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1. Altered Modularity and Disproportional Integration in Functional Networks are Markers of Abnormal Brain Organization in Schizophrenia

Author

Cinelli, M., Echegoyen, I., Oliveira, M., Orellana, S., and Gili, T.

Subjects
Quantitative Biology - Neurons and Cognition, Physics - Biological Physics
Abstract

Modularity plays an important role in brain networks' architecture and influences its dynamics and the ability to integrate and segregate different modules of cerebral regions. Alterations in community structure are associated with several clinical disorders, specially schizophrenia, although its time evolution is not clear yet. In the present work, we analyze fMRI functional networks of $65$ healthy subjects (HC) and $44$ patients of schizophrenia (SZ), $28$ of them in a chronic state (CR) of illness, and $16$ at early stage (ES). We find clear differences in edges' weights distribution, networks density, community structure consistency and robustness against edge removal. In comparison to healthy subjects, we found that networks from SZ patients exhibits wider weight distribution, larger overall connectivity, and are more consistent in the community structure across subjects. We also showed that the networks of SZ patients tend to be more robust to edge removal than healthy subjects, while having lower network density. In the case of early stages patients, we found that their networks exhibit topological features consistently in between the ones obtained from the other two groups, resulting in a tendency towards the chronic group state., Comment: This work is the output of the Complexity72h workshop, held at IMT School in Lucca, 7-11 May 2018. https://complexity72h.weebly.com/

Published
2018

4. A community detection analysis of malocclusion classes from orthodontics and upper airway data

Author

Di Carlo, G, Gili, T, Caldarelli, G, Polimeni, A, Cattaneo, PM, Di Carlo, G, Gili, T, Caldarelli, G, Polimeni, A, and Cattaneo, PM

Abstract

OBJECTIVE: The interaction between skeletal class and upper airway has been extensively studied. Nevertheless, this relationship has not been clearly elucidated, with the heterogeneity of results suggesting the existence of different patterns for patients' classification, which has been elusive so far, probably due to oversimplified approaches. Hence, a network analysis was applied to test whether different patterns in patients' grouping exist. SETTINGS AND SAMPLE POPULATION: Ninety young adult patients with no obvious signs of respiratory diseases and no previous adeno-tonsillectomy procedures, with thirty patients characterized as Class I (0 < ANB < 4); 30 Class II (ANB > 4); and 30 as Class III (ANB < 0). MATERIALS AND METHODS: A community detection approach was applied on a graph obtained from a previously analysed sample: thirty-two measurements (nineteen cephalometric and thirteen upper airways data) were considered. RESULTS: An airway-orthodontic complex network has been obtained by cross-correlating patients. Before entering the correlation, data were controlled for age and gender using linear regression and standardized. By including or not the upper airway measurements as independent variables, two different community structures were obtained. Each contained five modules, though with different patients' assignments. CONCLUSION: The community detection algorithm found the existence of more than the three classical skeletal classifications. These results support the development of alternative tools to classify subjects according to their craniofacial morphology. This approach could offer a powerful tool for implementing novel strategies for clinical and research in orthodontics.

