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5. Fourth meeting of the European Neurological Society 25–29 June 1994 Barcelona, Spain: Abstracts of Symposia and free communications

Author

Harms, L., Bock, A., JÄnisch, W., Valdueza, J., Weber, J., Link, I., De Keyser, J., Goossens, A., Wilczak, N., Vedeler, C., Bjorge, L., Uvestad, E., Conti, G., Williams, K., Ginsberg, L., Rafique, S., Rapoport, S. I., Gershfeld, N. L., De La Meilleure, G., Crevits, L., Faiss, J. H., Heye, N., Blanke, J., Sackmann, A., Kastrup, O., Doornbos, R., van der Worp, H. B., Kappelle, L. J., Bar, P. R., Davie, C. A., Barker, G. J., Brenton, D., Miller, D. H., Thompson, A. J., Block, F., Schwarz, M., Delodovici, L., Baruzzi, F., Bonaldi, G., Dario, A., Marra, A., Mercuri, A., Dworzak, F., Cavallari, P., Confalonieri, P., Zuffi, M., Antozzi, C., Cornelio, F., Baldissera, F., Chassande, B., Ameri, A., Eymard, B., Poisson, M., Vérier, A., Brunet, P., Congia, S., Murgia, P. L., Cannas, A., Borghero, G., Uselli, S., Mellino, G., Ferrai, R., Lampis, R., Massa, R., Muzzetto, B., Giannini, F., Rossi, S., Cioni, R., d'Aniello, C., Guarneri, A., Battistini, N., Ceriani, F., Del Santo, A., Poloni, M., Campo, J. F., Iglesias, F., Guitera, M. V., Farinas, C., Pascual, J., Leno, C., Berciano, J., Thorpe, I. W., Kendall, B. E., McDonald, W. I., Moulignier, A., Dromer, F., Baudrimont, M., Dupont, B., Gozlan, J., El Amrani, M., Petit, J. C., Roullet, E., Sterzi, R., Causaran, R., Protti, A., Riva, M., Erminio, F., Arena, O., Villa, F., Maccagnano, E., Miletta, M., Spinelli, F., Ben-Hur, T., Weidenfeldl, J., Rao, N. S., Chari, C. C., Laforet, P., Matheron, S., Adams, D., Chemouilli, Ph., Desi, M., Said, G., Davous, P., Lionnet, F., Pulik, M., Genet, P., Rozenberg, F., Cartier, L. M., Castillo, J. L., Cea, J. G., Villagra, R., de Saint Martin, L., Mahieux, F., Manifacier, M. J., Mattos, K., Queiros, C., Publio, L., Vinhas, V., PeÇanha-Martins, A. C., Melo, A., Liska, U., Zifko, U., Budka, H., Drlicek, M., Grisold, W., Kaufmann, R., Kaiser, R., Czygan, M., Gomes, I., Jones, N., Cunha, S., EmbiruÇu, E. Katiane, Vieira, V., Araujo, I., Alexandra, M., Ferreira, A., Goes, J., Chemouilli, P., Israel-Biet, Masson, H., Lacroix, C., Gasnault, J., Hildebrandt-Müller, B., Oschmann, P., Krack, P., Willems, W. R., Dorndorf, W., Freitas, V., Bittencourt, A., Fernandes, D., Nascimento, M. H., Severo, M., Moraes, D., Muller, M., Hasert, K., Merkelbach, S., Schimrigk, K., van