human Brain

    Christopher W Tyler

    2011-06-01

    Full Text Available Although brain imaging methods are highly effective for localizing the effects of neural activation throughout the human brain in terms of the blood oxygenation level dependent (BOLD response, there is currently no way to estimate the underlying neural signal dynamics in generating the BOLD response in each local activation region (except for processes slower than the BOLD time course. Knowledge of the neural signal is critical information if spatial mapping is to progress to the analysis of dynamic information flow through the cortical networks as the brain performs its tasks. We introduce an analytic approach that provides a new level of conceptualization and specificity in the study of brain processing by noninvasive methods. This technique allows us to use brain imaging methods to determine the dynamics of local neural population responses to their native temporal resolution throughout the human brain, with relatively narrow confidence intervals on many response properties. The ability to characterize local neural dynamics in the human brain represents a significant enhancement of brain imaging capabilities, with potential application from general cognitive studies to assessment of neuropathologies.

  1. Conscious brain-to-brain communication in humans using non-invasive technologies.

    Carles Grau

    Full Text Available Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI. These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B communication between subjects (hyperinteraction. Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG changes with a CBI inducing the conscious perception of phosphenes (light flashes through neuronavigated, robotized transcranial magnetic stimulation (TMS, with special care taken to block sensory (tactile, visual or auditory cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues.

  2. 18F-FDG and 18F-FLT-PET Imaging for Monitoring Everolimus Effect on Tumor-Growth in Neuroendocrine Tumors

    Johnbeck, Camilla Bardram; Munk Jensen, Mette; Nielsen, Carsten Haagen;

    2014-01-01

    INTRODUCTION: The mTOR inhibitor everolimus has shown promising results in some but not all neuroendocrine tumors. Therefore, early assessment of treatment response would be beneficial. In this study, we investigated the in vivo and in vitro treatment effect of everolimus in neuroendocrine tumors...

  3. Correlation of 18F-FLT and 18F-FDG uptake on PET with Ki-67 immunohistochemistry in non-small cell lung cancer

    The nucleoside analogue 3'-deoxy-3'-18F-fluorothymidine (FLT) has recently been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively evaluated whether FLT uptake reflects proliferative activity as indicated by the Ki-67 index in non-small cell lung cancer (NSCLC), in comparison with 2-deoxy-2-18F-fluoro-D-glucose (FDG). A total of 18 patients with newly diagnosed NSCLC were examined with both FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. Tumour lesions were identified as areas of focally increased uptake, exceeding background uptake in the lungs. For semi-quantitative analysis, the maximum standardised uptake value (SUV) was calculated. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Immunohistochemical findings were correlated with SUVs. The sensitivity of FLT and FDG PET for the detection of lung cancer was 72% and 89%, respectively. Four of the five false-negative FLT PET findings occurred in bronchiolo-alveolar carcinoma. The mean FLT SUV was significantly lower than the mean FDG SUV. A significant correlation was observed between FLT SUV and Ki-67 index (r = 0.77; p < 0.0002) and for FDG SUV (r = 0.81; p < 0.0001). The results of this preliminary study suggest that, compared with FDG, FLT may be less sensitive for primary staging in patients with NSCLC. Although FLT uptake correlated significantly with proliferative activity in NSCLC, the correlation was not better than that for FDG uptake. (orig.)

  4. Human capital in European peripheral regions: Brain - Drain and Brain - Gain : policies on brain drain

    CSTM,

    2004-01-01

    Policies on brain drain Many policies are related to the problem of brain drain and brain gain. For instance, every policy that makes a region more attractive to live in, will make a region a more attractive place for the highly educated to settle. In theory this can be everything ranging from infra

  5. Human brain activity with functional NIR optical imager

    Luo, Qingming

    2001-08-01

    In this paper we reviewed the applications of functional near infrared optical imager in human brain activity. Optical imaging results of brain activity, including memory for new association, emotional thinking, mental arithmetic, pattern recognition ' where's Waldo?, occipital cortex in visual stimulation, and motor cortex in finger tapping, are demonstrated. It is shown that the NIR optical method opens up new fields of study of the human population, in adults under conditions of simulated or real stress that may have important effects upon functional performance. It makes practical and affordable for large populations the complex technology of measuring brain function. It is portable and low cost. In cognitive tasks subjects could report orally. The temporal resolution could be millisecond or less in theory. NIR method will have good prospects in exploring human brain secret.

  6. A new antigen retrieval technique for human brain tissue.

    Raúl Alelú-Paz

    Full Text Available Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times.

  7. TV, Brain Waves and Human Behavior

    Science News, 1978

    1978-01-01

    Describes the procedure to test the hypothesis that subjects' brain waves in response to a television flicker (distraction) would be smaller in amplitude during television programs of high, in contrast to low, interest. Results from 12 viewers support the hypothesis. (CP)

  8. Evolution of the human brain: when bigger is better.

    Michel A. Hofman

    2014-03-01

    Full Text Available Comparative studies of the brain in mammals suggest that there are general architectural principles governing its growth and evolutionary development. We are beginning to understand the geometric, biophysical and energy constraints that have governed the evolution and functional organization of the brain and its underlying neuronal network. The object of this review is to present current perspectives on primate brain evolution, especially in humans, and to examine some hypothetical organizing principles that underlie the brain’s complex organization. Some of the design principles and operational modes that underlie the information processing capacity of the cerebral cortex in primates will be explored. It is shown that the development of the cortex coordinates folding with connectivity in a way that produces smaller and faster brains, then otherwise would have been possible. In view of the central importance placed on brain evolution in explaining the success of our own species, one may wonder whether there are physical limits that constrain its processing power and evolutionary potential. It will be argued that at a brain size of about 3500 cm3, corresponding to a brain volume two to three times that of modern man, the brain seems to reach its maximum processing capacity. The larger the brain grows beyond this critical size, the less efficient it will become, thus limiting any improvement in cognitive power.

  9. Expression of iron-related genes in human brain and brain tumors

    Britton Robert S

    2009-04-01

    Full Text Available Abstract Background Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (HAMP, HFE, neogenin (NEO1, transferrin receptor 1 (TFRC, transferrin receptor 2 (TFR2, and hemojuvelin (HFE2 in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines. Results Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens. Conclusion These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.

  10. Shortcomings of the Human Brain and Remedial Action by Religion

    Reich, K. Helmut

    2010-01-01

    There is no consensus as to whether, and if so, in which regard and to what extent science and religion is needed for human survival. Here a circumscribed domain is taken up: the sovereignty and sufficiency of the human brain in this context. Several of its shortcomings are pointed out. Religion and other aspects of culture are needed for remedial…

  11. Sibling rivalry among paralogs promotes evolution of the human brain

    Tyler-Smith, Chris; Xue, Yali

    2012-01-01

    Geneticists have long sought to identify the genetic changes that made us human, but pinpointing the functional-relevant changes has been challenging. Two papers in this issue suggest that partial duplication of SRGAP2, producing an incomplete protein that antagonizes the original, contributed to human brain evolution.

  12. Sibling rivalry among paralogs promotes evolution of the human brain.

    Tyler-Smith, Chris; Xue, Yali

    2012-05-11

    Geneticists have long sought to identify the genetic changes that made us human, but pinpointing the functionally relevant changes has been challenging. Two papers in this issue suggest that partial duplication of SRGAP2, producing an incomplete protein that antagonizes the original, contributed to human brain evolution. PMID:22579279

  13. The Evolution of Human Intelligence and the Coefficient of Additive Genetic Variance in Human Brain Size

    Miller, Geoffrey F.; Penke, Lars

    2007-01-01

    Most theories of human mental evolution assume that selection favored higher intelligence and larger brains, which should have reduced genetic variance in both. However, adult human intelligence remains highly heritable, and is genetically correlated with brain size. This conflict might be resolved by estimating the coefficient of additive genetic…

  14. Magnetoencephalography in studies of human cognitive brain function.

    Näätänen, R; Ilmoniemi, R J; Alho, K

    1994-09-01

    Magnetoencephalography provides a new dimension to the functional imaging of the brain. The cerebral magnetic fields recorded noninvasively enable the accurate determination of locations of cerebral activity with an uncompromized time resolution. The first whole-scalp sensor arrays have just recently come into operation, and significant advances are to be expected in both neurophysiological and cognitive studies, as well as in clinical practice. However, although the accuracy of locating isolated sources of brain activity has improved, identification of multiple simultaneous sources can still be a problem. Therefore, attempts are being made to combine magnetoencephalography with other brain-imaging methods to improve spatial localization of multiple sources and, simultaneously, to achieve a more complete characterization of different aspects of brain activity during cognitive processing. Owing to its good time resolution and considerably better spatial accuracy than that provided by EEG, magnetoencephalography holds great promise as a tool for revealing information-processing sequences of the human brain. PMID:7529443

  15. Three-dimensional morphology of the human embryonic brain

    N. Shiraishi

    2015-09-01

    Full Text Available The morphogenesis of the cerebral vesicles and ventricles was visualized in 3D movies using images derived from human embryo specimens between Carnegie stage 13 and 23 from the Kyoto Collection. These images were acquired with a magnetic resonance microscope equipped with a 2.35-T superconducting magnet. Three-dimensional images using the same scale demonstrated brain development and growth effectively. The non-uniform thickness of the brain tissue, which may indicate brain differentiation, was visualized with thickness-based surface color mapping. A closer view was obtained of the unique and complicated differentiation of the rhombencephalon, especially with regard to the internal view and thickening of the brain tissue. The present data contribute to a better understanding of brain and cerebral ventricle development.

  16. The bilingual brain: Flexibility and control in the human cortex

    Buchweitz, Augusto; Prat, Chantel

    2013-12-01

    The goal of the present review is to discuss recent cognitive neuroscientific findings concerning bilingualism. Three interrelated questions about the bilingual brain are addressed: How are multiple languages represented in the brain? how are languages controlled in the brain? and what are the real-world implications of experience with multiple languages? The review is based on neuroimaging research findings about the nature of bilingual processing, namely, how the brain adapts to accommodate multiple languages in the bilingual brain and to control which language should be used, and when. We also address how this adaptation results in differences observed in the general cognition of bilingual individuals. General implications for models of human learning, plasticity, and cognitive control are discussed.

  17. Decade of the Brain 1990--2000: Maximizing human potential

    1991-04-01

    The US Decade of the Brain offers scientists throughout the Federal Government a unique opportunity to advance and apply scientific knowledge about the brain and nervous system. During the next 10 years, scientists hope to maximize human potential through studies of human behavior, senses and communication, learning and memory, genetic/chemical alterations, and environmental interactions. Progress in these areas should lead to reductions in mortality from brain and nervous system disorders and to improvements in the quality of life. This report identifies nine research areas that could form the basis of an integrated program in the brain and behavioral sciences. A chart summarizing the Federal activities in these nine areas may be found at the back of the report. In addition, three areas that span the nine research areas -- basic research, technology and international activities -- are considered.

  18. Expectation modulates neural representations of valence throughout the human brain.

    Ramayya, Ashwin G; Pedisich, Isaac; Kahana, Michael J

    2015-07-15

    The brain's sensitivity to unexpected gains or losses plays an important role in our ability to learn new behaviors (Rescorla and Wagner, 1972; Sutton and Barto, 1990). Recent work suggests that gains and losses are ubiquitously encoded throughout the human brain (Vickery et al., 2011), however, the extent to which reward expectation modulates these valence representations is not known. To address this question, we analyzed recordings from 4306 intracranially implanted electrodes in 39 neurosurgical patients as they performed a two-alternative probability learning task. Using high-frequency activity (HFA, 70-200 Hz) as an indicator of local firing rates, we found that expectation modulated reward-related neural activity in widespread brain regions, including regions that receive sparse inputs from midbrain dopaminergic neurons. The strength of unexpected gain signals predicted subjects' abilities to encode stimulus-reward associations. Thus, neural signals that are functionally related to learning are widely distributed throughout the human brain. PMID:25937489

  19. Addiction Circuitry in the Human Brain*

    Volkow, Nora D.; Wang, Gene-Jack; Fowler, Joanna S.; Tomasi, Dardo

    2011-01-01

    A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person’s risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circ...

  20. Aluminum accumulation in human brain tissues

    Ishihara, R.; Takeuchi, T.; Ohta, T. [Dept. of Psychiatry, Nagoya University School of Medicine, Nagoya, Aichi (Japan); Ektessabi, A.M. [Graduate School of Engineering, Kyoto University, Kyoto (Japan); Hanaichi, T.; Ishihara, Y. [Hanaichi Ultrastructure Research Institute Co. Okazaki, Okazaki, Aichi (Japan); Fujita, Y. [Equipment Center for Research and Education, Nagoya, Aichi (Japan)

    1999-07-01

    Normal cell functions of the brain are often impaired by an excess accumulation of metal ions. There have been increasing efforts in recent years to measure and quantify excessive accumulations of biological constituent elements (such as Fe, Zn, Cu, and Ca), as well as the presence and distribution of contaminating elements (such as Al) in the brain tissues. Since Al might be associated with cases of neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amiotrophic lateral screlosis (ALS), it is very important to measure and quantify Al levels using precise analytical techniques. The aim of this investigation is to measure the Al contents present in the temporal cortices for three cases. The specimens concerned were taken from unfixed autopsy brains, which have been preserved in a deep freezer at -80degC. A tandem type accelerator of 2 MeV energy was used to measure the concentrations of Al in these specimen tissues. In order to increase the sensitivity of the signals in the low energy region of the spectra, the absorber was removed. The results show that peak intensity depends on the site measured. In certain cases, however, an extremely high concentration of Al was observed in PIXE spectra, with an intensity higher than those of the other major elements present in the brain. Samples from the same subjects were also analyzed using EPMA-EDX. X-ray maps produced by EPMA-EDX showed the presence of extremely high concentrations of Al. The results yielded by PIXE analysis was in good qualitative agreement with those from EPMA-EDX. (author)

  1. An Embodied Brain Model of the Human Foetus

    Yasunori Yamada; Hoshinori Kanazawa; Sho Iwasaki; Yuki Tsukahara; Osuke Iwata; Shigehito Yamada; Yasuo Kuniyoshi

    2016-01-01

    Cortical learning via sensorimotor experiences evoked by bodily movements begins as early as the foetal period. However, the learning mechanisms by which sensorimotor experiences guide cortical learning remain unknown owing to technical and ethical difficulties. To bridge this gap, we present an embodied brain model of a human foetus as a coupled brain-body-environment system by integrating anatomical/physiological data. Using this model, we show how intrauterine sensorimotor experiences rela...

  2. The intrinsic geometry of the human brain connectome

    Ye, Allen Q.; Ajilore, Olusola A.; Conte, Giorgio; GadElkarim, Johnson; Thomas-Ramos, Galen; Zhan, Liang; Yang, Shaolin; Kumar, Anand; Magin, Richard L.; G. Forbes, Angus; Leow, Alex D.

    2015-01-01

    This paper describes novel methods for constructing the intrinsic geometry of the human brain connectome using dimensionality-reduction techniques. We posit that the high-dimensional, complex geometry that represents this intrinsic topology can be mathematically embedded into lower dimensions using coupling patterns encoded in the corresponding brain connectivity graphs. We tested both linear and nonlinear dimensionality-reduction techniques using the diffusion-weighted structural connectome ...

  3. Gene Expression Profiling in the Brains of Human Cocaine Abusers

    Bannon, Michael J.; Kapatos, Gregory; ALBERTSON, DAWN N.

    2005-01-01

    Chronic cocaine abuse induces long-term neurochemical, structural and behavioural changes thought to result from altered gene expression within the nucleus accumbens and other brain regions playing a critical role in addiction. Recent methodological advances now allow the profiling of gene expression in human postmortem brain. In this article, we review studies in which we have used Affymetrix oligonucleotide microarrays to identify transcripts that are differentially expressed in the nucleus...

  4. Increased morphological asymmetry, evolvability and plasticity in human brain evolution

    Gómez-Robles, Aida; Hopkins, William D.; Sherwood, Chet C.

    2013-01-01

    The study of hominin brain evolution relies mostly on evaluation of the endocranial morphology of fossil skulls. However, only some general features of external brain morphology are evident from endocasts, and many anatomical details can be difficult or impossible to examine. In this study, we use geometric morphometric techniques to evaluate inter- and intraspecific differences in cerebral morphology in a sample of in vivo magnetic resonance imaging scans of chimpanzees and humans, with spec...

  5. Endocannabinoids modulate human blood–brain barrier permeability in vitro

    Hind, William H.; Tufarelli, Cristina; Neophytou, Maria; Anderson, Susan I; England, Timothy J.; O'Sullivan, Saoirse E

    2015-01-01

    Background and Purpose Endocannabinoids alter permeability at various epithelial barriers, and cannabinoid receptors and endocannabinoid levels are elevated by stroke, with potential neuroprotective effects. We therefore explored the role of endocannabinoids in modulating blood–brain barrier (BBB) permeability in normal conditions and in an ischaemia/reperfusion model. Experimental Approach Human brain microvascular endothelial cell and astrocyte co-cultures modelled the BBB. Ischaemia was mo...

  6. Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

    Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

    2016-03-01

    Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing. PMID:26966964

  7. Three-dimensional microtomographic imaging of human brain cortex

    Mizutania, Ryuta; Uesugi, Kentaro; Ohyama, Masami; Takekoshi, Susumu; Osamura, R Yoshiyuki; Suzuki, Yoshio

    2016-01-01

    This paper describes an x-ray microtomographic technique for imaging the three-dimensional structure of the human cerebral cortex. Neurons in the brain constitute a neural circuit as a three-dimensional network. The brain tissue is composed of light elements that give little contrast in a hard x-ray transmission image. The contrast was enhanced by staining neural cells with metal compounds. The obtained structure revealed the microarchitecture of the gray and white matter regions of the frontal cortex, which is responsible for the higher brain functions.

  8. Regional distribution of serotonin transporter protein in postmortem human brain

    Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met

  9. Pain perception and its genesis in the human brain

    Andrew CN CHEN

    2008-01-01

    In the past two decades, pain perception in the human brain has been studied with EEG/MEG brain topography and PET/ fMRI neuroimaging techniques. A host of cortical and subeortical loci can be activated by various nociceptive conditions. The activation in pain perception can be induced by physical (electrical, thermal, mechanical), chemical (capsacin, ascoric acid), psychological (anxiety, stress, nocebo) means, and pathological (e.g. migraine, neuropathic) diseases. This article deals mainly on the activation, but not modulation, of human pain in the brain. The brain areas identified are named pain representation, matrix, neuraxis, or signature. The sites are not uniformly isolated across various studies, but largely include a set of cores sites: thalamus and primary somatic area (SI), second somatic area (SII), insular cortex (IC), prefrontal cortex (PFC), cingnlate, and parietal cortices. Other areas less reported and considered important in pain perception include brainstem, hippocampus, amygdala and supplementary motor area (SMA). The issues of pain perception basically encompass both the site and the mode of brain function. Although the site issue is delineared to a large degree, the mode issue has been much less explored. From the temporal dynamics, IC can be considered as the initial stage in genesis of pain perception as conscious suffering, the unique aversion in the human brain.

  10. A navigational guidance system in the human brain.

    Spiers, Hugo J; Maguire, Eleanor A

    2007-01-01

    Finding your way in large-scale space requires knowing where you currently are and how to get to your goal destination. While much is understood about the neural basis of one's current position during navigation, surprisingly little is known about how the human brain guides navigation to goals. Computational accounts argue that specific brain regions support navigational guidance by coding the proximity and direction to the goal, but empirical evidence for such mechanisms is lacking. Here, we scanned subjects with functional magnetic resonance imaging as they navigated to goal destinations in a highly accurate virtual simulation of a real city. Brain activity was then analyzed in combination with metric measures of proximity and direction to goal destinations that were derived from each individual subject's coordinates at every second of navigation. We found that activity in the medial prefrontal cortex was positively correlated, and activity in a right subicular/entorhinal region was negatively correlated with goal proximity. By contrast, activity in bilateral posterior parietal cortex was correlated with egocentric direction to goals. Our results provide empirical evidence for a navigational guidance system in the human brain, and define more precisely the contribution of these three brain regions to human navigation. In addition, these findings may also have wider implications for how the brain monitors and integrates different types of information in the service of goal-directed behavior in general. PMID:17492693

  11. Distribution of vesicular glutamate transporters in the human brain

    Erika eVigneault

    2015-03-01

    Full Text Available Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3 are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains.

  12. Decoding the visual and subjective contents of the human brain.

    Kamitani, Yukiyasu; Tong, Frank

    2005-05-01

    The potential for human neuroimaging to read out the detailed contents of a person's mental state has yet to be fully explored. We investigated whether the perception of edge orientation, a fundamental visual feature, can be decoded from human brain activity measured with functional magnetic resonance imaging (fMRI). Using statistical algorithms to classify brain states, we found that ensemble fMRI signals in early visual areas could reliably predict on individual trials which of eight stimulus orientations the subject was seeing. Moreover, when subjects had to attend to one of two overlapping orthogonal gratings, feature-based attention strongly biased ensemble activity toward the attended orientation. These results demonstrate that fMRI activity patterns in early visual areas, including primary visual cortex (V1), contain detailed orientation information that can reliably predict subjective perception. Our approach provides a framework for the readout of fine-tuned representations in the human brain and their subjective contents. PMID:15852014

  13. Measuring dopamine release in the human brain with PET

    Volkow, N.D. [Brookhaven National Lab., Upton, NY (United States)]|[State Univ. of New York at Stony Brook, Stony Brook, NY (United States). Dept. of Psychiatry; Fowler, J.S.; Logan, J.; Wang, G.J. [Brookhaven National Lab., Upton, NY (United States)

    1995-12-01

    The dopamine system is involved in the regulation of brain regions that subserve motor, cognitive and motivational behaviors. Disruptions of dopamine (DA) function have ben implicated in neurological and psychiatric illnesses including substance abuse as well as on some of the deficits associated with aging of the human brain. This has made the DA system an important topic in research in the neurosciences and neuroimaging as well as an important molecular target for drug development. Positron Emission Tomography (PET), was the first technology that enabled direct measurement of components of the DA system in the living human brain. Imaging studies of DA in the living brain have been indirect, relying on the development of radiotracers to label DA receptors, DA transporters, compounds which have specificity for the enzymes which degrade synaptic DA. Additionally, through the use of tracers that provide information on regional brain activity (ie brain glucose metabolism and cerebral blood flow) and of appropriate pharmacological interventions, it has been possible to assess the functional consequences of changes in brain DA activity. DA specific ligands have been useful in the evaluation of patients with neuropsychiatric illnesses as well as to investigate receptor blockade by antipsychotic drugs. A limitation of strategies that rely on the use of DA specific ligands is that the measures do not necessarily reflect the functional state of the dopaminergic system and that there use to study the effects of drugs is limited to the investigation of receptor or transporter occupancy. Newer strategies have been developed in an attempt to provide with information on dopamine release and on the functional responsivity of the DA system in the human brain. This in turn allows to investigate the effects of pharmacological agent in an analogous way to what is done with microdialysis techniques.

  14. Magnetic resonance elastography in normal human brain: preliminary study

    Objective: To study the application of magnetic resonance elastography (MRE) in the human brain. Methods: An external force actuator was developed. The actuator was fixed to the head coil. During MRE scan, one side of the actuator was attached to the volunteers' head. Low frequency oscillation was produced by the actuator and generated shear waves propagating into brain tissue. The pulse sequence of MRE was designed. A modified gradient echo sequence was developed with motion sensitizing gradient (MSG) imposed along X, Y or Z direction. Cyclic displacement within brain tissue induced by shear waves caused a measurable phase shift in the received MR signal. From the measured phase shift, the displacement at each voxel could be calculated, and the shear waves within the brain were directly imaged. By adjusting the phase offset, the dynamic propagation of shear waves in a wave cycle was obtained. Phase images were processed with local frequency estimation (LFE) technique to obtain the elasticity images. Shear waves at 100 Hz, 150 Hz, and 200 Hz were applied. Results: The phase images of MRE directly imaged the propagating shear waves within the brain. The direction of the propagation was from surface of the brain to the center. The wavelength of shear waves varied with the change of actuating frequency. The change of wavelength of shear waves in gray and white matter of the brain was identified. The wavelength of shear waves in gray matter was shorter than that in white matter. The elasticity image of the brain revealed that the shear modulus of the white matter was higher than that of gray matter. Conclusion: The phase images of MRE can directly visualize the propagation of shear waves in the brain tissue. The elasticity image of the brain can demonstrate the change of elasticity between gray and white matter. (authors)

  15. The brain-mind quiddity: ethical issues in the use of human brain tissue for therapeutic and scientific purposes.

    Burd, L; Gregory, J.M.; Kerbeshian, J

    1998-01-01

    The use of human brain tissue in neuroscience research is increasing. Recent developments include transplanting neural tissue, growing or maintaining neural tissue in laboratories and using surgically removed tissue for experimentation. Also, it is likely that in the future there will be attempts at partial or complete brain transplants. A discussion of the ethical issues of using human brain tissue for research and brain transplantation has been organized around nine broadly defined topic ar...

  16. Common genetic variants influence human subcortical brain structures.

    Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M; Weale, Michael E; Weinberger, Daniel R; Adams, Hieab H H; Launer, Lenore J; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L; Becker, James T; Yanek, Lisa; van der Lee, Sven J; Ebling, Maritza; Fischl, Bruce; Longstreth, W T; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N; van Duijn, Cornelia M; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M Arfan; Martin, Nicholas G; Wright, Margaret J; Schumann, Gunter; Franke, Barbara; Thompson, Paul M; Medland, Sarah E

    2015-04-01

    The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

  17. The modular and integrative functional architecture of the human brain.

    Bertolero, Maxwell A; Yeo, B T Thomas; D'Esposito, Mark

    2015-12-01

    Network-based analyses of brain imaging data consistently reveal distinct modules and connector nodes with diverse global connectivity across the modules. How discrete the functions of modules are, how dependent the computational load of each module is to the other modules' processing, and what the precise role of connector nodes is for between-module communication remains underspecified. Here, we use a network model of the brain derived from resting-state functional MRI (rs-fMRI) data and investigate the modular functional architecture of the human brain by analyzing activity at different types of nodes in the network across 9,208 experiments of 77 cognitive tasks in the BrainMap database. Using an author-topic model of cognitive functions, we find a strong spatial correspondence between the cognitive functions and the network's modules, suggesting that each module performs a discrete cognitive function. Crucially, activity at local nodes within the modules does not increase in tasks that require more cognitive functions, demonstrating the autonomy of modules' functions. However, connector nodes do exhibit increased activity when more cognitive functions are engaged in a task. Moreover, connector nodes are located where brain activity is associated with many different cognitive functions. Connector nodes potentially play a role in between-module communication that maintains the modular function of the brain. Together, these findings provide a network account of the brain's modular yet integrated implementation of cognitive functions. PMID:26598686

  18. Addiction circuitry in the human brain (*).

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.

    2011-09-27

    A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person's risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circuits involved in reward, memory, executive function, and motivation, contribute to some of the differences in addiction vulnerability. A better understanding of the main circuits affected by chronic drug use and the influence of social stressors, developmental trajectories, and genetic background on these circuits is bound to lead to a better understanding of addiction and to more effective strategies for the prevention and treatment of substance-use disorders.

  19. Toward discovery science of human brain function

    Biswal, Bharat B; Mennes, Maarten; Zuo, Xi-Nian;

    2010-01-01

    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...... 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...

  20. A versatile new technique to clear mouse and human brain

    Costantini, Irene; Di Giovanna, Antonino Paolo; Allegra Mascaro, Anna Letizia; Silvestri, Ludovico; Müllenbroich, Marie Caroline; Sacconi, Leonardo; Pavone, Francesco S.

    2015-07-01

    Large volumes imaging with microscopic resolution is limited by light scattering. In the last few years based on refractive index matching, different clearing approaches have been developed. Organic solvents and water-based optical clearing agents have been used for optical clearing of entire mouse brain. Although these methods guarantee high transparency and preservation of the fluorescence, though present other non-negligible limitations. Tissue transformation by CLARITY allows high transparency, whole brain immunolabelling and structural and molecular preservation. This method however requires a highly expensive refractive index matching solution limiting practical applicability. In this work we investigate the effectiveness of a water-soluble clearing agent, the 2,2'-thiodiethanol (TDE) to clear mouse and human brain. TDE does not quench the fluorescence signal, is compatible with immunostaining and does not introduce any deformation at sub-cellular level. The not viscous nature of the TDE make it a suitable agent to perform brain slicing during serial two-photon (STP) tomography. In fact, by improving penetration depth it reduces tissue slicing, decreasing the acquisition time and cutting artefacts. TDE can also be used as a refractive index medium for CLARITY. The potential of this method has been explored by imaging a whole transgenic mouse brain with the light sheet microscope. Moreover we apply this technique also on blocks of dysplastic human brain tissue transformed with CLARITY and labeled with different antibody. This clearing approach significantly expands the application of single and two-photon imaging, providing a new useful method for quantitative morphological analysis of structure in mouse and human brain.

  1. Visual dictionaries as intermediate features in the human brain

    Kandan eRamakrishnan

    2015-01-01

    Full Text Available The human visual system is assumed to transform low level visual features to object and scene representations via features of intermediate complexity. How the brain computationally represents intermediate features is still unclear. To further elucidate this, we compared the biologically plausible HMAX model and Bag of Words (BoW model from computer vision. Both these computational models use visual dictionaries, candidate features of intermediate complexity, to represent visual scenes, and the models have been proven effective in automatic object and scene recognition. These models however differ in the computation of visual dictionaries and pooling techniques. We investigated where in the brain and to what extent human fMRI responses to short video can be accounted for by multiple hierarchical levels of the HMAX and BoW models. Brain activity of 20 subjects obtained while viewing a short video clip was analyzed voxel-wise using a distance-based variation partitioning method. Results revealed that both HMAX and BoW explain a significant amount of brain activity in early visual regions V1, V2 and V3. However BoW exhibits more consistency across subjects in accounting for brain activity compared to HMAX. Furthermore, visual dictionary representations by HMAX and BoW explain significantly some brain activity in higher areas which are believed to process intermediate features. Overall our results indicate that, although both HMAX and BoW account for activity in the human visual system, the BoW seems to more faithfully represent neural responses in low and intermediate level visual areas of the brain.

  2. Unveiling the mystery of visual information processing in human brain

    Diamant, Emanuel

    2008-01-01

    It is generally accepted that human vision is an extremely powerful information processing system that facilitates our interaction with the surrounding world. However, despite extended and extensive research efforts, which encompass many exploration fields, the underlying fundamentals and operational principles of visual information processing in human brain remain unknown. We still are unable to figure out where and how along the path from eyes to the cortex the sensory input perceived by the retina is converted into a meaningful object representation, which can be consciously manipulated by the brain. Studying the vast literature considering the various aspects of brain information processing, I was surprised to learn that the respected scholarly discussion is totally indifferent to the basic keynote question: "What is information?" in general or "What is visual information?" in particular. In the old days, it was assumed that any scientific research approach has first to define its basic departure points. ...

  3. Antigenic constituents of basic proteins from human brain

    Rajam, P. C.; Bogoch, S.; Rushworth, Mary A.; Forrester, P. C.

    1966-01-01

    1. A minimum of three distinct basic proteins have been chromatographically separated from a neutral, low ionic strength extract of human grey matter, using a discontinuous eluant series. 2. These chromatographic subfractions have been characterized by gradient elution chromatography and each subfraction analysed for distinct antigenic characteristics. 3. Evidence was adduced for the presence of a minimum of three distinct basic protein antigens, all of which may be specific to human brain but not to human liver. None of them appear to be human serum proteins. ImagesFIG. 2FIG. 3 PMID:4958738

  4. Rock magnetism linked to human brain magnetite

    Kirschvink, Joseph L.

    Magnetite has a long and distinguished career as one of the most important minerals in geophysics, as it is responsible for most of the remanent magnetization in marine sediments and the oceanic crust. It may come as a surprise to discover that it also ranks as the third or fourth most diverse mineral product formed biochemically by living organisms, and forms naturally in a variety of human tissues [Kirschvink et al., 1992].Magnetite was discovered in teeth of the Polyplacophora mollusks over 30 years ago, in magnetotactic bacteria nearly 20 years ago, in honey bees and homing pigeons nearly 15 years ago, but only recently in human tissue.

  5. Connectomics and new approaches for analyzing human brain functional connectivity

    Craddock, R. Cameron; Tungaraza, Rosalia L; Milham, Michael P.

    2015-01-01

    Estimating the functional interactions between brain regions and mapping those connections to corresponding inter-individual differences in cognitive, behavioral and psychiatric domains are central pursuits for understanding the human connectome. The number and complexity of functional interactions within the connectome and the large amounts of data required to study them position functional connectivity research as a “big data” problem. Maximizing the degree to which knowledge about human br...

  6. Frequency representation within the human brain: Stability versus plasticity

    Lim, Hubert H.; Minoo Lenarz; Gert Joseph; Thomas Lenarz

    2013-01-01

    A topographical representation for frequency has been identified throughout the auditory brain in animals but with limited evidence in humans. Using a midbrain implant, we identified an ordering of pitch percepts for electrical stimulation of sites across the human inferior colliculus (IC) that was consistent with the IC tonotopy shown in animals. Low pitches were perceived by the subject for stimulation of superficial IC sites while higher pitches were perceived for stimulation of deeper sit...

  7. Mapping Human Brain Function with MRI at 7 Tesla

    2002-01-01

    @@ In the past decade, the most significant development in MRI is the introduction of fMRI, which permits the mapping of human brain function with exquisite details noninvasively. Functional mapping can be achieved by measuring changes in the blood oxygenation level (I.e. The BOLD contrast) or cerebral blood flow.

  8. Stem Cells Expand Insights into Human Brain Evolution.

    Dyer, Michael A

    2016-04-01

    Substantial expansion in the number of cerebral cortex neurons is thought to underlie cognitive differences between humans and other primates, although the mechanisms underlying this expansion are unclear. Otani et al. (2016) utilize PSC-derived brain organoids to study how species-specific differences in cortical progenitor proliferation may underlie cortical evolution. PMID:27058930

  9. Proton NMR spectroscopy of human brain at 3 TESLA

    Mlynárik, V.; Starčuk, Zenon; Starčuk jr., Zenon; Gruber, S.; Moser, E.

    Valtice : Masarykova Univerzita, 2002, s. 30. ISBN 80-210-2808-4. [NMR Valtice. Valtice (CZ), 08.04.2002-10.04.2002] Institutional research plan: CEZ:AV0Z2065902 Keywords : spectroscopy * human brain Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

  10. The human brain response to dental pain relief.

    Meier, M L; Widmayer, S; Abazi, J; Brügger, M; Lukic, N; Lüchinger, R; Ettlin, D A

    2015-05-01

    Local anesthesia has made dental treatment more comfortable since 1884, but little is known about associated brain mechanisms. Functional magnetic resonance imaging is a modern neuroimaging tool widely used for investigating human brain activity related to sensory perceptions, including pain. Most brain regions that respond to experimental noxious stimuli have recently been found to react not only to nociception alone, but also to visual, auditory, and other stimuli. Thus, presumed functional attributions have come under scrutiny regarding selective pain processing in the brain. Evidently, innovative approaches are warranted to identify cerebral regions that are nociceptive specific. In this study, we aimed at circumventing known methodological confounders by applying a novel paradigm in 14 volunteers: rather than varying the intensity and thus the salience of painful stimuli, we applied repetitive noxious dental stimuli at constant intensity to the left mandibular canine. During the functional magnetic resonance imaging paradigm, we suppressed the nociceptive barrage by a mental nerve block. Brain activity before and after injection of 4% articaine was compared intraindividually on a group level. Dental pain extinction was observed to correspond to activity reduction in a discrete region of the left posterior insular cortex. These results confirm previous reports demonstrating that direct electrical stimulation of this brain region-but not of others-evokes bodily pain sensations. Hence, our investigation adds further evidence to the notion that the posterior insula plays a unique role in nociceptive processing. PMID:25691071

  11. Common genetic variants influence human subcortical brain structures

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

  12. Electrospray Ionization Ion Mobility Mass Spectrometry of Human Brain Gangliosides.

    Sarbu, Mirela; Robu, Adrian C; Ghiulai, Roxana M; Vukelić, Željka; Clemmer, David E; Zamfir, Alina D

    2016-05-17

    The progress of ion mobility spectrometry (IMS), together with its association to mass spectrometry (MS), opened new directions for the identification of various metabolites in complex biological matrices. However, glycolipidomics of the human brain by IMS MS represents an area untouched up to now, because of the difficulties encountered in brain sampling, analyte extraction, and IMS MS method optimization. In this study, IMS MS was introduced in human brain ganglioside (GG) research. The efficiency of the method in clinical glycolipidomics was demonstrated on a highly complex mixture extracted from a normal fetal frontal lobe (FL37). Using this approach, a remarkably rich molecular ion pattern was discovered, which proved the presence of a large number of glycoforms and an unpredicted diversity of the ceramide chains. Moreover, the results showed for the first time the occurrence of GGs in the human brain with a much higher degree of sialylation than previously reported. Using IMS MS, the entire series starting from mono- up to octasialylated GGs was detected in FL37. These findings substantiate early clinical reports on the direct correlation between GG sialylation degree and brain developmental stage. Using IMS CID MS/MS, applied here for the first time to gangliosides, a novel, tetrasialylated O-GalNAc modified species with a potential biomarker role in brain development was structurally characterized. Under variable collision energy, a high number of sequence ions was generated for the investigated GalNAc-GQ1(d18:1/18:0) species. Several fragment ions documented the presence of the tetrasialo element attached to the inner Gal, indicating that GalNAc-GQ1(d18:1/18:0) belongs to the d series. PMID:27088833

  13. Environmental influence in the brain, human welfare and mental health.

    Tost, Heike; Champagne, Frances A; Meyer-Lindenberg, Andreas

    2015-10-01

    The developing human brain is shaped by environmental exposures--for better or worse. Many exposures relevant to mental health are genuinely social in nature or believed to have social subcomponents, even those related to more complex societal or area-level influences. The nature of how these social experiences are embedded into the environment may be crucial. Here we review select neuroscience evidence on the neural correlates of adverse and protective social exposures in their environmental context, focusing on human neuroimaging data and supporting cellular and molecular studies in laboratory animals. We also propose the inclusion of innovative methods in social neuroscience research that may provide new and ecologically more valid insight into the social-environmental risk architecture of the human brain. PMID:26404717

  14. Xanthine oxidase activity regulates human embryonic brain cells growth

    Kevorkian G. A.