Published
2021

5. Polygenic burden in focal and generalized epilepsies

Author

Leu C., Stevelink R., Smith A. W., Goleva S. B., Kanai M., Ferguson L., Campbell C., Kamatani Y., Okada Y., Sisodiya S. M., Cavalleri G. L., Koeleman B. P. C., Lerche H., Jehi L., Davis L. K., Najm I. M., Palotie A., Daly M. J., Busch R. M., Lal D., Feng Y. -C. A., Howrigan D. P., Abbott L. E., Tashman K., Cerrato F., Churchhouse C., Gupta N., Neale B. M., Berkovic S. F., Goldstein D. B., Lowenstein D. H., Cossette P., Cotsapas C., De Jonghe P., Dixon-Salazar T., Guerrini R., Hakonarson H., Heinzen E. L., Helbig I., Kwan P., Marson A. G., Petrovski S., Kamalakaran S., Stewart R., Weckhuysen S., Depondt C., Dlugos D. J., Scheffer I. E., Striano P., Freyer C., Krause R., May P., McKenna K., Regan B. M., Bellows S. T., Bennett C. A., Johns E. M. C., Macdonald A., Shilling H., Burgess R., Weckhuysen D., Bahlo M., O'Brien T. J., Todaro M., Stamberger H., Andrade D. M., Sadoway T. R., Mo K., Krestel H., Gallati S., Papacostas S. S., Kousiappa I., Tanteles G. A., Sterbova K., Vlckova M., Sedlackova L., Lassuthova P., Klein K. M., Rosenow F., Reif P. S., Knake S., Kunz W. S., Zsurka G., Elger C. E., Bauer J., Rademacher M., Pendziwiat M., Muhle H., Rademacher A., Van Baalen A., Von Spiczak S., Stephani U., Afawi Z., Korczyn A. D., Kanaan M., Canavati C., Kurlemann G., Muller-Schluter K., Kluger G., Hausler M., Blatt I., Lemke J. R., Krey I., Weber Y. G., Wolking S., Becker F., Hengsbach C., Rau S., Maisch A. F., Steinhoff B. J., Schulze-Bonhage A., Schubert-Bast S., Schreiber H., Borggrafe I., Schankin C. J., Mayer T., Korinthenberg R., Brockmann K., Dennig D., Madeleyn R., Kalviainen R., Auvinen P., Saarela A., Linnankivi T., Lehesjoki A. -E., Rees M. I., Chung S. -K., Pickrell W. O., Powell R., Schneider N., Balestrini S., Zagaglia S., Braatz V., Johnson M. R., Auce P., Sills G. J., Baum L. W., Sham P. C., Cherny S. S., Lui C. H. T., Barisic N., Delanty N., Doherty C. P., Shukralla A., McCormack M., El-Naggar H., Canafoglia L., Franceschetti S., Castellotti B., Granata T., Zara F., Iacomino M., Madia F., Vari M. S., Mancardi M. M., Salpietro V., Bisulli F., Tinuper P., Licchetta L., Pippucci T., Stipa C., Muccioli L., Minardi R., Gambardella A., Labate A., Annesi G., Manna L., Gagliardi M., Parrini E., Mei D., Vetro A., Bianchini C., Montomoli M., Doccini V., Marini C., Suzuki T., Inoue Y., Yamakawa K., Birute T., Ruta M., Algirdas U., Ruta P., Jurgita G., Ruta S., Sadleir L. G., King C., Mountier E., Caglayan S. H., Arslan M., Yapici Z., Yis U., Topaloglu P., Kara B., Turkdogan D., Gundogdu-Eken A., Bebek N., Ugur-Iseri S., Baykan B., Salman B., Haryanyan G., Yucesan E., Kesim Y., Ozkara C., Sheidley B. R., Shain C., Poduri A., Buono R. J., Ferraro T. N., Sperling M. R., Lo W., Privitera M., French J. A., Schachter S., Kuzniecky R. I., Devinsky O., Hegde M., Khankhanian P., Helbig K. L., Ellis C. A., Spalletta G., Piras F., Gili T., Ciullo V., Leu C., Stevelink R., Smith A.W., Goleva S.B., Kanai M., Ferguson L., Campbell C., Kamatani Y., Okada Y., Sisodiya S.M., Cavalleri G.L., Koeleman B.P.C., Lerche H., Jehi L., Davis L.K., Najm I.M., Palotie A., Daly M.J., Busch R.M., Lal D., Feng Y.-C.A., Howrigan D.P., Abbott L.E., Tashman K., Cerrato F., Churchhouse C., Gupta N., Neale B.M., Berkovic S.F., Goldstein D.B., Lowenstein D.H., Cossette P., Cotsapas C., De Jonghe P., Dixon-Salazar T., Guerrini R., Hakonarson H., Heinzen E.L., Helbig I., Kwan P., Marson A.G., Petrovski S., Kamalakaran S., Stewart R., Weckhuysen S., Depondt C., Dlugos D.J., Scheffer I.E., Striano P., Freyer C., Krause R., May P., McKenna K., Regan B.M., Bellows S.T., Bennett C.A., Johns E.M.C., Macdonald A., Shilling H., Burgess R., Weckhuysen D., Bahlo M., O'Brien T.J., Todaro M., Stamberger H., Andrade D.M., Sadoway T.R., Mo K., Krestel H., Gallati S., Papacostas S.S., Kousiappa I., Tanteles G.A., Sterbova K., Vlckova M., Sedlackova L., Lassuthova P., Klein K.M., Rosenow F., Reif P.S., Knake S., Kunz W.S., Zsurka G., Elger C.E., Bauer J., Rademacher M., Pendziwiat M., Muhle H., Rademacher A., Van Baalen A., Von Spiczak S., Stephani U., Afawi Z., Korczyn A.D., Kanaan M., Canavati C., Kurlemann G., Muller-Schluter K., Kluger G., Hausler M., Blatt I., Lemke J.R., Krey I., Weber Y.G., Wolking S., Becker F., Hengsbach C., Rau S., Maisch A.F., Steinhoff B.J., Schulze-Bonhage A., Schubert-Bast S., Schreiber H., Borggrafe I., Schankin C.J., Mayer T., Korinthenberg R., Brockmann K., Dennig D., Madeleyn R., Kalviainen R., Auvinen P., Saarela A., Linnankivi T., Lehesjoki A.-E., Rees M.I., Chung S.-K., Pickrell W.O., Powell R., Schneider N., Balestrini S., Zagaglia S., Braatz V., Johnson M.R., Auce P., Sills G.J., Baum L.W., Sham P.C., Cherny S.S., Lui C.H.T., Barisic N., Delanty N., Doherty C.P., Shukralla A., McCormack M., El-Naggar H., Canafoglia L., Franceschetti S., Castellotti B., Granata T., Zara F., Iacomino M., Madia F., Vari M.S., Mancardi M.M., Salpietro V., Bisulli F., Tinuper P., Licchetta L., Pippucci T., Stipa C., Muccioli L., Minardi R., Gambardella A., Labate A., Annesi G., Manna L., Gagliardi M., Parrini E., Mei D., Vetro A., Bianchini C., Montomoli M., Doccini V., Marini C., Suzuki T., Inoue Y., Yamakawa K., Birute T., Ruta M., Algirdas U., Ruta P., Jurgita G., Ruta S., Sadleir L.G., King C., Mountier E., Caglayan S.H., Arslan M., Yapici Z., Yis U., Topaloglu P., Kara B., Turkdogan D., Gundogdu-Eken A., Bebek N., Ugur-Iseri S., Baykan B., Salman B., Haryanyan G., Yucesan E., Kesim Y., Ozkara C., Sheidley B.R., Shain C., Poduri A., Buono R.J., Ferraro T.N., Sperling M.R., Lo W., Privitera M., French J.A., Schachter S., Kuzniecky R.I., Devinsky O., Hegde M., Khankhanian P., Helbig K.L., Ellis C.A., Spalletta G., Piras F., Gili T., Ciullo V., Commission of the European Communities, Medical Research Council (MRC), Tumienė, Birutė, Mameniškienė, Rūta, Utkus, Algirdas, Praninskienė, Rūta, Grikinienė, Jurgita, Samaitienė-Aleknienė, Rūta, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, University of Helsinki, Helsinki Institute of Life Science HiLIFE, and Department of Medical and Clinical Genetics

Subjects
0301 basic medicine, Male, Multifactorial Inheritance, Epi25 Consortium, Databases, Factual, FEATURES, Genome-wide association study, Epilepsies, 3124 Neurology and psychiatry, Cohort Studies, Epilepsy, 0302 clinical medicine, Cost of Illness, 1ST SEIZURE, HISTORY, genetics, POPULATION, 11 Medical and Health Sciences, education.field_of_study, medicine.diagnostic_test, SCORES, Single Nucleotide, Biobank, 3. Good health, 17 Psychology and Cognitive Sciences, Genetic generalized epilepsy, Epilepsy, Generalized, Female, Partial, Cohort study, Human, medicine.medical_specialty, Population, European Continental Ancestry Group, Clinical Neurology, BIOBANK, Polymorphism, Single Nucleotide, epilepsy, genetic generalized epilepsy, common variant risk, Databases, 03 medical and health sciences, Genetic, Internal medicine, medicine, Journal Article, Genetics, Humans, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, Generalized epilepsy, education, SEIZURE RECURRENCE, Factual, METAANALYSIS, Genetic testing, Neurology & Neurosurgery, RISK PREDICTION, Generalized, business.industry, 3112 Neurosciences, Common variant risk, Genetic Variation, Original Articles, medicine.disease, Comorbidity, Cost of Illne, Epilepsies, Partial, Genome-Wide Association Study, 030104 developmental biology, Neurology (clinical), Cohort Studie, business, 030217 neurology & neurosurgery
Abstract