Oosten, B. W., Lai, M., Polman, C. H., Bertelsmann, F. W., Hodgkinson, S., Cabre, P. H., Volpe, L., Smadja, D., Vernant, J. P., Villaroya, H., Violleau, K., Younes-Chennoufi, A. Ben, Baumann, N., Villanueva-Hemandez, P., Ballabriga, J., Basart, E., Arbizu, T. X., Perez-Serra, J., Vinuels, F., Giron, J. M., Castilla, J. M., Redondo, L., Izquierdo, G., Lauer, K., Henneberg, A., Bittmann, N., Link, D., Wollinsky, K. H., Mobner, R., Fassbender, K., Kuhnen, J., Schwartz, A., Hennerici, M., Miller, A., Lider, O., Abramsky, O., Weiner, H. L., Offner, H., Vanderbark, A. A., Paoino, E., Fainardi, E., Addonizio, M. C., Ruppi, P., Tola, M. R., Granieri, E., Carreras, M., Sazdovitch, V., Joutel, A., Verdier-taillefer, M. H., Heinzlef, O., Radder, C., Tournier-Lasserve, E., Brenner, R. E., Munro, P. M. G., Williams, S. C. R., Bell, J. D., Hawkins, C. P., Filippi, M., Campi, A., Dousset, V., Canal, N., Comi, G., Zhu, J., Weber, F., Retska, R., List, J., Zhang, L., Brock, M., Taphoorn, M. J. B., Heimans, J. J., van der Veen, E. A., Karim, A. B. M. F., Sarazin, M., Argentino, N., Delattre, J. Y., Derkinderen, P., Buchwald, B., Schroter, G., Serve, G., Franke, C. H., Conrad, B., Kitchen, N. D., Thomas, D. G. T., Forman, A. D., Ang, Kie- Kian, Price, R., Stephens, C., Salmaggi, A., Nermni, R., Silvani, A., Forno, M. G., Luksch, R., Boiardi, A., Grzelec, H., Fryze, C., Nowacki, P., Zdziarska, B., Sanson, M., Merel, P., Richard, S., Rouleau, G., Thomas, G., Olsen, N. K., Pfeiffer, P., Egund, N., Bentzen, S. M., Johannesen, L., Mondrup, K., Rose, C., Zyluk, B., Wondrusch, E., Berger, O., Fast, N., Jellinger, K., Lindner, K., Urman, A., Thibault, J. L., Duyckaerts, Ch., Strik, H., Muller, B., Richter, E., Krauseneck, P., Steinbrecher, A., Schabet, M., Hess, C., Bamberg, M., Dichgans, J., Counsell, C. E., McLeod, M., Grant, R., Creel, G. B., Claus, D., Sieber, E., Engelhardt, A., Rechlin, T., Thierauf, P., Neubauer, U., Peresson, M., Di Giovacchino, G., Romani, G. L., Di Silverio, F., Danek, A., Kuffner, M., Hoermann, R., Schopohl, J., Laska, M., Heye, B., Zangaladze, A. T., Valls-SoIè, J., Cammarota, A., Alvarez, R., Tolosa, E., Hallett, M., Ulbricht, D., Ganslandt, O., Kober, H., Vieth, J., Grummich, P., Pongratz, H., Brigel, C., Fahlbusch, R., Serra, F. P., Palma, V., Nolfe, G., Buscaino, G. A., Rothstein, T. L., Gibson J. M., Morrison P. M., Collins A. D., Eiselt, M., Wagnur, H., Zwiener, U., Schindler, T., Efendi, H., Ertekin, C., Erfas, M., Larsson, L. E., Sirin, H., AraÇ, N., Toygar, A., Demir, Y., Seddigh, S., Vogt, T. H., Hundemer, H., Visbeck, A., Pastena, L., Faralli, F., Mainardi, G., Gagliardi, R., Linden, D., Berlit, P., Lopez, O. L., Becker, J. T., Jungreis, C., Brenner, R., Rezek, D., Dekesky, S. T., Estol, C., Boller, F., Fernandez, J. M., Mederer, S., Batlle, J., Turon, A., Codina, A., Hitzenberger, P., Vila, N., Valls-SolÇ, J., Chamorro, A., Pouget, J., Schmied, A., Morin, D., Azulay, J. Ph., Vedel, J. P., Montalt, J., Escudero, J., Barona, R., Campos, A., Varli, K., Ertem, E., Uludag, B., Yagiz, A., Privorkin, Z., Steinvil, Y., Kott, E., Combarros, O., Sanchez-Pernaute, R., Orizaola, P., Mokrusch, Th., Kutluaye, E., Selcuki, D., Ertikin, C., Zettl, U., Gold, R., Harvey, G. K., Hartung, H. P., Toyka, K. V., Wokke, J. H. J., Oey, P. L., Ippel, P. F., Jansen, G. H., Franssen, H., Toyooka, K., Fujimura, H., Ueno, S., Yoshikawa, H., Yorifuji, S., Yanagihara, T., Talamon, C., Tzourio, C., Kiefer, R., Jung, S., Toyka, K., Ruolt, I., Tranchant, C., Mohr, M., Warter, J. M., Younger, D. S., Rosoklija, G., Hays, A. P., Kurita, R., Hasegawa, O., Matsumto, M., Komiyama, A., Nara, Y., Oueslati, S., Belal, S., Turki, I., Ben Hamida, C., Hentati, F., Ben Hamida, M., Kwiecinski, H., Krolicki, L., Domzal-Stryga, A., Dellemijn, P. L. I., van Deventer, P., van Moll, B., Drogendijk, T., Vecht, Ch. J., Nemni S., Amadio, Fazio, R., Galardin, G., Delodovici, M. L., Peghi, E., Monticelli, M. L., Sessa, A., Viguera, M. L., Palomar, M., Gamez, J., Cervera, C., Navarro, C., Serena, J., Duran, I., Fernandez, A. L., Comabella, M., Nos, C., Rio, J., Montalban, J., Navarro, X., Verdu, E., Darbra, S., Buti, M., Mrabet, A., Fredj, M., Gouider, R., Tounsi, H., Khalfallah, N., Haddad, A., Dbaiss, T., Ghnassia, R., Rouillet, E., Chedru, F., Porsche, H., Strenge, H., Li, S. W., Young, Y. P., Garcia, A. A., Baron, P., Scarpini, E., Bianchi, R., Conti, A., Livraghi, S., Rees, J. H., Gregson, N. A., Hughes, R. A. C., Sedano, M. J., Calleja, J., Canga, E., Bahou, Y., Biary, N., Al Deeb, S. M., Guern, E. L. E., Gugenheim, M., Tardieu, S., Aisonobe, T. M., Agid, Y., Bouche, P., Brice, A., Rautenstrauss, B., Nelis, E., Grehl, H., Van Broeckhoven, C., Pfeiffer, R. A., Liehr, T., Ganzmann, E., Gehring, C., Neundörfer, B., Geremia, L., Doronzo, R., Sacilotto, G., Sergi, P., Pastorino, G. C., Scarlato, G., Planté-Bordeneuve, V., Mantel, A., Baas, F., Moser, H., Antonini, A., Psylla, M., Günther, I., Vontobell, P., Beer, H. F., Leenders, K. L., Chaudhuri, K. Ray, Parker, J., Pye, I. F., Millac, P. A. H., Abbott, R. J., Sutter, M., Albani, C., de Rijk, M. C., Breteler, M. M. B., Graveland, G. A., van der Mechè, F. G. A., Hofman, A., Keipes, M., Hilger, Ch., Diederich, N., Metz, H., Hentges, F., Pollak, P., Benabid, A. L., Limousin, P., Hoffmann, D., Benazzouz, A., Perret, J., Laihinen, A., Rinne, J. O., Ruottinen, H., Nagren, K., Lehikoinen, P., Oikonen, V., Ruotsalainen, U., Rinne, U. K., Cocozza, S., Pizzuti, A., Cavalcanti, F., Monticelli, A., Pianese, L., Redolfi, E., Paiau, F., Di Donato, S., Pandolfo, M., Palau, F., Monros, E., De Michele, G., Smeyers, P., Lopez-ArLandis, J., Uilchez, J., Filla, A., Genis, D., Matilla, T., Volpini, V., Blanchs, M. I., Davalos, A., Molins, A., Rosell, J., Estivill, X., De