    2011-10-01

    Full Text Available Aim. Involvement of Xanthine Oxidase (XO; EC1.1.3.22 in cellular proliferation and differentiation has been suggested by the numerous investigations. We have proposed that XO might have undoubtedly important role during the development, maturation as well as the death of human embryos brain cells. Methods. Human abortion material was utilized for the cultivation of brain cells (E90. XO activity was measured by the formation of uric acid in tissue. Cell death was detected by the utility of Trypan Blue dye. Results. Allopurinol suppressed the XO activity in the brain tissue (0.12 ± 0.02; 0.20 ± 0.03 resp., p < 0.05. On day 12th the number of cells in the culture treated with the Allopurinol at the early stage of development was higher in comparison with the Control (2350.1 ± 199.0 vs 2123 ± 96 and higher in comparison with the late period of treatment (1479.6 ± 103.8, p < < 0.05. In all groups, the number of the dead cells was less than in Control, indicating the protective nature of Allopurinol as an inhibitor of XO. Conclusions. Allopurinol initiates cells proliferation in case of the early treatment of the human brain derived cell culture whereas at the late stages it has an opposite effect.

  15. Cell culture: Progenitor cells from human brain after death

    Palmer, Theo D.; Schwartz, Philip H.; Taupin, Philippe; Kaspar, Brian; Stein, Stuart A.; Gage, Fred H.

    2001-05-01

    Culturing neural progenitor cells from the adult rodent brain has become routine and is also possible from human fetal tissue, but expansion of these cells from postnatal and adult human tissue, although preferred for ethical reasons, has encountered problems. Here we describe the isolation and successful propagation of neural progenitor cells from human postmortem tissues and surgical specimens. Although the relative therapeutic merits of adult and fetal progenitor cells still need to be assessed, our results may extend the application of these progenitor cells in the treatment of neurodegenerative diseases.

  16. Is the social brain theory applicable to human individual differences? Relationship between sociability personality dimension and brain size.

    Horváth, Klára; Martos, János; Mihalik, Béla; Bódizs, Róbert

    2011-01-01

    Our study intends to examine whether the social brain theory is applicable to human individual differences. According to the social brain theory primates have larger brains as it could be expected from their body sizes due to the adaptation to a more complex social life. Regarding humans there were few studies about the relationship between theory of mind and frontal and temporal brain lobes. We hypothesized that these brain lobes, as well as the whole cerebrum and neocortex are in connection with the Sociability personality dimension that is associated with individuals' social lives. Our findings support this hypothesis as Sociability correlated positively with the examined brain structures if we control the effects of body size differences and age. These results suggest that the social brain theory can be extended to human interindividual differences and they have some implications to personality psychology too. PMID:22947971

  17. Large-Scale Networks in the Human Brain revealed by Functional Connectivity MRI

    Krienen, Fenna Marie

    2013-01-01

    The human brain is composed of distributed networks that connect a disproportionately large neocortex to the brainstem, cerebellum and other subcortical structures. New methods for analyzing non-invasive imaging data have begun to reveal new insights into human brain organization. These methods permit characterization of functional interactions within and across brain networks, and allow us to appreciate points of departure between the human brain and non-human primates.

  18. A human-specific de novo protein-coding gene associated with human brain functions.

    Chuan-Yun Li

    2010-03-01

    Full Text Available To understand whether any human-specific new genes may be associated with human brain functions, we computationally screened the genetic vulnerable factors identified through Genome-Wide Association Studies and linkage analyses of nicotine addiction and found one human-specific de novo protein-coding gene, FLJ33706 (alternative gene symbol C20orf203. Cross-species analysis revealed interesting evolutionary paths of how this gene had originated from noncoding DNA sequences: insertion of repeat elements especially Alu contributed to the formation of the first coding exon and six standard splice junctions on the branch leading to humans and chimpanzees, and two subsequent substitutions in the human lineage escaped two stop codons and created an open reading frame of 194 amino acids. We experimentally verified FLJ33706's mRNA and protein expression in the brain. Real-Time PCR in multiple tissues demonstrated that FLJ33706 was most abundantly expressed in brain. Human polymorphism data suggested that FLJ33706 encodes a protein under purifying selection. A specifically designed antibody detected its protein expression across human cortex, cerebellum and midbrain. Immunohistochemistry study in normal human brain cortex revealed the localization of FLJ33706 protein in neurons. Elevated expressions of FLJ33706 were detected in Alzheimer's brain samples, suggesting the role of this novel gene in human-specific pathogenesis of Alzheimer's disease. FLJ33706 provided the strongest evidence so far that human-specific de novo genes can have protein-coding potential and differential protein expression, and be involved in human brain functions.

  19. MR-visible brain water content in human acute stroke

    Gideon, P; Rosenbaum, S; Sperling, B;

    1999-01-01

    Quantification of metabolite concentrations by proton magnetic resonance spectroscopy (1H-MRS) in the human brain using water as an internal standard is based on the assumption that water content does not change significantly in pathologic brain tissue. To test this, we used 1H-MRS to estimate......CBF from Day 0-3 to Day 4-7 (p = 0.050) and from Day 0-3 to Day 8-21 (p = 0.028). No correlation between rCBF and water content was found. Water content in ischemic brain tissue increased significantly between Day 4-7 after stroke. This should be considered when performing quantitative 1H-MRS using water...

  20. Brain-Computer Interfaces Revolutionizing Human-Computer Interaction

    Graimann, Bernhard; Allison, Brendan

    2010-01-01

    A brain-computer interface (BCI) establishes a direct output channel between the human brain and external devices. BCIs infer user intent via direct measures of brain activity and thus enable communication and control without movement. This book, authored by experts in the field, provides an accessible introduction to the neurophysiological and signal-processing background required for BCI, presents state-of-the-art non-invasive and invasive approaches, gives an overview of current hardware and software solutions, and reviews the most interesting as well as new, emerging BCI applications. The book is intended not only for students and young researchers, but also for newcomers and other readers from diverse backgrounds keen to learn about this vital scientific endeavour.

  1. The maternal brain and its plasticity in humans.

    Kim, Pilyoung; Strathearn, Lane; Swain, James E

    2016-01-01

    This article is part of a Special Issue "Parental Care". Early mother-infant relationships play important roles in infants' optimal development. New mothers undergo neurobiological changes that support developing mother-infant relationships regardless of great individual differences in those relationships. In this article, we review the neural plasticity in human mothers' brains based on functional magnetic resonance imaging (fMRI) studies. First, we review the neural circuits that are involved in establishing and maintaining mother-infant relationships. Second, we discuss early postpartum factors (e.g., birth and feeding methods, hormones, and parental sensitivity) that are associated with individual differences in maternal brain neuroplasticity. Third, we discuss abnormal changes in the maternal brain related to psychopathology (i.e., postpartum depression, posttraumatic stress disorder, substance abuse) and potential brain remodeling associated with interventions. Last, we highlight potentially important future research directions to better understand normative changes in the maternal brain and risks for abnormal changes that may disrupt early mother-infant relationships. PMID:26268151

  2. Interactions between occlusion and human brain function activities.

    Ohkubo, C; Morokuma, M; Yoneyama, Y; Matsuda, R; Lee, J S

    2013-02-01

    There are few review articles in the area of human research that focus on the interactions between occlusion and brain function. This systematic review discusses the effect of occlusion on the health of the entire body with a focus on brain function. Available relevant articles in English from 1999 to 2011 were assessed in an online database and as hard copies in libraries. The selected 19 articles were classified into the following five categories: chewing and tongue movements, clenching and grinding, occlusal splints and occlusal interference, prosthetic rehabilitation, and pain and stimulation. The relationships between the brain activity observed in the motor and sensory cortices and movements of the oral and maxillofacial area, such as those produced by gum chewing, tapping and clenching, were investigated. It was found that the sensorimotor cortex was also affected by the placement of the occlusal interference devices, splints and implant prostheses. Brain activity may change depending on the strength of the movements in the oral and maxillofacial area. Therefore, mastication and other movements stimulate the activity in the cerebral cortex and may be helpful in preventing degradation of a brain function. However, these findings must be verified by evidence gathered from more subjects. PMID:22624951

  3. Drug delivery to the human brain via the cerebrospinal fluid

    This Study investigates the flow of Cerebrospinal Fluid (CSF) inside the human ventricular system with particular emphasis on drug path flow for the purpose of medical drug injections. The investigation is conducted using the computational fluid dynamics package FLUENT. The role of the ventricular system is very important in protecting the brain from injury by cushioning it against the cranium during sudden movements. If for any reason the passage of CSF through the ventricular system is blocked (usually by stenosis) then a condition known as Hydrocephalus occurs, where by the blocked CSF causes the Intra Cranial Pressure (ICP) inside the brain to rise. If this is not treated then severe brain damage and death can occur. Previous work conducted by the authors on this subject has focused on the technique of ventriculostomy to treat hydrocephalus. The present study carries on from the previous work but focuses on delivering medical drugs to treat brain tumors that are conventionally not accessible and which require complicated surgical procedures to remove them. The study focuses on the possible paths for delivering drugs to tumors in the human nervous system through conventionally accessible locations without major surgery. The results of the investigation have shown that it is possible to reach over 95% of the ventricular system by injection of drugs however the results also show that there are many factors that can affect the drug flow paths through the ventricular system and thus the areas reachable, by these drugs. (author)

  4. Human plasma DNP level after severe brain injury

    GAO Yi-lu; XIN Hui-ning; FENG Yi; FAN Ji-wei

    2006-01-01

    Objective: To determine the relationship between DNP level after human severe brain injury and hyponatremia as well as isorrhea.Methods: The peripheral venous plasma as control was collected from 8 volunteers. The peripheral venous plasma from 14 severe brain injury patients were collected in the 1, 3, 7 days after injury. Radioimmunoassay was used to detect the DNP concentration. Meanwhile, daily plasma and urine electrolytes, osmotic pressure as well as 24 h liquid intake and output volume were detected.Results: The normal adult human plasma DNP level was 62. 46 pg/ml ± 27. 56 pg/ml. In the experimental group, the plasma DNP levels were higher from day 1 today 3 in 8 of the 14 patients than those in the control group (P1 =0.05, P3 =0.03). Negative fluid balance occurred in 8 patients and hyponatremia in 7 patients. The increase of plasma DNP level was significantly correlated with the development of a negative fluid balance (r=-0.69,P<0.01) and hyponatremia (x2 =4.38, P<0.05).Conclusions: The increase of plasma DNP level is accompanied by the enhancement of natriuretic and diuretic responses in severe brain-injured patients, which is associated with the development of a negative fluid balance and hyponatremia after brain injury.

  5. Virtual model of the human brain for neurosurgical simulation.

    De Paolis, Lucio T; De Mauro, Alessandro; Raczkowsky, Joerg; Aloisio, Giovanni

    2009-01-01

    The aim of this work is to develop a realistic virtual model of the human brain that could be used in a neurosurgical simulation for both educational and preoperative planning purposes. The goal of such a system would be to enhance the practice of surgery students, avoiding the use of animals, cadavers and plastic phantoms. A surgeon, before carrying out the real procedure, will, with this system, be able to rehearse by using a surgical simulator based on detailed virtual reality models of the human brain, reconstructed with real patient's medical images. In order to obtain a realistic and useful simulation we focused our research on the physical modelling of the brain as a deformable body and on the interactions with surgical instruments. The developed prototype is based on the mass-spring-damper model and, in order to obtain deformations similar to the real ones, a three tiered structure has been built. In this way, we have obtained local and realistic deformations using an ad-hoc point distribution in the volume where the contact between the brain surface and a surgical instrument takes place. PMID:19745425

  6. The Speculative Neuroscience of the Future Human Brain

    Robert A. Dielenberg

    2013-05-01

    Full Text Available The hallmark of our species is our ability to hybridize symbolic thinking with behavioral output. We began with the symmetrical hand axe around 1.7 mya and have progressed, slowly at first, then with greater rapidity, to producing increasingly more complex hybridized products. We now live in the age where our drive to hybridize has pushed us to the brink of a neuroscientific revolution, where for the first time we are in a position to willfully alter the brain and hence, our behavior and evolution. Nootropics, transcranial direct current stimulation (tDCS, transcranial magnetic stimulation (TMS, deep brain stimulation (DBS and invasive brain mind interface (BMI technology are allowing humans to treat previously inaccessible diseases as well as open up potential vistas for cognitive enhancement. In the future, the possibility exists for humans to hybridize with BMIs and mobile architectures. The notion of self is becoming increasingly extended. All of this to say: are we in control of our brains, or are they in control of us?

  7. The Evolution of Brains from Early Mammals to Humans.

    Kaas, Jon H

    2013-01-01

    The large size and complex organization of the human brain makes it unique among primate brains. In particular, the neocortex constitutes about 80% of the brain, and this cortex is subdivided into a large number of functionally specialized regions, the cortical areas. Such a brain mediates accomplishments and abilities unmatched by any other species. How did such a brain evolve? Answers come from comparative studies of the brains of present-day mammals and other vertebrates in conjunction with information about brain sizes and shapes from the fossil record, studies of brain development, and principles derived from studies of scaling and optimal design. Early mammals were small, with small brains, an emphasis on olfaction, and little neocortex. Neocortex was transformed from the single layer of output pyramidal neurons of the dorsal cortex of earlier ancestors to the six layers of all present-day mammals. This small cap of neocortex was divided into 20-25 cortical areas, including primary and some of the secondary sensory areas that characterize neocortex in nearly all mammals today. Early placental mammals had a corpus callosum connecting the neocortex of the two hemispheres, a primary motor area, M1, and perhaps one or more premotor areas. One line of evolution, Euarchontoglires, led to present-day primates, tree shrews, flying lemurs, rodents and rabbits. Early primates evolved from small-brained, nocturnal, insect-eating mammals with an expanded region of temporal visual cortex. These early nocturnal primates were adapted to the fine branch niche of the tropical rainforest by having an even more expanded visual system that mediated visually guided reaching and grasping of insects, small vertebrates, and fruits. Neocortex was greatly expanded, and included an array of cortical areas that characterize neocortex of all living primates. Specializations of the visual system included new visual areas that contributed to a dorsal stream of visuomotor processing in a

  8. A Novel Human Body Area Network for Brain Diseases Analysis.

    Lin, Kai; Xu, Tianlang

    2016-10-01

    Development of wireless sensor and mobile communication technology provide an unprecedented opportunity for realizing smart and interactive healthcare systems. Designing such systems aims to remotely monitor the health and diagnose the diseases for users. In this paper, we design a novel human body area network for brain diseases analysis, which is named BABDA. Considering the brain is one of the most complex organs in the human body, the BABDA system provides four function modules to ensure the high quality of the analysis result, which includes initial data collection, data correction, data transmission and comprehensive data analysis. The performance evaluation conducted in a realistic environment with several criteria shows the availability and practicability of the BABDA system. PMID:27526187

  9. Functional imaging of the human brain using conventional MRI

    It was shown in 1991 by Belliveau and coworkers that the activation of the human brain can be visualized in a completely noninvasive way by MRI. First publications coming from the US claimed that very high magnetic field strength or echo planar imaging, both available only at a few research sites, would be necessary to do this job. Recently, it was demonstrated that functional imaging of the human brain can be done with high spatial resolution MRI using conventional FLASH-sequences with the commercial widely available 1,5 Tesla systems. First results have been reported for visual as well as primary motor cortex activation in healthy volunteers. The key to a successful application of the conventional technique lies in the design of extremely low bandwidth, long echo-time FLASH-sequences with high spatial resolution. (orig.)

  10. “Messing with the mind”: evolutionary challenges to human brain augmentation

    Saniotis, Arthur; Henneberg, Maciej; Kumaratilake, Jaliya; Grantham, James P

    2014-01-01

    The issue of brain augmentation has received considerable scientific attention over the last two decades. A key factor to brain augmentation that has been widely overlooked are the complex evolutionary processes which have taken place in evolving the human brain to its current state of functioning. Like other bodily organs, the human brain has been subject to the forces of biological adaptation. The structure and function of the brain, is very complex and only now we are beginning to understa...

  11. Two distinct forms of functional lateralization in the human brain

    Gotts, Stephen J.; Jo, Hang Joon; Wallace, Gregory L.; Saad, Ziad S.; Cox, Robert W.; Martin, Alex

    2013-01-01

    This study alters our fundamental understanding of the functional interactions between the cerebral hemispheres of the human brain by establishing that the left and right hemispheres have qualitatively different biases in how they dynamically interact with one another. Left-hemisphere regions are biased to interact more strongly within the same hemisphere, whereas right-hemisphere regions interact more strongly with both hemispheres. These two different patterns of interaction are associated ...

  12. Dynamic Shimming of the Human Brain at 7 Tesla

    Juchem, Christoph; Nixon, Terence W.; Diduch, Piotr; Rothman, Douglas L.; Starewicz, Piotr; de Graaf, Robin A.

    2010-01-01

    Dynamic shim updating (DSU) of the zero- to second-order spherical harmonic field terms has previously been shown to improve the magnetic field homogeneity in the human brain at 4 Tesla. The increased magnetic field inhomogeneity at 7 Tesla can benefit from inclusion of third-order shims during DSU. However, pulsed higher-order shims can generate a multitude of temporally varying magnetic fields arising from eddy-currents that can strongly degrade the magnetic field homogeneity.

  13. A Collaborative Brain-Computer Interface for Improving Human Performance

    Wang, Yijun; Jung, Tzyy-Ping

    2011-01-01

    Electroencephalogram (EEG) based brain-computer interfaces (BCI) have been studied since the 1970s. Currently, the main focus of BCI research lies on the clinical use, which aims to provide a new communication channel to patients with motor disabilities to improve their quality of life. However, the BCI technology can also be used to improve human performance for normal healthy users. Although this application has been proposed for a long time, little progress has been made in real-world prac...

  14. Quantization of continuous arm movements in humans with brain injury

    Krebs, Hermano Igo; Aisen, Mindy L.; Volpe, Bruce T.; Hogan, Neville

    1999-01-01

    Segmentation of apparently continuous movement has been reported for over a century by human movement researchers, but the existence of primitive submovements has never been proved. In 20 patients recovering from a single cerebral vascular accident (stroke), we identified the apparent submovements that composed a continuous arm motion in an unloaded task. Kinematic analysis demonstrated a submovement speed profile that was invariant across patients with different brain lesions and provided ex...

  15. Motor Skill Acquisition Promotes Human Brain Myelin Plasticity

    Bimal Lakhani; Borich, Michael R.; Jackson, Jacob N.; Wadden, Katie P.; Sue Peters; Anica Villamayor; MacKay, Alex L.; Vavasour, Irene M.; Alexander Rauscher; Boyd, Lara A.

    2016-01-01

    Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI), the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent ch...

  16. Quantitative MRI of he human brain at 7 tesla

    Polders, D.L.

    2012-01-01

    This thesis describes the implementation of quantitative MR methods in the human brain at 7 T. By highlighting the drawbacks and advantages of the increased field strength, the use of 7 T MRI for quantitative measurements in clinical research was demonstrated. Inhomogeneities in the transmitted RF field limit the feasibility of methods that rely on the application of homogeneous RF pulses. The increased SNR at this high field strength enables rapid acquisition of high quality imaging volumes ...

  17. Predicting errors from reconfiguration patterns in human brain networks

    Ekman, Matthias; Derrfuss, Jan; Tittgemeyer, Marc; Fiebach, Christian J.

    2012-01-01

    Task preparation is a complex cognitive process that implements anticipatory adjustments to facilitate future task performance. Little is known about quantitative network parameters governing this process in humans. Using functional magnetic resonance imaging (fMRI) and functional connectivity measurements, we show that the large-scale topology of the brain network involved in task preparation shows a pattern of dynamic reconfigurations that guides optimal behavior. This network could be deco...

  18. Maintaining the Brain: Insight into Human Neurodegeneration From Drosophila Mutants

    Lessing, Derek; Bonini, Nancy M.

    2009-01-01

    The fruit fly Drosophila melanogaster has brought significant advances to research in neurodegenerative disease, notably in the identification of genes that are required to maintain the structural integrity of the brain, defined by recessive mutations that cause adult-onset neurodegeneration. Here, we survey these genes in the fly and classify them according to five key cell biological processes. Over half of these genes have counterparts in mouse or human that are also associated with neurod...

  19. Human functional neuroimaging of brain changes associated with practice

    GARAVAN, HUGH PATRICK

    2005-01-01

    PUBLISHED The discovery that experience-driven changes in the human brain can occur from a neural to a cortical level throughout the lifespan has stimulated a proliferation of research into how neural function changes in response to experience, enabled by neuroimaging methods such as positron emission tomography and functional magnetic resonance imaging. Studies attempt to characterize these changes by examining how practice on a task affects the functional anatomy underlying performance. ...

  20. Investigation of G72 (DAOA expression in the human brain

    Hirsch Steven

    2008-12-01

    Full Text Available Abstract Background Polymorphisms at the G72/G30 locus on chromosome 13q have been associated with schizophrenia or bipolar disorder in more than ten independent studies. Even though the genetic findings are very robust, the physiological role of the predicted G72 protein has thus far not been resolved. Initial reports suggested G72 as an activator of D-amino acid oxidase (DAO, supporting the glutamate dysfunction hypothesis of schizophrenia. However, these findings have subsequently not been reproduced and reports of endogenous human G72 mRNA and protein expression are extremely limited. In order to better understand the function of this putative schizophrenia susceptibility gene, we attempted to demonstrate G72 mRNA and protein expression in relevant human brain regions. Methods The expression of G72 mRNA was studied by northern blotting and semi-quantitative SYBR-Green and Taqman RT-PCR. Protein expression in human tissue lysates was investigated by western blotting using two custom-made specific anti-G72 peptide antibodies. An in-depth in silico analysis of the G72/G30 locus was performed in order to try and identify motifs or regulatory elements that provide insight to G72 mRNA expression and transcript stability. Results Despite using highly sensitive techniques, we failed to identify significant levels of G72 mRNA in a variety of human tissues (e.g. adult brain, amygdala, caudate nucleus, fetal brain, spinal cord and testis human cell lines or schizophrenia/control post mortem BA10 samples. Furthermore, using western blotting in combination with sensitive detection methods, we were also unable to detect G72 protein in a number of human brain regions (including cerebellum and amygdala, spinal cord or testis. A detailed in silico analysis provides several lines of evidence that support the apparent low or absent expression of G72. Conclusion Our results suggest that native G72 protein is not normally present in the tissues that we analysed

  1. Imaging synaptic density in the living human brain.

    Finnema, Sjoerd J; Nabulsi, Nabeel B; Eid, Tore; Detyniecki, Kamil; Lin, Shu-Fei; Chen, Ming-Kai; Dhaher, Roni; Matuskey, David; Baum, Evan; Holden, Daniel; Spencer, Dennis D; Mercier, Joël; Hannestad, Jonas; Huang, Yiyun; Carson, Richard E

    2016-07-20

    Chemical synapses are the predominant neuron-to-neuron contact in the central nervous system. Presynaptic boutons of neurons contain hundreds of vesicles filled with neurotransmitters, the diffusible signaling chemicals. Changes in the number of synapses are associated with numerous brain disorders, including Alzheimer's disease and epilepsy. However, all current approaches for measuring synaptic density in humans require brain tissue from autopsy or surgical resection. We report the use of the synaptic vesicle glycoprotein 2A (SV2A) radioligand [(11)C]UCB-J combined with positron emission tomography (PET) to quantify synaptic density in the living human brain. Validation studies in a baboon confirmed that SV2A is an alternative synaptic density marker to synaptophysin. First-in-human PET studies demonstrated that [(11)C]UCB-J had excellent imaging properties. Finally, we confirmed that PET imaging of SV2A was sensitive to synaptic loss in patients with temporal lobe epilepsy. Thus, [(11)C]UCB-J PET imaging is a promising approach for in vivo quantification of synaptic density with several potential applications in diagnosis and therapeutic monitoring of neurological and psychiatric disorders. PMID:27440727

  2. Brain tumors induced in rats by human adenovirus type 12

    Murao,Tsuyoshi

    1974-02-01

    Full Text Available Oncogenesis of human adenovirus type 12 in the brain of rats was examined. Newborn rats of Sprague-Dawley and Donryu strains were injected intracranially with human adenovirus type 12. The incidence of intracranial tumors was 91% (30/33 in SpragueDawley and 56% (14/25 in Donryu rats. Except for one tumor nodule located in the parietal cortex of a Sprague.Dawley rat, all tumors developed in the paraventricular areas or in the meninges. Tumors were quite similar histologically to those induced in hamsters and mice resembling the undifferentiated human brain tumors such as medulloblastoma, ependymoblastoma and embryonic gliomas. From the histological features and primary sites of tumor development, it is suggested that the tumors in the brain of rats induced by adenovirus type 12 originate from the embryonic cells in the paraventricular area and also from the undifferentiated supporting cells of the peripheral nerves in the leptomeninges.

  3. Relevance Of Human Brain Banking In Neuroscience - A National Facility

    Shankar S K

    1999-01-01

    Full Text Available The lack of animal models for many of the neurodegenerative and psychiatric disorders and the fact that animal models cannot substitute for human tissue led to the establishment of Brain Banks that collect, preserve and provide fresh human tissue for researchers. One such Bank has been set up at the National Institute of Mental Health and Neurosciences funded by Dept. of Biotechnology, Dept. of Science and Technology and ICMR. Brains and tissue fluids (serum and CSF are collected at autopsy following informed consent from close relatives. One half of the fresh brain from neurodegenerative and psychiatric disorders are frozen at -70′ C while the other half and brains from infective conditions are formalin fixed which can be used for pathomorphological studies. Only fresh frozen tissues that are tested and found negative for HIV and HbsAg are provided for research. The neural tissues as well as tissue fluids that are being supplied by the Brain Bank have supported a number of research projects in diverse fields of neurosciences. Many significant discoveries that have contributed towards understanding pathogenesis of disease, their genetic basis, and evolving prognostic and diagnostic markers for neurologic disease in the CSF have been made possible by the existence of such a facility. The continued functioning of such a facility requires the close co-operation of the clinical neuroscientists, pathologists and the other neuroscientists. Increased awareness and commitment amongst the scientific fraternity is necessary to keep alive the demand and ensure uninterrupted supply of fresh tissue for research. This will help usher in the era of molecular neurobiology with the fond hope that many more of the relentlessly progressive neurodegenerative disorders will eventually find a cause and cure.

  4. New peptide receptor radionuclide therapy of invasive cancer cells: in vivo studies using 177Lu-DOTA-AE105 targeting uPAR in human colorectal cancer xenografts

    Persson, Morten; Rasmussen, Palle; Madsen, Jacob;

    2012-01-01

    animals were treated day 0 and 7. A parallel 18F-FLT PET/CT study was performed on day 0, 1, 3 and 6. Dosimetry calculations were based on a biodistribution study, where organs and tissue of interest were collected 0.5, 1.0, 2.0, 4.0 and 24h post injection of 177Lu-DOTA-AE105. Toxicity was assessed by...... theranostic approach as treatment modality in a human xenograft colorectal cancer model. MethodsA DOTA-conjugated 9-mer high affinity uPAR binding peptide (DOTA-AE105) was radiolabeled with 64Cu and 177Lu, for PET imaging and targeted radionuclide therapy study, respectively. Human uPAR-positive CRC HT-29...... cells were inoculated in Nude mice and treated with 177Lu-DOTA-AE105 once a visible tumor had formed. To evaluate the true effect of the targeted radiotherapy, two controls groups were included in this study, one receiving a 177Lu-labeled non-binding control peptide and one receiving vehicle. All...

  5. Transolfactory neuroinvasion by viruses threatens the human brain.

    Mori, I

    2015-12-01

    Viral neuroinvasion via the olfactory system has been investigated in a variety of virus-animal models by scientists in many fields including virologists, pathologists, and neurologists. In humans, herpes simplex virus type 1 (HSV-1), human herpesvirus 6 (HHV-6), Borna disease virus, rabies virus, and influenza A virus have been shown to take the olfactory route for neuroinvasion based on forensic and post-mortem specimens. This article briefly summarizes the anatomy, physiology, and immunology of the olfactory system and presents a battery of neurovirulent viruses that may threaten the human brain by invading through this peripheral pathway, especially focusing on two of the most intensively studied viruses--HSV-1 and influenza A virus. Viruses may insidiously invade the olfactory neural network not only to precipitate encephalitis/encephalopathy but also to promote the development of neurodegenerative and demyelinating disorders. Substantial information obtained by analyzing human specimens is required to argue for or against this hypothesis. PMID:26666182

  6. Insulin and C-peptide in human brain neurons (insulin/C-peptide/brain peptides/immunohistochemistry/radioimmunoassay)

    The regional distribution and cellular localization of insulin and C-peptide immunoreactivities were studied in human cadaver brains using the indirect immunofluorescence method, the peroxidase-antiperoxidase technique, and radioimmunoassay. Products of the immune reactions to both polypeptides were observed in most nerve cells in all areas of the brain examined. Immunostaining was mainly restricted to the cell soma and proximal dendrites. Radioimmunoassay revealed that human brain contains insulin and C-peptide in concentrations much higher than the blood, the highest being in the hypothalamus. These findings support the hypothesis that the 'brain insulin' is - at least in part - produced in the CNS. (author)

  7. Canonical genetic signatures of the adult human brain.

    Hawrylycz, Michael; Miller, Jeremy A; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L; Jegga, Anil G; Aronow, Bruce J; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F; Dierker, Donna L; Menche, Jörg; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R; Jones, Allan; Van Essen, David C; Koch, Christof; Lein, Ed

    2015-12-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure and function. We applied a correlation-based metric called differential stability to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing mesoscale genetic organization. The genes with the highest differential stability are highly biologically relevant, with enrichment for brain-related annotations, disease associations, drug targets and literature citations. Using genes with high differential stability, we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely patterned genes displayed marked shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

  8. Specialisation in the human brain: the case of numbers

    Roi Cohen Kadosh

    2011-07-01

    Full Text Available How numerical representation is encoded in the adult human brain is important for a basic understanding of human brain organization, its typical and atypical development, its evolutionary precursors, cognitive architectures, education and rehabilitation. Previous studies have shown that numerical processing activates the same intraparietal regions irrespective of the presentation format (e.g. symbolic digits or non-symbolic dot arrays. This has led to claims that there is a single format independent, numerical representation. In the current study we used a functional magnetic resonance adaptation paradigm, and effective connectivity analysis to re-examine whether numerical processing in the intraparietal sulci is dependent or independent on the format of the stimuli. We obtained two novel results. First, the whole brain analysis revealed that format change (e.g., from dots to digits, in the absence of a change in magnitude, activated the same intraparietal regions as magnitude change, but to a greater degree. Second, using dynamic causal modeling (DCM as a tool to disentangle neuronal specialization across regions that are commonly activated, we found that the connectivity between the left and right intraparietal sulci is format-dependent. Together, this line of results supports the idea that numerical representation is subserved by multiple mechanisms within the same parietal regions.

  9. Mass spectrometry quantification of clusterin in the human brain

    Chen Junjun

    2012-08-01

    Full Text Available Abstract Background The multifunctional glycoprotein clusterin has been associated with late-onset Alzheimer’s disease (AD. Further investigation to define the role of clusterin in AD phenotypes would be aided by the development of techniques to quantify level, potential post-translational modifications, and isoforms of clusterin. We have developed a quantitative technique based on multiple reaction monitoring (MRM mass spectrometry to measure clusterin in human postmortem brain tissues. Results A stable isotope-labeled concatenated peptide (QconCAT bearing selected peptides from clusterin was expressed with an in vitro translation system and purified. This clusterin QconCAT was validated for use as an internal standard for clusterin quantification using MRM mass spectrometry. Measurements were performed on the human postmortem frontal and temporal cortex from control and severe AD cases. During brain tissues processing, 1% SDS was used in the homogenization buffer to preserve potential post-translational modifications of clusterin. However, MRM quantifications in the brain did not suggest phosphorylation of Thr393, Ser394, and Ser396 residues reported for clusterin in serum. MRM quantifications in the frontal cortex demonstrated significantly higher (P  Conclusions The proposed protocol is a universal quantitative technique to assess expression level of clusterin. It is expected that application of this protocol to quantification of various clusterin isoforms and potential post-translational modifications will be helpful in addressing the role of clusterin in AD.

  10. Felbamate increases [3H]glycine binding in rat brain and sections of human postmortem brain.

    McCabe, R T; Sofia, R D; Layer, R T; Leiner, K A; Faull, R L; Narang, N; Wamsley, J K

    1998-08-01

    The anticonvulsant compound felbamate (2-phenyl-1,3-propanediol dicarbamate; FBM) appears to inhibit the function of the N-methyl-D-aspartate (NMDA) receptor complex through an interaction with the strychnine-insensitive glycine recognition site. Since we have demonstrated previously that FBM inhibits the binding of [3H]5, 7-dichlorokynurenic acid (DCKA), a competitive antagonist at the glycine site, we assessed the ability of FBM to modulate the binding of an agonist, [3H]glycine, to rat forebrain membranes and human brain sections. In contrast to its ability to inhibit [3H]5,7-DCKA binding, FBM increased [3H]glycine binding (20 nM; EC50 = 485 microM; Emax = 211% of control; nH = 1.8). FBM, but not carbamazepine, phenytoin, valproic acid or phenobarbital, also increased [3H]glycine binding (50 nM; EC50 = 142 microM; Emax = 157% of control; nH = 1.6) in human cortex sections. Autoradiographic analysis of human brain slices demonstrated that FBM produced the largest increases in [3H]glycine binding in the cortex, hippocampus and the parahippocampal gyrus. Because various ions can influence the binding of glycine-site ligands, we assessed their effects on FBM-modulation of [3H]glycine binding. FBM-enhanced [3H]glycine binding was attenuated by Zn++ and not inhibited by Mg++ in human brain. These results suggest that FBM increases [3H]glycine binding in a manner sensitive to ions which modulate the NMDA receptor. These data support the hypothesis that FBM produces anticonvulsant and neuroprotective effects by inhibiting NMDA receptor function, likely through an allosteric modulation of the glycine site. PMID:9694960

  11. Memory-related brain lateralisation in birds and humans.

    Moorman, Sanne; Nicol, Alister U

    2015-03-01

    Visual imprinting in chicks and song learning in songbirds are prominent model systems for the study of the neural mechanisms of memory. In both systems, neural lateralisation has been found to be involved in memory formation. Although many processes in the human brain are lateralised--spatial memory and musical processing involves mostly right hemisphere dominance, whilst language is mostly left hemisphere dominant--it is unclear what the function of lateralisation is. It might enhance brain capacity, make processing more efficient, or prevent occurrence of conflicting signals. In both avian paradigms we find memory-related lateralisation. We will discuss avian lateralisation findings and propose that birds provide a strong model for studying neural mechanisms of memory-related lateralisation. PMID:25036892

  12. Human Brain Glycogen Metabolism During and After Hypoglycemia

    Öz, Gülin; Kumar, Anjali; Rao, Jyothi P.; Kodl, Christopher T.; Chow, Lisa; Eberly, Lynn E.; Seaquist, Elizabeth R.

    2009-01-01

    OBJECTIVE We tested the hypotheses that human brain glycogen is mobilized during hypoglycemia and its content increases above normal levels (“supercompensates”) after hypoglycemia. RESEARCH DESIGN AND METHODS We utilized in vivo 13C nuclear magnetic resonance spectroscopy in conjunction with intravenous infusions of [13C]glucose in healthy volunteers to measure brain glycogen metabolism during and after euglycemic and hypoglycemic clamps. RESULTS After an overnight intravenous infusion of 99% enriched [1-13C]glucose to prelabel glycogen, the rate of label wash-out from [1-13C]glycogen was higher (0.12 ± 0.05 vs. 0.03 ± 0.06 μmol · g−1 · h−1, means ± SD, P < 0.02, n = 5) during a 2-h hyperinsulinemic-hypoglycemic clamp (glucose concentration 57.2 ± 9.7 mg/dl) than during a hyperinsulinemic-euglycemic clamp (95.3 ± 3.3 mg/dl), indicating mobilization of glucose units from glycogen during moderate hypoglycemia. Five additional healthy volunteers received intravenous 25–50% enriched [1-13C]glucose over 22–54 h after undergoing hyperinsulinemic-euglycemic (glucose concentration 92.4 ± 2.3 mg/dl) and hyperinsulinemic-hypoglycemic (52.9 ± 4.8 mg/dl) clamps separated by at least 1 month. Levels of newly synthesized glycogen measured from 4 to 80 h were higher after hypoglycemia than after euglycemia (P ≤ 0.01 for each subject), indicating increased brain glycogen synthesis after moderate hypoglycemia. CONCLUSIONS These data indicate that brain glycogen supports energy metabolism when glucose supply from the blood is inadequate and that its levels rebound to levels higher than normal after a single episode of moderate hypoglycemia in humans. PMID:19502412

  13. Microtesla MRI of the human brain with simultaneous MEG

    Zotev, V S; Matlashov, A N; Savukov, I M; Espy, M A; Mosher, J C; Gómez, J J; Kraus, R H

    2007-01-01

    Magnetic resonance imaging at ultra-low fields (ULF MRI) uses SQUIDs (superconducting quantum interference devices) to measure spin precession at a microtesla-range field after sample magnetization is enhanced by a stronger pre-polarizing field. Here, the first ULF images of the human head acquired at 46 microtesla measurement field with pre-polarization at 30 mT are reported. The imaging was performed with 3 mm x 3 mm x 6 mm resolution using the seven-channel SQUID system designed for both ULF MRI and magnetoencephalography (MEG). Auditory MEG signals were measured immediately after the imaging while the human subject remained inside the system. These results demonstrate that ULF MRI of the human brain is feasible and can be naturally combined with MEG.

  14. Brain-Based Learning: The Neurological Findings About the Human Brain that Every Teacher Should Know to be Effective

    Ronald Jean Degen

    2011-01-01

    The purpose of this paper is to present the main neurological findings about the human brain that provide the basis for brain-based learning, and that represent a narrow field of cognitive science as a whole. The findings that are described were made primarily by neuroscientists who studied the structure and functions of the nervous system with the purpose of correcting abnormalities. Only recently have neuroscientists begun studying the brain-based learning processes of normal students in de...