See Hansen and Møller (doi:10.1093/brain/awz318) for a scientific commentary on this article. Using polygenic risk scores from a genome-wide association study in generalized and focal epilepsy, Leu et al. reveal a significantly higher genetic burden for epilepsy in multiple cohorts of people with epilepsy compared to population controls. Quantification of common variant burden may be valuable for epilepsy prognosis and treatment., Rare genetic variants can cause epilepsy, and genetic testing has been widely adopted for severe, paediatric-onset epilepsies. The phenotypic consequences of common genetic risk burden for epilepsies and their potential future clinical applications have not yet been determined. Using polygenic risk scores (PRS) from a European-ancestry genome-wide association study in generalized and focal epilepsy, we quantified common genetic burden in patients with generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) from two independent non-Finnish European cohorts (Epi25 Consortium, n = 5705; Cleveland Clinic Epilepsy Center, n = 620; both compared to 20 435 controls). One Finnish-ancestry population isolate (Finnish-ancestry Epi25, n = 449; compared to 1559 controls), two European-ancestry biobanks (UK Biobank, n = 383 656; Vanderbilt biorepository, n = 49 494), and one Japanese-ancestry biobank (BioBank Japan, n = 168 680) were used for additional replications. Across 8386 patients with epilepsy and 622 212 population controls, we found and replicated significantly higher GE-PRS in patients with generalized epilepsy of European-ancestry compared to patients with focal epilepsy (Epi25: P = 1.64×10−15; Cleveland: P = 2.85×10−4; Finnish-ancestry Epi25: P = 1.80×10−4) or population controls (Epi25: P = 2.35×10−70; Cleveland: P = 1.43×10−7; Finnish-ancestry Epi25: P = 3.11×10−4; UK Biobank and Vanderbilt biorepository meta-analysis: P = 7.99×10−4). FE-PRS were significantly higher in patients with focal epilepsy compared to controls in the non-Finnish, non-biobank cohorts (Epi25: P = 5.74×10−19; Cleveland: P = 1.69×10−6). European ancestry-derived PRS did not predict generalized epilepsy or focal epilepsy in Japanese-ancestry individuals. Finally, we observed a significant 4.6-fold and a 4.5-fold enrichment of patients with generalized epilepsy compared to controls in the top 0.5% highest GE-PRS of the two non-Finnish European cohorts (Epi25: P = 2.60×10−15; Cleveland: P = 1.39×10−2). We conclude that common variant risk associated with epilepsy is significantly enriched in multiple cohorts of patients with epilepsy compared to controls—in particular for generalized epilepsy. As sample sizes and PRS accuracy continue to increase with further common variant discovery, PRS could complement established clinical biomarkers and augment genetic testing for patient classification, comorbidity research, and potentially targeted treatment.

Published
2019

6. Electrical conductivity of polyelectrolyte solutions in the semidilute and concentrated regime: the role of counterion condensation

Author

Bordi, F., Colby, R.H., Cametti, C., De Lorenzo, L., and Gili, T.

Subjects
Electrical conductivity -- Analysis, Polyelectrolytes -- Electric properties, Polyelectrolytes -- Research, Chemicals, plastics and rubber industries
Abstract

The salt-free electrical behavior of aqueous solutions of linear, flexible polyelectrolytes (sodium polyacrylate and poly(acrylic acid)), in a wide range of concentrations and molecular weights are investigated. The Newtonian viscosity measurement data and on the basis of the electrical conductivity behavior different concentration regimes are identified clearly.

Published
2002

11. Integrating Cytoarchitectonic Probabilities with MRI-Based Signal Intensities to Calculate Regional Volumes of Interest

Author

Spalletta, Gianfranco, Piras, Fabrizio, Gili, Tommaso, Spalletta, G ( Gianfranco ), Piras, F ( Fabrizio ), Gili, T ( Tommaso ), Kurth, Florian, Jäncke, Lutz, Luders, Eileen, Spalletta, Gianfranco, Piras, Fabrizio, Gili, Tommaso, Spalletta, G ( Gianfranco ), Piras, F ( Fabrizio ), Gili, T ( Tommaso ), Kurth, Florian, Jäncke, Lutz, and Luders, Eileen

Abstract

Hypotheses on specific brain structures are frequently assessed using anatomically defined regions of interest (ROIs) in structural T1-weighted images. The definition of these ROIs is often based on macroscopic landmarks (sulci, gyri, etc.) that do not necessarily coincide with the functional architecture of the brain. Microscopic labeling, on the other hand, enables a precise localization of anatomical boundaries. Thus, defining ROIs using cytoarchitectonic information might be a suitable alternative to the traditional landmark-based approach. In this chapter, we describe in detail how to perform such cytoarchitectonic ROI analyses by integrating voxel-wise cytoarchitectonic probabilities (using freely available maps created post mortem) with MR-based signal intensities (using standard T1-weighted data obtained in vivo). After elucidating common techniques to create ROIs (see Sect. 1), detailed information is provided with respect to the cytoarchitectonically defined probabilistic maps, i.e., the foundation for the proposed cytoarchitectonic ROI approach (see Sect. 2). The methodological aspects pertaining to this approach constitute the heart of the chapter and comprise three main steps: probability map selection, preprocessing, and integration (see Sect. 3). The chapter concludes with practical tips and helpful pointers for conducting a cytoarchitectonic ROI analysis (see Sect. 4).

Published
2018

13. Conductometric properties of linear polyelectrolytes in poor-solvent condition: The necklace model.

Author

Bordi, F., Cametti, C., Gili, T., Sennato, S., Zuzzi, S., Dou, S., and Colby, R. H.