Jonghe, P., Smeyers, G., Krols, L., Mercelis, R., Hazan, J., Weissenbach, J., Martin, J. J., Warner, T. A. T., Williams, L., Orb, A. S., Harding, A. E., Giunti, P., Sweeney, M. G., Spadaro, M., Jodice, C., Novelletto, A., Malaspina, P., Frontali, M., Salmon, E., Gregoire, Del Fiore, Comar, Franck, G., Scheltens, P. H., Siegfried, K., Dartigues, E., De Deyn, P., Horn, R., Nelson, I., Hanna, M. G., Morgan-Hughes, J. A., Collinge, J., Palmer, M. S., Campbell, T., Mahal, S., Sidle, K., Humphreys, C., Tavitian, B., Pappata, S., Jobert, A., Crouzel, A. M., DiGiamberardino, L., Steimetz, G., Barbanti, P., Fabbrini, G., Salvatore, M., Buzzi, M. G., Di Piero, V., Petraroli, R., Sbriccoli, A., Pocchiari, M., Macchi, G., Lenzi, G. L., Spiegel, R., Maguire, P., Schmid, W., Ott, A., Bots, M. L., Grobbe, D. E., Hofman, A., Howard, R. S., Russell, S., Losseff, N., Hirsch, N. P., Couderc, R., Bailleul, S., Nargeot, M. C., Touchon, J., Picot, M. C., Rizzo, M., Watson, G., McGehee, D., Dingus, T., Kappos, L., Radü, E. W., Haas, J., Hartard, C. H., Spuler, S., Yousry, T., Voltz, R., Scheller, A., Holler, E., Hohlfeld, R., Scolding, N. J., Sussman, J., Kolar, O. J., Farlow, M. R., Rice, P. H., Zipp, F., Sotgiu, S., Weiss, E. H., Wekerle, H., Chalmers, R., Robertson, N., Compston, D. A. S., Martino, G., Clementi, E., Brambilla, E., Moiola, L., Martinelli, V., Colombo, B., Poggi, A., Rovaris, M., Grimaldi, L. M. E., Roth, M. P., Descoins, P., Ballivet, S., Ruidavets, J. B., Waubant, E., Nogueira, L., Cambon-Thomsen, A., Clanet, M., Leppert, D., Hauser, S., Lugaresi, A., Tartaro, A., D'aurelio, P., Befalo, L. L. O., Thomas, A., Malatesta, G., Gambi, D., Benedikz, J. E. G., Magnusson, H., Poser, C. M., Guomundsson, G., Bates, T. E., Davies, S. E. C., Clark, J. B., Landon, D. N., ùther, J. R., Rautenberg, W., Overgaard, K., Sereghy, T., Pedersen, H., Boysen, G., Diez-Tejedor, E., Carceller, F., Gutierrez, M., Lopez-Pajares, R., Roda, J. M., Chandra, B., Ricart, W., Gonzalez-Huix, F., Molina, A., Rundek, T., Demarin, V., De Reuck, J., Boon, P., Decoq, D., Strijckmans, K., Goethals, P., Lemahieu, I., Nibbio, A., Chabriat, H., Vahedi, K., Nagy, T., Verin, M., Mas, J. L., Julien, J., Ducrocq, X., Iba-Zizen, M. T., Cabanis, E. A., Bousser, M. G., Rolland, Y., Landgraf, F., Bompais, B., Lemaitre, M. H., Edan, G., Vorstrup, S., Knudsen, L., Olsen, K. Skovgaard, Videbaek, C., Schroeder, T., van Gijn, J., Jansen, H. M. L., Pruim, J., Paans, A. M. J., Willemsen, A. T. M., Hew, J. M., vd Vliet, A. M., Haaxma, R., Vaalburg, W., Minderhoud, J. M., Korf, J., Soudain, S. E., Ho, T. W., Mishu, B., Li, C. Y., Nachainkin, I., Gao, C. Y., Cornblath, D. R., Griffin, J. W., Asbury, A. K., Blaser, M. J., McKhann, G. M., Ho, T., Macko, C., Xue, P., Stadlan, E. M., Ramos-Alvarez, M., Valenciano, L., Visser, L. H., van