  15. Natural image classification driven by human brain activity

    Zhang, Dai; Peng, Hanyang; Wang, Jinqiao; Tang, Ming; Xue, Rong; Zuo, Zhentao

    2016-03-01

    Natural image classification has been a hot topic in computer vision and pattern recognition research field. Since the performance of an image classification system can be improved by feature selection, many image feature selection methods have been developed. However, the existing supervised feature selection methods are typically driven by the class label information that are identical for different samples from the same class, ignoring with-in class image variability and therefore degrading the feature selection performance. In this study, we propose a novel feature selection method, driven by human brain activity signals collected using fMRI technique when human subjects were viewing natural images of different categories. The fMRI signals associated with subjects viewing different images encode the human perception of natural images, and therefore may capture image variability within- and cross- categories. We then select image features with the guidance of fMRI signals from brain regions with active response to image viewing. Particularly, bag of words features based on GIST descriptor are extracted from natural images for classification, and a sparse regression base feature selection method is adapted to select image features that can best predict fMRI signals. Finally, a classification model is built on the select image features to classify images without fMRI signals. The validation experiments for classifying images from 4 categories of two subjects have demonstrated that our method could achieve much better classification performance than the classifiers built on image feature selected by traditional feature selection methods.

  16. Why our brains cherish humanity: Mirror neurons and colamus humanitatem

    John R. Skoyles

    2008-06-01

    Full Text Available Commonsense says we are isolated. After all, our bodies are physically separate. But Seneca’s colamus humanitatem, and John Donne’s observation that “no man is an island” suggests we are neither entirely isolated nor separate. A recent discovery in neuroscience—that of mirror neurons—argues that the brain and the mind is neither built nor functions remote from what happens in other individuals. What are mirror neurons? They are brain cells that process both what happens to or is done by an individual, and, as it were, its perceived “refl ection,” when that same thing happens or is done by another individual. Thus, mirror neurons are both activated when an individual does a particular action, and when that individual perceives that same action done by another. The discovery of mirror neurons suggests we need to radically revise our notions of human nature since they offer a means by which we may not be so separated as we think. Humans unlike other apes are adapted to mirror interact nonverbally when together. Notably, our faces have been evolved to display agile and nimble movements. While this is usually explained as enabling nonverbal communication, a better description would be nonverbal commune based upon mirror neurons. I argue we cherish humanity, colamus humanitatem, because mirror neurons and our adapted mirror interpersonal interface blur the physical boundaries that separate us.

  17. Multi-dimensional dynamics of human electromagnetic brain activity

    Tetsuo eKida

    2016-01-01

    Full Text Available Magnetoencephalography (MEG and electroencephalography (EEG are invaluable neuroscientific tools for unveiling human neural dynamics in three dimensions (space, time, and frequency, which are associated with a wide variety of perceptions, cognition, and actions. MEG/EEG also provides different categories of neuronal indices including activity magnitude, connectivity, and network properties along the three dimensions. In the last 20 years, interest has increased in inter-regional connectivity and complex network properties assessed by various sophisticated scientific analyses. We herein review the definition, computation, short history, and pros and cons of connectivity and complex network (graph-theory analyses applied to MEG/EEG signals. We briefly describe recent developments in source reconstruction algorithms essential for source-space connectivity and network analyses. Furthermore, we discuss a relatively novel approach used in MEG/EEG studies to examine the complex dynamics represented by human brain activity. The correct and effective use of these neuronal metrics provides a new insight into the multi-dimensional dynamics of the neural representations of various functions in the complex human brain.

  18. Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion.

    Natalay Kouprina

    2004-05-01

    Full Text Available Primary microcephaly (MCPH is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size.

  19. Imaging neuroreceptors in the human brain in health and disease

    For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human brain in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, and glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On 25 May 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 N-methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine-2 receptors than in serotonin-2 receptors. Preliminary studies of patients with neuropsychiatric disorders suggest that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits a quantitative assay of picomolar quantities of neuroreceptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. (author)

  20. Modelling Human Cortical Network in Real Brain Space

    ZHAO Qing-Bai; FENG Hong-Bo; TANG Yi-Yuan

    2007-01-01

    Highly specific structural organization is of great significance in the topology of cortical networks.We introduce a human cortical network model.taking the specific cortical structure into account,in which nodes are brain sites placed in the actual positions of cerebral cortex and the establishment of edges depends on the spatial path length rather than the linear distance.The resulting network exhibits the essential features of cortical connectivity,properties of small-world networks and multiple clusters structure.Additionally.assortative mixing is also found in this roodel.All of these findings may be attributed to the spedtic cortical architecture.

  1. MR-visible brain water content in human acute stroke

    Gideon, P; Rosenbaum, S; Sperling, B; Petersen, P

    1999-01-01

    Quantification of metabolite concentrations by proton magnetic resonance spectroscopy (1H-MRS) in the human brain using water as an internal standard is based on the assumption that water content does not change significantly in pathologic brain tissue. To test this, we used 1H-MRS to estimate...... brain water content during the course of cerebral infarction. Measurements were performed serially in the acute, subacute, and chronic phase of infarction. Fourteen patients with acute cerebral infarction were examined as well as 9 healthy controls. To correlate with regional cerebral blood flow (r......CBF) SPECT-scanning using 99mTc-HMPAO as flow tracer was performed in the patients. Mean water content (SD) in the infarct area was 37.7 (5.1); 41.8 (4.8); 35.2 (5.4); and 39.3 (5.1) mol x [kg wet weight](-1) at 0-3; 4-7; 8-21; and >180 days after stroke, respectively. Water content increased between Day 0...

  2. The structure of creative cognition in the human brain

    Rex Eugene Jung

    2013-07-01

    Full Text Available Creativity is a vast construct, seemingly intractable to scientific inquiry – perhaps due to the vague concepts applied to the field of research. One attempt to limit the purview of creative cognition formulates the construct in terms of evolutionary constraints, namely that of blind variation and selective retention (BVSR. Behaviorally, one can limit the “blind variation” component to idea generation tests as manifested by measures of divergent thinking. The “selective retention” component can be represented by measures of convergent thinking, as represented by measures of remote associates. We summarize results from measures of creative cognition, correlated with structural neuroimaging measures including structural magnetic resonance imaging (sMRI, Diffusion Tensor Imaging (DTI, and proton magnetic resonance imaging (1H-MRS. We also review lesion studies, considered to be the “gold standard” of brain-behavioral studies. What emerges is a picture consistent with theories of disinhibitory brain features subserving creative cognition, as described previously (Martindale, 1981. We provide a perspective, involving aspects of the default mode network, which might provide a “first approximation” regarding how creative cognition might map on to the human brain.

  3. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness

    Bozek, Katarzyna; Wei, Yuning; Yan, Zheng;

    2014-01-01

    Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees,...

  4. Alpha-synuclein expression in the developing human brain.

    Raghavan, Ravi; Kruijff, Loes de; Sterrenburg, Monique D; Rogers, Beverly B; Hladik, Christa L; White, Charles L

    2004-01-01

    Alpha (alpha)-synuclein is a presynaptic protein, abnormal expression of which has been associated with neurodegenerative and neoplastic diseases. It is abundant in the developing vertebrate central nervous system (CNS), but less is known about its developmental expression in the human CNS. Immunohistochemical expression of alpha-synuclein was studied in 39 fetal, perinatal, pediatric, and adolescent brains. Perikaryal expression of alpha-synuclein is observed as early as 11-wk gestation in the cortical plate. Several discrete neuronal groups in the hippocampus, basal ganglia, and brain stem express perikaryal alpha-synuclein by 20-wk gestation, persisting through the first few years of life. In the cerebellum, alpha-synuclein is present by 21-wk gestation and persists into adult life as a coarse granular neuropil reaction product in the internal granular layer, and as a diffuse neuropil "blush" in the molecular layer. The germinal matrix, glia, endothelial cells, external granular layer, Pukinje cells, and dentate neurons are consistently negative for alpha-synuclein. We conclude that alpha-synuclein is expressed very early in human gestation, and that its distribution and temporal sequence of expression varies in discrete neuronal groups. Perikaryal alpha-synuclein starts disappearing from the neuronal cytosol in early childhood, and only the neuropil retains immunoreactivity into adulthood. The reappearance of alpha-synuclein in the adult neuronal cytosol in certain disease processes may represent reemergence of cues from an earlier developmental stage as part of a stress response. PMID:15547775

  5. Flow distributions and spatial correlations in human brain capillary networks

    Lorthois, Sylvie; Peyrounette, Myriam; Larue, Anne; Le Borgne, Tanguy

    2015-11-01

    The vascular system of the human brain cortex is composed of a space filling mesh-like capillary network connected upstream and downstream to branched quasi-fractal arterioles and venules. The distribution of blood flow rates in these networks may affect the efficiency of oxygen transfer processes. Here, we investigate the distribution and correlation properties of blood flow velocities from numerical simulations in large 3D human intra-cortical vascular network (10000 segments) obtained from an anatomical database. In each segment, flow is solved from a 1D non-linear model taking account of the complex rheological properties of blood flow in microcirculation to deduce blood pressure, blood flow and red blood cell volume fraction distributions throughout the network. The network structural complexity is found to impart broad and spatially correlated Lagrangian velocity distributions, leading to power law transit time distributions. The origins of this behavior (existence of velocity correlations in capillary networks, influence of the coupling with the feeding arterioles and draining veins, topological disorder, complex blood rheology) are studied by comparison with results obtained in various model capillary networks of controlled disorder. ERC BrainMicroFlow GA615102, ERC ReactiveFronts GA648377.

  6. Human Development XII: A Theory for the Structure and Function of the Human Brain

    Søren Ventegodt

    2008-01-01

    Full Text Available The human brain is probably the most complicated single structure in the biological universe. The cerebral cortex that is traditionally connected with consciousness is extremely complex. The brain contains approximately 1,000,000 km of nerve fibers, indicating its enormous complexity and which makes it difficult for scientists to reveal the function of the brain. In this paper, we propose a new model for brain functions, i.e., information-guided self-organization of neural patterns, where information is provided from the abstract wholeness of the biophysical system of an organism (often called the true self, or the “soul””. We present a number of arguments in favor of this model that provide self-conscious control over the thought process or cognition. Our arguments arise from analyzing experimental data from different research fields: histology, anatomy, electroencephalography (EEG, cerebral blood flow, neuropsychology, evolutionary studies, and mathematics. We criticize the popular network theories as the consequence of a simplistic, mechanical interpretation of reality (philosophical materialism applied to the brain. We demonstrate how viewing brain functions as information-guided self-organization of neural patterns can explain the structure of conscious mentation; we seem to have a dual hierarchical representation in the cerebral cortex: one for sensation-perception and one for will-action. The model explains many of our unique mental abilities to think, memorize, associate, discriminate, and make abstractions. The presented model of the conscious brain also seems to be able to explain the function of the simpler brains, such as those of insects and hydra.

  7. Human development XII: a theory for the structure and function of the human brain.

    Ventegodt, Søren; Hermansen, Tyge Dahl; Kandel, Isack; Merrick, Joav

    2008-01-01

    The human brain is probably the most complicated single structure in the biological universe. The cerebral cortex that is traditionally connected with consciousness is extremely complex. The brain contains approximately 1,000,000 km of nerve fibers, indicating its enormous complexity and which makes it difficult for scientists to reveal the function of the brain. In this paper, we propose a new model for brain functions, i.e., information-guided self-organization of neural patterns, where information is provided from the abstract wholeness of the biophysical system of an organism (often called the true self, or the "soul"). We present a number of arguments in favor of this model that provide self-conscious control over the thought process or cognition. Our arguments arise from analyzing experimental data from different research fields: histology, anatomy, electroencephalography (EEG), cerebral blood flow, neuropsychology, evolutionary studies, and mathematics. We criticize the popular network theories as the consequence of a simplistic, mechanical interpretation of reality (philosophical materialism) applied to the brain. We demonstrate how viewing brain functions as information-guided self-organization of neural patterns can explain the structure of conscious mentation; we seem to have a dual hierarchical representation in the cerebral cortex: one for sensation-perception and one for will-action. The model explains many of our unique mental abilities to think, memorize, associate, discriminate, and make abstractions. The presented model of the conscious brain also seems to be able to explain the function of the simpler brains, such as those of insects and hydra. PMID:18661051

  8. Reconsolidation of human memory: brain mechanisms and clinical relevance.

    Schwabe, Lars; Nader, Karim; Pruessner, Jens C

    2014-08-15

    The processes of memory formation and storage are complex and highly dynamic. Once memories are consolidated, they are not necessarily fixed but can be changed long after storage. In particular, seemingly stable memories may re-enter an unstable state when they are retrieved, from which they must be re-stabilized during a process known as reconsolidation. During reconsolidation, memories are susceptible to modifications again, thus providing an opportunity to update seemingly stable memories. While initial demonstrations of memory reconsolidation came mainly from animal studies, evidence for reconsolidation in humans is now accumulating as well. Here, we review recent advances in our understanding of human memory reconsolidation. After a summary of findings on the reconsolidation of human fear and episodic memory, we focus particularly on recent neuroimaging data that provide first insights into how reconsolidation processes are implemented in the human brain. Finally, we discuss the implications of memory modifications during reconsolidation for the treatment of mental disorders such as posttraumatic stress disorder and drug addiction. PMID:24755493

  9. Epigenomic Landscape of Human Fetal Brain, Heart, and Liver.

    Yan, Liying; Guo, Hongshan; Hu, Boqiang; Li, Rong; Yong, Jun; Zhao, Yangyu; Zhi, Xu; Fan, Xiaoying; Guo, Fan; Wang, Xiaoye; Wang, Wei; Wei, Yuan; Wang, Yan; Wen, Lu; Qiao, Jie; Tang, Fuchou

    2016-02-26

    The epigenetic regulation of spatiotemporal gene expression is crucial for human development. Here, we present whole-genome chromatin immunoprecipitation followed by high throughput DNA sequencing (ChIP-seq) analyses of a wide variety of histone markers in the brain, heart, and liver of early human embryos shortly after their formation. We identified 40,181 active enhancers, with a large portion showing tissue-specific and developmental stage-specific patterns, pointing to their roles in controlling the ordered spatiotemporal expression of the developmental genes in early human embryos. Moreover, using sequential ChIP-seq, we showed that all three organs have hundreds to thousands of bivalent domains that are marked by both H3K4me3 and H3K27me3, probably to keep the progenitor cells in these organs ready for immediate differentiation into diverse cell types during subsequent developmental processes. Our work illustrates the potentially critical roles of tissue-specific and developmental stage-specific epigenomes in regulating the spatiotemporal expression of developmental genes during early human embryonic development. PMID:26719341

  10. Gorilla and Orangutan Brains Conform to the Primate Cellular Scaling Rules: Implications for Human Evolution

    Herculano-Houzel, Suzana; Kaas, Jon H.

    2011-01-01

    Gorillas and orangutans are primates at least as large as humans, but their brains amount to about one third of the size of the human brain. This discrepancy has been used as evidence that the human brain is about 3 times larger than it should be for a primate species of its body size. In contrast to the view that the human brain is special in its size, we have suggested that it is the great apes that might have evolved bodies that are unusually large, on the basis of our recent finding that ...

  11. Brain

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  12. Human capital in European peripheral regions: brain - drain and brain - gain [poster

    2004-01-01

    The issue of this project is brain drain and brain gain in peripheral European regions. It focuses on the design, implementation and evaluation of actions to reduce brain drain and foster so-called brain gain. The action areas are the Twente region in the Netherlands; the Central Switzerland Cantons

  13. Abstract representations of associated emotions in the human brain.

    Kim, Junsuk; Schultz, Johannes; Rohe, Tim; Wallraven, Christian; Lee, Seong-Whan; Bülthoff, Heinrich H

    2015-04-01

    Emotions can be aroused by various kinds of stimulus modalities. Recent neuroimaging studies indicate that several brain regions represent emotions at an abstract level, i.e., independently from the sensory cues from which they are perceived (e.g., face, body, or voice stimuli). If emotions are indeed represented at such an abstract level, then these abstract representations should also be activated by the memory of an emotional event. We tested this hypothesis by asking human participants to learn associations between emotional stimuli (videos of faces or bodies) and non-emotional stimuli (fractals). After successful learning, fMRI signals were recorded during the presentations of emotional stimuli and emotion-associated fractals. We tested whether emotions could be decoded from fMRI signals evoked by the fractal stimuli using a classifier trained on the responses to the emotional stimuli (and vice versa). This was implemented as a whole-brain searchlight, multivoxel activation pattern analysis, which revealed successful emotion decoding in four brain regions: posterior cingulate cortex (PCC), precuneus, MPFC, and angular gyrus. The same analysis run only on responses to emotional stimuli revealed clusters in PCC, precuneus, and MPFC. Multidimensional scaling analysis of the activation patterns revealed clear clustering of responses by emotion across stimulus types. Our results suggest that PCC, precuneus, and MPFC contain representations of emotions that can be evoked by stimuli that carry emotional information themselves or by stimuli that evoke memories of emotional stimuli, while angular gyrus is more likely to take part in emotional memory retrieval. PMID:25855179

  14. Mapping the calcitonin receptor in human brain stem.

    Bower, Rebekah L; Eftekhari, Sajedeh; Waldvogel, Henry J; Faull, Richard L M; Tajti, János; Edvinsson, Lars; Hay, Debbie L; Walker, Christopher S

    2016-05-01

    The calcitonin receptor (CTR) is relevant to three hormonal systems: amylin, calcitonin, and calcitonin gene-related peptide (CGRP). Receptors for amylin and calcitonin are targets for treating obesity, diabetes, and bone disorders. CGRP receptors represent a target for pain and migraine. Amylin receptors (AMY) are a heterodimer formed by the coexpression of CTR with receptor activity-modifying proteins (RAMPs). CTR with RAMP1 responds potently to both amylin and CGRP. The brain stem is a major site of action for circulating amylin and is a rich site of CGRP binding. This study aimed to enhance our understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract, the hypoglossal nucleus, the cuneate nucleus, spinal trigeminal nucleus, the gracile nucleus, and the inferior olivary nucleus. CTR staining was also observed in the area postrema, the lateral reticular nucleus, and the pyramidal tract. The extensive expression of CTR in the medulla suggests that CTR may be involved in a wider range of functions than currently appreciated. PMID:26911465

  15. The functional connectivity landscape of the human brain.

    Bratislav Mišić

    Full Text Available Functional brain networks emerge and dissipate over a primarily static anatomical foundation. The dynamic basis of these networks is inter-regional communication involving local and distal regions. It is assumed that inter-regional distances play a pivotal role in modulating network dynamics. Using three different neuroimaging modalities, 6 datasets were evaluated to determine whether experimental manipulations asymmetrically affect functional relationships based on the distance between brain regions in human participants. Contrary to previous assumptions, here we show that short- and long-range connections are equally likely to strengthen or weaken in response to task demands. Additionally, connections between homotopic areas are the most stable and less likely to change compared to any other type of connection. Our results point to a functional connectivity landscape characterized by fluid transitions between local specialization and global integration. This ability to mediate functional properties irrespective of spatial distance may engender a diverse repertoire of cognitive processes when faced with a dynamic environment.

  16. Motor Skill Acquisition Promotes Human Brain Myelin Plasticity.

    Lakhani, Bimal; Borich, Michael R; Jackson, Jacob N; Wadden, Katie P; Peters, Sue; Villamayor, Anica; MacKay, Alex L; Vavasour, Irene M; Rauscher, Alexander; Boyd, Lara A

    2016-01-01

    Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI), the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent change. In the current study, seventeen healthy young adults completed ten sessions of visuomotor skill training (10,000 total movements) using the right arm. Multicomponent relaxation imaging was performed before and after training. Significant increases in myelin water fraction, a quantitative measure of myelin, were observed in task dependent brain regions (left intraparietal sulcus [IPS] and left parieto-occipital sulcus). In addition, the rate of motor skill acquisition and overall change in myelin water fraction in the left IPS were negatively related, suggesting that a slower rate of learning resulted in greater neuroplastic change. This study provides the first evidence for experience-dependent changes in myelin that are associated with changes in skilled movements in healthy young adults. PMID:27293906

  17. Motor Skill Acquisition Promotes Human Brain Myelin Plasticity

    Bimal Lakhani

    2016-01-01

    Full Text Available Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI, the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent change. In the current study, seventeen healthy young adults completed ten sessions of visuomotor skill training (10,000 total movements using the right arm. Multicomponent relaxation imaging was performed before and after training. Significant increases in myelin water fraction, a quantitative measure of myelin, were observed in task dependent brain regions (left intraparietal sulcus [IPS] and left parieto-occipital sulcus. In addition, the rate of motor skill acquisition and overall change in myelin water fraction in the left IPS were negatively related, suggesting that a slower rate of learning resulted in greater neuroplastic change. This study provides the first evidence for experience-dependent changes in myelin that are associated with changes in skilled movements in healthy young adults.

  18. Phenylethylamine N-methylation by human brain preparations

    Alterations in the brain metabolism of biogenic amines has been postulated to play a role in the pathophysiology of several psychiatric disorders. There is some evidence suggesting schizogenic properties for some abnormal neuroamine methylated derivatives. The authors now report that postmortem human brain preparations, obtained from the putamen and thalamus, convert phenylethylamine (PEA) to its behaviorally active derivative N-methyl PEA, a reaction which is carried out by the 100,000 xg supernatant (in presence of 1 x 10 -5M pargyline) and enhanced by the addition of NADPH. PEA N-methylation occurred in schizophrenics as well as in sex and age matched controls. The formation of increased amounts of (3H-) or (14C-) N-methyl PEA when incubating either cold amine and 3H-SAM or 1-14C PEA and cold SAM, respectively, indicates that SAM is a methyl group donor in this reaction. They will discuss the physiological and pharmacological implications of these results

  19. Motor Skill Acquisition Promotes Human Brain Myelin Plasticity

    Lakhani, Bimal; Borich, Michael R.; Jackson, Jacob N.; Wadden, Katie P.; Peters, Sue; Villamayor, Anica; MacKay, Alex L.; Vavasour, Irene M.; Rauscher, Alexander; Boyd, Lara A.

    2016-01-01

    Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI), the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent change. In the current study, seventeen healthy young adults completed ten sessions of visuomotor skill training (10,000 total movements) using the right arm. Multicomponent relaxation imaging was performed before and after training. Significant increases in myelin water fraction, a quantitative measure of myelin, were observed in task dependent brain regions (left intraparietal sulcus [IPS] and left parieto-occipital sulcus). In addition, the rate of motor skill acquisition and overall change in myelin water fraction in the left IPS were negatively related, suggesting that a slower rate of learning resulted in greater neuroplastic change. This study provides the first evidence for experience-dependent changes in myelin that are associated with changes in skilled movements in healthy young adults. PMID:27293906

  20. Dynamic magnetic resonance inverse imaging of human brain function.

    Lin, Fa-Hsuan; Wald, Lawrence L; Ahlfors, Seppo P; Hämäläinen, Matti S; Kwong, Kenneth K; Belliveau, John W

    2006-10-01

    MRI is widely used for noninvasive hemodynamic-based functional brain imaging. In traditional spatial encoding, however, gradient switching limits the temporal resolution, which makes it difficult to unambiguously identify possible fast nonhemodynamic changes. In this paper we propose a novel reconstruction approach, called dynamic inverse imaging (InI), that is capable of providing millisecond temporal resolution when highly parallel detection is used. To achieve an order-of-magnitude speedup in generating time-resolved contrast estimates and dynamic statistical parametric maps (dSPMs), the spatial information is derived from an array of detectors rather than by time-consuming gradient-encoding methods. The InI approach was inspired by electroencephalography (EEG) and magnetoencephalography (MEG) source localization techniques. Dynamic MR InI was evaluated by means of numerical simulations. InI was also applied to measure BOLD hemodynamic time curves at 20-ms temporal resolution in a visual stimulation experiment using a 90-channel head array. InI is expected to improve the time resolution of MRI and provide increased flexibility in the trade-off between spatial and temporal resolution for studies of dynamic activation patterns in the human brain. PMID:16964616

  1. Gorilla and orangutan brains conform to the primate cellular scaling rules: implications for human evolution.

    Herculano-Houzel, Suzana; Kaas, Jon H

    2011-01-01

    Gorillas and orangutans are primates at least as large as humans, but their brains amount to about one third of the size of the human brain. This discrepancy has been used as evidence that the human brain is about 3 times larger than it should be for a primate species of its body size. In contrast to the view that the human brain is special in its size, we have suggested that it is the great apes that might have evolved bodies that are unusually large, on the basis of our recent finding that the cellular composition of the human brain matches that expected for a primate brain of its size, making the human brain a linearly scaled-up primate brain in its number of cells. To investigate whether the brain of great apes also conforms to the primate cellular scaling rules identified previously, we determine the numbers of neuronal and other cells that compose the orangutan and gorilla cerebella, use these numbers to calculate the size of the brain and of the cerebral cortex expected for these species, and show that these match the sizes described in the literature. Our results suggest that the brains of great apes also scale linearly in their numbers of neurons like other primate brains, including humans. The conformity of great apes and humans to the linear cellular scaling rules that apply to other primates that diverged earlier in primate evolution indicates that prehistoric Homo species as well as other hominins must have had brains that conformed to the same scaling rules, irrespective of their body size. We then used those scaling rules and published estimated brain volumes for various hominin species to predict the numbers of neurons that composed their brains. We predict that Homo heidelbergensis and Homo neanderthalensis had brains with approximately 80 billion neurons, within the range of variation found in modern Homo sapiens. We propose that while the cellular scaling rules that apply to the primate brain have remained stable in hominin evolution (since they

  2. The brain's functional network architecture reveals human motives.

    Hein, Grit; Morishima, Yosuke; Leiberg, Susanne; Sul, Sunhae; Fehr, Ernst

    2016-03-01

    Goal-directed human behaviors are driven by motives. Motives are, however, purely mental constructs that are not directly observable. Here, we show that the brain's functional network architecture captures information that predicts different motives behind the same altruistic act with high accuracy. In contrast, mere activity in these regions contains no information about motives. Empathy-based altruism is primarily characterized by a positive connectivity from the anterior cingulate cortex (ACC) to the anterior insula (AI), whereas reciprocity-based altruism additionally invokes strong positive connectivity from the AI to the ACC and even stronger positive connectivity from the AI to the ventral striatum. Moreover, predominantly selfish individuals show distinct functional architectures compared to altruists, and they only increase altruistic behavior in response to empathy inductions, but not reciprocity inductions. PMID:26941317

  3. Exclusive neuronal expression of SUCLA2 in the human brain

    Dobolyi, Arpád; Ostergaard, Elsebet; Bagó, Attila G;

    2015-01-01

    associated with SUCLA2 mutations, the precise localization of SUCLA2 protein has never been investigated. Here, we show that immunoreactivity of A-SUCL-β in surgical human cortical tissue samples was present exclusively in neurons, identified by their morphology and visualized by double labeling with a...... was absent in glial cells, identified by antibodies directed against the glial markers GFAP and S100. Furthermore, in situ hybridization histochemistry demonstrated that SUCLA2 mRNA was present in Nissl-labeled neurons but not glial cells labeled with S100. Immunoreactivity of the GTP-forming β...... subunit (G-SUCL-β) encoded by SUCLG2, or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated in either neurons or astrocytes. Western blotting of post mortem brain samples revealed minor G-SUCL-β immunoreactivity that was, however, not upregulated in samples obtained from...

  4. A collaborative brain-computer interface for improving human performance.

    Yijun Wang

    Full Text Available Electroencephalogram (EEG based brain-computer interfaces (BCI have been studied since the 1970s. Currently, the main focus of BCI research lies on the clinical use, which aims to provide a new communication channel to patients with motor disabilities to improve their quality of life. However, the BCI technology can also be used to improve human performance for normal healthy users. Although this application has been proposed for a long time, little progress has been made in real-world practices due to technical limits of EEG. To overcome the bottleneck of low single-user BCI performance, this study proposes a collaborative paradigm to improve overall BCI performance by integrating information from multiple users. To test the feasibility of a collaborative BCI, this study quantitatively compares the classification accuracies of collaborative and single-user BCI applied to the EEG data collected from 20 subjects in a movement-planning experiment. This study also explores three different methods for fusing and analyzing EEG data from multiple subjects: (1 Event-related potentials (ERP averaging, (2 Feature concatenating, and (3 Voting. In a demonstration system using the Voting method, the classification accuracy of predicting movement directions (reaching left vs. reaching right was enhanced substantially from 66% to 80%, 88%, 93%, and 95% as the numbers of subjects increased from 1 to 5, 10, 15, and 20, respectively. Furthermore, the decision of reaching direction could be made around 100-250 ms earlier than the subject's actual motor response by decoding the ERP activities arising mainly from the posterior parietal cortex (PPC, which are related to the processing of visuomotor transmission. Taken together, these results suggest that a collaborative BCI can effectively fuse brain activities of a group of people to improve the overall performance of natural human behavior.

  5. MR Diffusion Studies of Human Brain in-vivo

    M Nezamzadeh

    2005-10-01

    Full Text Available Diffusion MRI has become one of the most powerful tools for the detection of acute stroke. The signal attenuation caused by the diffusion process is normally assumed to be exponential .The decay constant which is often called the “apparent diffusion coefficient”(ADC is measured by 2 or 3 points in clinical applications yielding mono-exponential decay curves. The diffusion signal attenuation of water molecules on human brain was measured with a certain pulse sequence. The sequence was modified to work over a range of diffusion times and high gradients. The decay was measured precisely for 96 b-values up to the maximum possible gradient amplitude of 28.8 mT/m. A significant deviation from mono-exponential behavior was observed consistent to the multi-exponential model. The NNLS-diff computational code, using a non-negative least squares (NNLS algorithm was developed for the data analysis. The diffusion time dependence of human brain tissue was studied for diffusion times between 20 to 53 ms using 16 b-values ranged from b=0 to the maximum possible b-value in each case. At all diffusion times, there was a diffusion coefficient at approximately 1x10-3 mm2/s and another at about 6x10–5 mm2/s. For some diffusion times a small contribution at about 1x10 -2 mm2/s was also detected. Our results were consistent with work of others. However, we observe small diffusion time dependence for the smallest diffusion coefficient, which has not previously been reported. More work is required to identify the source of the new observation.

  6. Discovering transnosological molecular basis of human brain diseases using biclustering analysis of integrated gene expression data

    Cha, Kihoon; Hwang, Taeho; Oh, Kimin; Yi, Gwan-Su

    2015-01-01

    Background It has been reported that several brain diseases can be treated as transnosological manner implicating possible common molecular basis under those diseases. However, molecular level commonality among those brain diseases has been largely unexplored. Gene expression analyses of human brain have been used to find genes associated with brain diseases but most of those studies were restricted either to an individual disease or to a couple of diseases. In addition, identifying significa...

  7. Towards next generation human-computer interaction -- brain-computer interfaces: applications and challenges

    Yang, Yuan; Wiart, Joe; Bloch, Isabelle

    2013-01-01

    Brain-computer interfaces (BCIs) are systems that record brain signals and transfer them into commands to build a direct communication pathway between a human brain and a computer. Decades of development make BCI a promising tool for next generation human-computer interaction (HCI). This paper briefly discusses one of its applications in the HCI field and some key challenges for its widespread adoption.

  8. The human sexual response cycle : Brain imaging evidence linking sex to other pleasures

    Georgiadis, J. R.; Kringelbach, M. L.

    2012-01-01

    Sexual behavior is critical to species survival, yet comparatively little is known about the neural mechanisms in the human brain. Here we systematically review the existing human brain imaging literature on sexual behavior and show that the functional neuroanatomy of sexual behavior is comparable t

  9. Noninvasive quantification of human brain antioxidant concentrations after an intravenous bolus of vitamin C

    Background: Until now, antioxidant based initiatives for preventing dementia have lacked a means to detect deficiency or measure pharmacologic effect in the human brain in situ. Objective: Our objective was to apply a novel method to measure key human brain antioxidant concentrations throughout the ...

  10. Temperament, character and serotonin activity in the human brain

    Tuominen, L; Salo, J; Hirvonen, J;

    2013-01-01

    The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT...

  11. Interactions between cardiac, respiratory, and brain activity in humans

    Musizza, Bojan; Stefanovska, Aneta

    2005-05-01

    The electrical activity of the heart (ECG), respiratory function and electric activity of the brain (EEG) were simultaneously recorded in conscious, healthy humans. Instantaneous frequencies of the heart beat, respiration and α-waves were then determined from 30-minutes recordings. The instantaneous cardiac frequency was defined as the inverse value of the time interval between two consecutive R-peaks. The instantaneous respiratory frequency was obtained from recordings of the excursions of thorax by application of the Hilbert transform. To obtain the instantaneous frequency of α-waves, the EEG signal recorded from the forehead was first analysed using the wavelet transform. Then the frequency band corresponding to α-waves was extracted and the Hilbert transform applied. Synchronization analysis was performed and the direction of coupling was ascertained, using pairs of instantaneous frequencies in each case. It is shown that the systems are weakly bidirectionally coupled. It was confirmed that, in conscious healthy humans, respiration drives cardiac activity. We also demonstrate from these analyses that α-activity drives both respiration and cardiac activity.

  12. The Future of Neuroepigenetics in the Human Brain

    Mitchell, Amanda; Roussos, Panos; Peter, Cyril; Tsankova, Nadejda; Akbarian, Schahram

    2016-01-01

    Complex mechanisms shape the genome of brain cells into transcriptional units, clusters of condensed chromatin, and many other features that distinguish between various cell types and developmental stages sharing the same genetic material. Only a few years ago, the field’s focus was almost entirely on a single mark, CpG methylation; the emerging complexity of neuronal and glial epigenomes now includes multiple types of DNA cytosine methylation, more than 100 residue-specific posttranslational histone modifications and histone variants, all of which superimposed by a dynamic and highly regulated three-dimensional organization of the chromosomal material inside the cell nucleus. Here, we provide an update on the most innovative approaches in neuroepigenetics and their potential contributions to approach cognitive functions and disorders unique to human. We propose that comprehensive, cell type-specific mappings of DNA and histone modifications, chromatin-associated RNAs, and chromosomal “loopings” and other determinants of three-dimensional genome organization will critically advance insight into the pathophysiology of the disease. For example, superimposing the epigenetic landscapes of neuronal and glial genomes onto genetic maps for complex disorders, ranging from Alzheimer’s disease to schizophrenia, could provide important clues about neurological function for some of the risk-associated noncoding sequences in the human genome. PMID:25410546

  13. Fractional Diffusion Based Modelling and Prediction of Human Brain Response to External Stimuli

    Hamidreza Namazi

    2015-01-01

    Full Text Available Human brain response is the result of the overall ability of the brain in analyzing different internal and external stimuli and thus making the proper decisions. During the last decades scientists have discovered more about this phenomenon and proposed some models based on computational, biological, or neuropsychological methods. Despite some advances in studies related to this area of the brain research, there were fewer efforts which have been done on the mathematical modeling of the human brain response to external stimuli. This research is devoted to the modeling and prediction of the human EEG signal, as an alert state of overall human brain activity monitoring, upon receiving external stimuli, based on fractional diffusion equations. The results of this modeling show very good agreement with the real human EEG signal and thus this model can be used for many types of applications such as prediction of seizure onset in patient with epilepsy.

  14. Equal ≠ The Same: Sex Differences in the Human Brain

    Cahill, Larry

    2014-01-01

    Editor’s Note: While advances in brain imaging confirm that men and women think in their own way and that their brains are different, the biomedical community mainly uses male animals as testing subjects with the assumption that sex differences in the brain hardly matter. This month’s Cerebrum highlights some of the thinking and research that invalidates that assumption.

  15. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness.

    Katarzyna Bozek

    2014-05-01

    Full Text Available Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.

  16. Endocannabinoids modulate human blood–brain barrier permeability in vitro

    Hind, William H; Tufarelli, Cristina; Neophytou, Maria; Anderson, Susan I; England, Timothy J; O'Sullivan, Saoirse E

    2015-01-01

    Background and Purpose Endocannabinoids alter permeability at various epithelial barriers, and cannabinoid receptors and endocannabinoid levels are elevated by stroke, with potential neuroprotective effects. We therefore explored the role of endocannabinoids in modulating blood–brain barrier (BBB) permeability in normal conditions and in an ischaemia/reperfusion model. Experimental Approach Human brain microvascular endothelial cell and astrocyte co-cultures modelled the BBB. Ischaemia was modelled by oxygen-glucose deprivation (OGD) and permeability was measured by transepithelial electrical resistance. Endocannabinoids or endocannabinoid-like compounds were assessed for their ability to modulate baseline permeability or OGD-induced hyperpermeability. Target sites of action were investigated using receptor antagonists and subsequently identified with real-time PCR. Key Results Anandamide (10 μM) and oleoylethanolamide (OEA, 10 μM) decreased BBB permeability (i.e. increased resistance). This was mediated by cannabinoid CB2 receptors, transient receptor potential vanilloid 1 (TRPV1) channels, calcitonin gene-regulated peptide (CGRP) receptor (anandamide only) and PPARα (OEA only). Application of OEA, palmitoylethanolamide (both PPARα mediated) or virodhamine (all 10 μM) decreased the OGD-induced increase in permeability during reperfusion. 2-Arachidonoyl glycerol, noladin ether and oleamide did not affect BBB permeability in normal or OGD conditions. N-arachidonoyl-dopamine increased permeability through a cytotoxic mechanism. PPARα and γ, CB1 receptors, TRPV1 channels and CGRP receptors were expressed in both cell types, but mRNA for CB2 receptors was only present in astrocytes. Conclusion and Implication The endocannabinoids may play an important modulatory role in normal BBB physiology, and also afford protection to the BBB during ischaemic stroke, through a number of target sites. PMID:25651941

  17. Rate of evolution in brain-expressed genes in humans and other primates.

    Hurng-Yi Wang

    2007-02-01

    Full Text Available Brain-expressed genes are known to evolve slowly in mammals. Nevertheless, since brains of higher primates have evolved rapidly, one might expect acceleration in DNA sequence evolution in their brain-expressed genes. In this study, we carried out full-length cDNA sequencing on the brain transcriptome of an Old World monkey (OWM and then conducted three-way comparisons among (i mouse, OWM, and human, and (ii OWM, chimpanzee, and human. Although brain-expressed genes indeed appear to evolve more rapidly in species with more advanced brains (apes > OWM > mouse, a similar lineage effect is observable for most other genes. The broad inclusion of genes in the reference set to represent the genomic average is therefore critical to this type of analysis. Calibrated against the genomic average, the rate of evolution among brain-expressed genes is probably lower (or at most equal in humans than in chimpanzee and OWM. Interestingly, the trend of slow evolution in coding sequence is no less pronounced among brain-specific genes, vis-à-vis brain-expressed genes in general. The human brain may thus differ from those of our close relatives in two opposite directions: (i faster evolution in gene expression, and (ii a likely slowdown in the evolution of protein sequences. Possible explanations and hypotheses are discussed.