Subjects
ELECTROLYTES, POLYMERS, SALT, MACROMOLECULES, SOLUTION (Chemistry), SOLVENTS
Abstract

We present a set of low-frequency electrical conductivity measurements of solutions of differently charged, salt-free polyelectrolytes in poor- and in good-solvent conditions, in the semidilute concentration regime. The data have been analyzed and discussed in light of the necklace model for hydrophobic polyelectrolytes recently proposed by Dobrynin et al. [Macromolecules 29, 2974 (1996)] that predicts the chains to collapse into spheroidal cores connected by narrow strings. By varying the quality of the solvent, we have measured the polyion equivalent conductance λp in an extended concentration range in the semidilute regime and have demonstrated that this parameter is influenced by the polyion chain conformation, giving further support, when the poor-solvent condition prevails, to the picture of a string of electrostatic blobs. On the contrary, in good-solvent condition, the electrical conductivity data are in reasonable good agreement with the picture of an extended chain consisting of a collection of electrostatic blobs. These electrical conductivity measurements, in light of scaling theory, furnish new experimental support for the necklace model for hydrophobic polyions in poor solvents. [ABSTRACT FROM AUTHOR]

Published
2005
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25. Trisomy (12p) with telocentric and pseudoisodicentric chromosome formation in a fetus

Author

Plaja A, Mediano C, Farran I, Vendrell T, Toran N, Gili T, M Angeles Sanchez-Duran, and Sarret E

Subjects
Adult, Chromosome Aberrations, Chromosomes, Human, Pair 12, Abortion, Induced, Chromosome Disorders, Gestational Age, Trisomy, Fetal Diseases, Fetus, Pregnancy, Face, Karyotyping, Amniocentesis, Humans, Abnormalities, Multiple, Female, Brachiocephalic Trunk
Abstract

We report an 18-week-old fetus with at 47, XY, -12, +12q, +psu idic(12p) karyotype, mild dysmorphic features and absence of the brachiocephalic truncus.

Published
1998

27. TOPEM: A multimodality probe (PET TOF, MRI, and MRS) for diagnosis and follow up of prostate cancer

Author

Garibaldi, F, primary, De Leo, R, additional, Ranieri, A, additional, Loddo, F, additional, Floresta, M, additional, Tamma, C, additional, Gabrielli, A, additional, Giorgi, F, additional, Cusanno, F, additional, Musico, P, additional, Perrino, R, additional, Finocchiaro, P, additional, Cosentino, L, additional, Pappalardo, A, additional, Meddi, F, additional, Maraviglia, B, additional, Giove, F, additional, Gili, T, additional, Capuani, S, additional, Turisini, M, additional, Clinthorne, N, additional, Huh, S, additional, Majewski, S, additional, Lucentini, M, additional, Gricia, M, additional, Giuliani, F, additional, and Monno, E, additional

Published
2010
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29. Variegated aneuploidy related to premature centromere division (PCD) is expressed in vivo and is a cancer-prone disease.

Author

Plaja, A., Vendrell, T., Smeets, D.F.C.M., Sarret, E., Gili, T., Catala, V., Mediano, C., Scheres, J.M.J.C., Plaja, A., Vendrell, T., Smeets, D.F.C.M., Sarret, E., Gili, T., Catala, V., Mediano, C., and Scheres, J.M.J.C.

Abstract

Item does not contain fulltext, We present three patients with variegated aneuploidy and premature centromere division (PCD), a rare chromosomal abnormality in humans. Comparison of these three and eight other patients with variegated aneuploidy related to PCD demonstrates a phenotype comprising most frequently microcephaly, CNS anomalies (with cerebellar affection and migration defects), mental retardation, pre-and postnatal growth retardation, flat and broad nasal bridge, apparently low-set ears, eye and skin abnormalities, and ambiguous genitalia in male patients. The occurrence of Wilms tumor in three patients, rhabdomyosarcoma in two others and acute leukemia in a fifth characterizes this condition as a chromosome or genome instability disorder with a high risk of malignancy. FISH studies in uncultured blood and buccal smear cells demonstrate that the random aneuploidies are not limited to cultured cells, but also occur in vivo.

Published
2001

42. Structural alteration of erythrocyte cell membrane in presence of artificial prostheses: A radiowave dielectric spectroscopy study

Author

Basoli, A., Bordi, F., Cametti, C., and Gili, T.

Abstract

The exposure of a biomaterial to blood gives rise to complex reactions playing an important role in many biological phenomena, such as the problem of biocompatibility and the mechanism of cardiovascular and thromboembolic diseases. In the present work, we use a frequencydomain dielectric spectroscopy approach to evaluate possible changes in the passive electrical parameters of the erythrocyte membrane, i.e., the membrane conductivity σsand the membrane permittivity s, after the insertion of a prosthesis mean implantation time 8 days in the circulatory system of patients treated for aortic aneurysm and the consequent interactions of erythrocyte cells with the biomaterial surface. We observe an increase of both the membrane conductivity and membrane permittivity, indicating changes at molecular level in the structural organization of the membrane. These membrane alterations can be viewed as precursory events for the initiation of the complex sequence of enzymatic reactions that take place on the material surface. Our results, although preliminary imply that a direct interaction between erythrocyte cell membrane and vascular prostheses may occur, causing a marked alteration in the electrical properties of the cell membrane. These findings might have relevant clinical implications and might offer possibilities to predict biocompatibility of biomaterials and give some further suggestions to resolve the problem of biomaterialassociated thrombogenicity. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 100–109, 2002

Published
2002
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44. The unbalanced reorganization of weaker functional connections induces the altered brain network topology in schizophrenia

Author

Fabrizio Piras, Nerisa Banaj, Rossana Mastrandrea, Tommaso Gili, Gianfranco Spalletta, Guido Caldarelli, Andrea Gabrielli, Mastrandrea, R., Piras, F., Gabrielli, A., Banaj, N., Caldarelli, G., Spalletta, G., and Gili, T.