der Meché, F. G. A., van Darn, P. A., Meulstee, J., Schmitz, P. I. M., Jacobs, B., Oomes, P. G., Kleyweg, R. P., Jacobs, B. C., Endtz, H. P., van Doorn, P. A., van der Mech, F. G. A., Van den Berg, L. H., Mollee, I., Logtenberg, T., Thomas, P. K., Plant, G., Baxter, P. J., Luis, R. Santiago, Matsumoto, M., Notermans, N. C., Wokke, J. H. J., Lokhorst, H. M., van der Graaf, Y., Jennekens, F. G. I., Azulay, J. P., Bille-Turg, F., Valentin, P., Farnarier, G. G., Pellissier, J. F., Serratrice, G., Quasthoff, S., Schneider, U., Grafe, P., Hilkens, P. H. E., Moll, J. W. B., van der Burg, M. E. L., Planting, A. S. T., van Putten, W. L. J., van den Bent, M. J., Birklein, F., Spitzer, A., Lang, E., Neundorfer, B., Diehl, R. R., Lücke, D., Smith, G. D. P., Mathias, C. J., Serra, J., Campera, M., Ochoa, J. L., Ray Chaudhuri, K., Pavitt, D., Alam, M., Handwerker, H. O., Bleasdale-Barr, K., Smith, G., Murray, N. M. F., Hawkins, P., Pepys, M., Gellera, C., DiDonato, S., Taroni, F., Uncini, A., Di Muzio, A., Servidei, S., Silvestri, G., Lodi, R., Iotti, S., Barbiroli, B., Morrissey, S. P., Borruat, F. X., Francis, D., Mosely, I., Hansen, H. C., Helmke, K., Kunze, K., Sadzot, B., Maquet, P., Lemaire, Plenevaux, Damhaut, Sommer, C., Myers, R. R., Berta, E., Mantegazza, R., Argov, Z., Shapira, Y., Wirguin, I., Beuuer, J., Franke, C., Roberts, M., Willison, H., Vincent, A., Newsom-Davis, J., Morrison, K. E., Damels, R., Francis, M., Campbell, L., Davies, K. E., Kohler, W., Bucka, C., Hertel, G., Kanovsky, P., Auer, D., Ackermann, H., Klose, U., Naegele, Th., Bien, S., Voigt, K., Fink, G. R., Stephan, K. M., Wise, R. J. S., Mullatti, N., Hewer, L., Frackowiak, R. S. J., Weiller, C. S., Rijnites, M., Jueptner, M., Bauermann, T., Krams, M., Diener, H. C., van Walderveen, M. A. A., Barkhof, F., Hommes, O. R., Valk, J., Willmer, J. P., Guzman, D. A., Passingham, R. E., Silbersweig, D., Ceballos-Baumann, A., Frith, C. D., Frackowiak, R., Lucas, C. H., Goullard, L., Marchau, M. J., Godefroy, O., Rondepierre, P. H., Chamas, E., Mounier-Vehier, F., Leys, D., Renato, J., Verdugo, M. S. C., Campero, M., Jose, L., Ochoa, D. S. C., Vivancos, F., Tejedor, E. Diez, Martinez, N., Roda, J., Frank, A., Barreiro, P., Satoh, Y., Nagata, K., Maeda, T., Hirata, Y., YalÇinerner, B., Ozkara, C., Ozer, F., Ozer, S., Hanoglu, L., Zunker, P., Pozo, J. L., Oberwittler, C., Schick, A., Buschmann, H. -Ch., Ringelstein, E. Bernd, Lara, M., Anzola, G. P., Magoni, M., Volta, G. Dalla, Tarasov, A., Feigin, V., Beaudry, M. G., Carrier, S., Chicoutimi, Henriques, I. L., Bogoussslavsky, J., van Melle, G., Mathieu, J., Perusse, L., Allard, P., Prevost, C., Cantin, L., Bouchard, J. M., De