  18. Endocasts-the direct evidence and recent advances in the study of human brain evolution

    2007-01-01

    Brain evolution is one of the most important aspects of human evolution, usually studied through endocasts. Analysis of fossil hominid endocasts allows inferences on functional anatomy, physiology, and phylogeny. In this paper, we describe the general features of endocast studies and review some of the major topics in paleoneurology. These are: absolute and relative brain size evolution; brain shape variation; brain asymmetry and lateralization; middle meningeal vessels and venous sinuses; application of computed tomography and virtual imaging; the history of Chinese brain endocast studies. In particular, this review emphasizes endocast studies on Chinese hominin fossils.

  19. The Human Brainnetome Atlas: A New Brain Atlas Based on Connectional Architecture.

    Fan, Lingzhong; Li, Hai; Zhuo, Junjie; Zhang, Yu; Wang, Jiaojian; Chen, Liangfu; Yang, Zhengyi; Chu, Congying; Xie, Sangma; Laird, Angela R; Fox, Peter T; Eickhoff, Simon B; Yu, Chunshui; Jiang, Tianzi

    2016-08-01

    The human brain atlases that allow correlating brain anatomy with psychological and cognitive functions are in transition from ex vivo histology-based printed atlases to digital brain maps providing multimodal in vivo information. Many current human brain atlases cover only specific structures, lack fine-grained parcellations, and fail to provide functionally important connectivity information. Using noninvasive multimodal neuroimaging techniques, we designed a connectivity-based parcellation framework that identifies the subdivisions of the entire human brain, revealing the in vivo connectivity architecture. The resulting human Brainnetome Atlas, with 210 cortical and 36 subcortical subregions, provides a fine-grained, cross-validated atlas and contains information on both anatomical and functional connections. Additionally, we further mapped the delineated structures to mental processes by reference to the BrainMap database. It thus provides an objective and stable starting point from which to explore the complex relationships between structure, connectivity, and function, and eventually improves understanding of how the human brain works. The human Brainnetome Atlas will be made freely available for download at http://atlas.brainnetome.org, so that whole brain parcellations, connections, and functional data will be readily available for researchers to use in their investigations into healthy and pathological states. PMID:27230218

  20. Traversal of Candida albicans across Human Blood-Brain Barrier In Vitro

    Jong, Ambrose Y.; Stins, Monique F.; Huang, Sheng-He; Chen, Steven H. M.; Kim, Kwang Sik

    2001-01-01

    Candida albicans is an opportunistic pathogen, which primarily affects neonates and immunocompromised individuals. The pathogen can invade the central nervous system, resulting in meningitis. At present, the pathogenesis of C. albicans meningitis is unclear. We used an in vitro model of the human blood-brain barrier to investigate the interaction(s) of C. albicans with human brain microvascular endothelial cells (BMEC). Binding of C. albicans to human BMEC was time and inoculum dependent. Inv...

  1. An animal-to-human scaling law for blast-induced traumatic brain injury risk assessment

    Jean, Aurélie; Nyein, Michelle K.; Zheng, James Q.; Moore, David F.; Joannopoulos, John D.; Radovitzky, Raúl

    2014-01-01

    A physics-based animal-to-human scaling law for the effects of a blast wave on brain tissue is proposed. This scaling law, or transfer function, enables the translation of animal-based assessments of injury to the human, thus effectively enabling the derivation of human injury criteria based on animal tests. This is critical both in the diagnosis of traumatic brain injury as well as in the design of blast-protective helmets.

  2. Local Model of Arteriovenous Malformation of the Human Brain

    Nadezhda Telegina, Ms; Aleksandr Chupakhin, Mr; Aleksandr Cherevko, Mr

    2013-02-01

    Vascular diseases of the human brain are one of the reasons of deaths and people's incapacitation not only in Russia, but also in the world. The danger of an arteriovenous malformation (AVM) is in premature rupture of pathological vessels of an AVM which may cause haemorrhage. Long-term prognosis without surgical treatment is unfavorable. The reduced impact method of AVM treatment is embolization of a malformation which often results in complete obliteration of an AVM. Pre-surgical mathematical modeling of an arteriovenous malformation can help surgeons with an optimal sequence of the operation. During investigations, the simple mathematical model of arteriovenous malformation is developed and calculated, and stationary and non-stationary processes of its embolization are considered. Various sequences of embolization of a malformation are also considered. Calculations were done with approximate steady flow on the basis of balanced equations derived from conservation laws. Depending on pressure difference, a fistula-type AVM should be embolized at first, and then small racemose AVMs are embolized. Obtained results are in good correspondence with neurosurgical AVM practice.

  3. Local Model of Arteriovenous Malformation of the Human Brain

    Vascular diseases of the human brain are one of the reasons of deaths and people's incapacitation not only in Russia, but also in the world. The danger of an arteriovenous malformation (AVM) is in premature rupture of pathological vessels of an AVM which may cause haemorrhage. Long-term prognosis without surgical treatment is unfavorable. The reduced impact method of AVM treatment is embolization of a malformation which often results in complete obliteration of an AVM. Pre-surgical mathematical modeling of an arteriovenous malformation can help surgeons with an optimal sequence of the operation. During investigations, the simple mathematical model of arteriovenous malformation is developed and calculated, and stationary and non-stationary processes of its embolization are considered. Various sequences of embolization of a malformation are also considered. Calculations were done with approximate steady flow on the basis of balanced equations derived from conservation laws. Depending on pressure difference, a fistula-type AVM should be embolized at first, and then small racemose AVMs are embolized. Obtained results are in good correspondence with neurosurgical AVM practice.

  4. Human capital in European peripheral regions: brain - drain and brain - gain: project design [poster

    2004-01-01

    Project design - The action plan consists of two overlapping phases. In the initial analytic phase the specific details of brain gain/ brain drain and their underlying processes in three regions are analyzed. This is not meant as a study project but rather a method to evaluate, design and implement brain drain gain instruments through a thorough analysis of processes. The implementation phase deals with the development, implementation and evaluation of instruments as well as the dissemination...

  5. Combining EEG source connectivity and network similarity: Application to object categorization in the human brain

    Mheich, Ahmad; Hassan, Mahmoud; Dufor, Olivier; Khalil, Mohamad; Wendling, Fabrice

    2016-01-01

    A major challenge in cognitive neuroscience is to evaluate the ability of the human brain to categorize or group visual stimuli based on common features. This categorization process is very fast and occurs in few hundreds of millisecond time scale. However, an accurate tracking of the spatiotemporal dynamics of large-scale brain networks is still an unsolved issue. Here, we show the combination of recently developed method called dense-EEG source connectivity to identify functional brain netw...

  6. Individual human brain areas can be identified from their characteristic spectral activation fingerprints

    Keitel, Anne; Gross, Joachim

    2016-01-01

    The human brain can be parcellated into diverse anatomical areas. We investigated whether rhythmic brain activity in these areas is characteristic and can be used for automatic classification. To this end, resting-state MEG data of 22 healthy adults was analysed. Power spectra of 1-s long data segments for atlas-defined brain areas were clustered into spectral profiles (“fingerprints”), using k-means and Gaussian mixture (GM) modelling. We demonstrate that individual areas can be identified f...

  7. The Structural Connectome of the Human Brain in Agenesis of the Corpus Callosum

    Owen, Julia P.; Li, Yi-Ou; Ziv, Etay; Strominger, Zoe; Gold, Jacquelyn; Bukhpun, Polina; Wakahiro, Mari; Friedman, Eric J.; Sherr, Elliott H; Mukherjee, Pratik

    2012-01-01

    Adopting a network perspective, the structural connectome reveals the large-scale white matter connectivity of the human brain, yielding insights into cerebral organization otherwise inaccessible to researchers and clinicians. Connectomics has great potential for elucidating abnormal connectivity in congenital brain malformations, especially axonal pathfinding disorders. Agenesis of the corpus callosum (AgCC) is one of the most common brain malformations and can also be considered a prototypi...

  8. Time-invariant person-specific frequency templates in human brain activity

    Doron, Itai; Hulata, Eyal; Baruchi, Itay; Towle, Vernon L.; Ben-Jacob, Eshel

    2006-01-01

    The various human brain tasks are performed at different locations and time scales. Yet, we discovered the existence of time-invariant (above an essential time scale) partitioning of the brain activity into personal state-specific frequency bands. For that, we perform temporal and ensemble averaging of best wavelet packet bases from multi-electrode EEG recordings. These personal frequency-bands provide new templates for quantitative analyses of brain function, e.g., normal vs. epileptic activ...

  9. Generative models of rich clubs in Hebbian neuronal networks and large-scale human brain networks

    Vértes, Petra E.; Alexander-Bloch, Aaron; Bullmore, Edward T

    2014-01-01

    Rich clubs arise when nodes that are ‘rich’ in connections also form an elite, densely connected ‘club’. In brain networks, rich clubs incur high physical connection costs but also appear to be especially valuable to brain function. However, little is known about the selection pressures that drive their formation. Here, we take two complementary approaches to this question: firstly we show, using generative modelling, that the emergence of rich clubs in large-scale human brain networks can be...

  10. Higher cortical modulation of pain perception in the human brain: Psychological determinant.

    Chen, Andrew Cn

    2009-10-01

    Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down effect, particularly studied in psychological determinants. Pain modulation can be examined by gene therapy, physical modulation, pharmacological modulation, psychological modulation, and pathophysiological modulation. In psychological modulation, this article examined (a) willed determination, (b) distraction, (c) placebo, (d) hypnosis, (e) meditation, (f) qi-gong, (g) belief, and (h) emotions, respectively, in the brain function for pain modulation. In each, the operational definition, cortical processing, neuroimaging, and pain modulation were systematically deliberated. However, not all studies had featured the brain modulation processing but rather demonstrated potential effects on human pain. In our own studies on the emotional modulation on human pain, we observed that emotions could be induced from music melodies or pictures perception for reduction of tonic human pain, mainly in potentiation of the posterior alpha EEG fields, likely resulted from underneath activities of precuneous in regulation of consciousness, including pain perception. To sum, higher brain functions become the leading edge research in all sciences. How to solve the information bit of thinking and feeling in the brain can be the greatest challenge of human intelligence. Application of higher cortical modulation of human pain and suffering can lead to the progress of social humanity and civilization. PMID:19784081

  11. Differing levels of excision repair in human fetal dermis and brain cells

    Gibson, R.E. (Ohio State Univ., Columbus (USA). Dept. of Radiology); D' Ambrosio, S.M. (Ohio State Univ., Columbus (USA). Dept. of Radiology; Ohio State Univ., Columbus (USA). Dept. of Pharmacology)

    1982-01-01

    The levels of DNA excision repair, as measured by unscheduled DNA synthesis (UDS) and the UV-endonuclease sensitive site assay, were compared in cells derived from human fetal brain and dermal tissues. The level of UDS induced following ultraviolet (UV) irradiation was found to be lower (approx. 60%) in the fetal brain cells than in fetal dermal cells. It was determined, using the UV-endonuclease sensitive site assay to confirm the UDS observation, that 50% of the dimers induced by UV in fetal dermal cells were repaired in 8 h. while only 15% were removed in the fetal brain cells during the same period of time. Even after 24 h. only 44% of the dimers induced by UV in the fetal brain cells were repaired, while 65% were removed in the dermal cells. These data suggest that cultured human fetal brain cells exhibit lower levels of excision repair compared to cultured human fetal dermal cells.

  12. EXPRESSION OF IL-13Ra2 GENE IN HUMAN BRAIN TUMORS

    WU An-hua; TIE Xin-xin; WANG Yun-jie; YANG Guo-rui

    2005-01-01

    Objective: To investigate the expression of IL-13Ra2 gene in brain tumors. Methods: Seventy-nine human brain tumors were obtained from the department of Neurosurgery of China Medical University. Human IL-13Ra2 expression was evaluated by reverse transcriptase polymerase chain reaction and immunohistochemical analysis. Results: IL-13Ra2 gene was highly expressed in glioblastoma, medulloblastoma, malignant meningioma and benign meningioma. Conclusion:Human IL-13Ra2 gene is expressed in brain tumors in addition to gliomas, and our result indicates that the IL-13Ra2 gene promoter based gene therapy method can be used to treat brain tumors in addition to gliomas. Further studies involving larger numbers of samples are necessary to fully understand the expression profile of IL-13Ra2 gene in the brain tumors.

  13. Evolution, development, and plasticity of the human brain: from molecules to bones

    Branka eHrvoj-Mihic

    2013-10-01

    Full Text Available Neuroanatomical, molecular, and paleontological evidence is examined in light of human brain evolution. The brain of extant humans differs from the brains of other primates in its overall size and organization, and differences in size and organization of specific cortical areas and subcortical structures implicated into complex cognition and social and emotional processing. The human brain is also characterized by functional lateralizations, reflecting specializations of the cerebral hemispheres in humans for different types of processing, facilitating fast and reliable communication between neural cells in an enlarged brain. The features observed in the adult brain reflect human-specific patterns of brain development. Compared to the brains of other primates, the human brain takes longer to mature, promoting an extended period for establishing cortical microcircuitry and its modifications. Together, these features may underlie the prolonged period of learning and acquisition of technical and social skills necessary for survival, creating a unique cognitive and behavioral niche typical of our species.The neuroanatomical findings are in concordance with molecular analyses, which suggest a trend toward heterochrony in the expression of genes implicated in different functions. These include synaptogenesis, neuronal maturation and plasticity in humans, mutations in genes implicated in neurite outgrowth and plasticity, and an increased role of regulatory mechanisms, potentially promoting fast modification of neuronal morphologies in response to new computational demands. At the same time, endocranial casts of fossil hominins provide an insight into the timing of the emergence of uniquely human features in the course of evolution. We conclude by proposing several ways of combining comparative neuroanatomy, molecular biology and insights gained from fossil endocasts in future research.

  14. Human Behavior, Learning, and the Developing Brain: Typical Development

    Coch, Donna, Ed.; Fischer, Kurt W., Ed.; Dawson, Geraldine, Ed.

    2010-01-01

    This volume brings together leading authorities from multiple disciplines to examine the relationship between brain development and behavior in typically developing children. Presented are innovative cross-sectional and longitudinal studies that shed light on brain-behavior connections in infancy and toddlerhood through adolescence. Chapters…

  15. Human capital in European peripheral regions: brain - drain and brain - gain [poster

    Coenen, Frans H.J.M.

    2004-01-01

    Project goal - The overall goal of the project is to build a legitimate transnational network to transfer ideas and experiences and implement measures to reduce brain drain and foster brain gain while reinforcing the economical and spatial development of peripheral regions in NWE. This means a highe

  16. Human capital in European peripheral regions: brain - drain and brain - gain: project design [poster

    2004-01-01

    Project design - The action plan consists of two overlapping phases. In the initial analytic phase the specific details of brain gain/ brain drain and their underlying processes in three regions are analyzed. This is not meant as a study project but rather a method to evaluate, design and implement

  17. Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans.

    Kullmann, Stephanie; Heni, Martin; Hallschmid, Manfred; Fritsche, Andreas; Preissl, Hubert; Häring, Hans-Ulrich

    2016-10-01

    Ever since the brain was identified as an insulin-sensitive organ, evidence has rapidly accumulated that insulin action in the brain produces multiple behavioral and metabolic effects, influencing eating behavior, peripheral metabolism, and cognition. Disturbances in brain insulin action can be observed in obesity and type 2 diabetes (T2D), as well as in aging and dementia. Decreases in insulin sensitivity of central nervous pathways, i.e., brain insulin resistance, may therefore constitute a joint pathological feature of metabolic and cognitive dysfunctions. Modern neuroimaging methods have provided new means of probing brain insulin action, revealing the influence of insulin on both global and regional brain function. In this review, we highlight recent findings on brain insulin action in humans and its impact on metabolism and cognition. Furthermore, we elaborate on the most prominent factors associated with brain insulin resistance, i.e., obesity, T2D, genes, maternal metabolism, normal aging, inflammation, and dementia, and on their roles regarding causes and consequences of brain insulin resistance. We also describe the beneficial effects of enhanced brain insulin signaling on human eating behavior and cognition and discuss potential applications in the treatment of metabolic and cognitive disorders. PMID:27489306

  18. Effect of Antimicrobial Compounds on Balamuthia mandrillaris Encystment and Human Brain Microvascular Endothelial Cell Cytopathogenicity▿

    Siddiqui, Ruqaiyyah; Matin, Abdul; Warhurst, David; Stins, Monique; Khan, Naveed Ahmed

    2007-01-01

    Cycloheximide, ketoconazole, or preexposure of organisms to cytochalasin D prevented Balamuthia mandrillaris-associated cytopathogenicity in human brain microvascular endothelial cells, which constitute the blood-brain barrier. In an assay for inhibition of cyst production, these three agents prevented the production of cysts, suggesting that the biosynthesis of proteins and ergosterol and the polymerization of actin are important in cytopathogenicity and encystment.

  19. Use of Neuroimaging to Clarify How Human Brains Perform Mental Calculations

    Ortiz, Enrique

    2010-01-01

    The purpose of this study was to analyze participants' levels of hemoglobin as they performed arithmetic mental calculations using Optical Topography (OT, helmet type brain-scanning system, also known as Functional Near-Infrared Spectroscopy or fNIRS). A central issue in cognitive neuroscience involves the study of how the human brain encodes and…

  20. Notch-1 Signalling Is Activated in Brain Arteriovenous Malformations in Humans

    ZhuGe, Qichuan; Zhong, Ming; Zheng, WeiMing; Yang, Guo-Yuan; Mao, XiaoOu; Xie, Lin; Chen, Gourong; Chen, Yongmei; Lawton, Michael T.; Young, William L.; Greenberg, David A.; Jin, Kunlin

    2009-01-01

    A role for the Notch signalling pathway in the formation of arteriovenous malformations during development has been suggested. However, whether Notch signalling is involved in brain arteriovenous malformations in humans remains unclear. Here, we performed immunohistochemistry on surgically resected brain arteriovenous malformations and found that,…

  1. Natural Learning for a Connected World: Education, Technology, and the Human Brain

    Caine, Renate N.; Caine, Geoffrey

    2011-01-01

    Why do video games fascinate kids so much that they will spend hours pursuing a difficult skill? Why don't they apply this kind of intensity to their schoolwork? These questions are answered by the authors who pioneered brain/mind learning with the publication of "Making Connections: Teaching and the Human Brain". In their new book, "Natural…

  2. The Human Nervous System: A Framework for Teaching and the Teaching Brain

    Rodriguez, Vanessa

    2013-01-01

    The teaching brain is a new concept that mirrors the complex, dynamic, and context-dependent nature of the learning brain. In this article, I use the structure of the human nervous system and its sensing, processing, and responding components as a framework for a re-conceptualized teaching system. This teaching system is capable of responses on an…

  3. Human brain cancer studied by resonance Raman spectroscopy

    Zhou, Yan; Liu, Cheng-Hui; Sun, Yi; Pu, Yang; Boydston-White, Susie; Liu, Yulong; Alfano, Robert R.

    2012-11-01

    The resonance Raman (RR) spectra of six types of human brain tissues are examined using a confocal micro-Raman system with 532-nm excitation in vitro. Forty-three RR spectra from seven subjects are investigated. The spectral peaks from malignant meningioma, stage III (cancer), benign meningioma (benign), normal meningeal tissues (normal), glioblastoma multiforme grade IV (cancer), acoustic neuroma (benign), and pituitary adenoma (benign) are analyzed. Using a 532-nm excitation, the resonance-enhanced peak at 1548 cm-1 (amide II) is observed in all of the tissue specimens, but is not observed in the spectra collected using the nonresonance Raman system. An increase in the intensity ratio of 1587 to 1605 cm-1 is observed in the RR spectra collected from meningeal cancer tissue as compared with the spectra collected from the benign and normal meningeal tissue. The peak around 1732 cm-1 attributed to fatty acids (lipids) are diminished in the spectra collected from the meningeal cancer tumors as compared with the spectra from normal and benign tissues. The characteristic band of spectral peaks observed between 2800 and 3100 cm-1 are attributed to the vibrations of methyl (-CH3) and methylene (-CH2-) groups. The ratio of the intensities of the spectral peaks of 2935 to 2880 cm-1 from the meningeal cancer tissues is found to be lower in comparison with that of the spectral peaks from normal, and benign tissues, which may be used as a distinct marker for distinguishing cancerous tissues from normal meningeal tissues. The statistical methods of principal component analysis and the support vector machine are used to analyze the RR spectral data collected from meningeal tissues, yielding a diagnostic sensitivity of 90.9% and specificity of 100% when two principal components are used.

  4. A reproducible brain tumour model established from human glioblastoma biopsies

    Li Xingang

    2009-12-01

    Full Text Available Abstract Background Establishing clinically relevant animal models of glioblastoma multiforme (GBM remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. Methods In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. Results The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. Conclusions In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression.

  5. Temporal lobe epilepsy: a unique window into living human brain epigenetic gene regulation

    Grote, Alexander; Schoch, Susanne; Becker, Albert J.

    2015-01-01

    This scientific commentary refers to ‘Differential DNA methylation profiles of coding and non-coding genes define hippocampal sclerosis in human temporal lobe epilepsy’ by Miller-Delaney et al. (10.1093/brain/awu373).

  6. Information flow between interacting human brains: Identification, validation, and relationship to social expertise.

    Bilek, Edda; Ruf, Matthias; Schäfer, Axel; Akdeniz, Ceren; Calhoun, Vince D; Schmahl, Christian; Demanuele, Charmaine; Tost, Heike; Kirsch, Peter; Meyer-Lindenberg, Andreas

    2015-04-21

    Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender's and receiver's temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions. PMID:25848050

  7. Immunohistochemical demonstration of specific antigens in the human brain fixed in zinc-ethanol-formaldehyde.

    Korzhevskii, D E; Sukhorukova, E G; Kirik, O V; Grigorev, I P

    2015-01-01

    Tissue fixation is critical for immunohistochemistry. Recently, we developed a zinc-ethanol-formalin fixative (ZEF), and the present study was aimed to assess the applicability of the ZEF for the human brain histology and immunohistochemistry and to evaluate the detectability of different antigens in the human brain fixed with ZEF. In total, 11 antigens were tested, including NeuN, neuron-specific enolase, GFAP, Iba-1, calbindin, calretinin, choline acetyltransferase, glutamic acid decarboxylase (GAD65), tyrosine hydroxylase, synaptophysin, and α-tubulin. The obtained data show that: i) the ZEF has potential for use in general histological practice, where detailed characterization of human brain morphology is needed; ii) the antigens tested are well-preserved in the human brain specimens fixed in the ZEF. PMID:26428887

  8. Immunohistochemical demonstration of specific antigens in the human brain fixed in zinc-ethanol-formaldehyde

    D.E. Korzhevskii

    2015-08-01

    Full Text Available Tissue fixation is critical for immunohistochemistry. Recently, we developed a zinc-ethanol-formalin fixative (ZEF, and the present study was aimed to assess the applicability of the ZEF for the human brain histology and immunohistochemistry and to evaluate the detectability of different antigens in the human brain fixed with ZEF. In total, 11 antigens were tested, including NeuN, neuron-specific enolase, GFAP, Iba-1, calbindin, calretinin, choline acetyltransferase, glutamic acid decarboxylase (GAD65, tyrosine hydroxylase, synaptophysin, and α-tubulin. The obtained data show that: i the ZEF has potential for use in general histological practice, where detailed characterization of human brain morphology is needed; ii the antigens tested are well-preserved in the human brain specimens fixed in the ZEF.

  9. Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans

    Objective: In animals, intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation. In humans, functional brain magnetic resonance imaging (fMRI) studies during carbohydrate ingestion suggest that glucose may regulate HT signaling but are potentially confoun...

  10. Convergent transcriptional specializations in the brains of humans and song-learning birds

    Pfenning, Andreas R.; Hara, Erina; Whitney, Osceola;

    2014-01-01

    Song-learning birds and humans share independently evolved similarities in brain pathways for vocal learning that are essential for song and speech and are not found in most other species. Comparisons of brain transcriptomes of song-learning birds and humans relative to vocal nonlearners identified...... convergent gene expression specializations in specific song and speech brain regions of avian vocal learners and humans. The strongest shared profiles relate bird motor and striatal song-learning nuclei, respectively, with human laryngeal motor cortex and parts of the striatum that control speech production...... and learning. Most of the associated genes function in motor control and brain connectivity. Thus, convergent behavior and neural connectivity for a complex trait are associated with convergent specialized expression of multiple genes....

  11. ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size.

    Rotem Kadir

    2016-03-01

    Full Text Available Primary microcephaly is a congenital neurodevelopmental disorder of reduced head circumference and brain volume, with fewer neurons in the cortex of the developing brain due to premature transition between symmetrical and asymmetrical cellular division of the neuronal stem cell layer during neurogenesis. We now show through linkage analysis and whole exome sequencing, that a dominant mutation in ALFY, encoding an autophagy scaffold protein, causes human primary microcephaly. We demonstrate the dominant effect of the mutation in drosophila: transgenic flies harboring the human mutant allele display small brain volume, recapitulating the disease phenotype. Moreover, eye-specific expression of human mutant ALFY causes rough eye phenotype. In molecular terms, we demonstrate that normally ALFY attenuates the canonical Wnt signaling pathway via autophagy-dependent removal specifically of aggregates of DVL3 and not of Dvl1 or Dvl2. Thus, autophagic attenuation of Wnt signaling through removal of Dvl3 aggregates by ALFY acts in determining human brain size.

  12. Transcriptional profiling of human brain endothelial cells reveals key properties crucial for predictive in vitro blood-brain barrier models.

    Eduard Urich

    Full Text Available Brain microvascular endothelial cells (BEC constitute the blood-brain barrier (BBB which forms a dynamic interface between the blood and the central nervous system (CNS. This highly specialized interface restricts paracellular diffusion of fluids and solutes including chemicals, toxins and drugs from entering the brain. In this study we compared the transcriptome profiles of the human immortalized brain endothelial cell line hCMEC/D3 and human primary BEC. We identified transcriptional differences in immune response genes which are directly related to the immortalization procedure of the hCMEC/D3 cells. Interestingly, astrocytic co-culturing reduced cell adhesion and migration molecules in both BECs, which possibly could be related to regulation of immune surveillance of the CNS controlled by astrocytic cells within the neurovascular unit. By matching the transcriptome data from these two cell lines with published transcriptional data from freshly isolated mouse BECs, we discovered striking differences that could explain some of the limitations of using cultured BECs to study BBB properties. Key protein classes such as tight junction proteins, transporters and cell surface receptors show differing expression profiles. For example, the claudin-5, occludin and JAM2 expression is dramatically reduced in the two human BEC lines, which likely explains their low transcellular electric resistance and paracellular leakiness. In addition, the human BEC lines express low levels of unique brain endothelial transporters such as Glut1 and Pgp. Cell surface receptors such as LRP1, RAGE and the insulin receptor that are involved in receptor-mediated transport are also expressed at very low levels. Taken together, these data illustrate that BECs lose their unique protein expression pattern outside of their native environment and display a more generic endothelial cell phenotype. A collection of key genes that seems to be highly regulated by the local

  13. MR-visible water content in human brain: a proton MRS study

    Christiansen, P; Toft, P B; Gideon, P; Danielsen, E R; Ring, P; Henriksen, O

    1994-01-01

    In vivo measurement of metabolite concentrations in the human brain by means of proton-MRS contributes significantly to the clinical evaluation of patients with diseases of the brain. The fully relaxed water signal has been proposed as an internal standard for calibration of the MRS measurements....... The major drawbacks are the necessity to make the assumptions that the water concentrations in the brain and that all tissue water is MR-visible. A number of in vivo measurements were carried out to estimate the concentration of MR-visible water in the brain of healthy volunteers divided into four age...

  14. Noninvasive quantification of human brain antioxidant concentrations after an intravenous bolus of vitamin C

    Terpstra, Melissa; Torkelson, Carolyn; Emir, Uzay; Hodges, James S.; Raatz, Susan

    2010-01-01

    Until now, the lack of a means to detect a deficiency or to measure the pharmacologic effect in the human brain in situ has been a hindrance to the development of antioxidant-based prevention and treatment of dementia. In this study, a recently developed 1H MRS approach was applied to quantify key human brain antioxidant concentrations throughout the course of an aggressive antioxidant-based intervention. The concentrations of the two most abundant central nervous system chemical antioxidants...

  15. Dynamic Multi-Coil Shimming of the Human Brain at 7 Tesla

    Juchem, Christoph; Nixon, Terence W.; McIntyre, Scott; Boer, Vincent O.; Rothman, Douglas L.; de Graaf, Robin A.

    2011-01-01

    High quality magnetic field homogenization of the human brain (i.e. shimming) for MR imaging and spectroscopy is a demanding task. The susceptibility differences between air and tissue are a longstanding problem as they induce complex field distortions in the prefrontal cortex and the temporal lobes. To date, the theoretical gains of high field MR have only been realized partially in the human brain due to limited magnetic field homogeneity.

  16. Information flow between interacting human brains: Identification, validation, and relationship to social expertise

    Bilek, Edda; Ruf, Matthias; Schäfer, Axel; Akdeniz, Ceren; Calhoun, Vince D.; Schmahl, Christian; Demanuele, Charmaine; Tost, Heike; Kirsch, Peter; Meyer-Lindenberg, Andreas

    2015-01-01

    Social interaction is the likely driver of human brain evolution, critical for health, and underlies phenomena as varied as childhood development, stock market behavior, and much of what is studied in the humanities. However, appropriate experimental methods to study the underlying brain processes are still developing and technically challenging. Here, we extend previous pioneering approaches in neuroimaging [functional MRI (fMRI) hyperscanning] to provide a method for studying information fl...

  17. Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

    Guangjun Zhao; Xuchu Wang; Yanmin Niu; Liwen Tan; Shao-Xiang Zhang

    2016-01-01

    Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging da...

  18. Intergenic and Repeat Transcription in Human, Chimpanzee and Macaque Brains Measured by RNA-Seq

    Augix Guohua Xu; Liu He; Zhongshan Li; Ying Xu; Mingfeng Li; Xing Fu; Zheng Yan; Yuan Yuan; Corinna Menzel; Na Li; Mehmet Somel; Hao Hu; Wei Chen; Svante Pääbo; Philipp Khaitovich

    2010-01-01

    Transcription is the first step connecting genetic information with an organism's phenotype. While expression of annotated genes in the human brain has been characterized extensively, our knowledge about the scope and the conservation of transcripts located outside of the known genes' boundaries is limited. Here, we use high-throughput transcriptome sequencing (RNA-Seq) to characterize the total non-ribosomal transcriptome of human, chimpanzee, and rhesus macaque brain. In all species, only 2...

  19. Blood-brain transfer of Pittsburgh compound B in humans

    Gjedde, Albert; Aanerud, Joel; Braendgaard, Hans;

    2013-01-01

    In the labeled form, the Pittsburgh compound B (2-(4'-{N-methyl-[(11)C]}methyl-aminophenyl)-6-hydroxy-benzothiazole, [(11)C]PiB), is used as a biomarker for positron emission tomography (PET) of brain β-amyloid deposition in Alzheimer's disease (AD). The permeability of [(11)C]PiB in the blood......-brain barrier is held to be high but the permeability-surface area product and extraction fractions in patients or healthy volunteers are not known. We used PET to determine the clearance associated with the unidrectional blood-brain transfer of [(11)C]PiB and the corresponding cerebral blood flow rates in......-brain clearances of [(11)C]PiB in the patients....

  20. Brain potentials related to the human penile erection.

    Ponseti, J; Kropp, P; Bosinski, H A

    2009-01-01

    The aim of this study was to elucidate the brain processes preceding penile responses. Electroencephalographic (EEG) potentials and penile circumference were recorded simultaneously while male subjects were exposed to visual sexual stimuli (VSS). The trials were sorted by the penile response of the subjects (erection, maintenance or detumescence). The corresponding EEG recordings were then subjected to independent component analysis. We found that 200 ms after VSS onset brain potentials differ according to the genital response to follow. Whereas early posterior negativity (EPN) was predominantly related to erection and maintenance, P3-like activity was found to precede detumescence. EPN indicates a more 'emotional' processing state of the brain, whereas P3-like activity related to detumescence indicates a more 'cognitive' processing state. The latter is assumed to reflect activity of the locus coeruleus-norepinephrine system. Further research should evaluate the contribution of P3-related brain activity to psychogenic erectile dysfunction. PMID:19587685

  1. Automatic segmentation and classification of human brain image based on a fuzzy brain atlas

    Tan, Ou; Jia, Chunguang; Duan, Huilong; Lu, Weixue

    1998-09-01

    It is difficult to automatically segment and classify tomograph images of actual patient's brain. Therefore, many interactive operations are performed. It is very time consuming and its precision is much depended on the user. In this paper, we combine a brain atlas and 3D fuzzy image segmentation into the image matching. It can not only find out the precise boundary of anatomic structure but also save time of the interactive operation. At first, the anatomic information of atlas is mapped into tomograph images of actual brain with a two step image matching method. Then, based on the mapping result, a 3D fuzzy structure mask is calculated. With the fuzzy information of anatomic structure, a new method of fuzzy clustering based on genetic algorithm is used to segment and classify the real brain image. There is only a minimum requirement of interaction in the whole process, including removing the skull and selecting some intrinsic point pairs.

  2. Hyper-Brain Networks Support Romantic Kissing in Humans

    Müller, Viktor; Lindenberger, Ulman

    2014-01-01

    Coordinated social interaction is associated with, and presumably dependent on, oscillatory couplings within and between brains, which, in turn, consist of an interplay across different frequencies. Here, we introduce a method of network construction based on the cross-frequency coupling (CFC) and examine whether coordinated social interaction is associated with CFC within and between brains. Specifically, we compare the electroencephalograms (EEG) of 15 heterosexual couples during romantic k...

  3. Methodological Considerations For Gene Expression Profiling Of Human Brain

    Atz, Mary; Walsh, David; Cartagena, Preston; Li, Jun; Evans, Simon; Choudary, Prabhakara; Overman, Kevin; Stein, Richard; Tomita, Hiro; Potkin, Steven; Myers, Rick; Watson, Stanley J.; Jones, E G; Akil, Huda; Bunney, William E.

    2007-01-01

    Gene expression profiles of postmortem brain tissue represent important resources for understanding neuropsychiatric illnesses. The impact(s) of quality covariables on the analysis and results of gene expression studies are important questions. This paper addressed critical variables which might affect gene expression in two brain regions. Four broad groups of quality indicators in gene expression profiling studies (clinical, tissue, RNA, and microarray quality) were identified. These quality...

  4. Laser Doppler imaging for intraoperative human brain mapping

    Raabe, A; Van De Ville, D.; Leutenegger, M.; Szelényi, A; Hattingen, E; R. Gerlach; Seifert, V.; Hauger, C.; Lopez, A; Leitgeb, R.; Unser, M.; Martin-Williams, E.J.; Lasser, T.

    2009-01-01

    The identification and accurate location of centers of brain activity are vital both in neuro-surgery and brain research. This study aimed to provide a non-invasive, non-contact, accurate, rapid and user-friendly means of producing functional images intraoperatively. To this end a full field Laser Doppler imager was developed and integrated within the surgical microscope and perfusion images of the cortical surface were acquired during awake surgery whilst the patient performed a predet...

  5. Brain Tocopherols Related to Alzheimer Disease Neuropathology in Humans

    Morris, Martha Clare; Schneider, Julie A.; LI Hong; Tangney, Christy C; Nag, Sukrit; Bennett, David A.; Honer, William G.; Barnes, Lisa

    2014-01-01

    Randomized trials of α-tocopherol supplements on cognitive decline are negative whereas studies of dietary tocopherols show benefit. We investigated these inconsistencies by analyzing the relations of α- and γ-tocopherol brain concentrations to Alzheimer disease (AD) neuropathology among 115 deceased participants of the prospective Rush Memory and Aging Project. Associations of amyloid load and neurofibrillary tangle severity with brain tocopherol concentrations were examined in separate adju...

  6. Imaging structural co-variance between human brain regions

    Alexander-Bloch, Aaron; Giedd, Jay N.; Bullmore, Ed

    2013-01-01

    Brain structure varies between people in a markedly organized fashion. Communities of brain regions co-vary in their morphological properties. For example, cortical thickness in one region influences the thickness of structurally and functionally connected regions. Such networks of structural co-variance partially recapitulate the functional networks of healthy individuals and the foci of grey matter loss in neurodegenerative disease. This architecture is genetically heritable, is associated ...

  7. Natural brain-information interfaces: Recommending information by relevance inferred from human brain signals

    Eugster, Manuel J. A.; Ruotsalo, Tuukka; Spapé, Michiel M.; Barral, Oswald; Ravaja, Niklas; Jacucci, Giulio; Kaski, Samuel

    2016-01-01

    Finding relevant information from large document collections such as the World Wide Web is a common task in our daily lives. Estimation of a user's interest or search intention is necessary to recommend and retrieve relevant information from these collections. We introduce a brain-information interface used for recommending information by relevance inferred directly from brain signals. In experiments, participants were asked to read Wikipedia documents about a selection of topics while their ...