Subjects
Male, 0302 clinical medicine, 0303 health sciences, Brain Mapping, Multidisciplinary, Functional integration (neurobiology), medicine.diagnostic_test, fMRI, Brain, Middle Aged, Magnetic Resonance Imaging, Settore FIS/02 - Fisica Teorica, Modelli e Metodi Matematici, Biological Physics (physics.bio-ph), Medicine, Female, Neurons and Cognition (q-bio.NC), Disconnection, Psychology, Human, Adult, Adolescent, Science, Schizophrenia (object-oriented programming), Complex networks, FOS: Physical sciences, Clustering, Article, Young Adult, 03 medical and health sciences, medicine, Connectome, Humans, Physics - Biological Physics, Condensed Matter - Statistical Mechanics, Aged, 030304 developmental biology, Allometry, Modularity (networks), Statistical Mechanics (cond-mat.stat-mech), Percolation (cognitive psychology), Brain functional network, Percolation, Robustness (evolution), Degree distribution, Quantitative Biology - Neurons and Cognition, FOS: Biological sciences, Schizophrenia, Nerve Net, Functional magnetic resonance imaging, Network Neuroscience, Neuroscience, 030217 neurology & neurosurgery
Abstract

Network neuroscience shed some light on the functional and structural modifications occurring to the brain associated with the phenomenology of schizophrenia. In particular, resting-state functional networks have helped our understanding of the illness by highlighting the global and local alterations within the cerebral organization. We investigated the robustness of the brain functional architecture in forty-four medicated schizophrenic patients and forty healthy comparators through an advanced network analysis of resting-state functional magnetic resonance imaging data. The networks in patients showed more resistance to disconnection than in healthy controls, with an evident discrepancy between the two groups in the node degree distribution computed along a percolation process. Despite a substantial similarity of the basal functional organization between the two groups, the expected hierarchy of healthy brains modular organization is crumbled in schizophrenia, showing a peculiar arrangement of the functional connections, characterized by several topologically equivalent backbones., Comment: 37 pages, 8 figures

Published
2021

45. Stairways to the brain: Transcutaneous spinal direct current stimulation (tsDCS) modulates a cerebellar-cortical network enhancing verb recovery

Author

Carlo Caltagirone, Tommaso Gili, Paola Marangolo, Valentina Fiori, Chiara Incoccia, Marangolo, P., Fiori, V., Caltagirone, C., Incoccia, C., and Gili, T.

Subjects
0301 basic medicine, Adult, Male, Cerebellum, Verb, Premotor cortex, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Language recovery, Neuromodulation, Aphasia, Neural Pathways, medicine, Humans, Molecular Biology, Aged, Language, Cerebral Cortex, Spinal cord, Brain Mapping, Spinal Cord Stimulation, Resting state fMRI, business.industry, General Neuroscience, Middle Aged, Magnetic Resonance Imaging, 030104 developmental biology, medicine.anatomical_structure, Thoracic vertebrae, Transcutaneous Electric Nerve Stimulation, Female, Neurology (clinical), medicine.symptom, business, Neuroscience, 030217 neurology & neurosurgery, Developmental Biology
Abstract

It has long been assumed that the language function is hierarchically organized into specific cortical areas. Here, for the first time, we present direct evidence that the spinal cord takes part in language processing. In a randomized-double blind design, sixteen aphasics underwent a language treatment combined with transcutaneous spinal direct current stimulation (tsDCS). During the treatment, each subject received tsDCS (20 min, 2 mA) over the thoracic vertebrae (IX-X vertebrae) in two different conditions: (1) anodal, and (2) sham while performing a verb naming task. Each experimental condition was run in five consecutive daily sessions over two weeks. Before and after each condition, all patients underwent a resting state functional magnetic resonance imaging (rs-fMRI). After anodal tsDCS, significant functional connectivity changes were found in a cerebellar-cortical network recruiting regions such as the left cerebellum, the right parietal and premotor cortex known to be also involved in action-related verb processing. Indeed, this increase of connectivity significantly correlated with the greatest amount of improvement found in verb naming. In line with our experimental data, we also found a greater improvement after anodal tsDCS also on untreated items of the language test but only on tasks which required the use of verbs, such as verb naming and picture description. No significant changes were found in noun naming. Thus, this evidence emphasizes, for the first time, that the neural response due to tsDCS combined with language treatment changes during the course of recovery by enhancing activity into cortical regions which influence verb processing.