Braekeleer, M., Agbo, C., Neau, J. P., Tantot, A. M., Dary-Auriol, M., Ingrand, P., Gil, R., Baltadjiev, D., Zekin, D., Sabey, K., Gennaula, C. P., Pope, B. A., Caparros-Lefebvre, D., Girard-Buttaz, I., Pruvo, J. P., Petit, H., Hipola, D., Martin, M., Giménez-Roldan, S., Ivanez, V., Japaridze, G., Carrasco, J. L., Picomell, I., Herranz, J. L., Macias, J. A., Nieto, M., Noya, M., Oller, L., Kiteva-Trencevska, G., Delgado, M. R., Liu, H., Luengo, A., Parra, J., Colas, J., Fernandez, M. J., Manzanares, R., Kornhuber, M. E., Malashkhia, V., Orkodashili, G., Martinez, M., Bonaventura, I., Porta, G., Martinez, I., Fernandez, A., Aguilar, M., Masnou, P., Drouet, A., Dreyfus, M., Cartron, J., Morel-Kopp, M. C., Tchernia, G., Kaplan, C., Lammers, M. W., Hekster, Y. A., Keyser, A., Meinardi, H., Renier, W. O., Boon, P. A. J. M., Have, M. D., Kint, B., Cruz, P., Cadilha, A., Almeida, R., Goncalves, M., Pimenta, M., Ramos, L. M. P., Polder, T. W., Broere, C. A., Polman, L., Rother, I., Rother, M., Schlaug, G., Arnold, S., Holthausen, H., Wunderlich, G., Ebner, A., Luders, H., Witte, O. W., Seitz, R. J., Serra, L. L., Gallicchio, B., Rotondi, F., Wieshmann, U., Meierkord, H., Sabev, K., Di Carlo, V., Gueguen, B., Derouesné, Ch., Ancri, D., Bourdel, M. C., Guillou, S., Aliaga, R., Chornet, M. A., Rodrigo, A., Pascual, A. Pascual -Leone, Catala, M. D., Pascual-Leone, A., Benbadis, S. R., Dinner, D. S., Chelune, G. J., Lüders, H. O., Piedmonte, M. R., Blanco, T., Lopez, M. P., Romero, B., Deltoro, A., Pascual, A., Pascual, Leone, Bolgert, F., Josse, M. O., Tassan, P., Touze, E., Laplane, D., Godenberg, F., Brizioli, E., Del Gobbo, M., Pelliccioni, G., Scarpino, O., Durak, H., Damlacik, G., Tunca, Z., Fidaner, H., Yurekli, Y., Yemez, B., Kaygisiz, A., Anllo, E. A., Esperet, E., Giovagnoli, A. R., Casazza, M., Spreafico, R., Avanzini, G., Mascheroni, S., Vecchio, I., Tornali, C., Antonuzzo, A., Grasso, A. A., Bella, R., Pennisi, G., Raffaele, R., Broeckx, J., Schildermans, F., Hospers, W., Deberdt, W., Carney, J. M., Aksenova, M., Chen, M. S., Juncadella, M., Busquets, N., De la Fuente, I., Rodriguez, A., Rubio, F., Soler, R., Khati, C., Pillon, B., Deweer, B., Malapani, C., Malichard, N., Dubois, B., Rancurel, G., Lopez, D. L., Jungreia, G., DeKosky, S. T., Boiler, F., Weiller, C., Rijntjes, M., Mueller, S. P., Maguire, E. A., Burke, E. T., Staunton, H., Phillips, J., Rousseaux, M., Pena, J., Bertran, I., Santacruz, P., Lopez, R., Catafau, A., Lomena, F., Blesa, R., Rampello, L., Nicoletti, A., Cabaret, M., Lesoin, F., Steinling, M., Tournev, I., Maier-Hauff, K., Schroeder, M., Wolf, A., Cochin, J. P., Noel, I., Augustin, P., Auzou, P., Hannequin, D., Maria, V., Lopez-Bresnahan, Danielle, D. M., Antin-Ozerkis B. A., Bartels, E., Rodiek, S. O., Flugel, K. A., Campos, D. M., Salas-Puig, J., Del