  8. Docosahexaenoic acid and human brain development: evidence that a dietary supply is needed for optimal development.

    Brenna, J Thomas; Carlson, Susan E

    2014-12-01

    Humans evolved a uniquely large brain among terrestrial mammals. Brain and nervous tissue is rich in the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA). Docosahexaenoic acid is required for lower and high order functions in humans because of understood and emerging molecular mechanisms. Among brain components that depend on dietary components, DHA is limiting because its synthesis from terrestrial plant food precursors is low but its utilization when consumed in diet is very efficient. Negligible DHA is found in terrestrial plants, but in contrast, DHA is plentiful at the shoreline where it is made by single-celled organisms and plants, and in the seas supports development of very large marine mammal brains. Modern human brains accumulate DHA up to age 18, most aggressively from about half-way through gestation to about two years of age. Studies in modern humans and non-human primates show that modern infants consuming infant formulas that include only DHA precursors have lower DHA levels than for those with a source of preformed DHA. Functional measures show that infants consuming preformed DHA have improved visual and cognitive function. Dietary preformed DHA in the breast milk of modern mothers supports many-fold greater breast milk DHA than is found in the breast milk of vegans, a phenomenon linked to consumption of shore-based foods. Most current evidence suggests that the DHA-rich human brain required an ample and sustained source of dietary DHA to reach its full potential. PMID:24780861

  9. Individual Human Brain Areas Can Be Identified from Their Characteristic Spectral Activation Fingerprints.

    Keitel, Anne; Gross, Joachim

    2016-06-01

    The human brain can be parcellated into diverse anatomical areas. We investigated whether rhythmic brain activity in these areas is characteristic and can be used for automatic classification. To this end, resting-state MEG data of 22 healthy adults was analysed. Power spectra of 1-s long data segments for atlas-defined brain areas were clustered into spectral profiles ("fingerprints"), using k-means and Gaussian mixture (GM) modelling. We demonstrate that individual areas can be identified from these spectral profiles with high accuracy. Our results suggest that each brain area engages in different spectral modes that are characteristic for individual areas. Clustering of brain areas according to similarity of spectral profiles reveals well-known brain networks. Furthermore, we demonstrate task-specific modulations of auditory spectral profiles during auditory processing. These findings have important implications for the classification of regional spectral activity and allow for novel approaches in neuroimaging and neurostimulation in health and disease. PMID:27355236

  10. Blood lactate is an important energy source for the human brain

    G., van Hall; Stromstad, M.; Rasmussen, P.; Jans, O.; Zaar, M.; Gam, Christiane Marie Bourgin; Quistorff, B.; Secher, Niels H.; Nielsen, H.B.

    2009-01-01

    Lactate is a potential energy source for the brain. The aim of this study was to establish whether systemic lactate is a brain energy source. We measured in vivo cerebral lactate kinetics and oxidation rates in 6 healthy individuals at rest with and without 90 mins of intravenous lactate infusion...... is taken up and oxidized by the human brain and is an important substrate for the brain both under basal and hyperlactatemic conditions.Journal of Cerebral Blood Flow & Metabolism advance online publication, 1 April 2009; doi:10.1038/jcbfm.2009.35.......Lactate is a potential energy source for the brain. The aim of this study was to establish whether systemic lactate is a brain energy source. We measured in vivo cerebral lactate kinetics and oxidation rates in 6 healthy individuals at rest with and without 90 mins of intravenous lactate infusion...

  11. Studying variability in human brain aging in a population-based German cohort – Rationale and design of 1000BRAINS

    Svenja eCaspers

    2014-07-01

    Full Text Available The ongoing 1000 brains study (1000BRAINS is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions & language; examination of motor skills; ratings of personality, life quality, mood & daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla of the brain. The latter includes (i 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fibre tracking and for diffusion kurtosis imaging; (iii resting-state and task-based functional MRI; and (iv fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates.

  12. Studying variability in human brain aging in a population-based German cohort-rationale and design of 1000BRAINS.

    Caspers, Svenja; Moebus, Susanne; Lux, Silke; Pundt, Noreen; Schütz, Holger; Mühleisen, Thomas W; Gras, Vincent; Eickhoff, Simon B; Romanzetti, Sandro; Stöcker, Tony; Stirnberg, Rüdiger; Kirlangic, Mehmet E; Minnerop, Martina; Pieperhoff, Peter; Mödder, Ulrich; Das, Samir; Evans, Alan C; Jöckel, Karl-Heinz; Erbel, Raimund; Cichon, Sven; Nöthen, Markus M; Sturma, Dieter; Bauer, Andreas; Jon Shah, N; Zilles, Karl; Amunts, Katrin

    2014-01-01

    The ongoing 1000 brains study (1000BRAINS) is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR) Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions and language; examination of motor skills; ratings of personality, life quality, mood and daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla) of the brain. The latter includes (i) 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii) three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fiber tracking and for diffusion kurtosis imaging; (iii) resting-state and task-based functional MRI; and (iv) fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i) comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii) identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates. PMID:25071558

  13. Lactate, Glucose and Oxygen Uptake in Human Brain During Recovery from Maximal Exercise

    Kojiro, I.; Schmalbruch, I.K.; Quistorff, B.; Horn, A.; Secher, Niels Henry

    Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake......Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake...

  14. Laser Doppler imaging for intraoperative human brain mapping.

    Raabe, A; Van De Ville, D; Leutenegger, M; Szelényi, A; Hattingen, E; Gerlach, R; Seifert, V; Hauger, C; Lopez, A; Leitgeb, R; Unser, M; Martin-Williams, E J; Lasser, T

    2009-02-15

    The identification and accurate location of centers of brain activity are vital both in neuro-surgery and brain research. This study aimed to provide a non-invasive, non-contact, accurate, rapid and user-friendly means of producing functional images intraoperatively. To this end a full field Laser Doppler imager was developed and integrated within the surgical microscope and perfusion images of the cortical surface were acquired during awake surgery whilst the patient performed a predetermined task. The regions of brain activity showed a clear signal (10-20% with respect to the baseline) related to the stimulation protocol which lead to intraoperative functional brain maps of strong statistical significance and which correlate well with the preoperative fMRI and intraoperative cortical electro-stimulation. These initial results achieved with a prototype device and wavelet based regressor analysis (the hemodynamic response function being derived from MRI applications) demonstrate the feasibility of LDI as an appropriate technique for intraoperative functional brain imaging. PMID:19049824

  15. Frequency-specific network topologies in the resting human brain.

    Sasai, Shuntaro; Homae, Fumitaka; Watanabe, Hama; Sasaki, Akihiro T; Tanabe, Hiroki C; Sadato, Norihiro; Taga, Gentaro

    2014-01-01

    A community is a set of nodes with dense inter-connections, while there are sparse connections between different communities. A hub is a highly connected node with high centrality. It has been shown that both "communities" and "hubs" exist simultaneously in the brain's functional connectivity network (FCN), as estimated by correlations among low-frequency spontaneous fluctuations in functional magnetic resonance imaging (fMRI) signal changes (0.01-0.10 Hz). This indicates that the brain has a spatial organization that promotes both segregation and integration of information. Here, we demonstrate that frequency-specific network topologies that characterize segregation and integration also exist within this frequency range. In investigating the coherence spectrum among 87 brain regions, we found that two frequency bands, 0.01-0.03 Hz (very low frequency [VLF] band) and 0.07-0.09 Hz (low frequency [LF] band), mainly contributed to functional connectivity. Comparing graph theoretical indices for the VLF and LF bands revealed that the network in the former had a higher capacity for information segregation between identified communities than the latter. Hubs in the VLF band were mainly located within the anterior cingulate cortices, whereas those in the LF band were located in the posterior cingulate cortices and thalamus. Thus, depending on the timescale of brain activity, at least two distinct network topologies contributed to information segregation and integration. This suggests that the brain intrinsically has timescale-dependent functional organizations. PMID:25566037

  16. Detecting positive darwinian selection in brain-expressed genes during human evolution

    QI XueBin; Alice A. LIN; Luca L. CAVALLI-SFORZA; WANG Jun; SU Bing; YANG Su; ZHENG HongKun; WANG YinQiu; LIAO ChengHong; LIU Ying; CHEN XiaoHua; SHI Hong; YU XiaoJing

    2007-01-01

    To understand the genetic basis that underlies the phenotypic divergence between human and nonhuman primates, we screened a total of 7176 protein-coding genes expressed in the human brain and compared them with the chimpanzee orthologs to identify genes that show evidence of rapid evolution in the human lineage. Our results showed that the nonsynonymous/synonymous substitution (Ka/Ks) ratio for genes expressed in the brain of human and chimpanzee is 0.3854, suggesting that the brain-expressed genes are under functional constraint. The X-linked human brain-expressed genes evolved more rapidly than autosomal ones. We further dissected the molecular evolutionary patterns of 34 candidate genes by sequencing representative primate species to identify lineage-specific adaptive evolution. Fifteen out of the 34 candidate genes showed evidence of positive Darwinian selection in human and/or chimpanzee lineages. These genes are predicted to play diverse functional roles in embryonic development, spermatogenesis and male fertility, signal transduction, sensory nociception, and neural function. This study together with others demonstrated the usefulness and power of phylogenetic comparison of multiple closely related species in detecting lineage-specific adaptive evolution, and the identification of the positively selected brain-expressed genes may add new knowledge to the understanding of molecular mechanism of human origin.

  17. The Connectome Visualization Utility: Software for Visualization of Human Brain Networks

    LaPlante, Roan A.; Douw, Linda; Tang, Wei; Stufflebeam, Steven M

    2014-01-01

    In analysis of the human connectome, the connectivity of the human brain is collected from multiple imaging modalities and analyzed using graph theoretical techniques. The dimensionality of human connectivity data is high, and making sense of the complex networks in connectomics requires sophisticated visualization and analysis software. The current availability of software packages to analyze the human connectome is limited. The Connectome Visualization Utility (CVU) is a new software packag...

  18. Spontaneous Functional Network Dynamics and Associated Structural Substrates in the Human Brain

    Xuhong Liao

    2015-09-01

    Full Text Available Recent imaging connectomics studies have demonstrated that the spontaneous human brain functional networks derived from resting-state functional MRI (R-fMRI include many non-trivial topological properties, such as highly efficient small-world architecture and densely connected hub regions. However, very little is known about dynamic functional connectivity (D-FC patterns of spontaneous human brain networks during rest and about how these spontaneous brain dynamics are constrained by the underlying structural connectivity. Here, we combined sub-second multiband R-fMRI data with graph-theoretical approaches to comprehensively investigate the dynamic characteristics of the topological organization of human whole-brain functional networks, and then employed diffusion imaging data in the same participants to further explore the associated structural substrates. At the connection level, we found that human whole-brain D-FC patterns spontaneously fluctuated over time, while homotopic D-FC exhibited high connectivity strength and low temporal variability. At the network level, dynamic functional networks exhibited time-varying but evident small-world and assortativity architecture, with several regions (e.g., insula, sensorimotor cortex and medial prefrontal cortex emerging as functionally persistent hubs (i.e., highly connected regions while possessing large temporal variability in their degree centrality. Finally, the temporal characteristics (i.e., strength and variability of the connectional and nodal properties of the dynamic brain networks were significantly associated with their structural counterparts. Collectively, we demonstrate the economical, efficient and flexible characteristics of dynamic functional coordination in large-scale human brain networks during rest, and highlight their relationship with underlying structural connectivity, which deepens our understandings of spontaneous brain network dynamics in humans.

  19. Outer brain barriers in rat and human development

    Brøchner, Christian B; Holst, Camilla Bjørnbak; Møllgård, Kjeld

    2015-01-01

    Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides...... adults using immunohistochemistry and confocal microscopy. Antibodies against claudin-11, BLBP, collagen 1, SSEA-4, MAP2, YKL-40, and its receptor IL-13Rα2 and EAAT1 were used to describe morphological characteristics and functional aspects of the outer brain barriers. Claudin-11 was a reliable marker of...... the arachnoid blood-CSF barrier. Collagen 1 delineated the subarachnoid space and stained pial surface layer. BLBP defined radial glial end feet layer and SSEA-4 and YKL-40 were present in both leptomeningeal cells and end feet layer, which transformed into glial limitans. IL-13Rα2 and EAAT1 were...

  20. General solutions to poroviscoelastic model of hydrocephalic human brain tissue.

    Mehrabian, Amin; Abousleiman, Younane

    2011-12-21

    Hydrocephalus is a well-known disorder of brain fluidic system. It is commonly associated with complexities in cerebrospinal fluid (CSF) circulation in brain. In this paper, hydrocephalus and shunting surgery which is used in its treatment are modeled. Brain tissues are considered to follow a poroviscoelastic constitutive model in order to address the effects of time dependence of mechanical properties of soft tissues and fluid flow hydraulics. Our solution draws from Biot's theory of poroelasticity, generalized to account for viscoelastic effects through the correspondence principle. Geometrically, the brain is conceived to be spherically symmetric, where the ventricles are assumed to be a hollow concentric space filled with cerebrospinal fluid. A generalized Kelvin model is considered for the rheological properties of brain tissues. The solution presented is useful in the analysis of the disorder of hydrocephalus as well as the treatment associated with it, namely, ventriclostomy surgery. The sensitivity of the solution to various factors such as aqueduct blockage level and trabeculae stiffness is thoroughly analyzed using numerical examples. Results indicate that partial aqueduct stenosis may be a cause of hydrocephalus. However, only severe occlusion of the aqueduct can cause a significant increase in the ventricle and brain's extracellular fluid pressure. Ventriculostomy shunts are commonly used as a remedy to hydrocephalus. They serve to reduce the ventricular pressure to the normal level. However, sensitivity analysis on the shunt's fluid deliverability parameter has shown that inappropriate design or selection of design shunt may cause under-drainage or over-drainage of the ventricles. Excessive drainage of CSF may increase the normal tensile stress on trabeculae. It can cause rupture of superior cerebral veins or damage to trabeculae or even brain tissues which in turn may lead to subdural hematoma, a common side-effect of the surgery. These Post

  1. Measuring the local electrical conductivity of human brain tissue

    Akhtari, M.; Emin, D.; Ellingson, B. M.; Woodworth, D.; Frew, A.; Mathern, G. W.

    2016-02-01

    The electrical conductivities of freshly excised brain tissues from 24 patients were measured. The diffusion-MRI of the hydrogen nuclei of water molecules from regions that were subsequently excised was also measured. Analysis of these measurements indicates that differences between samples' conductivities are primarily due to differences of their densities of solvated sodium cations. Concomitantly, the sample-to-sample variations of their diffusion constants are relatively small. This finding suggests that non-invasive in-vivo measurements of brain tissues' local sodium-cation density can be utilized to estimate its local electrical conductivity.

  2. Brain stem auditory evoked responses in human infants and adults

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  3. Distribution of PSA-NCAM in normal, Alzheimer's and Parkinson's disease human brain.

    Murray, Helen C; Low, Victoria F; Swanson, Molly E V; Dieriks, Birger V; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

    2016-08-25

    Polysialated neural cell adhesion molecule (PSA-NCAM) is a membrane bound glycoprotein widely expressed during nervous system development. While commonly described in the neurogenic niches of the adult human brain, there is limited evidence of its distribution in other brain regions. PSA-NCAM is an important regulator of cell-cell interactions and facilitates cell migration and plasticity. Recent evidence suggests these functions may be altered in neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD). This study provides a detailed description of the PSA-NCAM distribution throughout the human brain and quantitatively compares the staining load in cortical regions and sub-cortical structures between the control, AD and PD brain. Our results provide evidence of widespread, yet specific, PSA-NCAM expression throughout the human brain including regions devoid of PSA-NCAM in the rodent brain such as the caudate nucleus (CN) and cerebellum (CB). We also detected a significant reduction in PSA-NCAM load in the entorhinal cortex (EC) of cases that was inversely correlated with hyperphosphorylated tau load. These results demonstrate that PSA-NCAM-mediated structural plasticity may not be limited to neurogenic niches and is conserved in the aged brain. We also provide evidence that PSA-NCAM is reduced in the EC, a region severely affected by AD pathology. PMID:27282086

  4. Glucose-coated gold nanoparticles transfer across human brain endothelium and enter astrocytes in vitro.

    Radka Gromnicova

    Full Text Available The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes. The transfer rate of glucose-coated gold nanoparticles across primary human brain endothelium was at least three times faster than across non-brain endothelia. Movement of these nanoparticles occurred across the apical and basal plasma membranes via the cytosol with relatively little vesicular or paracellular migration; antibiotics that interfere with vesicular transport did not block migration. The transfer rate was also dependent on the surface coating of the nanoparticle and incubation temperature. Using a novel 3-dimensional co-culture system, which includes primary human astrocytes and a brain endothelial cell line hCMEC/D3, we demonstrated that the glucose-coated nanoparticles traverse the endothelium, move through the extracellular matrix and localize in astrocytes. The movement of the nanoparticles through the matrix was >10 µm/hour and they appeared in the nuclei of the astrocytes in considerable numbers. These nanoparticles have the correct properties for efficient and selective carriers of therapeutic agents across the blood-brain barrier.

  5. Significance of MDR1 and multiple drug resistance in refractory human epileptic brain

    Dini Gabriele

    2004-10-01

    Full Text Available Abstract Background The multiple drug resistance protein (MDR1/P-glycoprotein is overexpressed in glia and blood-brain barrier (BBB endothelium in drug refractory human epileptic tissue. Since various antiepileptic drugs (AEDs can act as substrates for MDR1, the enhanced expression/function of this protein may increase their active extrusion from the brain, resulting in decreased responsiveness to AEDs. Methods Human drug resistant epileptic brain tissues were collected after surgical resection. Astrocyte cell cultures were established from these tissues, and commercially available normal human astrocytes were used as controls. Uptake of fluorescent doxorubicin and radioactive-labeled Phenytoin was measured in the two cell populations, and the effect of MDR1 blockers was evaluated. Frozen human epileptic brain tissue slices were double immunostained to locate MDR1 in neurons and glia. Other slices were exposed to toxic concentrations of Phenytoin to study cell viability in the presence or absence of a specific MDR1 blocker. Results MDR1 was overexpressed in blood vessels, astrocytes and neurons in human epileptic drug-resistant brain. In addition, MDR1-mediated cellular drug extrusion was increased in human 'epileptic' astrocytes compared to 'normal' ones. Concomitantly, cell viability in the presence of cytotoxic compounds was increased. Conclusions Overexpression of MDR1 in different cell types in drug-resistant epileptic human brain leads to functional alterations, not all of which are linked to drug pharmacokinetics. In particular, the modulation of glioneuronal MDR1 function in epileptic brain in the presence of toxic concentrations of xenobiotics may constitute a novel cytoprotective mechanism.

  6. Astrocyte cultures derived from human brain tissue express angiotensinogen mRNA

    Milsted, A.; Barna, B.P.; Ransohoff, R.M.; Brosnihan, K.B.; Ferrario, C.M. (Cleveland Clinic Foundation, OH (USA))

    1990-08-01

    The authors have identified human cultured cell lines that are useful for studying angiotensinogen gene expression and its regulation in the central nervous system. A model cell system of human central nervous system origin expressing angiotensinogen has not previously been available. Expression of angiotensinogen mRNA appears to be a basal property of noninduced human astrocytes, since astrocytic cell lines derived from human glioblastomas or nonneoplastic human brain tissue invariably produced angiotensinogen mRNA. In situ hybridization histochemistry revealed that angiotensinogen mRNA production was not limited to a subpopulation of astrocytes because >99% of cells in these cultures contained angiotensinogen mRNA. These cell lines will be useful in studies of the molecular mechanisms controlling angiotensin synthesis and the role of biologically active angiotensin in the human brain by allowing the authors to examine regulation of expression of the renin-angiotensin system in human astrocyte cultures.

  7. Astrocyte cultures derived from human brain tissue express angiotensinogen mRNA

    The authors have identified human cultured cell lines that are useful for studying angiotensinogen gene expression and its regulation in the central nervous system. A model cell system of human central nervous system origin expressing angiotensinogen has not previously been available. Expression of angiotensinogen mRNA appears to be a basal property of noninduced human astrocytes, since astrocytic cell lines derived from human glioblastomas or nonneoplastic human brain tissue invariably produced angiotensinogen mRNA. In situ hybridization histochemistry revealed that angiotensinogen mRNA production was not limited to a subpopulation of astrocytes because >99% of cells in these cultures contained angiotensinogen mRNA. These cell lines will be useful in studies of the molecular mechanisms controlling angiotensin synthesis and the role of biologically active angiotensin in the human brain by allowing the authors to examine regulation of expression of the renin-angiotensin system in human astrocyte cultures

  8. Human brain activation during sexual stimulation of the penis

    Georgiadis, [No Value; Holstege, G; Georgiadis, Janniko R.

    2005-01-01

    Penile sensory information is essential for reproduction, but almost nothing is known about how sexually salient inputs from the penis are processed in the brain. We used positron emission tomography to measure regional cerebral blood flow (rCBF) during various stages of male sexual performance. Com

  9. Steroid sulfatase and sulfuryl transferase activities in human brain tumors

    Kříž, L.; Bičíková, M.; Mohapl, M.; Hill, M.; Černý, Ivan; Hampl, R.

    2008-01-01

    Roč. 109, č. 1 (2008), s. 31-39. ISSN 0960-0760 Institutional research plan: CEZ:AV0Z40550506 Keywords : dehydroepiandrosterone * steroid sulfatase * steroid sulfuryl transferase * brain Subject RIV: CC - Organic Chemistry Impact factor: 2.827, year: 2008

  10. Testosterone affects language areas of the adult human brain.

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

    2016-05-01

    Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  11. Mapping Multiplex Hubs in Human Functional Brain Networks.

    De Domenico, Manlio; Sasai, Shuntaro; Arenas, Alex

    2016-01-01

    Typical brain networks consist of many peripheral regions and a few highly central ones, i.e., hubs, playing key functional roles in cerebral inter-regional interactions. Studies have shown that networks, obtained from the analysis of specific frequency components of brain activity, present peculiar architectures with unique profiles of region centrality. However, the identification of hubs in networks built from different frequency bands simultaneously is still a challenging problem, remaining largely unexplored. Here we identify each frequency component with one layer of a multiplex network and face this challenge by exploiting the recent advances in the analysis of multiplex topologies. First, we show that each frequency band carries unique topological information, fundamental to accurately model brain functional networks. We then demonstrate that hubs in the multiplex network, in general different from those ones obtained after discarding or aggregating the measured signals as usual, provide a more accurate map of brain's most important functional regions, allowing to distinguish between healthy and schizophrenic populations better than conventional network approaches. PMID:27471443

  12. Neural Correlates of Socioeconomic Status in the Developing Human Brain

    Noble, Kimberly G.; Houston, Suzanne M.; Kan, Eric; Sowell, Elizabeth R.

    2012-01-01

    Socioeconomic disparities in childhood are associated with remarkable differences in cognitive and socio-emotional development during a time when dramatic changes are occurring in the brain. Yet, the neurobiological pathways through which socioeconomic status (SES) shapes development remain poorly understood. Behavioral evidence suggests that…

  13. Topological organization of the human brain functional connectome across the lifespan

    Miao Cao

    2014-01-01

    Full Text Available Human brain function undergoes complex transformations across the lifespan. We employed resting-state functional MRI and graph-theory approaches to systematically chart the lifespan trajectory of the topological organization of human whole-brain functional networks in 126 healthy individuals ranging in age from 7 to 85 years. Brain networks were constructed by computing Pearson's correlations in blood-oxygenation-level-dependent temporal fluctuations among 1024 parcellation units followed by graph-based network analyses. We observed that the human brain functional connectome exhibited highly preserved non-random modular and rich club organization over the entire age range studied. Further quantitative analyses revealed linear decreases in modularity and inverted-U shaped trajectories of local efficiency and rich club architecture. Regionally heterogeneous age effects were mainly located in several hubs (e.g., default network, dorsal attention regions. Finally, we observed inverse trajectories of long- and short-distance functional connections, indicating that the reorganization of connectivity concentrates and distributes the brain's functional networks. Our results demonstrate topological changes in the whole-brain functional connectome across nearly the entire human lifespan, providing insights into the neural substrates underlying individual variations in behavior and cognition. These results have important implications for disease connectomics because they provide a baseline for evaluating network impairments in age-related neuropsychiatric disorders.

  14. Low-field MRI for studies of human pulmonary physiology and traumatic brain injury

    Wilson, Alyssa; Devience, Stephen; Rosen, Matthew; Walsworth, Ronald

    2011-05-01

    We describe recent progress on the development of an open-access low-magnetic-field MRI system for studies of human pulmonary physiology and traumatic brain injury. Low-field MRI benefits from reduced magnetic susceptibility effects and can provide high-resolution images of the human body when used with hyperpolarized media such as 3He and 129Xe.

  15. Differences in distribution and regulation of astrocytic aquaporin-4 in human and rat hydrocephalic brain

    Skjolding, Anders Daehli; Holst, Anders Vedel; Broholm, Helle;

    2013-01-01

    human hydrocephalic cortex relative to controls was quantified by western blotting (n=28). A second biopsy (n=13) was processed for immunohistochemistry (GFAP, CD68, CD34 and aquaporin-4) and double immunofluorescence (aquaporin-4+GFAP and aquaporin-4+CD34). Brain tissue from human controls and kaolin...

  16. Family poverty affects the rate of human infant brain growth.

    Jamie L Hanson

    Full Text Available Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77. In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES, with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems.

  17. Radiological study of the brain at various stages of human immunodeficiency virus infection: early development of brain atrophy

    One hundred and one persons infected with human immunodeficiency virus (HIV-1), in whom other central nervous system infections or diseases were excluded, underwent brain CT and/or MRI at various stages of HIV-1 infection: 29 were asymptomatic (ASX), 35 had lymphadenopathy syndrome (LAS), 17 had AIDS-related complex (ARC), and 20 had AIDS. A control group of 32 HIV-1-seronegative healthy persons underwent brain MRI. The most common finding was brain atrophy. The changes were bilateral and symmetrical, and they were more severe at later stages of infection. Non-specific small hyperintense foci were found on MRI in 13% of controls and 6-15% of the infected groups. Larger, diffuse, bilateral white matter infiltrates were detected in 4 demented patients with AIDS. Four patients with AIDS and 1 with LAS had focal hyperintense lesions in the internal capsules, lentiform nuclei or thalamus, often bilateral on MRI. One patient with AIDS examined with CT only, had low density in the lentiform nucleus. Loss of brain parenchyma can occur at an early stage of HIV-1 infection, and the atrophic process becomes more intense at later stages (ARC and AIDS). (orig./GDG)

  18. 18F-FLT PET/CT as an imaging tool for early prediction of pathological response in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy: a pilot study

    We evaluated whether 18F-3'-deoxy-3'-fluorothymidine positron emission tomography (FLT PET) can predict the final postoperative histopathological response in primary breast cancer after the first cycle of neoadjuvant chemotherapy (NCT). In this prospective cohort study of 15 patients with locally advanced operable breast cancer, FLT PET evaluations were performed before NCT, after the first cycle of NCT, and at the end of NCT. All patients subsequently underwent surgery. Variables from FLT PET examinations were correlated with postoperative histopathological results. At baseline, median of maximum standardized uptake values (SUVmax) in the groups showing a complete pathological response (pCR) + residual cancer burden (RCB) I, RCB II or RCB III did not differ significantly for the primary tumour (5.0 vs. 2.9 vs. 8.9, p = 0.293) or for axillary nodes (7.9 vs. 1.6 vs. 7.0, p = 0.363), whereas the Spearman correlation between SUVmax and Ki67 proliferation rate index was significant (r = 0.69, p < 0.001). Analysis of the relative percentage change of SUVmaxin the primary tumour (∇SUVTmax(t1)) and axillary nodes (∇SUVNmax(t1)) after the first NCT cycle showed that the power of ∇SUVTmax(t1) to predict pCR + RCB I responses (AUC = 0.91, p < 0.001) was statistically significant, whereas ∇SUVNmax(t1) had a moderate ability (AUC = 0.77, p = 0.119) to separate subjects with ΔSUVTmax(t1) > -52.9 % into two groups: RCB III patients and a heterogeneous group that included RCB I and RCB II patients. A predictive score μ based on ΔSUVTmax(t1) and ΔSUVNmax(t1) parameters is proposed. The preliminary findings of the present study suggest the potential utility of FLT PET scans for early monitoring of response to NCT and to formulate a therapeutic strategy consistent with the estimated efficacy of NCT. However, these results in a small patient population need to be validated in a larger independent cohort. (orig.)

  19. {sup 18}F-FLT PET/CT as an imaging tool for early prediction of pathological response in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy: a pilot study

    Crippa, Flavio; Padovano, Barbara; Alessi, Alessandra; Bombardieri, Emilio; Pascali, Claudio; Bogni, Anna [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Nuclear Medicine Unit; Agresti, Roberto; Maugeri, Ilaria; Rampa, Mario; Martelli, Gabriele [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Breast Surgery Unit; Sandri, Marco [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Molecular Targeting Unit; Mariani, Gabriella; Bianchi, Giulia; De Braud, Filippo [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Medical Oncology Unit; Carcangiu, Maria Luisa [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Pathology Unit; Trecate, Giovanna [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy). Radiology-RMI Unit

    2015-05-01

    We evaluated whether {sup 18}F-3'-deoxy-3'-fluorothymidine positron emission tomography (FLT PET) can predict the final postoperative histopathological response in primary breast cancer after the first cycle of neoadjuvant chemotherapy (NCT). In this prospective cohort study of 15 patients with locally advanced operable breast cancer, FLT PET evaluations were performed before NCT, after the first cycle of NCT, and at the end of NCT. All patients subsequently underwent surgery. Variables from FLT PET examinations were correlated with postoperative histopathological results. At baseline, median of maximum standardized uptake values (SUV{sub max}) in the groups showing a complete pathological response (pCR) + residual cancer burden (RCB) I, RCB II or RCB III did not differ significantly for the primary tumour (5.0 vs. 2.9 vs. 8.9, p = 0.293) or for axillary nodes (7.9 vs. 1.6 vs. 7.0, p = 0.363), whereas the Spearman correlation between SUV{sub max} and Ki67 proliferation rate index was significant (r = 0.69, p < 0.001). Analysis of the relative percentage change of SUV{sub max}in the primary tumour (∇SUVT{sub max}(t{sub 1})) and axillary nodes (∇SUVN{sub max}(t{sub 1})) after the first NCT cycle showed that the power of ∇SUVT{sub max}(t{sub 1}) to predict pCR + RCB I responses (AUC = 0.91, p < 0.001) was statistically significant, whereas ∇SUVN{sub max}(t{sub 1}) had a moderate ability (AUC = 0.77, p = 0.119) to separate subjects with ΔSUVT{sub max}(t{sub 1}) > -52.9 % into two groups: RCB III patients and a heterogeneous group that included RCB I and RCB II patients. A predictive score μ based on ΔSUVT{sub max}(t{sub 1}) and ΔSUVN{sub max}(t{sub 1}) parameters is proposed. The preliminary findings of the present study suggest the potential utility of FLT PET scans for early monitoring of response to NCT and to formulate a therapeutic strategy consistent with the estimated efficacy of NCT. However, these results in a small patient population need to be validated in a larger independent cohort. (orig.)

  20. 18F-FLT Positron Emission Tomography and Diffusion-Weighted Magnetic Resonance Imaging in Planning Surgery and Radiation Therapy and Measuring Response in Patients With Newly Diagnosed Ewing Sarcoma

    2016-03-15

    Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Ewing Sarcoma of Bone; Extraosseous Ewing Sarcoma; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

  1. Comparison of (18)F-FET and (18)F-FLT small animal PET for the assessment of anti-VEGF treatment response in an orthotopic model of glioblastoma

    Nedergaard, Mette Kjoelhede; Michaelsen, Signe Regner; Perryman, Lara;

    2016-01-01

    was to compare FLT and FET PET for the assessment of anti-VEGF response in glioblastoma xenografts. METHODS: Xenografts with confirmed intracranial glioblastoma were treated with anti-VEGF therapy (B20-4.1) or saline as control. Weekly bioluminescence imaging (BLI), FLT and FET PET/CT were used to follow...

  2. Novel theory of the human brain: information-commutation basis of architecture and principles of operation

    Bryukhovetskiy AS

    2015-02-01

    Full Text Available Andrey S Bryukhovetskiy Center for Biomedical Technologies, Federal Research and Clinical Center for Specialized Types of Medical Assistance and Medical Technologies of the Federal Medical Biological Agency, NeuroVita Clinic of Interventional and Restorative Neurology and Therapy, Moscow, Russia Abstract: Based on the methodology of the informational approach and research of the genome, proteome, and complete transcriptome profiles of different cells in the nervous tissue of the human brain, the author proposes a new theory of information-commutation organization and architecture of the human brain which is an alternative to the conventional systemic connective morphofunctional paradigm of the brain framework. Informational principles of brain operation are defined: the modular principle, holographic principle, principle of systematicity of vertical commutative connection and complexity of horizontal commutative connection, regulatory principle, relay principle, modulation principle, “illumination” principle, principle of personalized memory and intellect, and principle of low energy consumption. The author demonstrates that the cortex functions only as a switchboard and router of information, while information is processed outside the nervous tissue of the brain in the intermeningeal space. The main structural element of information-commutation in the brain is not the neuron, but information-commutation modules that are subdivided into receiver modules, transmitter modules, and subscriber modules, forming a vertical architecture of nervous tissue in the brain as information lines and information channels, and a horizontal architecture as central, intermediate, and peripheral information-commutation platforms. Information in information-commutation modules is transferred by means of the carriers that are characteristic to the specific information level from inductome to genome, transcriptome, proteome, metabolome, secretome, and magnetome

  3. Visual image reconstruction from human brain activity: A modular decoding approach

    Brain activity represents our perceptual experience. But the potential for reading out perceptual contents from human brain activity has not been fully explored. In this study, we demonstrate constraint-free reconstruction of visual images perceived by a subject, from the brain activity pattern. We reconstructed visual images by combining local image bases with multiple scales, whose contrasts were independently decoded from fMRI activity by automatically selecting relevant voxels and exploiting their correlated patterns. Binary-contrast, 10 x 10-patch images (2100 possible states), were accurately reconstructed without any image prior by measuring brain activity only for several hundred random images. The results suggest that our approach provides an effective means to read out complex perceptual states from brain activity while discovering information representation in multi-voxel patterns.

  4. Evidence for the presence of beta 3-adrenergic receptor mRNA in the human brain.

    Rodriguez, M; Carillon, C; Coquerel, A; Le Fur, G; Ferrara, P; Caput, D; Shire, D

    1995-04-01

    The beta 3-adrenergic receptor (AR) is widely distributed in peripheral tissues, but up to now it has not been detected in the central nervous system. By using the polymerase chain reaction (PCR) technique, we found the beta 3-AR mRNA to be present in all the regions of the human brain we investigated. The quantities found were very low compared to those of the beta 1-AR and beta 2-AR mRNAs, being hardly detectable in adult brain. In contrast, the brain of very young infants contained about 100 times more beta 3-AR mRNA than the adult brain, whereas the amounts of beta 1-AR and beta 2-AR transcripts were essentially the same. In addition, using PCR we have cloned a central beta 3-AR coding region from a human frontal cortex cDNA library and have found it to be identical to the corresponding peripheral sequence. PMID:7609625

  5. Human brain diffusion tensor imaging at submillimeter isotropic resolution on a 3Tesla clinical MRI scanner.

    Chang, Hing-Chiu; Sundman, Mark; Petit, Laurent; Guhaniyogi, Shayan; Chu, Mei-Lan; Petty, Christopher; Song, Allen W; Chen, Nan-kuei

    2015-09-01

    The advantages of high-resolution diffusion tensor imaging (DTI) have been demonstrated in a recent post-mortem human brain study (Miller et al., NeuroImage 2011;57(1):167-181), showing that white matter fiber tracts can be much more accurately detected in data at a submillimeter isotropic resolution. To our knowledge, in vivo human brain DTI at a submillimeter isotropic resolution has not been routinely achieved yet because of the difficulty in simultaneously achieving high resolution and high signal-to-noise ratio (SNR) in DTI scans. Here we report a 3D multi-slab interleaved EPI acquisition integrated with multiplexed sensitivity encoded (MUSE) reconstruction, to achieve high-quality, high-SNR and submillimeter isotropic resolution (0.85×0.85×0.85mm(3)) in vivo human brain DTI on a 3Tesla clinical MRI scanner. In agreement with the previously reported post-mortem human brain DTI study, our in vivo data show that the structural connectivity networks of human brains can be mapped more accurately and completely with high-resolution DTI as compared with conventional DTI (e.g., 2×2×2mm(3)). PMID:26072250

  6. Intergenic and repeat transcription in human, chimpanzee and macaque brains measured by RNA-Seq.

    Augix Guohua Xu

    Full Text Available Transcription is the first step connecting genetic information with an organism's phenotype. While expression of annotated genes in the human brain has been characterized extensively, our knowledge about the scope and the conservation of transcripts located outside of the known genes' boundaries is limited. Here, we use high-throughput transcriptome sequencing (RNA-Seq to characterize the total non-ribosomal transcriptome of human, chimpanzee, and rhesus macaque brain. In all species, only 20-28% of non-ribosomal transcripts correspond to annotated exons and 20-23% to introns. By contrast, transcripts originating within intronic and intergenic repetitive sequences constitute 40-48% of the total brain transcriptome. Notably, some repeat families show elevated transcription. In non-repetitive intergenic regions, we identify and characterize 1,093 distinct regions highly expressed in the human brain. These regions are conserved at the RNA expression level across primates studied and at the DNA sequence level across mammals. A large proportion of these transcripts (20% represents 3'UTR extensions of known genes and may play roles in alternative microRNA-directed regulation. Finally, we show that while transcriptome divergence between species increases with evolutionary time, intergenic transcripts show more expression differences among species and exons show less. Our results show that many yet uncharacterized evolutionary conserved transcripts exist in the human brain. Some of these transcripts may play roles in transcriptional regulation and contribute to evolution of human-specific phenotypic traits.