Published
2019

46. Ultra-Rare Genetic Variation in the Epilepsies: A Whole-Exome Sequencing Study of 17,606 Individuals

Author

Yen-Chen Anne Feng, Daniel P. Howrigan, Liam E. Abbott, Katherine Tashman, Felecia Cerrato, Tarjinder Singh, Henrike Heyne, Andrea Byrnes, Claire Churchhouse, Nick Watts, Matthew Solomonson, Dennis Lal, Erin L. Heinzen, Ryan S. Dhindsa, Kate E. Stanley, Gianpiero L. Cavalleri, Hakon Hakonarson, Ingo Helbig, Roland Krause, Patrick May, Sarah Weckhuysen, Slavé Petrovski, Sitharthan Kamalakaran, Sanjay M. Sisodiya, Patrick Cossette, Chris Cotsapas, Peter De Jonghe, Tracy Dixon-Salazar, Renzo Guerrini, Patrick Kwan, Anthony G. Marson, Randy Stewart, Chantal Depondt, Dennis J. Dlugos, Ingrid E. Scheffer, Pasquale Striano, Catharine Freyer, Kevin McKenna, Brigid M. Regan, Susannah T. Bellows, Costin Leu, Caitlin A. Bennett, Esther M.C. Johns, Alexandra Macdonald, Hannah Shilling, Rosemary Burgess, Dorien Weckhuysen, Melanie Bahlo, Terence J. O’Brien, Marian Todaro, Hannah Stamberger, Danielle M. Andrade, Tara R. Sadoway, Kelly Mo, Heinz Krestel, Sabina Gallati, Savvas S. Papacostas, Ioanna Kousiappa, George A. Tanteles, Katalin Štěrbová, Markéta Vlčková, Lucie Sedláčková, Petra Laššuthová, Karl Martin Klein, Felix Rosenow, Philipp S. Reif, Susanne Knake, Wolfram S. Kunz, Gábor Zsurka, Christian E. Elger, Jürgen Bauer, Michael Rademacher, Manuela Pendziwiat, Hiltrud Muhle, Annika Rademacher, Andreas van Baalen, Sarah von Spiczak, Ulrich Stephani, Zaid Afawi, Amos D. Korczyn, Moien Kanaan, Christina Canavati, Gerhard Kurlemann, Karen Müller-Schlüter, Gerhard Kluger, Martin Häusler, Ilan Blatt, Johannes R. Lemke, Ilona Krey, Yvonne G. Weber, Stefan Wolking, Felicitas Becker, Christian Hengsbach, Sarah Rau, Ana F. Maisch, Bernhard J. Steinhoff, Andreas Schulze-Bonhage, Susanne Schubert-Bast, Herbert Schreiber, Ingo Borggräfe, Christoph J. Schankin, Thomas Mayer, Rudolf Korinthenberg, Knut Brockmann, Dieter Dennig, Rene Madeleyn, Reetta Kälviäinen, Pia Auvinen, Anni Saarela, Tarja Linnankivi, Anna-Elina Lehesjoki, Mark I. Rees, Seo-Kyung Chung, William O. Pickrell, Robert Powell, Natascha Schneider, Simona Balestrini, Sara Zagaglia, Vera Braatz, Michael R. Johnson, Pauls Auce, Graeme J. Sills, Larry W. Baum, Pak C. Sham, Stacey S. Cherny, Colin H.T. Lui, Nina Barišić, Norman Delanty, Colin P. Doherty, Arif Shukralla, Mark McCormack, Hany El-Naggar, Laura Canafoglia, Silvana Franceschetti, Barbara Castellotti, Tiziana Granata, Federico Zara, Michele Iacomino, Francesca Madia, Maria Stella Vari, Maria Margherita Mancardi, Vincenzo Salpietro, Francesca Bisulli, Paolo Tinuper, Laura Licchetta, Tommaso Pippucci, Carlotta Stipa, Raffaella Minardi, Antonio Gambardella, Angelo Labate, Grazia Annesi, Lorella Manna, Monica Gagliardi, Elena Parrini, Davide Mei, Annalisa Vetro, Claudia Bianchini, Martino Montomoli, Viola Doccini, Carla Marini, Toshimitsu Suzuki, Yushi Inoue, Kazuhiro Yamakawa, Birute Tumiene, Lynette G. Sadleir, Chontelle King, Emily Mountier, S. Hande Caglayan, Mutluay Arslan, Zuhal Yapıcı, Uluc Yis, Pınar Topaloglu, Bulent Kara, Dilsad Turkdogan, Aslı Gundogdu-Eken, Nerses Bebek, Sibel Uğur-İşeri, Betül Baykan, Barış Salman, Garen Haryanyan, Emrah Yücesan, Yeşim Kesim, Çiğdem Özkara, Annapurna Poduri, Beth R. Shiedley, Catherine Shain, Russell J. Buono, Thomas N. Ferraro, Michael R. Sperling, Warren Lo, Michael Privitera, Jacqueline A. French, Steven Schachter, Ruben I. Kuzniecky, Orrin Devinsky, Manu Hegde, Pouya Khankhanian, Katherine L. Helbig, Colin A. Ellis, Gianfranco Spalletta, Fabrizio Piras, Federica Piras, Tommaso Gili, Valentina Ciullo, Andreas Reif, Andrew McQuillin, Nick Bass, Andrew McIntosh, Douglas Blackwood, Mandy Johnstone, Aarno Palotie, Michele T. Pato, Carlos N. Pato, Evelyn J. Bromet, Celia Barreto Carvalho, Eric D. Achtyes, Maria Helena Azevedo, Roman Kotov, Douglas S. Lehrer, Dolores Malaspina, Stephen R. Marder, Helena Medeiros, Christopher P. Morley, Diana O. Perkins, Janet L. Sobell, Peter F. Buckley, Fabio Macciardi, Mark H. Rapaport, James A. Knowles, Ayman H. Fanous, Steven A. McCarroll, Namrata Gupta, Stacey B. Gabriel, Mark J. Daly, Eric S. Lander, Daniel H. Lowenstein, David B. Goldstein, Holger Lerche, Samuel F. Berkovic, Benjamin M. Neale, Wellcome Trust, Department of Health, Institute of Neurology, UCL, Imperial College Healthcare NHS Trust- BRC Funding, Commission of the European Communities, Medical Research Council (MRC), Feng Y.-C.A., Howrigan D.P., Abbott L.E., Tashman K., Cerrato F., Singh T., Heyne H., Byrnes A., Churchhouse C., Watts N., Solomonson M., Lal D., Heinzen E.L., Dhindsa R.S., Stanley K.E., Cavalleri G.L., Hakonarson H., Helbig I., Krause R., May P., Weckhuysen S., Petrovski S., Kamalakaran S., Sisodiya S.M., Cossette P., Cotsapas C., De Jonghe P., Dixon-Salazar T., Guerrini R., Kwan P., Marson A.G., Stewart R., Depondt C., Dlugos D.J., Scheffer I.E., Striano P., Freyer C., McKenna K., Regan B.M., Bellows S.T., Leu C., Bennett C.A., Johns E.M.C., Macdonald A., Shilling H., Burgess R., Weckhuysen D., Bahlo M., O'Brien T.J., Todaro M., Stamberger H., Andrade D.M., Sadoway T.R., Mo K., Krestel H., Gallati S., Papacostas S.S., Kousiappa I., Tanteles G.A., Sterbova K., Vlckova M., Sedlackova L., Lassuthova P., Klein K.M., Rosenow F., Reif P.S., Knake S., Kunz W.S., Zsurka G., Elger C.E., Bauer J., Rademacher M., Pendziwiat M., Muhle H., Rademacher A., van Baalen A., von Spiczak S., Stephani U., Afawi Z., Korczyn A.D., Kanaan M., Canavati C., Kurlemann G., Muller-Schluter K., Kluger G., Hausler M., Blatt I., Lemke J.R., Krey I., Weber Y.G., Wolking S., Becker F., Hengsbach C., Rau S., Maisch A.F., Steinhoff B.J., Schulze-Bonhage A., Schubert-Bast S., Schreiber H., Borggrafe I., Schankin C.J., Mayer T., Korinthenberg R., Brockmann K., Dennig D., Madeleyn R., Kalviainen R., Auvinen P., Saarela A., Linnankivi T., Lehesjoki A.-E., Rees M.I., Chung S.-K., Pickrell W.O., Powell R., Schneider N., Balestrini S., Zagaglia S., Braatz V., Johnson M.R., Auce P., Sills G.J., Baum L.W., Sham P.C., Cherny S.S., Lui C.H.T., Barisic N., Delanty N., Doherty C.P., Shukralla A., McCormack M., El-Naggar H., Canafoglia L., Franceschetti S., Castellotti B., Granata T., Zara F., Iacomino M., Madia F., Vari M.S., Mancardi M.M., Salpietro V., Bisulli F., Tinuper P., Licchetta L., Pippucci T., Stipa C., Minardi R., Gambardella A., Labate A., Annesi G., Manna L., Gagliardi M., Parrini E., Mei D., Vetro A., Bianchini C., Montomoli M., Doccini V., Marini C., Suzuki T., Inoue Y., Yamakawa K., Tumiene B., Sadleir L.G., King C., Mountier E., Caglayan S.H., Arslan M., Yapici Z., Yis U., Topaloglu P., Kara B., Turkdogan D., Gundogdu-Eken A., Bebek N., Ugur-Iseri S., Baykan B., Salman B., Haryanyan G., Yucesan E., Kesim Y., Ozkara C., Poduri A., Shiedley B.R., Shain C., Buono R.J., Ferraro T.N., Sperling M.R., Lo W., Privitera M., French J.A., Schachter S., Kuzniecky R.I., Devinsky O., Hegde M., Khankhanian P., Helbig K.L., Ellis C.A., Spalletta G., Piras F., Gili T., Ciullo V., Reif A., McQuillin A., Bass N., McIntosh A., Blackwood D., Johnstone M., Palotie A., Pato M.T., Pato C.N., Bromet E.J., Carvalho C.B., Achtyes E.D., Azevedo M.H., Kotov R., Lehrer D.S., Malaspina D., Marder S.R., Medeiros H., Morley C.P., Perkins D.O., Sobell J.L., Buckley P.F., Macciardi F., Rapaport M.H., Knowles J.A., Fanous A.H., McCarroll S.A., Gupta N., Gabriel S.B., Daly M.J., Lander E.S., Lowenstein D.H., Goldstein D.B., Lerche H., Berkovic S.F., Neale B.M., Epi25 Collaborative, YÜCESAN, EMRAH, Institute for Molecular Medicine Finland, Children's Hospital, HUS Children and Adolescents, Department of Medical and Clinical Genetics, University Management, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, and Genomics of Neurological and Neuropsychiatric Disorders