  7. Regional Variations in Brain Gyrification Are Associated with General Cognitive Ability in Humans.

    Gregory, Michael D; Kippenhan, J Shane; Dickinson, Dwight; Carrasco, Jessica; Mattay, Venkata S; Weinberger, Daniel R; Berman, Karen F

    2016-05-23

    Searching for a neurobiological understanding of human intellectual capabilities has long occupied those very capabilities. Brain gyrification, or folding of the cortex, is as highly evolved and variable a characteristic in humans as is intelligence. Indeed, gyrification scales with brain size, and relationships between brain size and intelligence have been demonstrated in humans [1-3]. However, gyrification shows a large degree of variability that is independent from brain size [4-6], suggesting that the former may independently contribute to cognitive abilities and thus supporting a direct investigation of this parameter in the context of intelligence. Moreover, uncovering the regional pattern of such an association could offer insights into evolutionary and neural mechanisms. We tested for this brain-behavior relationship in two separate, independently collected, large cohorts-440 healthy adults and 662 healthy children-using high-resolution structural neuroimaging and comprehensive neuropsychometric batteries. In both samples, general cognitive ability was significantly associated (pFDR distribution that was nearly identical in both samples (Dice similarity coefficient = 0.80). This neuroanatomical pattern is consistent with an existing, well-known proposal, the Parieto-Frontal Integration Theory of intelligence [7], and is also consistent with research in comparative evolutionary biology showing rapid neocortical expansion of these regions in humans relative to other species. These data provide a framework for understanding the neurobiology of human cognitive abilities and suggest a potential neurocellular association. PMID:27133866

  8. Human brain somatic representation: a functional magnetic resonance mapping

    Romero-Romo, Juan; Rojas, Rafael; Salgado, Perla; Sánchez-Cortázar, Julián; Vazquez-Vela, Arturo; Barrios, Fernando A.

    2001-10-01

    Central nervous system studies of injury and plasticity for the reorganization in the phantom limb sensation area presented. In particular functional magnetic resonance imaging (fMRI) mapping of the somatic and motor cortex of amputee patients, in the case of referred sensations. Using fMRI we can show the correlation between structure and functional field and study the reorganization due to plasticity in the brain.

  9. Subliminal Instrumental Conditioning Demonstrated in the Human Brain

    Pessiglione, M.; Petrovic, P.; Daunizeau, J.; Palminteri, S; Dolan, R. J.; Frith, C D

    2008-01-01

    Summary How the brain uses success and failure to optimize future decisions is a long-standing question in neuroscience. One computational solution involves updating the values of context-action associations in proportion to a reward prediction error. Previous evidence suggests that such computations are expressed in the striatum and, as they are cognitively impenetrable, represent an unconscious learning mechanism. Here, we formally test this by studying instrumental conditioning in a situat...

  10. Paramagnetic artifact and safety criteria for human brain mapping

    Seiyama, Akitoshi; Seki, Junji; Iwamoto, Mari; Yanagida, Toshio

    2005-01-01

    Biological effects of magnetic field and their safety criteria, especially effects of gradient magnetic field on the cerebral and pulmonary circulation during functional brain mapping are still unclear. Here we estimated that magnetically induced artifacts for the blood oxygenation level- and flow- based functional magnetic resonance imaging are less than 0.1%, and disturbance in the pulmonary circulation is less than 1.3% even if the field strength of magnetic resonance system is risen up to...

  11. Genetic dissection of sex differences in human brain and behaviour

    Tan, G. C. -Y

    2011-01-01

    The importance of sex differences in the brain and behaviour is indisputable. It forms the basis for differences in risk across a range of neurological and psychiatric disorders, as well as gender roles within society. The classical approach to investigating sex differences primarily involves comparisons between males and females. While informative for characterizing the wide array of sexually dimorphic traits, straight comparisons are insufficient to elucidate specific molecul...

  12. Baseline brain activity fluctuations predict somatosensory perception in humans

    Boly, M; Balteau, E.; Schnakers, C; Degueldre, C.; Moonen, G.; Luxen, A.; Phillips, C.; Peigneux, P; Maquet, P; Laureys, S.

    2007-01-01

    In perceptual experiments, within-individual fluctuations in perception are observed across multiple presentations of the same stimuli, a phenomenon that remains only partially understood. Here, by means of thulium–yttrium/aluminum–garnet laser and event-related functional MRI, we tested whether variability in perception of identical stimuli relates to differences in prestimulus, baseline brain activity. Results indicate a positive relationship between conscious perception of low-intensity so...

  13. Frequency-specific network topologies in the resting human brain

    Shuntaro Sasai

    2014-12-01

    Full Text Available A community is a set of nodes with dense inter-connections, while there are sparse connections between different communities. A hub is a highly connected node with high centrality. It has been shown that both “communities” and “hubs” exist simultaneously in the brain’s functional connectivity network, as estimated by correlations among low-frequency spontaneous fluctuations in functional magnetic resonance imaging (fMRI signal changes (0.01–0.10 Hz. This indicates that the brain has a spatial organization that promotes both segregation and integration of information. Here, we demonstrate that frequency-specific network topologies that characterize segregation and integration also exist within this frequency range. In investigating the coherence spectrum among 87 brain regions, we found that two frequency bands, 0.01–0.03 Hz (very low frequency [VLF] band and 0.07–0.09 Hz (low frequency [LF] band, mainly contributed to functional connectivity. Comparing graph theoretical indices for the VLF and LF bands revealed that the network in the former had a higher capacity for information segregation between identified communities than the latter. Hubs in the VLF band were mainly located within the anterior cingulate cortices, whereas those in the LF band were located in the posterior cingulate cortices and thalamus. Thus, depending on the timescale of brain activity, at least two distinct network topologies contributed to information segregation and integration. This suggests that the brain intrinsically has timescale-dependent functional organizations.

  14. Visualizing the site of drug action in living human brain

    Suhara, Tetsuya [National Inst. of Radiological Sciences, Chiba (Japan)

    1997-03-01

    PET is the only technique available to date to measure molecular interactions in vivo, but the basic mechanism of molecular interaction in vivo is not yet fully understood. However, PET can allow visualization of various phenomena which we can not observe with in vitro techniques. Progress in PET study will provide a new viewpoint for drug development and the study of molecular mechanism in the brain. (J.P.N.)

  15. Sex-related variation in human behavior and the brain

    Hines, Melissa

    2010-01-01

    Male and female fetuses differ in testosterone concentrations beginning as early as week 8 of gestation. This early hormone difference exerts permanent influences on brain development and behavior. Contemporary research shows that hormones are particularly important for the development of sex-typical childhood behavior, including toy choices, which until recently were thought to result solely from sociocultural influences. Prenatal testosterone exposure also appears to influence sexual orient...

  16. Biochemical imaging of the human brain in development and disease

    The authors used positron emission tomography (PET) to image cerebral glucose metabolism in more than 140 children aged 5 days to 15 years. Twenty-nine children were studied during normal development and the remainder because of infantile spasm, seizure, Lennox-Gastaut syndrome, or cerebral palsy. This exhibit demonstrates the temporal course of normal function (metabolic) development of the brain, and compares the relative value of PET, MR imaging, and x-ray CT in abnormal cases

  17. The effects of acute alcohol administration on the human brain: Insights from neuroimaging

    Bjork, James M.; Gilman, Jodi M

    2013-01-01

    Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same...

  18. Dieescting the effects of sweet tastants in the human gut-brain axis

    Bryant, Charlotte Elizabeth

    2014-01-01

    The importance of nutrient induced gut-brain signalling in the regulation of human food intake has become increasingly apparent as the obesity epidemic progresses. Much of the caloric excess consumed comes from dietary sugars, but our knowledge about the mechanisms mediating the physiological and appetitive effects of sweet tastants in the gut-brain axis is far from complete. The comparative effects of natural sugars vs. artificial non-nutritive sweeteners are also poorly understood. Research...

  19. Engines of the Brain: The Computational Instruction Set of Human Cognition

    Granger, Richard

    2006-01-01

    Vast information from the neurosciences may enable bottom-up understanding of human intelligence; that is, derivation of function from mechanism. This article describes such a research program: simulation and analysis of the circuits of the brain has led to derivation of a detailed set of elemental and composed operations emerging from individual and combined circuits. The specific hypothesis is forwarded that these operations constitute the "instruction set" of the brain, that is, the basic ...

  20. Effect of Antimicrobial Compounds on Balamuthia mandrillaris Encystment and Human Brain Microvascular Endothelial Cell Cytopathogenicity▿

    Siddiqui, Ruqaiyyah; Matin, Abdul; Warhurst, David; Stins, Monique; Khan, Naveed Ahmed

    2007-01-01

    Cycloheximide, ketoconazole, or preexposure of organisms to cytochalasin D prevented Balamuthia mandrillaris-associated cytopathogenicity in human brain microvascular endothelial cells, which constitute the blood-brain barrier. In an assay for inhibition of cyst production, these three agents prevented the production of cysts, suggesting that the biosynthesis of proteins and ergosterol and the polymerization of actin are important in cytopathogenicity and encystment. PMID:17875991

  1. The Potential of the Human Connectome as a Biomarker of Brain Disease

    Marcus Kaiser

    2013-01-01

    The human connectome at the level of fiber tracts between brain regions has been shown to differ in patients with brain disorders compared to healthy control groups. Nonetheless, there is a potentially large number of different network organizations for individual patients that could lead to cognitive deficits prohibiting correct diagnosis. Therefore changes that can distinguish groups might not be sufficient to diagnose the disease that an individual patient suffers from and to indicate the ...

  2. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases.

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and brain tumors. PMID:27375363

  3. Demonstration of brain noise on human EEG signals in perception of bistable images

    Grubov, Vadim V.; Runnova, Anastasiya E.; Kurovskaya, Maria K.; Pavlov, Alexey N.; Koronovskii, Alexey A.; Hramov, Alexander E.

    2016-03-01

    In this report we studied human brain activity in the case of bistable visual perception. We proposed a new approach for quantitative characterization of this activity based on analysis of EEG oscillatory patterns and evoked potentials. Accordingly to theoretical background, obtained experimental EEG data and results of its analysis we studied a characteristics of brain activity during decision-making. Also we have shown that decisionmaking process has the special patterns on the EEG data.

  4. Adaptive reconfiguration of fractal small-world human brain functional networks

    Bassett, Danielle S; Meyer-Lindenberg, Andreas; Achard, Sophie; Duke, Thomas; Bullmore, Edward

    2006-01-01

    Brain function depends on adaptive self-organization of large-scale neural assemblies, but little is known about quantitative network parameters governing these processes in humans. Here, we describe the topology and synchronizability of frequency-specific brain functional networks using wavelet decomposition of magnetoencephalographic time series, followed by construction and analysis of undirected graphs. Magnetoencephalographic data were acquired from 22 subjects, half of whom performed a ...

  5. Bridging animal and human models of exercise-induced brain plasticity

    Voss, Michelle W.; Vivar, Carmen; Arthur F Kramer; Van Praag, Henriette

    2013-01-01

    Significant progress has been made in understanding the neurobiological mechanisms through which exercise protects and restores the brain. In this feature review, we integrate animal and human research, examining physical activity effects across multiple levels of description (neurons up to inter-regional pathways). We evaluate the influence of exercise on hippocampal structure and function, addressing common themes such as spatial memory and pattern separation, brain structure and plasticity...

  6. Brain imaging reveals neuronal circuitry underlying the crow’s perception of human faces

    Marzluff, John M.; Miyaoka, Robert; Minoshima, Satoshi; Cross, Donna J.

    2012-01-01

    Crows pay close attention to people and can remember specific faces for several years after a single encounter. In mammals, including humans, faces are evaluated by an integrated neural system involving the sensory cortex, limbic system, and striatum. Here we test the hypothesis that birds use a similar system by providing an imaging analysis of an awake, wild animal’s brain as it performs an adaptive, complex cognitive task. We show that in vivo imaging of crow brain activity during exposure...

  7. Ischemia Alters the Expression of Connexins in the Aged Human Brain

    Taizen Nakase; Tetsuya Maeda; Yasuji Yoshida; Ken Nagata

    2009-01-01

    Although the function of astrocytic gap junctions under ischemia is still under debate, increased expression of connexin 43 (Cx43) has been observed in ischemic brain lesions, suggesting that astrocytic gap junctions could provide neuronal protection against ischemic insult. Moreover, different connexin subtypes may play different roles in pathological conditions. We used immunohistochemical analysis to investigate alterations in the expression of connexin subtypes in human stroke brains. Sev...

  8. Novel Humanized Recombinant T Cell Receptor Ligands Protect the Female Brain After Experimental Stroke

    Pan, Jie; Palmateer, Julie; Schallert, Timothy; Hart, Madison; Pandya, Arushi; Vandenbark, Arthur A.; Offner, Halina; Hurn, Patricia D.

    2014-01-01

    Transmigration of peripheral leukocytes to the brain is a major contributor to cerebral ischemic cell death mechanisms. Humanized partial major histocompatibility complex class II constructs (pMHC), covalently linked to myelin peptides, are effective for treating experimental stroke in males, but new evidence suggests that some inflammatory cell death mechanisms after brain injury are sex-specific. We here demonstrate that treatment with pMHC constructs also improves outcomes in female mice w...

  9. Non-invasive assessment of intracranial biomechanics of the human brain

    Ragauskas, A.; Daubaris, G.; Petkus, V.; Raišutis, R.; Chomskis, R; Šliteris, R.; Deksnys, V.; Guzaitis, J.; Lengvinas, G.

    2008-01-01

    This review paper describes innovative methods and technology for non-invasive human brain physiological monitoring based on measuring the acoustic properties of the brain parenchyma. The clinical investigation of new technology shows the similarity between the invasively recorded intracranial pressure (ICP) and non-invasively recorded intracranial blood volume (IBV) pulse waves, slow waves and slow trends under intensive care unit (ICU) conditions. Also, the applicability of the non-invasive...

  10. A functional architecture of the human brain: Emerging insights from the science of emotion

    Lindquist, Kristen A; Barrett, Lisa Feldman

    2012-01-01

    The ‘faculty psychology’ approach to the mind, which attempts to explain mental function in terms of categories that reflect modular ‘faculties’, such as emotions, cognitions, and perceptions, has dominated research into the mind and its physical correlates. In this paper, we argue that brain organization does not respect the commonsense categories belonging to the faculty psychology approach. We review recent research from the science of emotion demonstrating that the human brain contains br...

  11. Mathematical Models of Visual Information Processing in the Human Brain and Applications to Image Processing

    Arai, Hitoshi

    2013-01-01

    In this lecture I give a survey of joint works of Hitoshi Arai and Shinobu Arai. The main purpose of our study is to construct mathematical models of visual information processing in the brain, and to give applications to image processing. On the past few decades, several studies have been made on mathematical models of visual information processing in the human brain. Our new models are constructed by using simple pinwheel framelets ([4]) and pinwheel framelets ([6]), which are a new class o...

  12. Ovarian steroids in rat and human brain : effects of different endocrine states

    Bixo, Marie

    1987-01-01

    Ovarian steroid hormones are known to produce several different effects in the brain. In addition to their role in gonadotropin release, ovulation and sexual behaviour they also seem to affect mood and emotions, as shown in women with the premenstrual tension syndrome. Some steroids have the ability to affect brain excitability. Estradiol decreases the electroshock threshold while progesterone acts as an anti-convulsant and anaesthetic in both animals and humans. Several earlier studies have ...

  13. Local Modulation of Human Brain Responses by Circadian Rhythmicity and Sleep Debt

    Muto, V.; Jaspar, M; Meyer, C.; Kussé, C; Chellappa, SL; Degueldre, C.; Balteau, E.; Shaffii-Le Bourdiec, A; Luxen, A; Middleton, B; Archer, SN; Phillips, C.; Collette, F.; Vandewalle, G; Dijk, D

    2016-01-01

    Human performance results from an interaction between circadian rhythmicity and homeostatic sleep pressure. Whether and how this interaction is represented at the regional brain level is not established. We quantified changes in brain responses to a sustained-attention task during 13 functional magnetic resonance imaging (fMRI) sessions scheduled across the circadian cycle during 42h of wakefulness and following recovery sleep, in 33 healthy participants. Cortical responses showed significant...

  14. The brain functional networks associated to human and animal suffering differ among omnivores, vegetarians and vegans

    Filippi, Massimo; Riccitelli, Gianna; Falini, Andrea; Di Salle, Francesco; Vuilleumier, Patrik; Comi, Giancarlo; Rocca, M. A.

    2010-01-01

    Empathy and affective appraisals for conspecifics are among the hallmarks of social interaction. Using functional MRI, we hypothesized that vegetarians and vegans, who made their feeding choice for ethical reasons, might show brain responses to conditions of suffering involving humans or animals different from omnivores. We recruited 20 omnivore subjects, 19 vegetarians, and 21 vegans. The groups were matched for sex and age. Brain activation was investigated using fMRI and an event-related d...

  15. Parallel workflow tools to facilitate human brain MRI post-processing

    Gaolang Gong

    2015-01-01

    Multi-modal magnetic resonance imaging (MRI) techniques are widely applied in human brain studies. To obtain specific brain measures of interest from MRI datasets, a number of complex image post-processing steps are typically required. Parallel workflow tools have recently been developed, concatenating individual processing steps and enabling fully automated processing of raw MRI data to obtain the final results. These workflow tools are also designed to make optimal use of available computat...

  16. Development of Spatial and Verbal Working Memory Capacity in the Human Brain

    Thomason, Moriah E.; Race, Elizabeth; Burrows, Brittany; Whitfield-Gabrieli, Susan; Glover, Gary H.; Gabrieli, John D. E.

    2009-01-01

    A core aspect of working memory (WM) is the capacity to maintain goal-relevant information in mind, but little is known about how this capacity develops in the human brain. We compared brain activation, via fMRI, between children (ages 7-12 years) and adults (ages 20-29 years) performing tests of verbal and spatial WM with varying amounts (loads)…

  17. Transmission, attenuation and reflection of shear waves in the human brain

    Clayton, Erik H.; Guy M. Genin; Bayly, Philip V.

    2012-01-01

    Traumatic brain injuries (TBIs) are caused by acceleration of the skull or exposure to explosive blast, but the processes by which mechanical loads lead to neurological injury remain poorly understood. We adapted motion-sensitive magnetic resonance imaging methods to measure the motion of the human brain in vivo as the skull was exposed to harmonic pressure excitation (45, 60 and 80 Hz). We analysed displacement fields to quantify the transmission, attenuation and reflection of distortional (...

  18. Cognition-activated low-frequency modulation of light absorption in human brain.

    Chance, B; Zhuang, Z.; UnAh, C; Alter, C; Lipton, L

    1993-01-01

    Animal model studies indicate light-absorption changes of the exposed animal brain in response to visual stimulation. Here we report observations of red-light absorbance changes, attributable to repetitive blood concentration changes in response to stimulation in the human brain frontal region by a cognitive process. These responses are observed as low-frequency recurrence of changes by Fourier transform analysis and are attributed to blood concentration change stimulated by the increased met...

  19. Phenotypic Heterogeneity and Plasticity of Isocortical and Hippocampal Astrocytes in the Human Brain

    Sosunov, Alexander A.; Wu, Xiaoping; Tsankova, Nadejda M.; Guilfoyle, Eileen; Guy M McKhann; Goldman, James E.

    2014-01-01

    To examine the diversity of astrocytes in the human brain, we immunostained surgical specimens of temporal cortex and hippocampus and autopsy brains for CD44, a plasma membrane protein and extracellular matrix receptor. CD44 antibodies outline the details of astrocyte morphology to a degree not possible with glial fibrillary acidic protein (GFAP) antibodies. CD44+ astrocytes could be subdivided into two groups. First, CD44+ astrocytes with long processes were consistently found in the subpial...

  20. Brain perihematoma genomic profile following spontaneous human intracerebral hemorrhage.

    Anna Rosell

    Full Text Available BACKGROUND: Spontaneous intracerebral hemorrhage (ICH represents about 15% of all strokes and is associated with high mortality rates. Our aim was to identify the gene expression changes and biological pathways altered in the brain following ICH. METHODOLOGY/PRINCIPAL FINDINGS: Twelve brain samples were obtained from four deceased patients who suffered an ICH including perihematomal tissue (PH and the corresponding contralateral white (CW and grey (CG matter. Affymetrix GeneChip platform for analysis of over 47,000 transcripts was conducted. Microarray Analysis Suite 5.0 was used to process array images and the Ingenuity Pathway Analysis System was used to analyze biological mechanisms and functions of the genes. We identified 468 genes in the PH areas displaying a different expression pattern with a fold change between -3.74 and +5.16 when compared to the contralateral areas (291 overexpressed and 177 underexpressed. The top genes which appeared most significantly overexpressed in the PH areas codify for cytokines, chemokines, coagulation factors, cell growth and proliferation factors while the underexpressed codify for proteins involved in cell cycle or neurotrophins. Validation and replication studies at gene and protein level in brain samples confirmed microarray results. CONCLUSIONS: The genomic responses identified in this study provide valuable information about potential biomarkers and target molecules altered in the perihematomal regions.

  1. Genotype and ancestry modulate brain's DAT availability in healthy humans

    The dopamine transporter (DAT) is a principal regulator of dopaminergic neurotransmission and its gene (the SLC6A3) is a strong biological candidate gene for various behavioral- and neurological disorders. Intense investigation of the link between the SLC6A3 polymorphisms and behavioral phenotypes yielded inconsistent and even contradictory results. Reliance on objective brain phenotype measures, for example, those afforded by brain imaging, might critically improve detection of DAT genotype-phenotype association. Here, we tested the relationship between the DAT brain availability and the SLC6A3 genotypes using an aggregate sample of 95 healthy participants of several imaging studies. These studies employed positron emission tomography (PET) with [11C] cocaine wherein the DAT availability was estimated as Bmax/Kd; while the genotype values were obtained on two repeat polymorphisms - 3-UTR- and intron 8- VNTRs. The main findings are the following: (1) both polymorphisms analyzed as single genetic markers and in combination (haplotype) modulate DAT density in midbrain; (2) ethnic background and age influence the strength of these associations; and (3) age-related changes in DAT availability differ in the 3-UTR and intron8 - genotype groups.

  2. Genotype and ancestry modulate brain's DAT availability in healthy humans.

    Elena Shumay

    Full Text Available The dopamine transporter (DAT is a principal regulator of dopaminergic neurotransmission and its gene (the SLC6A3 is a strong biological candidate gene for various behavioral- and neurological disorders. Intense investigation of the link between the SLC6A3 polymorphisms and behavioral phenotypes yielded inconsistent and even contradictory results. Reliance on objective brain phenotype measures, for example, those afforded by brain imaging, might critically improve detection of DAT genotype-phenotype association. Here, we tested the relationship between the DAT brain availability and the SLC6A3 genotypes using an aggregate sample of 95 healthy participants of several imaging studies. These studies employed positron emission tomography (PET with [¹¹C]cocaine wherein the DAT availability was estimated as Bmax/Kd; while the genotype values were obtained on two repeat polymorphisms--3-UTR- and intron 8--VNTRs. The main findings are the following: 1 both polymorphisms analyzed as single genetic markers and in combination (haplotype modulate DAT density in midbrain; 2 ethnic background and age influence the strength of these associations; and 3 age-related changes in DAT availability differ in the 3-UTR and intron 8--genotype groups.

  3. Human Brain Expansion during Evolution Is Independent of Fire Control and Cooking.

    Cornélio, Alianda M; de Bittencourt-Navarrete, Ruben E; de Bittencourt Brum, Ricardo; Queiroz, Claudio M; Costa, Marcos R

    2016-01-01

    What makes humans unique? This question has fascinated scientists and philosophers for centuries and it is still a matter of intense debate. Nowadays, human brain expansion during evolution has been acknowledged to explain our empowered cognitive capabilities. The drivers for such accelerated expansion remain, however, largely unknown. In this sense, studies have suggested that the cooking of food could be a pre-requisite for the expansion of brain size in early hominins. However, this appealing hypothesis is only supported by a mathematical model suggesting that the increasing number of neurons in the brain would constrain body size among primates due to a limited amount of calories obtained from diets. Here, we show, by using a similar mathematical model, that a tradeoff between body mass and the number of brain neurons imposed by dietary constraints during hominin evolution is unlikely. Instead, the predictable number of neurons in the hominin brain varies much more in function of foraging efficiency than body mass. We also review archeological data to show that the expansion of the brain volume in the hominin lineage is described by a linear function independent of evidence of fire control, and therefore, thermal processing of food does not account for this phenomenon. Finally, we report experiments in mice showing that thermal processing of meat does not increase its caloric availability in mice. Altogether, our data indicate that cooking is neither sufficient nor necessary to explain hominin brain expansion. PMID:27199631

  4. 1/f Noise Outperforms White Noise in Sensitizing Baroreflex Function in the Human Brain

    Soma, Rika; Nozaki, Daichi; Kwak, Shin; Yamamoto, Yoshiharu

    2003-08-01

    We show that externally added 1/f noise more effectively sensitizes the baroreflex centers in the human brain than white noise. We examined the compensatory heart rate response to a weak periodic signal introduced via venous blood pressure receptors while adding 1/f or white noise with the same variance to the brain stem through bilateral cutaneous stimulation of the vestibular afferents. In both cases, this noisy galvanic vestibular stimulation optimized covariance between the weak input signals and the heart rate responses. However, the optimal level with 1/f noise was significantly lower than with white noise, suggesting a functional benefit of 1/f noise for neuronal information transfer in the brain.

  5. Measurement of human blood brain barrier integrity using 11C-inulin and positron emission tomography

    Positron emission tomography (PET) using 11C-inulin was demonstrated to be applicable to the clinical measurement of blood brain barrier permeability and cerebral interstitial fluid volume. Kinetic data were analyzed by application of a two compartment model, in which blood plasma and interstitial fluid spaces constitute the compartments. The blood activity contribution was subtracted from the PET count with the aid of the 11CO inhalation technique. The values we estimated in a human brain were in agreement with the reported values obtained for animal brains by the use of 14C-inulin. (orig.)

  6. Autoradiographic analysis of alpha 1-noradrenergic receptors in the human brain postmortem. Effect of suicide

    In vitro quantitative autoradiography of alpha 1-noradrenergic receptors, using tritiated prazosin as a ligand, was performed on 24 human brains postmortem. Twelve brains were obtained from suicide victims and 12 from matched controls. We found significant lower binding to alpha 1 receptors in several brain regions of the suicide group as compared with matched controls. This decrease in receptor density was evident in portions of the prefrontal cortex, as well as the temporal cortex and in the caudate nucleus. Age, sex, presence of alcohol, and time of death to autopsy did not affect prazosin binding, in our sample, as measured by autoradiography

  7. Ultrasound fails to induce proliferation of human brain and mouse endothelial cell lines

    Rodemer, Claus; Jenne, Jürgen; Fatar, Marc; Hennerici, Michael G.; Meairs, Stephen

    2012-11-01

    Both in vitro and in vivo studies suggest that ultrasound (US) is capable of inducing angiogenesis. There is no information, however, on whether ultrasound can induce proliferation of brain endothelial cells. We therefore explored the angiogenic potential of ultrasound on a novel immortalised human brain endothelial cell line (hCMEC/D3) and on mouse brain microvascular endothelial cells (bEND3). Ultrasound failed to enhance cell proliferation in both cell lines at all acoustic pressures studied. Endothelial cell damage occurred at 0.24 MPa with significantly slower proliferation. Cells growing in Opticell{trade mark, serif} dishes did not show damage or reduced proliferation at these pressures.

  8. Reorganization and plastic changes of the human brain associated with skill learning and expertise

    Yongmin eChang

    2014-02-01

    Full Text Available Novel experience and learning new skills are known as modulators of brain function. Advances in non-invasive brain imaging have provided new insight into structural and functional reorganization associated with skill learning and expertise. Especially, significant imaging evidences come from the domains of sports and music. Data from in vivo imaging studies in sports and music have provided vital information on plausible neural substrates contributing to brain reorganization underlying skill acquisition in humans. This mini review will attempt to take a narrow snapshot of imaging findings demonstrating functional and structural plasticity that mediate skill learning and expertise while identifying converging areas of interest and possible avenues for future research.

  9. Increase in human brain size a key to increase in body size

    S.P.Singh

    2016-05-01

    Full Text Available Lucy, considered to be the ancestor to all humanity was a very short creature about three and a half feet tall, weighing some 60 to 65 pounds and lived around 3.2 million years ago in Ethiopia. Perhaps the growth period among the australopithecines was much shorter than that of the modern day humans and hence simply by this yardstick, there has to be a lot of difference in body size between them. The longer the growth period the larger the body size and this is what seemed to happen to the humans during evolutionary history. Recently Mark Grabowski, a researcher at American Museum of Natural History, New York,observed in his research paper that "Bigger brains led to bigger bodies... as over the last four million years, brain size and body size increased substantially in our human ancestors" (Current Anthropology, Vol. 57, 174-196, April 2016. These observations were not new and were clearly understood by the scientific community earlier also. However, numerous hypotheses put forth had emphasized the role of natural selection on different traits independently. But none of them had gone in the direction of a correlated response to natural selection in favour of enlarging the brain size and the body size together. These viewpoints had concluded that increase in brain size and body size were the products of separate natural selection forces. However, Mark Grabowski states that "some genes cause variation in both brain and body size, with the result that selection on either trait can lead to a correlated response in the unselected trait." This is a new explanation to the problem. It highlights the role of correlated outcomes of the natural selection phenomena occurring to one trait but affecting the other trait even if that is not selected for. It is similar to saying that as the brain size increased from Lucy to Homo erectus so did the body size as if the animal pulled itself up and increased in size proportionately as well to keep pace with the

  10. Amplification of a transcriptionally active DNA sequence in the human brain

    The authors present their findings of tissue-specific amplification of a DNA fragment actively transcribed in the human brain. This genome fragment was found in the library complement of cDNA of the human brain and evidently belongs to a new class of moderate repetitions of DNA with an unstable copying capacity in the human genome. The authors isolated total cell RNA from various human tissues (brain, placenta), and rat tissues (brain, liver), by the method of hot phenol extraction with guanidine thiocynate. The poly(A+) RNA fraction was isolated by chromatography. Synthesis of cDNA was done on a matrix of poly(A+) RNA of human brain. The cDNA obtained was cloned in plasmid pBR322 for the PstI site using (dC/dG) sequences synthesized on the 3' ends of the vector molecule and cDNA respectively. In cloning 75 ng cDNA, the authors obtained approximately 105 recombinant. This library was analyzed by the hybridization method on columns with two radioactive (32P) probes: the total cDNA preparation and the total nuclear DNA from the human brain. The number of copies of the cloned DNA fragment in the genome was determined by dot hybridization. Restricting fragments of human and rat DNA genomes homologous to the cloned cDNA were identified on radio-autographs. In each case, 10 micrograms of EcoRI DNA hydrolyzate was fractionated in 1% agarose gel. The probe was also readied with RNA samples fractionated in agarose gel with formaldehyde and transferred to a nitrocellulose filter under weak vacuum. The filter was hybridized with 0.1 micrograms DNA pAG 02, labeled with (32P) to a specific activity of 0.5-1 x 109 counts/min x microgram. The autograph was exposed with amplifying screens at -700C for 2 days

  11. Development of functional human embryonic stem cell-derived neurons in mouse brain

    Muotri, Alysson R.; Nakashima, Kinichi; Toni, Nicolas; Sandler, Vladislav M.; Gage, Fred H

    2005-01-01

    Human embryonic stem cells are pluripotent entities, theoretically capable of generating a whole-body spectrum of distinct cell types. However, differentiation of these cells has been observed only in culture or during teratoma formation. Our results show that human embryonic stem cells implanted in the brain ventricles of embryonic mice can differentiate into functional neural lineages and generate mature, active human neurons that successfully integrate into the adult mouse forebrain. Moreo...

  12. PHANTOM MODEL OF HUMAN BRAIN TISSUE FOR CELLULAR PHONE FREQUENCIES IN ELECTROMAGNETIC FIELD RADIATION ABSORPTION STUDIES

    Özen, Şükrü; Köylü, Halis

    2010-01-01

    ABSTRACTThere is a necessity of tissue equivalent (phantom) models in research of electromagnetic (EM) effects in biologic tissues. Recently, many kinds of tissue models depend on the different aim were proposed. So many studies were carried on the interaction of human-head and cellular phone. The most of them are related to numerical models. Owing to difficulty of study on human body, simulation of human tissues is required. In this study two different, for 900MHz and for 1800MHz, brain equi...

  13. Signals Analysis and Clinical Validation of Blood and Oxygen Data in Human Brain

    LI Kai-yang; LIU Li-jun; WANG Xiang; QIN Zhao; XIE Ze-ping

    2005-01-01

    With a self-made near-infrared analytical instrument to blood and oxygen parameters in human brain, 80 cases in which 20 are healthy persons and 30are anaesthetised cases and others are patients with heart function lack is taken to examine, and the data of blood and oxygen in brain tissue were collected and analyzed by the method of power spectrum and correlation function. The results indicate that: (1) The average brain oxygen saturation of healthy persons and anaesthetised cases is about 80%, in accord with normal parameter of physiology. Contrastively, the average brain oxygen saturation of patients with heart function lack is 72. 8%, which is obviously less than that of healthy persons and anaesthetised cases. The probability of medical statistics is less than 0. 01. (2) The shapes of wave of brain blood and oxygen for the healthy person and the anaesthetised case reveal small periodical fluctuations with stable shape and base line, and the trend of increase or decrease of blood and oxygen parameters in brain tissue is synchronous and a phase reversal, but for the patient with heart function lack in a brain oxygen lack state, the shapes of wave are irregular. This is a hint that near infrared light passing through tissue can reflect the intuitionistic change of brain blood and oxygen parameters. (3) The power spectra of brain blood and oxygen for the healthy person and the anaesthetised case has a clear main peak, narrow bandwidth and perfect superposition each other, but the power spectra for the patient with heart function lack in a brain oxygen lack state is on the contrary. (4) The average cross correlation coefficient of brain blood and oxygen for healthy persons and anaesthetised cases is -0. 9825±0. 1027 close to -1. But the average cross correlation coefficient for patients with heart function lack in a brain oxygen lack state is merely -0. 8923± 0. 1035 which is obviously greater than -1 and the probability of medical statistics is less than 0. 01

  14. Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields

    Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela

    2016-06-01

    An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform’s size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257–65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke’s brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz.

  15. Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields.

    Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela

    2016-06-21

    An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform's size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257-65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke's brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz. PMID:27223143

  16. BrainCrafter: An investigation into human-based neural network engineering

    Piskur, J.; Greve, P.; Togelius, J.;

    2015-01-01

    This paper presents the online application Brain-Crafter, in which users can manually build artificial neural networks (ANNs) to control a robot in a maze environment. Users can either start to construct networks from scratch or elaborate on networks created by other users. In particular, Brain......) collaboration between users presented difficulties and (3) the human-developed ANNs that managed to solve the task had certain regularities, suggesting that humans can use some of their intuition and spatial understanding in the design of ANNs. Most importantly, the initial results in this paper can serve as a...... starting point for investigating how to best combine human and machine design capabilities to create more complex artificial brains....

  17. Differentiation and characterization of human pluripotent stem cell-derived brain microvascular endothelial cells.

    Stebbins, Matthew J; Wilson, Hannah K; Canfield, Scott G; Qian, Tongcheng; Palecek, Sean P; Shusta, Eric V

    2016-05-15

    The blood-brain barrier (BBB) is a critical component of the central nervous system (CNS) that regulates the flux of material between the blood and the brain. Because of its barrier properties, the BBB creates a bottleneck to CNS drug delivery. Human in vitro BBB models offer a potential tool to screen pharmaceutical libraries for CNS penetration as well as for BBB modulators in development and disease, yet primary and immortalized models respectively lack scalability and robust phenotypes. Recently, in vitro BBB models derived from human pluripotent stem cells (hPSCs) have helped overcome these challenges by providing a scalable and renewable source of human brain microvascular endothelial cells (BMECs). We have demonstrated that hPSC-derived BMECs exhibit robust structural and functional characteristics reminiscent of the in vivo BBB. Here, we provide a detailed description of the methods required to differentiate and functionally characterize hPSC-derived BMECs to facilitate their widespread use in downstream applications. PMID:26518252

  18. Characterization of the melanoma brain metastatic niche in mice and humans

    Brain metastases occur in 15% of patients with melanoma and are associated with a dismal prognosis. Here, we investigate the architectural phenotype and stromal reaction of melanoma brain metastasis in mice and humans. A syngeneic, green fluorescence protein (GFP)-expressing murine B16-F1 melanoma clone was introduced via intracardiac injection, and was examined in vivo in comparison with human specimens. Immunofluorescence analyses of the brain metastases revealed that F4/80+ macrophages/microglia were most abundant at the tumor front, but rare in its core, where they were found only around blood vessels (P = 0.01). Similar pattern of infiltration was found in CD3+ T cells (P < 0.01). Infiltrating T cells were prominently CD4+ compared with CD8+ T cells (P < 0.001). Blood vessels (CD31+) were less abundant at the tumor front than in its center (12 ± 1 vs. 4 ± 0.6 vessels per high-power field [HPF], P < 0.001). In contrast, there were few vessels at the tumor front, but their diameter was significantly larger at the front (8236 μm2 vs. 4617 μm2 average cross-sectional area, P < 0.005). This is the first comparative analysis of melanoma brain metastases showing similar stromal reaction in murine models and human specimens. Our results validate the utility of this murine model of melanoma brain metastases for investigating the mechanism of the human disease

  19. Sphingosine 1-phosphate receptor 5 mediates the immune quiescence of the human brain endothelial barrier

    van Doorn Ruben

    2012-06-01

    Full Text Available Abstract Background The sphingosine 1-phosphate (S1P receptor modulator FTY720P (Gilenya® potently reduces relapse rate and lesion activity in the neuroinflammatory disorder multiple sclerosis. Although most of its efficacy has been shown to be related to immunosuppression through the induction of lymphopenia, it has been suggested that a number of its beneficial effects are related to altered endothelial and blood–brain barrier (BBB functionality. However, to date it remains unknown whether brain endothelial S1P receptors are involved in the maintenance of the function of the BBB thereby mediating immune quiescence of the brain. Here we demonstrate that the brain endothelial receptor S1P5 largely contributes to the maintenance of brain endothelial barrier function. Methods We analyzed the expression of S1P5 in human post-mortem tissues using immunohistochemistry. The function of S1P5 at the BBB was assessed in cultured human brain endothelial cells (ECs using agonists and lentivirus-mediated knockdown of S1P5. Subsequent analyses of different aspects of the brain EC barrier included the formation of a tight barrier, the expression of BBB proteins and markers of inflammation and monocyte transmigration. Results We show that activation of S1P5 on cultured human brain ECs by a selective agonist elicits enhanced barrier integrity and reduced transendothelial migration of monocytes in vitro. These results were corroborated by genetically silencing S1P5 in brain ECs. Interestingly, functional studies with these cells revealed that S1P5 strongly contributes to brain EC barrier function and underlies the expression of specific BBB endothelial characteristics such as tight junctions and permeability. In addition, S1P5 maintains the immunoquiescent state of brain ECs with low expression levels of leukocyte adhesion molecules and inflammatory chemokines and cytokines through lowering the activation of the transcription factor NFκB. Conclusion Our

  20. Geomagnetic Storms and their Influence on the Human Brain Functional State

    Elchin S. Babayev

    2005-01-01

    Full Text Available An investigation of the influence of geomagnetic storms of various intensities on healthy adults' human brain activity and its functional state was conducted. Results of electroencephalogram (EEG investigations were used as the most objective method reflecting functional state of the human brain. Studies on the influence of geomagnetic storms on the human brain functional state of healthy adult women patients (permanent group in states of relaxation, photo-stimulation and hyper-ventilation have revealed a negative influence of severe geomagnetic storms on functional state of the human brain. As a rule, during periods of strong geomagnetic disturbances, indisposition, weakness and presence of indistinct localized headaches were recorded for majority of patients. Complex of nonspecific shifts on EEG reflects disorganization of functional activity of cortex of large hemispheres of the human brain at geomagnetically disturbed days, which is likely connected with dysfunction of integrative subcortical systems, with disbalance of its ascending synchronizing and desynchronizing influences. Imbalance of activating and deactivating mechanisms including dysfunctions of ergo- and tropho-tropic over-segmentary centers was registered. Strengthening cortical connections in the right cortical hemisphere and their short circuit on temporal sections during geomagnetically disturbed days were observed, while, in geomagnetically quiet days, a profile of correlation interrelations reflected weak internal- and inter-hemispheric connections. The threshold of convulsive (spasmodic readiness of the human brain is reduced, which is especially dangerous for risk group persons. It is established that, in general, weak and moderate geomagnetic storms exert stimulating influence while strong disturbances of geomagnetic conditions activate braking (inhibiting processes.

  1. The Speculative Neuroscience of the Future Human Brain

    Robert A. Dielenberg

    2013-01-01

    The hallmark of our species is our ability to hybridize symbolic thinking with behavioral output. We began with the symmetrical hand axe around 1.7 mya and have progressed, slowly at first, then with greater rapidity, to producing increasingly more complex hybridized products. We now live in the age where our drive to hybridize has pushed us to the brink of a neuroscientific revolution, where for the first time we are in a position to willfully alter the brain and hence, our behavior and evol...

  2. Human brain activity patterns beyond the isoelectric line of extreme deep coma.

    Daniel Kroeger

    Full Text Available The electroencephalogram (EEG reflects brain electrical activity. A flat (isoelectric EEG, which is usually recorded during very deep coma, is considered to be a turning point between a living brain and a deceased brain. Therefore the isoelectric EEG constitutes, together with evidence of irreversible structural brain damage, one of the criteria for the assessment of brain death. In this study we use EEG recordings for humans on the one hand, and on the other hand double simultaneous intracellular recordings in the cortex and hippocampus, combined with EEG, in cats. They serve to demonstrate that a novel brain phenomenon is observable in both humans and animals during coma that is deeper than the one reflected by the isoelectric EEG, and that this state is characterized by brain activity generated within the hippocampal formation. This new state was induced either by medication applied to postanoxic coma (in human or by application of high doses of anesthesia (isoflurane in animals leading to an EEG activity of quasi-rhythmic sharp waves which henceforth we propose to call ν-complexes (Nu-complexes. Using simultaneous intracellular recordings in vivo in the cortex and hippocampus (especially in the CA3 region we demonstrate that ν-complexes arise in the hippocampus and are subsequently transmitted to the cortex. The genesis of a hippocampal ν-complex depends upon another hippocampal activity, known as ripple activity, which is not overtly detectable at the cortical level. Based on our observations, we propose a scenario of how self-oscillations in hippocampal neurons can lead to a whole brain phenomenon during coma.

  3. Intra- and interhemispheric connectivity between face-selective regions in the human brain

    Davies-Thompson, Jodie; Andrews, Timothy J.

    2012-01-01

    Neuroimaging studies have revealed a number of regions in the human brain that respond to faces. However, the way these regions interact is a matter of current debate. The aim of this study was to use functional MRI to define face-selective regions in the human brain and then determine how these regions interact in a large population of subjects (n = 72). We found consistent face selectivity in the core face regions of the occipital and temporal lobes: the fusiform face area (FFA), occipital ...

  4. Brain-Computer Interfaces Applying Our Minds to Human-computer Interaction

    Tan, Desney S

    2010-01-01

    For generations, humans have fantasized about the ability to create devices that can see into a person's mind and thoughts, or to communicate and interact with machines through thought alone. Such ideas have long captured the imagination of humankind in the form of ancient myths and modern science fiction stories. Recent advances in cognitive neuroscience and brain imaging technologies have started to turn these myths into a reality, and are providing us with the ability to interface directly with the human brain. This ability is made possible through the use of sensors that monitor physical p

  5. The topology of large Open Connectome networks for the human brain

    Gastner, Michael T.; Géza Ódor

    2016-01-01

    The structural human connectome (i.e.\\ the network of fiber connections in the brain) can be analyzed at ever finer spatial resolution thanks to advances in neuroimaging. Here we analyze several large data sets for the human brain network made available by the Open Connectome Project. We apply statistical model selection to characterize the degree distributions of graphs containing up to $\\simeq 10^6$ nodes and $\\simeq 10^8$ edges. A three-parameter generalized Weibull (also known as a stretc...

  6. Simulation of Local Blood Flow in Human Brain under Altered Gravity

    Kim, Chang Sung; Kiris, Cetin; Kwak, Dochan

    2003-01-01

    In addition to the altered gravitational forces, specific shapes and connections of arteries in the brain vary in the human population (Cebral et al., 2000; Ferrandez et al., 2002). Considering the geometric variations, pulsatile unsteadiness, and moving walls, computational approach in analyzing altered blood circulation will offer an economical alternative to experiments. This paper presents a computational approach for modeling the local blood flow through the human brain under altered gravity. This computational approach has been verified through steady and unsteady experimental measurements and then applied to the unsteady blood flows through a carotid bifurcation model and an idealized Circle of Willis (COW) configuration under altered gravity conditions.

  7. The remarkable, yet not extraordinary, human brain as a scaled-up primate brain and its associated cost

    Herculano-Houzel, Suzana

    2012-01-01

    Neuroscientists have become used to a number of “facts” about the human brain: It has 100 billion neurons and 10- to 50-fold more glial cells; it is the largest-than-expected for its body among primates and mammals in general, and therefore the most cognitively able; it consumes an outstanding 20% of the total body energy budget despite representing only 2% of body mass because of an increased metabolic need of its neurons; and it is endowed with an overdeveloped cerebral cortex, the largest ...

  8. Interleukin-6 release from the human brain during prolonged exercise

    Nybo, Lars; Nielsen, Bodil; Pedersen, Bente Klarlund;

    2002-01-01

    be linked with central fatigue, which is enhanced by hyperthermia. Exercise-induced IL-6 may also stimulate hepatic glycogenolysis, which is important during prolonged and repeated exercise. Thus, in a randomised order and separated by 60 min of rest, eight young male subjects completed two 60 min exercise......Interleukin (IL)-6 is a pleiotropic cytokine, which has a variety of physiological roles including functions within the central nervous system. Circulating IL-6 increases markedly during exercise, partly due to the release of IL-6 from the contracting skeletal muscles, and exercise-induced IL-6 may...... in the brain at rest or after 15 min of exercise, but a small release of IL-6 was observed after 60 min of exercise in the first bout (0.06 +/- 0.03 ng min(-1)). This release of IL-6 from the brain was five-fold greater at the end of the second bout (0.30 +/- 0.08 ng min(-1); P

  9. Mapping blood flow directionality in the human brain.

    Park, Sung-Hong; Do, Won-Joon; Choi, Seung Hong; Zhao, Tiejun; Bae, Kyongtae Ty

    2016-07-01

    Diffusion properties of tissue are often expressed on the basis of directional variance, i.e., diffusion tensor imaging. In comparison, common perfusion-weighted imaging such as arterial spin labeling yields perfusion in a scalar quantity. The purpose of this study was to test the feasibility of mapping cerebral blood flow directionality using alternate ascending/descending directional navigation (ALADDIN), a recently-developed arterial spin labeling technique with sensitivity to blood flow directions. ALADDIN was applied along 3 orthogonal directions to assess directional blood flow in a vector form and also along 6 equally-spaced directions to extract blood flow tensor matrix (P) based on a blood flow ellipsoid model. Tensor elements (eigenvalues, eigenvectors, etc) were calculated to investigate characteristics of the blood flow tensor, in comparison with time-of-flight MR angiogram. While the directions of the main eigenvectors were heterogeneous throughout the brain, regional clusters of blood flow directionality were reproducible across subjects. The technique could show heterogeneous blood flow directionality within and around brain tumor, which was different from that of the contralateral normal side. The proposed method is deemed to provide information of blood flow directionality, which has not been demonstrated before. The results warrant further studies to assess changes in the directionality map as a function of scan parameters, to understand the signal sources, to investigate the possibility of mapping local blood perfusion directionality, and to evaluate its usefulness for clinical diagnosis. PMID:26968145

  10. Different methods of measuring ADC values in normal human brain

    Objective: To investigate better method of measuring ADC values of normal brain, and provide reference for further research. Methods: Twenty healthy people's MR imaging were reviewed. All of them underwent routine MRI scans and echo-planar diffusion-weighted imaging (DWI), and ADC maps were reconstructed on work station. Six regions of interest (ROI) were selected for each object, the mean ADC values were obtained for each position on DWI and ADC maps respectively. Results: On the anisotropic DWI map calculated in the hypothalamus, ADCM, ADCP, ADCS values were no significant difference (P>0.05), in the frontal white matter and internal capsule hindlimb, there was a significant difference (Pave value exist significant difference to direct measurement on the anisotropic (isotropic) ADC map (P<0.001). Conclusion: Diffusion of water in the frontal white matter and internal capsule are anisotropic, but it is isotropic in the hypothalamus; different quantitative methods of diffusion measurement of 4ADC values have significant difference, but ADC values calculated through the DWI map is more accurate, quantitative diffusion study of brain tissue should also consider the diffusion measurement method. (authors)

  11. Baseline brain activity fluctuations predict somatosensory perception in humans

    Boly, M.; Balteau, E.; Schnakers, C.; Degueldre, C.; Moonen, G.; Luxen, A.; Phillips, C.; Peigneux, P.; Maquet, P.; Laureys, S.

    2007-01-01

    In perceptual experiments, within-individual fluctuations in perception are observed across multiple presentations of the same stimuli, a phenomenon that remains only partially understood. Here, by means of thulium–yttrium/aluminum–garnet laser and event-related functional MRI, we tested whether variability in perception of identical stimuli relates to differences in prestimulus, baseline brain activity. Results indicate a positive relationship between conscious perception of low-intensity somatosensory stimuli and immediately preceding levels of baseline activity in medial thalamus and the lateral frontoparietal network, respectively, which are thought to relate to vigilance and “external monitoring.” Conversely, there was a negative correlation between subsequent reporting of conscious perception and baseline activity in a set of regions encompassing posterior cingulate/precuneus and temporoparietal cortices, possibly relating to introspection and self-oriented processes. At nociceptive levels of stimulation, pain-intensity ratings positively correlated with baseline fluctuations in anterior cingulate cortex in an area known to be involved in the affective dimension of pain. These results suggest that baseline brain-activity fluctuations may profoundly modify our conscious perception of the external world. PMID:17616583

  12. Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution.

    Zeng, Jia; Konopka, Genevieve; Hunt, Brendan G; Preuss, Todd M; Geschwind, Dan; Yi, Soojin V

    2012-09-01

    DNA methylation is a pervasive epigenetic DNA modification that strongly affects chromatin regulation and gene expression. To date, it remains largely unknown how patterns of DNA methylation differ between closely related species and whether such differences contribute to species-specific phenotypes. To investigate these questions, we generated nucleotide-resolution whole-genome methylation maps of the prefrontal cortex of multiple humans and chimpanzees. Levels and patterns of DNA methylation vary across individuals within species according to the age and the sex of the individuals. We also found extensive species-level divergence in patterns of DNA methylation and that hundreds of genes exhibit significantly lower levels of promoter methylation in the human brain than in the chimpanzee brain. Furthermore, we investigated the functional consequences of methylation differences in humans and chimpanzees by integrating data on gene expression generated with next-generation sequencing methods, and we found a strong relationship between differential methylation and gene expression. Finally, we found that differentially methylated genes are strikingly enriched with loci associated with neurological disorders, psychological disorders, and cancers. Our results demonstrate that differential DNA methylation might be an important molecular mechanism driving gene-expression divergence between human and chimpanzee brains and might potentially contribute to the evolution of disease vulnerabilities. Thus, comparative studies of humans and chimpanzees stand to identify key epigenomic modifications underlying the evolution of human-specific traits. PMID:22922032

  13. Isolation and characterization of human malignant glioma cells from histologically normal brain.

    Silbergeld, D L; Chicoine, M R

    1997-03-01

    Brain invasion prevents complete surgical extirpation of malignant gliomas; however, invasive cells from distant, histologically normal brain previously have not been isolated, cultured, and characterized. To evaluate invasive human malignant glioma cells, the authors established cultures from gross tumor and histologically normal brain. Three men and one woman, with a mean age of 67 years, underwent two frontal and two temporal lobectomies for tumors, which yielded specimens of both gross tumor and histologically normal brain. Each specimen was acquired a minimum of 4 cm from the gross tumor. The specimens were split: a portion was sent for neuropathological evaluation (three glioblastomas multiforme and one oligodendroglioma) and a portion was used to establish cell lines. Morphologically, the specimens of gross tumor and histologically normal brain were identical in three of the four cell culture pairs. Histochemical staining characteristics were consistent both within each pair and when compared with the specimens sent for neuropathological evaluation. Cultures demonstrated anchorage-independent growth in soft agarose and neoplastic karyotypes. Growth rates in culture were greater for histologically normal brain than for gross tumor in three of the four culture pairs. Although the observed increases in growth rates of histologically normal brain cultures do not correlate with in vivo behavior, these findings corroborate the previously reported stem cell potential of invasive glioma cells. Using the radial dish assay, no significant differences in motility between cultures of gross tumor and histologically normal brain were found. In summary, tumor cells were cultured from histologically normal brain acquired from a distance greater than 4 cm from the gross tumor, indicating the relative insensitivity of standard histopathological identification of invasive glioma cells (and hence the inadequacy of frozen-section evaluation of resection margins). Cell lines

  14. Cognition beyond the brain computation, interactivity and human artifice

    Cowley, Stephen J

    2013-01-01

    Arguing that a collective dimension has given cognitive flexibility to human intelligence, this book shows that traditional cognitive psychology underplays the role of bodies, dialogue, diagrams, tools, talk, customs, habits, computers and cultural practices.

  15. Is there a gender difference of somatostatin-receptor density in the human brain?

    Pichler, Robert; Maschek, Wilhelmine; Crespillo, Carmen; Esteva, Isabel; Soriguer, Federico

    2002-01-01

    Animal experiments and observations in human brains have convincingly shown that sexual differentiation not only concerns the genitalia but also the brain. This has been investigated also in the light of a possible explanation of a presumed biological aetiology of transsexuality. The volume of the central subdivision of the bed nucleus of the stria terminalis, a brain area that is essential for sexual behaviour, has been reported to be larger in men than in women. Additionally, the number of somatostatin expressing neurons in this region was shown to be higher in men than in women. As neuronal production of somatostatin is involved the idea is striking whether somatostatin-receptor density in the cortex of cerebral hemispheres might be related to gender identity. We investigated in vivo the density of somatostatin-receptors in selected regions of the human brain in both sexes by means of receptor scintigraphy. Basal ganglia tracer uptake of 111-In-Pentreotide was equally low in both genders at 0,80% +/ 0,26 (related to tracer uptake of the whole brain layer). Temporal cortex accumulated at 2,9% +/ 1,1 in men and at 2,3% +/ 0,76 in women. Frontal brain region had an uptake of 3,0% +/ 1,4 in male and of 2,5% +/ 1,3 in female. This shows a tendency in males for relatively augmented uptake indicating higher somatostatin receptor density in temporal and frontal cerebral cortex. PMID:12500167

  16. Finite element modeling of human brain response to football helmet impacts.

    Darling, T; Muthuswamy, J; Rajan, S D

    2016-10-01

    The football helmet is used to help mitigate the occurrence of impact-related traumatic (TBI) and minor traumatic brain injuries (mTBI) in the game of American football. While the current helmet design methodology may be adequate for reducing linear acceleration of the head and minimizing TBI, it however has had less effect in minimizing mTBI. The objectives of this study are (a) to develop and validate a coupled finite element (FE) model of a football helmet and the human body, and (b) to assess responses of different regions of the brain to two different impact conditions - frontal oblique and crown impact conditions. The FE helmet model was validated using experimental results of drop tests. Subsequently, the integrated helmet-human body FE model was used to assess the responses of different regions of the brain to impact loads. Strain-rate, strain, and stress measures in the corpus callosum, midbrain, and brain stem were assessed. Results show that maximum strain-rates of 27 and 19 s(-1) are observed in the brain-stem and mid-brain, respectively. This could potentially lead to axonal injuries and neuronal cell death during crown impact conditions. The developed experimental-numerical framework can be used in the study of other helmet-related impact conditions. PMID:26867124

  17. Unraveling the multiscale structural organization and connectivity of the human brain: the role of diffusion MRI

    Matteo eBastiani

    2015-06-01

    Full Text Available The structural architecture and the anatomical connectivity of the human brain show different organizational principles at distinct spatial scales. Histological staining and light microscopy techniques have been widely used in classical neuroanatomical studies to unravel brain organization. Using such techniques is a laborious task performed on 2-dimensional histological sections by skilled anatomists possibly aided by semi-automated algorithms. With the recent advent of modern magnetic resonance imaging (MRI contrast mechanisms, cortical layers and columns can now be reliably identified and their structural properties quantified post mortem. These developments are allowing the investigation of neuroanatomical features of the brain at a spatial resolution that could be interfaced with that of histology. Diffusion MRI and tractography techniques, in particular, have been used to probe the architecture of both white and gray matter in three dimensions. Combined with mathematical network analysis, these techniques are increasingly influential in the investigation of the macro-, meso- and microscopic organization of brain connectivity and anatomy, both in vivo and ex vivo. Diffusion MRI-based techniques in combination with histology approaches can therefore support the endeavor of creating multimodal atlases that take into account the different spatial scales or levels on which the brain is organized. The aim of this review is to illustrate and discuss the structural architecture and the anatomical connectivity of the human brain at different spatial scales and how recently developed diffusion MRI techniques can help investigate these.

  18. A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

    Romeo Cecchelli

    Full Text Available The human blood brain barrier (BBB is a selective barrier formed by human brain endothelial cells (hBECs, which is important to ensure adequate neuronal function and protect the central nervous system (CNS from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

  19. Trace element concentration differences in regions of human brain by INAA

    Studies have shown that there is a potential relationship between the levels of trace elements in cerebral tissues and neurological disorders. However, there are few publications available on the elemental composition of these tissues as well as for different regions of the brain. The aim of this study was to investigate trace element differences in various regions of the human brain from an elderly population of normal individuals. Brain samples from 31 individuals of both genders, aged 51-95 years were provided by the Brain Bank of the Brazilian Aging Study Group of the Sao Paulo University, Medical School. The tissues from the regions of the hippocampus, cerebellum and frontal, parietal, temporal, occipital cortex were dissected using a titanium knife, ground, freeze-dried and then analyzed by instrumental neutron activation analysis (INAA). Samples and element standards were irradiated with a neutron flux at the IEA-R1 nuclear research reactor for Br, Fe, K, Na, Rb, Se and Zn determinations. One-way ANOVA test (p < 0.05) was used to compare the results which showed significant differences for several elements among the brain regions. Most of our brain analysis results agreed with the literature data. The results were also submitted for brain region classification by cluster analysis. (author)

  20. MR-visible water content in human brain: a proton MRS study

    Christiansen, P; Toft, P B; Gideon, P; Danielsen, E R; Ring, P; Henriksen, O

    1994-01-01

    In vivo measurement of metabolite concentrations in the human brain by means of proton-MRS contributes significantly to the clinical evaluation of patients with diseases of the brain. The fully relaxed water signal has been proposed as an internal standard for calibration of the MRS measurements...... groups: newborn (0-23 days), adolescents (10-15 yr), adults (22-28 yr), and elderly people (60-74 yr). The examinations were carried out using a Siemens Helicon SP 63/84 MR-scanner operating at 1.5 T. Except for the newborn, four regions were studied in each subject using stimulated echo (STEAM....... The major drawbacks are the necessity to make the assumptions that the water concentrations in the brain and that all tissue water is MR-visible. A number of in vivo measurements were carried out to estimate the concentration of MR-visible water in the brain of healthy volunteers divided into four age...

  1. Magnetic particle spectroscopy allows precise quantification of nanoparticles after passage through human brain microvascular endothelial cells

    Gräfe, C.; Slabu, I.; Wiekhorst, F.; Bergemann, C.; von Eggeling, F.; Hochhaus, A.; Trahms, L.; Clement, J. H.

    2016-06-01

    Crossing the blood–brain barrier is an urgent requirement for the treatment of brain disorders. Superparamagnetic iron oxide nanoparticles (SPIONs) are a promising tool as carriers for therapeutics because of their physical properties, biocompatibility, and their biodegradability. In order to investigate the interaction of nanoparticles with endothelial cell layers in detail, in vitro systems are of great importance. Human brain microvascular endothelial cells are a well-suited blood–brain barrier model. Apart from generating optimal conditions for the barrier-forming cell units, the accurate detection and quantification of SPIONs is a major challenge. For that purpose we use magnetic particle spectroscopy to sensitively and directly quantify the SPION-specific iron content. We could show that SPION concentration depends on incubation time, nanoparticle concentration and location. This model system allows for further investigations on particle uptake and transport at cellular barriers with regard to parameters including particles’ shape, material, size, and coating.

  2. Magnetic particle spectroscopy allows precise quantification of nanoparticles after passage through human brain microvascular endothelial cells.

    Gräfe, C; Slabu, I; Wiekhorst, F; Bergemann, C; von Eggeling, F; Hochhaus, A; Trahms, L; Clement, J H

    2016-06-01

    Crossing the blood-brain barrier is an urgent requirement for the treatment of brain disorders. Superparamagnetic iron oxide nanoparticles (SPIONs) are a promising tool as carriers for therapeutics because of their physical properties, biocompatibility, and their biodegradability. In order to investigate the interaction of nanoparticles with endothelial cell layers in detail, in vitro systems are of great importance. Human brain microvascular endothelial cells are a well-suited blood-brain barrier model. Apart from generating optimal conditions for the barrier-forming cell units, the accurate detection and quantification of SPIONs is a major challenge. For that purpose we use magnetic particle spectroscopy to sensitively and directly quantify the SPION-specific iron content. We could show that SPION concentration depends on incubation time, nanoparticle concentration and location. This model system allows for further investigations on particle uptake and transport at cellular barriers with regard to parameters including particles' shape, material, size, and coating. PMID:27163489

  3. Simultaneous fMRI-PET of the opioidergic pain system in human brain

    Wey, Hsiao-Ying; Catana, Ciprian; Hooker, Jacob M;

    2014-01-01

    MRI and PET provide complementary information for studying brain function. While the potential use of simultaneous MRI/PET for clinical diagnostic and disease staging has been demonstrated recently; the biological relevance of concurrent functional MRI-PET brain imaging to dissect neurochemically...... and striatum related to pain processing, while modality specific brain networks were also found. Co-localized fMRI and PET signal changes in the thalamus were positively correlated suggesting that pain-induced changes in opioid neurotransmission contribute a significant component of the fMRI signal...... change in this region. Simultaneous fMRI-PET provides unique opportunities allowing us to relate specific neurochemical events to functional hemodynamic activation and to investigate the impacts of neurotransmission on neurovascular coupling of the human brain in vivo....

  4. 1H chemical shift imaging characterization of human brain tumor and edema

    Longitudinal (T1) and transverse (T2) relaxation times of metabolites in human brain tumor, peritumoral edema, and unaffected brain tissue were assessed from point resolved spectroscopy (PRESS) 1H chemical shift imaging results at different repetition times (TR=1500 and 5000 ms; T1: n=19) and echo times (TE=135 and 270 ms; T2: n=7). Metabolite T1 and T2 relaxation times in unaffected brain tissue corresponded with those published for healthy volunteers. T2 relaxation times were reduced in tumor (choline, N-acetyl aspartate) and edema (choline, creatine) compared with unaffected brain tissue (p1H chemical shift imaging is most suited in the use of choline elevation as tumor marker. (orig.)

  5. THE SIGNIFICANCE OF THE SUBPLATE FOR EVOLUTION AND DEVELOPMENTAL PLASTICITY OF THE HUMAN BRAIN

    MILOS eJUDAS

    2013-08-01

    Full Text Available The human life-history is characterized by long development and introduction of new developmental stages, such as childhood and adolescence. The developing brain had important role in these life-history changes because it is expensive tissue which uses up to 80% of resting metabolic rate in the newborn and continues to use almost 50% of it during the first 5 postnatal years. Our hominid ancestors managed to lift-up metabolic constraints to increase in brain size by several interrelated ecological, behavioral and social adaptations, such as dietary change, invention of cooking, creation of family-bonded reproductive units, and life-history changes. This opened new vistas for the developing brain, because it became possible to metabolically support transient patterns of brain organization as well as developmental brain plasticity for much longer period and with much greater number of neurons and connectivity combinations in comparison to apes. This included the shaping of cortical connections through the interaction with infant's social environment, which probably enhanced typically human evolution of language, cognition and self-awareness. In this review, we propose that the transient subplate zone and its postnatal remnant (interstitial neurons of the gyral white matter probably served as the main playground for evolution of these developmental shifts, and describe various features that makes human subplate uniquely positioned to have such a role in comparison with other primates.

  6. On the Photonic Cellular Interaction and the Electric Activity of Neurons in the Human Brain

    The subject of Ultraweak Photon Emission (UPE) by biological systems is very fascinating, and both evidence of its effects and applications are growing rapidly due to improvements in experimental techniques. Since the relevant equipment should be ultrasensitive with high quantum efficiencies and very low noise levels, the subject of UPE is still hotly debated and some of the interpretations need stronger empirical evidence to be accepted at face value. In this paper we first review different types of interactions between light and living systems based on recent publications. We then discuss the feasibility of UPE production in the human brain. The subject of UPE in the brain is still in early stages of development and needs more accurate experimental methods for proper analysis. In this work we also discuss a possible role of mitochondria in the production of UPE in the neurons of the brain and the plausibility of their effects on microtubules (MTs). MTs have been implicated as playing an important role in the signal and information processing taking place in the mammalian (especially human) brain. Finally, we provide a short discussion about the feasible effects of MTs on electric neural activity in the human brain.

  7. Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

    Guangjun Zhao

    2016-01-01

    Full Text Available Cryosection brain images in Chinese Visible Human (CVH dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel. Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain.

  8. Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder.

    Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

    2016-01-01

    Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain. PMID:27057543

  9. Differences in neural connectivity between the substantia nigra and ventral tegmental area in the human brain

    Sung Ho Jang

    2014-02-01

    Full Text Available Objectives: Many animal and a few human studies have reported on the neural connectivity of the substantia nigra (SN and the ventral tegmental area (VTA. However, it has not been clearly elucidated so far. We attempted to investigate any differences in neural connectivity of the SN/VTA in the human brain, using diffusion tensor imaging (DTI.Methods: Sixty-three healthy subjects were recruited for this study. DTIs were acquired using a sensitivity-encoding head coil at 1.5T. Connectivity was defined as the incidence of connection between the SN/VTA and each brain regions in the brain.Results: The connectivity of SN was higher than that of the VTA. This included in the primary motor cortex, primary somatosensory cortex, premotor cortex, prefrontal cortex, caudate nucleus, globus pallidus, putamen, nucleus accumbens, temporal lobe, amygdala, pontine basis, occipital lobe, anterior and posterior lobe of cerebellum, corpus callosum, and external capsule (p.05.Conclusions: We found the differences in neural connectivity of the SN/VTA in the human brain. The method and results of this study can provide useful information for clinicians and researchers in neuroscience, especially who work for Parkinson’s disease and patients with brain injury.

  10. Radiation-related damage to the developing human brain

    The authors summarize the significant dose-related effects on brain development which have emerged largely within the last six years of study of prenatally exposed A-bomb survivors. The results are described primarily in terms of the DS86 estimates and differences between these and the older T65DR dose estimates are discussed. The severe mental retardation sample was based on 1598 individuals taken from the PE-86 sample, and the intelligence test scores considered from the same sample involved 1673 children. The authors also discuss some of the recent neurobiological developments that appear relevant to an understanding of the biological bases of dose-related events observed, and suggest future research that may contribute either to further delineation of exposure consequences or to the explanation of the cellular and molecular origins of observed effects. (UK)

  11. Functional MR imaging of working memory in the human brain

    In order to investigate the functional brain anatomy associated with verbal and visual working memory, functional magnetic resonance imaging was performed. In ten normal right handed subjects, functional MR images were obtained using a 1.5-T MR scanner and the EPI BOLD technique. An item recognition task was used for stimulation, and during the activation period of the verbal working memory task, consonant letters were used. During the activation period of the visual working memory task, symbols or diagrams were employed instead of letters. For the post-processing of images, the SPM program was used, with the threshold of significance set at p < .001. We assessed activated brain areas during the two stimulation tasks and compared the activated regions between the two tasks. The prefrontal cortex and secondary visual cortex were activated bilaterally by both verbal and visual working memory tasks, and the patterns of activated signals were similar in both tasks. The superior parietal cortex was also activated by both tasks, with lateralization to the left in the verbal task, and bilaterally without lateralization in the visual task. The inferior frontal cortex, inferior parietal cortex and temporal gyrus were activated exclusively by the verbal working memory task, predominantly in the left hemisphere. The prefrontal cortex is activated by two stimulation tasks, and this is related to the function of the central executive. The language areas activated by the verbal working memory task may be a function of the phonological loop. Bilateral prefrontal and superior parietal cortices activated by the visual working memory task may be related to the visual maintenance of objects, representing visual working memory

  12. The Potential Impact of Biofield Treatment on Human Brain Tumor Cells: A Time-Lapse Video Microscopy

    Trivedi, Mahendra Kumar

    2015-01-01

    Study background: Glioblastoma (GBM) is the most common subtype of primary brain tumor in adults. The aim was to evaluate the impact of biofield treatment potential on human GBM and non-GBM brain cells using two time-lapse video microscopy technique. Methods: The human brain tumor, GBM cultured cells were divided into two groups viz. GBM control and GBM treatment. Similarly, human normal brain cultured cells (non-GBM) were taken and divided into two groups viz. non- GBM control ...

  13. Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain.

    Lake, Blue B; Ai, Rizi; Kaeser, Gwendolyn E; Salathia, Neeraj S; Yung, Yun C; Liu, Rui; Wildberg, Andre; Gao, Derek; Fung, Ho-Lim; Chen, Song; Vijayaraghavan, Raakhee; Wong, Julian; Chen, Allison; Sheng, Xiaoyan; Kaper, Fiona; Shen, Richard; Ronaghi, Mostafa; Fan, Jian-Bing; Wang, Wei; Chun, Jerold; Zhang, Kun

    2016-06-24

    The human brain has enormously complex cellular diversity and connectivities fundamental to our neural functions, yet difficulties in interrogating individual neurons has impeded understanding of the underlying transcriptional landscape. We developed a scalable approach to sequence and quantify RNA molecules in isolated neuronal nuclei from a postmortem brain, generating 3227 sets of single-neuron data from six distinct regions of the cerebral cortex. Using an iterative clustering and classification approach, we identified 16 neuronal subtypes that were further annotated on the basis of known markers and cortical cytoarchitecture. These data demonstrate a robust and scalable method for identifying and categorizing single nuclear transcriptomes, revealing shared genes sufficient to distinguish previously unknown and orthologous neuronal subtypes as well as regional identity and transcriptomic heterogeneity within the human brain. PMID:27339989

  14. Effects of frequency, irradiation geometry and polarisation on computation of sar in human brain

    The power absorbed by the human brain has possible implications in the study of the central nervous system-related biological effects of electromagnetic fields. In order to determine the specific absorption rate (SAR) of radio frequency (RF) waves in the human brain, and to investigate the effects of geometry and polarisation on SAR value, the finite-difference time-domain method was applied for the SAR computation. An anatomically realistic model scaled to a height of 1.70 m and a mass of 63 kg was selected, which included 14 million voxels segmented into 39 tissue types. The results suggested that high SAR values were found in the brain, i.e. ∼250 MHz for vertical polarisation and 900-1200 MHz both for vertical and horizontal polarisation, which may be the result of head resonance at these frequencies. (authors)

  15. Brain Response to a Humanoid Robot in Areas Implicated in the Perception of Human Emotional Gestures

    Chaminade, T.; Zecca, M; Blakemore, S. J.; Takanishi, A; Frith, C D; Micera, S.; Dario, P.; Rizzolatti, G.; V. Gallese; Umilta, M. A.

    2010-01-01

    Background: The humanoid robot WE4-RII was designed to express human emotions in order to improve human-robot interaction. We can read the emotions depicted in its gestures, yet might utilize different neural processes than those used for reading the emotions in human agents.Methodology: Here, fMRI was used to assess how brain areas activated by the perception of human basic emotions (facial expression of Anger, Joy, Disgust) and silent speech respond to a humanoid robot impersonating the sam...

  16. Neural plasticity in human brain connectivity: the effects of long term deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

    Tim J van Hartevelt

    Full Text Available BACKGROUND: Positive clinical outcomes are now well established for deep brain stimulation, but little is known about the effects of long-term deep brain stimulation on brain structural and functional connectivity. Here, we used the rare opportunity to acquire pre- and postoperative diffusion tensor imaging in a patient undergoing deep brain stimulation in bilateral subthalamic nuclei for Parkinson's Disease. This allowed us to analyse the differences in structural connectivity before and after deep brain stimulation. Further, a computational model of spontaneous brain activity was used to estimate the changes in functional connectivity arising from the specific changes in structural connectivity. RESULTS: We found significant localised structural changes as a result of long-term deep brain stimulation. These changes were found in sensory-motor, prefrontal/limbic, and olfactory brain regions which are known to be affected in Parkinson's Disease. The nature of these changes was an increase of nodal efficiency in most areas and a decrease of nodal efficiency in the precentral sensory-motor area. Importantly, the computational model clearly shows the impact of deep brain stimulation-induced structural alterations on functional brain changes, which is to shift the neural dynamics back towards a healthy regime. The results demonstrate that deep brain stimulation in Parkinson's Disease leads to a topological reorganisation towards healthy bifurcation of the functional networks measured in controls, which suggests a potential neural mechanism for the alleviation of symptoms. CONCLUSIONS: The findings suggest that long-term deep brain stimulation has not only restorative effects on the structural connectivity, but also affects the functional connectivity at a global level. Overall, our results support causal changes in human neural plasticity after long-term deep brain stimulation and may help to identify the underlying mechanisms of deep brain

  17. Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

    Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

    2013-01-01

    Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in v

  18. Differential synchronization in default and task-specific networks of the human brain

    Aaron Kirschner

    2012-05-01

    Full Text Available On a regional scale the brain is organized into dynamic functional networks. The activity within one of these, the default network, can be dissociated from that in other task-specific networks. All brain networks are connected structurally, but evidently are only transiently connected functionally. One hypothesis as to how such transient functional coupling occurs is that network formation and dissolution is mediated, or at least accompanied, by increases and decreases in oscillatory synchronization between constituent brain regions. If so, then we should be able to find transient differences in intra-network synchronization between the default network and a task-specific network. In order to investigate this hypothesis we conducted two experiments in which subjects engaged in a Sustained Attention to Response Task (SART while having brain activity recorded via high-density electroencephalography (EEG. We found that during periods when attention was focused internally (mind-wandering there was significantly more neural phase synchronization between brain regions associated with the default network, whereas during periods when subjects were focused on performing the visual task there was significantly more neural phase synchrony within a task-specific brain network that shared some of the same brain regions. These differences in network synchrony occurred in each of theta, alpha, and gamma frequency bands. A similar pattern of differential oscillatory power changes, indicating modulation of local synchronization by attention state, was also found. These results provide further evidence that the human brain is intrinsically organized into default and task-specific brain networks, and confirm that oscillatory synchronization is a potential mechanism for functional coupling within these networks.

  19. Expression of nestin by neural cells in the adult rat and human brain.

    Michael L Hendrickson

    Full Text Available Neurons and glial cells in the developing brain arise from neural progenitor cells (NPCs. Nestin, an intermediate filament protein, is thought to be expressed exclusively by NPCs in the normal brain, and is replaced by the expression of proteins specific for neurons or glia in differentiated cells. Nestin expressing NPCs are found in the adult brain in the subventricular zone (SVZ of the lateral ventricle and the subgranular zone (SGZ of the dentate gyrus. While significant attention has been paid to studying NPCs in the SVZ and SGZ in the adult brain, relatively little attention has been paid to determining whether nestin-expressing neural cells (NECs exist outside of the SVZ and SGZ. We therefore stained sections immunocytochemically from the adult rat and human brain for NECs, observed four distinct classes of these cells, and present here the first comprehensive report on these cells. Class I cells are among the smallest neural cells in the brain and are widely distributed. Class II cells are located in the walls of the aqueduct and third ventricle. Class IV cells are found throughout the forebrain and typically reside immediately adjacent to a neuron. Class III cells are observed only in the basal forebrain and closely related areas such as the hippocampus and corpus striatum. Class III cells resemble neurons structurally and co-express markers associated exclusively with neurons. Cell proliferation experiments demonstrate that Class III cells are not recently born. Instead, these cells appear to be mature neurons in the adult brain that express nestin. Neurons that express nestin are not supposed to exist in the brain at any stage of development. That these unique neurons are found only in brain regions involved in higher order cognitive function suggests that they may be remodeling their cytoskeleton in supporting the neural plasticity required for these functions.