Subjects
s.berkovic@unimelb.edu.au [Epi25 Collaborative. Electronic address], 0301 basic medicine, GAMMA-2-SUBUNIT, burden analysi, DNA Mutational Analysis, PROTEIN, Neurodegenerative, VARIANTS, SUSCEPTIBILITY, Medical and Health Sciences, Epilepsy, 0302 clinical medicine, 2.1 Biological and endogenous factors, EPIDEMIOLOGY, Missense mutation, Exome, Aetiology, Genetics (clinical), Exome sequencing, 11 Medical and Health Sciences, seizures, GABRG2, Genetics, Genetics & Heredity, 0303 health sciences, biology, COMMON EPILEPSIES, 1184 Genetics, developmental biology, physiology, sequencing, Biological Sciences, Epi25 Collaborative, Phenotype, GENOME, epileptic encephalopathy, burden analysis, Neurological, Biotechnology, Genetic Markers, seizure, EEF1A2, Burden analysis, epilepsy, exome, Article, 03 medical and health sciences, Clinical Research, Exome Sequencing, Genetic variation, medicine, Humans, Genetic Predisposition to Disease, Gene, EPILEPTIC SEIZURES, METAANALYSIS, 030304 developmental biology, Human Genome, Neurosciences, Genetic Variation, 06 Biological Sciences, medicine.disease, Brain Disorders, 030104 developmental biology, Genetic marker, DE-NOVO MUTATIONS, Case-Control Studies, biology.protein, 3111 Biomedicine, Human medicine, 030217 neurology & neurosurgery
Abstract

Sequencing-based studies have identified novel risk genes for rare, severe epilepsies and revealed a role of rare deleterious variation in common epilepsies. To identify the shared and distinct ultra-rare genetic risk factors for rare and common epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,364 controls of European ancestry. We focused on three phenotypic groups; the rare but severe developmental and epileptic encephalopathies (DEE), and the commoner phenotypes of genetic generalized epilepsy (GGE) and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy, with the strongest enrichment seen in DEE and the least in NAFE. Moreover, we found that inhibitory GABAA receptor genes were enriched for missense variants across all three classes of epilepsy, while no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEE and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the top associations, including CACNA1G, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study confirms a convergence in the genetics of common and rare epilepsies associated with ultra-rare coding variation and highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology in the largest epilepsy WES study to date.

Published
2019

47. Moving Beyond the Brain: Transcutaneous Spinal Direct Current Stimulation in Post-Stroke Aphasia

Author

Paola Marangolo, Valentina Fiori, Jacob Shofany, Tommaso Gili, Carlo Caltagirone, Gabriella Cucuzza, Alberto Priori, Marangolo, Paola, Fiori, V, Shofany, J, Gili, T, Caltagirone, C, Cucuzza, G, and Priori, A.

Subjects
medicine.medical_treatment, aphasia, neurostimulation, spinal cord, stroke, transcutaneous spinal direct current stimulation, verb recovery, Verb, Cognitive neuroscience, Somatosensory system, 050105 experimental psychology, lcsh:RC346-429, 03 medical and health sciences, 0302 clinical medicine, Aphasia, Noun, Subject (grammar), medicine, 0501 psychology and cognitive sciences, Neurostimulation, lcsh:Neurology. Diseases of the nervous system, Original Research, 05 social sciences, Neurophysiology, Neurology, Settore MED/26 - Neurologia, Neurology (clinical), medicine.symptom, Psychology, Neuroscience, 030217 neurology & neurosurgery, Cognitive psychology
Abstract

Over the last 20 years, major advances in cognitive neuroscience have clearly shown that the language function is not restricted into the classical language areas but it involves brain regions, which had never previously considered. Indeed, recent lines of evidence have suggested that the processing of words associated to motor schemata, such as action verbs, modulates the activity of the sensorimotor cortex, which, in turn, facilitates its retrieval. To date, no studies have investigated whether the spinal cord, which is func- tionally connected to the sensorimotor system, might also work as an auxiliary support for language processing. We explored the combined effect of transcutaneous spinal direct current stimulation (tsDCS) and language treatment in a randomized double-blind design for the recovery of verbs and nouns in 14 chronic aphasics. During each treatment, each subject received tsDCS (20 min, 2 mA) over the thoracic vertebrae (10th vertebra) in three different conditions: (1) anodic, (2) cathodic and (3) sham, while performing a verb and noun naming tasks. Each experimental condition was run in five consecutive daily sessions over 3 weeks. Overall, a significant greater improvement in verb naming was found during the anodic condition with respect to the other two conditions, which per- sisted at 1 week after the end of the treatment. No significant differences were present for noun naming among the three conditions. The hypothesis is advanced that anodic tsDCS might have influenced activity along the ascending somatosensory pathways, ultimately eliciting neurophysiological changes into the sensorimotor areas which, in turn, supported the retrieval of verbs. These results further support the evidence that action words, due to their sensorimotor semantic properties, are partly represented into the sensorimotor cortex. Moreover, they also document, for the first time, that tsDCS enhances verb recov- ery in chronic aphasia and it may represent a promising new tool for language treatment.