  20. How do we make friends and why: An investigation into the human social brain

    Brockerhoff, Maja Andrea

    2008-01-01

    The Social Brain Hypothesis regards large social groups of primates and particularly in humans as the result of the development of cognitive skills necessary for social interactions. However, it has not yet been discovered how humans can maintain numerous social relationships at the same time, and why differences exist between the size and nature of peoples social networks. This study tested whether cognitive capacity, measured by general intelligence, accounts for differences in social netwo...

  1. Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain.

    Krienen, Fenna M; Yeo, B T Thomas; Ge, Tian; Buckner, Randy L; Sherwood, Chet C

    2016-01-26

    The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute's human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections. PMID:26739559

  2. Morphology cluster and prediction of growth of human brain pyramidal neurons★

    Yu, Chao; Han, Zengxin; Zeng, Wencong; Liu, Shenquan

    2012-01-01

    Predicting neuron growth is valuable to understand the morphology of neurons, thus it is helpful in the research of neuron classification. This study sought to propose a new method of predicting the growth of human neurons using 1 907 sets of data in human brain pyramidal neurons obtained from the website of NeuroMorpho.Org. First, we analyzed neurons in a morphology field and used an expectation-maximization algorithm to specify the neurons into six clusters. Second, naive Bayes classifier w...

  3. Reduced cell number in the neocortical part of the human fetal brain in Down syndrome

    Larsen, K.B.; Laursen, H.; Graem, N.;

    2008-01-01

    Mental retardation is seen in all individuals with Down syndrome (DS) and different brain abnormalities are reported. The aim of this study was to investigate if mental retardation at least in part is a result of a lower cell number in the neocortical part of the human fetal forebrain. We therefore...

  4. Anatomically matched short-echo time spectroscopy of human brain at 3T

    Mlynárik, V.; Gruber, S.; Stadlbauer, A.; Starčuk, Zenon; Moser, E.

    2003-01-01

    Roč. 16, Sup. 1 (2003), s. S205. E-ISSN 1352-8661. [ESMRMB 2003. 18.09.2003-21.09.2003, Rotterdam] Institutional research plan: CEZ:AV0Z2065902 Keywords : proton spectroscopic imaging * metabolite concentrations mapping * human brain Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

  5. Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants

    In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown. The objective of this study is to compare BDNF concentrations of subjects wi...

  6. Rethinking International Migration of Human Capital and Brain Circulation: The Case of Chinese-Canadian Academics

    Blachford, Dongyan Ru; Zhang, Bailing

    2014-01-01

    This article examines the dynamics of brain circulation through a historical review of the debates over international migration of human capital and a case study on Chinese-Canadian academics. Interviews with 22 Chinese-Canadian professors who originally came from China provide rich data regarding the possibilities and problems of the contemporary…

  7. Improvement of Motivation and Learning Level in Neuroanatomy Among Hamadan Medical Students Using Human Brain Sections

    2015-01-01

    Background Using new methods in teaching anatomy could have a significant impact on students’ learning. Objectives Neuroanatomy is one of the most complicated courses in anatomy. Absence of educational assistance equipment is one the most important problems in this field. Using human brain sections could solve some of the problems and enhance students’ learning. Materials and Methods ...

  8. In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

    Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

    2016-05-01

    High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining. PMID:26830089

  9. Human obesity associated with an intronic SNP in the brain-derived neurotrophic factor locus

    Brain-derived neurotrophic factor (BDNF) plays a key role in energy balance. In population studies, SNPs of the BDNF locus have been linked to obesity, but the mechanism by which these variants cause weight gain is unknown. Here, we examined human hypothalamic BDNF expression in association with 44 ...

  10. Sexual differentiation of the human brain: relevance for gender identity, transsexualism and sexual orientation.

    Swaab, D.F.

    2004-01-01

    Male sexual differentiation of the brain and behavior are thought, on the basis of experiments in rodents, to be caused by androgens, following conversion to estrogens. However, observations in human subjects with genetic and other disorders show that direct effects of testosterone on the developing

  11. Early gene response of human brain endothelial cells to Listeria monocytogenes

    The gene expression of human brain microvascular endothelial cells (HBMEC) to Listeria monocytogenes at 4 hour infection was analyzed. Four hours after infection, the expression of 456 genes of HBMEC had changed (p<0.05). We noted that many active genes were involved in the formyl-methionylleucylph...

  12. Gene × Smoking Interactions on Human Brain Gene Expression: Finding Common Mechanisms in Adolescents and Adults

    Wolock, Samuel L.; Yates, Andrew; Petrill, Stephen A.; Bohland, Jason W.; Blair, Clancy; Li, Ning; Machiraju, Raghu; Huang, Kun; Bartlett, Christopher W.

    2013-01-01

    Background: Numerous studies have examined gene × environment interactions (G × E) in cognitive and behavioral domains. However, these studies have been limited in that they have not been able to directly assess differential patterns of gene expression in the human brain. Here, we assessed G × E interactions using two publically available datasets…

  13. Language Impairments in ASD Resulting from a Failed Domestication of the Human Brain.

    Benítez-Burraco, Antonio; Lattanzi, Wanda; Murphy, Elliot

    2016-01-01

    Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders entailing social and cognitive deficits, including marked problems with language. Numerous genes have been associated with ASD, but it is unclear how language deficits arise from gene mutation or dysregulation. It is also unclear why ASD shows such high prevalence within human populations. Interestingly, the emergence of a modern faculty of language has been hypothesized to be linked to changes in the human brain/skull, but also to the process of self-domestication of the human species. It is our intention to show that people with ASD exhibit less marked domesticated traits at the morphological, physiological, and behavioral levels. We also discuss many ASD candidates represented among the genes known to be involved in the "domestication syndrome" (the constellation of traits exhibited by domesticated mammals, which seemingly results from the hypofunction of the neural crest) and among the set of genes involved in language function closely connected to them. Moreover, many of these genes show altered expression profiles in the brain of autists. In addition, some candidates for domestication and language-readiness show the same expression profile in people with ASD and chimps in different brain areas involved in language processing. Similarities regarding the brain oscillatory behavior of these areas can be expected too. We conclude that ASD may represent an abnormal ontogenetic itinerary for the human faculty of language resulting in part from changes in genes important for the "domestication syndrome" and, ultimately, from the normal functioning of the neural crest. PMID:27621700

  14. Coercion Changes the Sense of Agency in the Human Brain.

    Caspar, Emilie A; Christensen, Julia F; Cleeremans, Axel; Haggard, Patrick

    2016-03-01

    People may deny responsibility for negative consequences of their actions by claiming that they were "only obeying orders." The "Nuremberg defense" offers one extreme example, though it is often dismissed as merely an attempt to avoid responsibility. Milgram's classic laboratory studies reported widespread obedience to an instruction to harm, suggesting that social coercion may alter mechanisms of voluntary agency, and hence abolish the normal experience of being in control of one's own actions. However, Milgram's and other studies relied on dissembling and on explicit measures of agency, which are known to be biased by social norms. Here, we combined coercive instructions to administer harm to a co-participant, with implicit measures of sense of agency, based on perceived compression of time intervals between voluntary actions and their outcomes, and with electrophysiological recordings. In two experiments, an experimenter ordered a volunteer to make a key-press action that caused either financial penalty or demonstrably painful electric shock to their co-participant, thereby increasing their own financial gain. Coercion increased the perceived interval between action and outcome, relative to a situation where participants freely chose to inflict the same harms. Interestingly, coercion also reduced the neural processing of the outcomes of one's own action. Thus, people who obey orders may subjectively experience their actions as closer to passive movements than fully voluntary actions. Our results highlight the complex relation between the brain mechanisms that generate the subjective experience of voluntary actions and social constructs, such as responsibility. PMID:26898470

  15. [Brain oscillations and individual variability of cardiac defense in human].

    2013-11-01

    Cardiac defense response (CDR) is a specific dynamic pattern of the short- and long-latency cardiovascular reactivity (usually based on HR and/or arterial BP variables) in response an intense aversive unexpected stimulus. The CDR reflects activity of the defensive motivational system along with behavioral coping programs. The aim of the study was to estimate the putative contribution of brain oscillations into the central mechanisms of the CDR individual variability. EEG and cardiovascular concomitants of the CDR were estimated using the event-related synchroniza- tion/desynchronization (ERD/ERS) in different frequency bands as well as Finapres dependent variables obtained on the "beat-by-beat" basis. The first-ever findings evidenced significant cor- relations of the theta-2 (6-8 Hz) ERD/ERS with the sort-latency, whereas alpha-2 (10-12 Hz) ERD/ERS with the long-latency CDR variability. The hyperreactive long-latency systolic blood pressure CDR component was accompanied by the phase of deficient alpha-2 synchronization. It is suggested that upper theta oscillations are involved into central mechanisms scaling magnitude, whereas high frequency alpha oscillations may be responsible for the top-down inhibitory control of the short-and long-latency ABP stress-reactivity in the CDR. PMID:25507638

  16. High-field proton MRS of human brain

    Di Costanzo, Alfonso E-mail: alfonso.dicostanzo@unina2.it; Trojsi, F.; Tosetti, M.; Giannatempo, G.M.; Nemore, F.; Piccirillo, M.; Bonavita, S.; Tedeschi, G.; Scarabino, T

    2003-11-01

    Proton magnetic resonance spectroscopy ({sup 1}H-MRS) of the brain reveals specific biochemical information about cerebral metabolites, which may support clinical diagnoses and enhance the understanding of neurological disorders. The advantages of performing {sup 1}H-MRS at higher field strengths include better signal to noise ratio (SNR) and increased spectral, spatial and temporal resolution, allowing the acquisition of high quality, easily quantifiable spectra in acceptable imaging times. In addition to improved measurement precision of N-acetylaspartate, choline, creatine and myo-inositol, high-field systems allow the high-resolution measurement of other metabolites, such as glutamate, glutamine, {gamma}-aminobutyric acid, scyllo-inositol, aspartate, taurine, N-acetylaspartylglutamate, glucose and branched amino acids, thus extending the range of metabolic information. However, these advantages may be hampered by intrinsic field-dependent technical difficulties, such as decreased T2 signal, chemical shift dispersion errors, J-modulation anomalies, increased magnetic susceptibility, eddy current artifacts, limitations in the design of homogeneous and sensitive radiofrequency (RF) coils, magnetic field instability and safety issues. Several studies demonstrated that these limitations could be overcome, suggesting that the appropriate optimization of high-field {sup 1}H-MRS would expand the application in the fields of clinical research and diagnostic routine.

  17. High-field proton MRS of human brain

    Proton magnetic resonance spectroscopy (1H-MRS) of the brain reveals specific biochemical information about cerebral metabolites, which may support clinical diagnoses and enhance the understanding of neurological disorders. The advantages of performing 1H-MRS at higher field strengths include better signal to noise ratio (SNR) and increased spectral, spatial and temporal resolution, allowing the acquisition of high quality, easily quantifiable spectra in acceptable imaging times. In addition to improved measurement precision of N-acetylaspartate, choline, creatine and myo-inositol, high-field systems allow the high-resolution measurement of other metabolites, such as glutamate, glutamine, γ-aminobutyric acid, scyllo-inositol, aspartate, taurine, N-acetylaspartylglutamate, glucose and branched amino acids, thus extending the range of metabolic information. However, these advantages may be hampered by intrinsic field-dependent technical difficulties, such as decreased T2 signal, chemical shift dispersion errors, J-modulation anomalies, increased magnetic susceptibility, eddy current artifacts, limitations in the design of homogeneous and sensitive radiofrequency (RF) coils, magnetic field instability and safety issues. Several studies demonstrated that these limitations could be overcome, suggesting that the appropriate optimization of high-field 1H-MRS would expand the application in the fields of clinical research and diagnostic routine

  18. Brain antigens: components of subfractions from human grey matter

    Rajam, P. C.; Bogoch, S.

    1966-01-01

    1. Using chromatography on DEAE-cellulose, a neutral, low ionic strength extract of human grey matter has been separated into fractions of proteins with basic and progressively acidic groups. 2. The reactions of each group with rabbit antiserum against the original extract, in double-diffusion tests, suggest the presence of a minimum total of thirteen distinct antigens between them. These results are supported by immunoelectrophoretic findings, which indicate the basic group to contain five, and the progressively acidic group seven to eight distinct antigens. These antigens do not appear to be human serum proteins. 3. Antigens belonging to the BE class (resistant to boiling and relatively soluble in ethanol) are present among the progressively acidic proteins, and possibly among the basic proteins also. ImagesFIG. 2 PMID:4958737

  19. Brain connectivity reflects human aesthetic responses to music.

    Sachs, Matthew E; Ellis, Robert J; Schlaug, Gottfried; Loui, Psyche

    2016-06-01

    Humans uniquely appreciate aesthetics, experiencing pleasurable responses to complex stimuli that confer no clear intrinsic value for survival. However, substantial variability exists in the frequency and specificity of aesthetic responses. While pleasure from aesthetics is attributed to the neural circuitry for reward, what accounts for individual differences in aesthetic reward sensitivity remains unclear. Using a combination of survey data, behavioral and psychophysiological measures and diffusion tensor imaging, we found that white matter connectivity between sensory processing areas in the superior temporal gyrus and emotional and social processing areas in the insula and medial prefrontal cortex explains individual differences in reward sensitivity to music. Our findings provide the first evidence for a neural basis of individual differences in sensory access to the reward system, and suggest that social-emotional communication through the auditory channel may offer an evolutionary basis for music making as an aesthetically rewarding function in humans. PMID:26966157

  20. Neurophysiological origin of human brain asymmetry for speech and language

    Morillon, Benjamin; Lehongre, Katia; Frackowiak, Richard S. J.; Ducorps, Antoine; Kleinschmidt, Andréas Karl; Poeppel, David; Giraud Mamessier, Anne-Lise

    2010-01-01

    The physiological basis of human cerebral asymmetry for language remains mysterious. We have used simultaneous physiological and anatomical measurements to investigate the issue. Concentrating on neural oscillatory activity in speech-specific frequency bands and exploring interactions between gestural (motor) and auditory-evoked activity, we find, in the absence of language-related processing, that left auditory, somatosensory, articulatory motor, and inferior parietal cortices show specific,...

  1. Brain mechanisms underlying sensation-seeking in humans

    Norbury, A. E.

    2015-01-01

    Sensation-seeking is a personality trait concerned with motivation for intense and unusual sensory experiences, that has been identified as risk factor for a variety of psychopathologies with high social cost; in particular gambling and substance addictions. It has previously proved difficult to tease out neural mechanisms underlying sensation-seeking in humans, due to a lack of cognitive-behavioural paradigms probing sensation-seeking-like behaviour in the lab. The first aim of this thesis w...

  2. Brain mechanisms for processing perceived emotional vocalizations in humans

    Scott, S; Sauter, D.; McGettigan, C.

    2009-01-01

    Humans express emotional information in their facial expressions and body movements, as well as in their voice. In this chapter we consider the neural processing of a specific kind of vocal expressions, non-verbal emotional vocalizations e.g. laughs and sobs. We outline evidence, from patient studies and functional imaging studies, for both emotion specific and more general processing of emotional information in the voice. We relate these findings to evidence for both basic and dimensional ac...

  3. Neuronal Avalanches in the Resting MEG of the Human Brain

    Shriki, Oren; Alstott, Jeff; Carver, Frederick; Holroyd, Tom; Henson, Richard N. A.; Smith, Marie L.; Coppola, Richard; Bullmore, Edward,; Plenz, Dietmar

    2013-01-01

    What constitutes normal cortical dynamics in healthy human subjects is a major question in systems neuroscience. Numerous in vitro and in vivo animal studies have shown that ongoing or resting cortical dynamics are characterized by cascades of activity across many spatial scales, termed neuronal avalanches. In experiment and theory, avalanche dynamics are identified by two measures: (1) a power law in the size distribution of activity cascades with an exponent of −3/2 and (2) a branching para...

  4. Neurodegenerative diseases studied in human brain and rodent models

    Gellhaar, Sandra

    2015-01-01

    Parkinson’s and Alzheimer’s disease are the two most common neurodegenerative diseases world-wide, but are still little understood. Papers in this thesis examine some of the possible pathogenic mechanisms with the help of mouse models and analysis of human post-mortem tissue. Gene-based animal models have been developed to study pathological pathways during disease progression. Using mouse models with overexpression or ablation of disease-related genes we analyzed effects of pathogenic...

  5. Effects of Diet on Brain Plasticity in Animal and Human Studies: Mind the Gap

    Tytus Murphy

    2014-01-01

    Full Text Available Dietary interventions have emerged as effective environmental inducers of brain plasticity. Among these dietary interventions, we here highlight the impact of caloric restriction (CR: a consistent reduction of total daily food intake, intermittent fasting (IF, every-other-day feeding, and diet supplementation with polyphenols and polyunsaturated fatty acids (PUFAs on markers of brain plasticity in animal studies. Moreover, we also discuss epidemiological and intervention studies reporting the effects of CR, IF and dietary polyphenols and PUFAs on learning, memory, and mood. In particular, we evaluate the gap in mechanistic understanding between recent findings from animal studies and those human studies reporting that these dietary factors can benefit cognition, mood, and anxiety, aging, and Alzheimer’s disease—with focus on the enhancement of structural and functional plasticity markers in the hippocampus, such as increased expression of neurotrophic factors, synaptic function and adult neurogenesis. Lastly, we discuss some of the obstacles to harnessing the promising effects of diet on brain plasticity in animal studies into effective recommendations and interventions to promote healthy brain function in humans. Together, these data reinforce the important translational concept that diet, a modifiable lifestyle factor, holds the ability to modulate brain health and function.

  6. Effects of Diet on Brain Plasticity in Animal and Human Studies: Mind the Gap

    Dias, Gisele Pereira

    2014-01-01

    Dietary interventions have emerged as effective environmental inducers of brain plasticity. Among these dietary interventions, we here highlight the impact of caloric restriction (CR: a consistent reduction of total daily food intake), intermittent fasting (IF, every-other-day feeding), and diet supplementation with polyphenols and polyunsaturated fatty acids (PUFAs) on markers of brain plasticity in animal studies. Moreover, we also discuss epidemiological and intervention studies reporting the effects of CR, IF and dietary polyphenols and PUFAs on learning, memory, and mood. In particular, we evaluate the gap in mechanistic understanding between recent findings from animal studies and those human studies reporting that these dietary factors can benefit cognition, mood, and anxiety, aging, and Alzheimer's disease—with focus on the enhancement of structural and functional plasticity markers in the hippocampus, such as increased expression of neurotrophic factors, synaptic function and adult neurogenesis. Lastly, we discuss some of the obstacles to harnessing the promising effects of diet on brain plasticity in animal studies into effective recommendations and interventions to promote healthy brain function in humans. Together, these data reinforce the important translational concept that diet, a modifiable lifestyle factor, holds the ability to modulate brain health and function. PMID:24900924

  7. A geometric network model of intrinsic grey-matter connectivity of the human brain

    Lo, Yi-Ping; O'Dea, Reuben; Crofts, Jonathan J.; Han, Cheol E.; Kaiser, Marcus

    2015-10-01

    Network science provides a general framework for analysing the large-scale brain networks that naturally arise from modern neuroimaging studies, and a key goal in theoretical neuroscience is to understand the extent to which these neural architectures influence the dynamical processes they sustain. To date, brain network modelling has largely been conducted at the macroscale level (i.e. white-matter tracts), despite growing evidence of the role that local grey matter architecture plays in a variety of brain disorders. Here, we present a new model of intrinsic grey matter connectivity of the human connectome. Importantly, the new model incorporates detailed information on cortical geometry to construct ‘shortcuts’ through the thickness of the cortex, thus enabling spatially distant brain regions, as measured along the cortical surface, to communicate. Our study indicates that structures based on human brain surface information differ significantly, both in terms of their topological network characteristics and activity propagation properties, when compared against a variety of alternative geometries and generative algorithms. In particular, this might help explain histological patterns of grey matter connectivity, highlighting that observed connection distances may have arisen to maximise information processing ability, and that such gains are consistent with (and enhanced by) the presence of short-cut connections.

  8. Uptake and transport of superparamagnetic iron oxide nanoparticles through human brain capillary endothelial cells.

    Thomsen, L B; Linemann, T; Pondman, K M; Lichota, J; Kim, K S; Pieters, R J; Visser, G M; Moos, T

    2013-10-16

    The blood-brain barrier (BBB) formed by brain capillary endothelial cells (BCECs) constitutes a firm physical, chemical, and immunological barrier, making the brain accessible to only a few percent of potential drugs intended for treatment inside the central nervous system. With the purpose of overcoming the restraints of the BBB by allowing the transport of drugs, siRNA, or DNA into the brain, a novel approach is to use superparamagnetic iron oxide nanoparticles (SPIONs) as drug carriers. The aim of this study was to investigate the ability of fluorescent SPIONs to pass through human brain microvascular endothelial cells facilitated by an external magnet. The ability of SPIONs to penetrate the barrier was shown to be significantly stronger in the presence of an external magnetic force in an in vitro BBB model. Hence, particles added to the luminal side of the in vitro BBB model were found in astrocytes cocultured at a remote distance on the abluminal side, indicating that particles were transported through the barrier and taken up by astrocytes. Addition of the SPIONs to the culture medium did not negatively affect the viability of the endothelial cells. The magnetic force-mediated dragging of SPIONs through BCECs may denote a novel mechanism for the delivery of drugs to the brain. PMID:23919894

  9. A hyperspectral time resolved DOT system to monitor physiological changes of the human brain activity

    Lange, F.; Peyrin, F.; Montcel, B.

    2015-07-01

    Diffuse optical tomography (DOT) is a growing area of research in the field of biomedical optics and neurosciences. Over the past 20 years, technical development allowed a more and more accurate detection of the brain activation, both spatially and in the calculation of the variations of chromophores's concentrations such as Hemoglobin, cytochrome c oxidase, etc. In particular, time resolved systems are able to distinguish between superficial layers (skin, skull) and deep layers (brain) allowing the differentiation between the systemic response and the response of the brain. In order to increase the accuracy of the brain's activation detection, we have developed a Hyperspectral Time Resolved DOT system. It is composed of a compact supercontinuum laser within the picosecond range for the source part and of an ICCD camera coupled with an imaging spectrometer for the detection part. This allows a simultaneous detection of the spatial and spectral dimension, as well as the time of flight of photons. Through the information acquired by our system, we've been able to retrieve, to our knowledge, the first spectrum of the physiology of the human brain activity as function as depth. Here we present the instrument and show our first in-vivo results that are demonstrating its capabilities to distinguish between the skin's response and the brain's responses during a cognitive task. We are also focused on the detection of the Fast Optical Signal.

  10. Ad cerebrum per scientia: Ira Hirsh, psychoacoustics, and new approaches to understanding the human brain

    Lauter, Judith

    2002-05-01

    As Research Director of CID, Ira emphasized the importance of combining information from biology with rigorous studies of behavior, such as psychophysics, to better understand how the brain and body accomplish the goals of everyday life. In line with this philosophy, my doctoral dissertation sought to explain brain functional asymmetries (studied with dichotic listening) in terms of the physical dimensions of a library of test sounds designed to represent a speech-music continuum. Results highlighted individual differences plus similarities in terms of patterns of relative ear advantages, suggesting an organizational basis for brain asymmetries depending on physical dimensions of stimulus and gesture with analogs in auditory, visual, somatosensory, and motor systems. My subsequent work has employed a number of noninvasive methods (OAEs, EPs, qEEG, PET, MRI) to explore the neurobiological bases of individual differences in general and functional asymmetries in particular. This research has led to (1) the AXS test battery for assessing the neurobiology of human sensory-motor function; (2) the handshaking model of brain function, describing dynamic relations along all three body/brain axes; (3) the four-domain EPIC model of functional asymmetries; and (4) the trimodal brain, a new model of individual differences based on psychoimmunoneuroendocrinology.

  11. Intrinsic connectivity in the human brain does not reveal networks for 'basic' emotions.

    Touroutoglou, Alexandra; Lindquist, Kristen A; Dickerson, Bradford C; Barrett, Lisa Feldman

    2015-09-01

    We tested two competing models for the brain basis of emotion, the basic emotion theory and the conceptual act theory of emotion, using resting-state functional connectivity magnetic resonance imaging (rs-fcMRI). The basic emotion view hypothesizes that anger, sadness, fear, disgust and happiness each arise from a brain network that is innate, anatomically constrained and homologous in other animals. The conceptual act theory of emotion hypothesizes that an instance of emotion is a brain state constructed from the interaction of domain-general, core systems within the brain such as the salience, default mode and frontoparietal control networks. Using peak coordinates derived from a meta-analysis of task-evoked emotion fMRI studies, we generated a set of whole-brain rs-fcMRI 'discovery' maps for each emotion category and examined the spatial overlap in their conjunctions. Instead of discovering a specific network for each emotion category, variance in the discovery maps was accounted for by the known domain-general network. Furthermore, the salience network is observed as part of every emotion category. These results indicate that specific networks for each emotion do not exist within the intrinsic architecture of the human brain and instead support the conceptual act theory of emotion. PMID:25680990

  12. Prevalence of incidental findings on magnetic resonance imaging: Cuban project to map the human brain

    To determine the prevalence of incidental findings in healthy subjects of the Cuban Human Brain Mapping Project sample, it was performed a retrospective descriptive study of the magnetic resonance imaging (MRI) obtained from 394 healthy subjects that make up the sample of the project, between 2006-2007, with an age range of 18 to 68 years (mean 33,12), of which 269 (68,27 %) are male and 125 (31,73 %) are women. It was shown that 40,36 % had one or more anomaly in the magnetic resonance imaging (MRI). In total, the number of incidental findings was 188, 23,6 % of which were brain findings and 24,11 % were non-brain findings, among the latter, were the sinusopathy with 20,81 % and maxillary polyps with 3,30 %. The most prevalent brain findings were: intrasellar arachnoidocele, 11,93 %, followed by the prominence of the pituitary gland, 5,84 %, ventricular asymmetry, 1,77 % and bone defects, 1,02 %. Other brain abnormalities found with very low prevalence had no pathological significance, except for two cases with brain tumor, which were immediately sent to a specialist. Incidental findings in MRI are common in the general population (40,36 %), being the sinusopathy, and intrasellar arachnoidocele the most common findings. Asymptomatic individuals who have any type of structural abnormality provide invaluable information on the prevalence of these abnormalities in a presumably healthy population, which may be used as references for epidemiological studies

  13. Functional MRI studies of acupuncture analgesia modulating within the human brain

    Objective: To evaluate the correlation between acupuncture analgesia and specific functional areas of the brain using functional magnetic resonance imaging (fMRI). Methods: Acupuncture stimulation was induced by manipulating acupuncture needle at the acupuncture point, large intestine 4 (LI 4, Hegu) on the right (dominant) hand of 8 healthy subjects. Functional MRI data were obtained from scanning the whole brain. A block-design paradigm was applied. Functional responses were established by students' group t-test analysis. Results: The data sets from 6 of 8 subjects were used in the study. Signal increases and signal decreases elicited by acupuncture stimulating were demonstrated in multiple brain regions. Signal increases in periaqueductal gray matter and ventral posterior nucleus of the left thalamus, and signal decreases in bilateral anterior cingulate cortex and bilateral occipital lobes were considered as the response to the acupuncture modulating within the human brain. Conclusion: The therapeutic effect of acupuncture analgesia was probably produced by the interaction of multiple brain structures of functional connectivity rather than through the activation of a single brain region

  14. Brain expression genome-wide association study (eGWAS identifies human disease-associated variants.

    Fanggeng Zou

    Full Text Available Genetic variants that modify brain gene expression may also influence risk for human diseases. We measured expression levels of 24,526 transcripts in brain samples from the cerebellum and temporal cortex of autopsied subjects with Alzheimer's disease (AD, cerebellar n=197, temporal cortex n=202 and with other brain pathologies (non-AD, cerebellar n=177, temporal cortex n=197. We conducted an expression genome-wide association study (eGWAS using 213,528 cisSNPs within ± 100 kb of the tested transcripts. We identified 2,980 cerebellar cisSNP/transcript level associations (2,596 unique cisSNPs significant in both ADs and non-ADs (q<0.05, p=7.70 × 10(-5-1.67 × 10(-82. Of these, 2,089 were also significant in the temporal cortex (p=1.85 × 10(-5-1.70 × 10(-141. The top cerebellar cisSNPs had 2.4-fold enrichment for human disease-associated variants (p<10(-6. We identified novel cisSNP/transcript associations for human disease-associated variants, including progressive supranuclear palsy SLCO1A2/rs11568563, Parkinson's disease (PD MMRN1/rs6532197, Paget's disease OPTN/rs1561570; and we confirmed others, including PD MAPT/rs242557, systemic lupus erythematosus and ulcerative colitis IRF5/rs4728142, and type 1 diabetes mellitus RPS26/rs1701704. In our eGWAS, there was 2.9-3.3 fold enrichment (p<10(-6 of significant cisSNPs with suggestive AD-risk association (p<10(-3 in the Alzheimer's Disease Genetics Consortium GWAS. These results demonstrate the significant contributions of genetic factors to human brain gene expression, which are reliably detected across different brain regions and pathologies. The significant enrichment of brain cisSNPs among disease-associated variants advocates gene expression changes as a mechanism for many central nervous system (CNS and non-CNS diseases. Combined assessment of expression and disease GWAS may provide complementary information in discovery of human disease variants with functional implications. Our findings

  15. Human blood-brain barrier insulin-like growth factor receptor

    Insulin-like growth factor (IGF)-1 and IGF-2, may be important regulatory molecules in the CNS. Possible origins of IGFs in brain include either de novo synthesis or transport of circulating IGFs from blood into brain via receptor mediated transcytosis mechanisms at the brain capillary endothelial wall, ie, the blood-brain barrier (BBB). In the present studies, isolated human brain capillaries are used as an in vitro model system of the human BBB and the characteristics of IGF-1 or IGF-2 binding to this preparation were assessed. The total binding of IGF-2 at 37 degrees C exceeded 130% per mg protein and was threefold greater than the total binding for IGF-1. However, at 37 degrees C nonsaturable binding equaled total binding, suggesting that endocytosis is rate limiting at physiologic temperatures. Binding studies performed at 4 degrees C slowed endocytosis to a greater extent than membrane binding, and specific binding of either IGF-1 or IGF-2 was detectable. Scatchard plots for either peptide were linear and the molar dissociation constant of IGF-1 and IGF-2 binding was 2.1 +/- 0.4 and 1.1 +/- 0.1 nmol/L, respectively. Superphysiologic concentrations of porcine insulin inhibited the binding of both IGF-1 (ED50 = 2 micrograms/mL) and IGF-2 (ED50 = 0.5 microgram/mL). Affinity cross linking of 125I-IGF-1, 125I-IGF-2, and 125I-insulin to isolated human brain capillaries was performed using disuccinimidylsuberate (DSS). These studies revealed a 141 kd binding site for both IGF-1 and IGF-2, and a 133 kd binding site for insulin

  16. Changing Balance of Spinal Cord Excitability and Nociceptive Brain Activity in Early Human Development.

    Hartley, Caroline; Moultrie, Fiona; Gursul, Deniz; Hoskin, Amy; Adams, Eleri; Rogers, Richard; Slater, Rebeccah

    2016-08-01

    In adults, nociceptive reflexes and behavioral responses are modulated by a network of brain regions via descending projections to the spinal dorsal horn [1]. Coordinated responses to noxious inputs manifest from a balance of descending facilitation and inhibition. In contrast, young infants display exaggerated and uncoordinated limb reflexes [2]. Our understanding of nociceptive processing in the infant brain has been advanced by the use of electrophysiological and hemodynamic imaging [3-6]. From approximately 35 weeks' gestation, nociceptive-specific patterns of brain activity emerge [7], whereas prior to this, non-specific bursts of activity occur in response to noxious, tactile, visual, and auditory stimulation [7-10]. During the preterm period, refinement of spinal cord excitability is also observed: reflex duration shortens, response threshold increases, and improved discrimination between tactile and noxious events occurs [2, 11, 12]. However, the development of descending modulation in human infants remains relatively unexplored. In 40 infants aged 28-42 weeks' gestation, we examined the relationship between nociceptive brain activity and spinal reflex withdrawal activity in response to a clinically essential noxious procedure. Nociceptive-specific brain activity increases in magnitude with gestational age, whereas reflex withdrawal activity decreases in magnitude, duration, and latency across the same developmental period. By recording brain and spinal cord activity in the same infants, we demonstrate that the maturation of nociceptive brain activity is concomitant with the refinement of noxious-evoked limb reflexes. We postulate that, consistent with studies in animals, infant reflexes are influenced by the development of top-down inhibitory modulation from maturing subcortical and cortical brain networks. PMID:27374336

  17. Genetic contributions to human brain morphology and intelligence

    Hulshoff Pol, HE; Schnack, HG; Posthuma, D;

    2006-01-01

    .79), corticospinal tract (0.78, 0.79), medial frontal cortex (0.78, 0.83), superior frontal cortex (0.76, 0.80), superior temporal cortex (0.80, 0.77), left occipital cortex (0.85), left postcentral cortex (0.83), left posterior cingulate cortex (0.83), right parahippocampal cortex (0.69), and amygdala (0.80, 0.......55). Intelligence shared a common genetic origin with superior occipitofrontal, callosal, and left optical radiation WM and frontal, occipital, and parahippocampal GM (phenotypic correlations up to 0.35). These findings point to a neural network that shares a common genetic origin with human intelligence...

  18. Human neuronal changes in brain edema and increased intracranial pressure.

    Faragó, Nóra; Kocsis, Ágnes Katalin; Braskó, Csilla; Lovas, Sándor; Rózsa, Márton; Baka, Judith; Kovács, Balázs; Mikite, Katalin; Szemenyei, Viktor; Molnár, Gábor; Ozsvár, Attila; Oláh, Gáspár; Piszár, Ildikó; Zvara, Ágnes; Patócs, Attila; Barzó, Pál; Puskás, László G; Tamás, Gábor

    2016-01-01

    Functional and molecular changes associated with pathophysiological conditions are relatively easily detected based on tissue samples collected from patients. Population specific cellular responses to disease might remain undiscovered in samples taken from organs formed by a multitude of cell types. This is particularly apparent in the human cerebral cortex composed of a yet undefined number of neuron types with a potentially different involvement in disease processes. We combined cellular electrophysiology, anatomy and single cell digital PCR in human neurons identified in situ for the first time to assess mRNA expression and corresponding functional changes in response to edema and increased intracranial pressure. In single pyramidal cells, mRNA copy numbers of AQP1, AQP3, HMOX1, KCNN4, SCN3B and SOD2 increased, while CACNA1B, CRH decreased in edema. In addition, single pyramidal cells increased the copy number of AQP1, HTR5A and KCNS1 mRNAs in response to increased intracranial pressure. In contrast to pyramidal cells, AQP1, HMOX1and KCNN4 remained unchanged in single cell digital PCR performed on fast spiking cells in edema. Corroborating single cell digital PCR results, pharmacological and immunohistochemical results also suggested the presence of KCNN4 encoding the α-subunit of KCa3.1 channels in edema on pyramidal cells, but not on interneurons. We measured the frequency of spontaneous EPSPs on pyramidal cells in both pathophysiological conditions and on fast spiking interneurons in edema and found a significant decrease in each case, which was accompanied by an increase in input resistances on both cell types and by a drop in dendritic spine density on pyramidal cells consistent with a loss of excitatory synapses. Our results identify anatomical and/or physiological changes in human pyramidal and fast spiking cells in edema and increased intracranial pressure revealing cell type specific quantitative changes in gene expression. Some of the edema

  19. Study of cerebral metabolism of glucose in normal human brain correlated with age

    Full text: The objective was to determine whether cerebral metabolism in various regions of the brain differs with advancing age by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They (with the age ranging from 21 to 88; mean age+/-SD: 49.77+/-13.51) were selected with: (i)absence of clear focal brain lesions (epilepsy.cerebrovascular diseases etc);(ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes;(iii) absence of psychiatric disorders and abuse of drugs and alcohol. They were sub grouped into six groups with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose were matched. All subgroups were compared to the control group of 31-40 years old (84 samples; mean age+/-SD: 37.15+/-2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later, their brains were scanned for 10min. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2) .The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three-dimensional localized by MNI Space utility (MSU) software. Results:Relative hypometabolic brain areas detected are mainly in the cortical structures such as bilateral prefrontal cortex, superior temporal gyrus(BA22), parietal cortex (inferior parietal lobule and precuneus(BA40, insula(BA13)), parahippocampal gyrus and amygdala (p<0.01).It is especially apparent in the prefrontal cortex (BA9)and sensory-motor cortex(BA5, 7) (p<0.001), while basal ganglia and cerebellum remained metabolically unchanged with advancing age. Conclusions Regional cerebral metabolism of glucose shows a descent tendency with aging, especially in the prefrontal cortex (BA9)and

  20. New perspectives in EEG/MEG brain mapping and PET/fMRI neuroimaging of human pain.

    Chen, A C

    2001-10-01

    With the maturation of EEG/MEG brain mapping and PET/fMRI neuroimaging in the 1990s, greater understanding of pain processing in the brain now elucidates and may even challenge the classical theory of pain mechanisms. This review scans across the cultural diversity of pain expression and modulation in man. It outlines the difficulties in defining and studying human pain. It then focuses on methods of studying the brain in experimental and clinical pain, the cohesive results of brain mapping and neuroimaging of noxious perception, the implication of pain research in understanding human consciousness and the relevance to clinical care as well as to the basic science of human psychophysiology. Non-invasive brain studies in man start to unveil the age-old puzzles of pain-illusion, hypnosis and placebo in pain modulation. The neurophysiological and neurohemodynamic brain measures of experimental pain can now largely satisfy the psychophysiologist's dream, unimaginable only a few years ago, of modelling the body-brain, brain-mind, mind-matter duality in an inter-linking 3-P triad: physics (stimulus energy); physiology (brain activities); and psyche (perception). For neuropsychophysiology greater challenges lie ahead: (a) how to integrate a cohesive theory of human pain in the brain; (b) what levels of analyses are necessary and sufficient; (c) what constitutes the structural organisation of the pain matrix; (d) what are the modes of processing among and across the sites of these structures; and (e) how can neural computation of these processes in the brain be carried out? We may envision that modular identification and delineation of the arousal-attention, emotion-motivation and perception-cognition neural networks of pain processing in the brain will also lead to deeper understanding of the human mind. Two foreseeable impacts on clinical sciences and basic theories from brain mapping/neuroimaging are the plausible central origin in persistent pain and integration of