Published
2017

48. Organization and hierarchy of the human functional brain network lead to a chain-like core

Author

Fabrizio Piras, Andrea Gabrielli, Tommaso Gili, Rossana Mastrandrea, Guido Caldarelli, Gianfranco Spalletta, Mastrandrea, R., Gabrielli, A., Piras, F., Spalletta, G., Caldarelli, G., and Gili, T.

Subjects
Male, FOS: Computer and information sciences, 0301 basic medicine, Nerve net, 0302 clinical medicine, Multidisciplinary, Hierarchy (mathematics), medicine.diagnostic_test, Brain, Middle Aged, Complex network, Healthy Volunteer, Magnetic Resonance Imaging, Healthy Volunteers, Settore FIS/02 - Fisica Teorica, Modelli e Metodi Matematici, medicine.anatomical_structure, Biological Physics (physics.bio-ph), Medicine, Female, Neurons and Cognition (q-bio.NC), RESTING-STATE FMRI, VON ECONOMO NEURONS, LOW-FREQUENCY, SMALL-WORLD, CONNECTIVITY, ARCHITECTURE, CORTEX, FLUCTUATIONS, INTEGRATION, CEREBELLUM, Human, Adult, Physics - Physics and Society, Science, Complex system, FOS: Physical sciences, Physics and Society (physics.soc-ph), Biology, Grey matter, Statistics - Applications, Article, 03 medical and health sciences, medicine, Humans, Applications (stat.AP), Physics - Biological Physics, Spanning tree, Quantitative Biology::Neurons and Cognition, business.industry, 030104 developmental biology, FOS: Biological sciences, Quantitative Biology - Neurons and Cognition, Artificial intelligence, Nerve Net, Centrality, business, Functional magnetic resonance imaging, Neuroscience, 030217 neurology & neurosurgery
Abstract

The brain is a paradigmatic example of a complex system: its functionality emerges as a global property of local mesoscopic and microscopic interactions. Complex network theory allows to elicit the functional architecture of the brain in terms of links (correlations) between nodes (grey matter regions) and to extract information out of the noise. Here we present the analysis of functional magnetic resonance imaging data from forty healthy humans at rest for the investigation of the basal scaffold of the functional brain network organization. We show how brain regions tend to coordinate by forming a highly hierarchical chain-like structure of homogeneously clustered anatomical areas. A maximum spanning tree approach revealed the centrality of the occipital cortex and the peculiar aggregation of cerebellar regions to form a closed core. We also report the hierarchy of network segregation and the level of clusters integration as a function of the connectivity strength between brain regions.

Published
2017

49. L-dopa preloading increases the uptake of boronophenylalanine in C6 glioma rat model: a new strategy to improve BNCT efficacy

Author

Silvia Capuani, Marco Colasanti, Paola Porcari, S. Russo, Francesco Pastore, Tommaso Gili, Emanuela D'Amore, Marco Bozzali, Cesare Cametti, Giuseppe Lazzarino, Giorgio Venturini, Bruno Maraviglia, Capuani, S, Gili, T, Bozzali, M, Russo, S, Porcari, P, Cametti, C, D'Amore, E, Colasanti, Marco, Venturini, Giorgio, Maraviglia, B, Lazzarino, G, and Pastore, Fs

Subjects
Boron Compounds, Male, Cancer Research, endocrine system, Phenylalanine, Rat model, Dopamine Agents, L-DOPA, Tumor cells, Boron Neutron Capture Therapy, GLIOBLASTOMA-MULTIFORME, C6-glioma, Pharmacology, High-performance liquid chromatography, C6 glioma, Levodopa, BNCT, C6-glioma, rat brain, L-DOPA, BPA, HPLC, MRI, Dielectric Spectroscopy, BRAIN-BARRIER DISRUPTION, rat brain, Medicine, Animals, Radiology, Nuclear Medicine and imaging, Tumor growth, BNCT, BPA, HPLC, MRI, Dielectric Spectroscopy, Incubation, Radiation, business.industry, Settore MED/27 - Neurochirurgia, Brain Neoplasms, NEUTRON-CAPTURE THERAPY, Brain, I CLINICAL-TRIAL, BORON-COMPOUNDS, Glioma, Membrane transport, In vitro, Rats, nervous system diseases, Oncology, business, Nuclear medicine
Abstract

"Purpose: Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on B-10(n, alpha)Li-7 reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of B-10 nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for B-10-drug 4-dihydroxy-borylphenylaianine (BPA) uptake in the C6-glioma model. The investigation was first performed in vitro and then extended to the animal model. Methods and Materials: BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectroscopy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All animals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. Results: L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. Conclusions: This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms. (C) 2008 Elsevier Inc."

Published
2008

50. Radiowave dielectric investigation of boron compounds distribution in cultured tumour cells: Relevance to boron neutron capture therapy

Author

Giorgio Venturini, Cesare Cametti, Tommaso Gili, Marco Colasanti, Bruno Maraviglia, Silvia Capuani, Massimo Muolo, Capuani, S, Gili, T, Cametti, C, Maraviglia, B, Colasanti, Marco, Muolo, M, and Venturini, Giorgio

Subjects
inorganic chemicals, Biodistribution, Radiochemistry, General Physics and Astronomy, chemistry.chemical_element, Dielectric, Cellular level, Dielectric spectroscopy, Borocaptate sodium, Neutron capture, chemistry, Distribution (pharmacology), Physical and Theoretical Chemistry, Boron
Abstract

The distribution of two main Boron neutron capture therapy (BNCT) agents, borocaptate sodium ( BSH ) and borono-phenylalanine ( BPA ), in C6 rat glioma cells has been investigated by means of radiowave dielectric spectroscopy measurements. Significant differences between cells treated with the two different boron carriers were found in the magnitude of passive electrical cell parameters. This technique offers a new procedure for the measurement of boron compounds interactions with different biological environments at cellular level and is suggested to have the potentiality for becoming an attractive tool for biodistribution studies of BNCT compounds in biological tissues.

Published
2002

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