Rio, J. Sanhez, Vidal, J. A., Lahoz, C. H., Eraksoy, M., Barlas, O., Barlas, M., Bayindir, C., Ozcan, H., Birbamer, G., Gerstenbrand, F., Felber, S., Luz, G., Aichner, F., Seidel, G., Kaps, M., Hutzelmann, A., Gerriets, T., Kruggel, F., Martin, P. J., Gaunt, M. E., Abbot, R. J., Naylor, A. R., Meary, E., Dilouya, A., Meder, J. F., De Recondo, J., Lebtahi, R., Neff, K. W., Meairs, S., Viola, S., Matta, E., Aquilone, L., Rise, I. R., Authier, F. J., Kondo, H., Ghnassia, R. T., Degos, J. D., Gherardi, R. K., Bardoni A., Ciafaloni E., Comi G. P., Bresolin N., Robotti M., Moggio M., Rigoletto C., Roses A., Scarlato G., Castelli, E., Turconi, A., Bresolin, N., Perani, D., Felisari, G., Chariot, P., de Pinieux, G., Astier, A., Jacotot, B., Gherardi, R., Fischer-Gagnepain, V., Louboutin, J. P., Crespo, F., Florea-Strat, A., Fromont, G., Sabourin, J. -C., Gonano, E. -F., Moroni, I., Prelle, A., Iannaccone, S., Quattrini, A., deRino, F., Sessa, M., Golzi, V., Smirne, S., Nemni, R., Turpin, J. C., Lucotte, G., Jacobs, S. C. J. M., Willems, P. W. A., Bootsma, A. L., Lasa, A., Calaf, M., Baiget, M., Gallano, B., Fichter-Gagnepain, V., Mazzucchelli, F., D'Angelo, M. G., Velicogna, M., Bet, L., Comi, G. P., Bordoni, A., Gonano, E. F., Bazzi, P., Rapuzzi, S., Moggio, M., Fagiolari, G., Ciscato, P., Messina, A., Battistel, A., Ryniewicz, B., Sangla, I., Desnuelle, C., Paquis, V., Cozzone, P. J., Bendahan, D., Sturenburg, H. 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L., Constantin, C., Cassatella, M. A., Langdon, D. W., Webb, S., Gasparini, P., Zeviani, A., Kidd, D., Mammi, S., Cahalon, L., Hershkoviz, R., Lahat, N., Wallach, D., Annunziata, P., Martino, T., Maimone, D., Guazzi, G. C., Porrini, A. M., Dell'Arciprete, L., Rothwell, P. M., Stewart, R. R. C., Cull, R. E., Willmes, K., Poeck, K., Russell, D., Braekken, S. K., Brucher, R., Svennevig, J., Hermesl, M., Bruckmann, H., Biraben, A., Sliwka, U., Meyer, B., Schondube, F., Noth, J., Lavenu, I., Lammers, C., Waldecker, B., Haberbosch, W., Stam, J., Schneider, R., Gautier, J. C., Berlit, T. P., Fauser, B., Kuhne, D., Geraud, G., Danielli, A., Larrue, V., Bes, A., Timmerman, E., Bono, F., Bruni, A. C., Valalentino, P., Montesi, M. P., Talerico, G., Zappia, M., Sabatelli, M., Quattrone, A., Pareyson, D., Lorenzetti, D., Sghirlanzoni, A., Castellotti, B., Lupski, J. R., Archidiacono, N., Antonacci, R., Marzella, R., Rocchi, M., Samuel, D., Goulon-Goeau, C., Costa, P. 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M., Pleiffer, G., Kunre, K., Dieterich, M., Brandt, Th., Guarino, M., Stracciari, A., Pazzaglia, P., D'Alessandro, R., Santilli, I., Donato, M., The European Velnacrine Study Group, The Dutch Guillain-Barré study group, The COP-1 Multicenter Clinical and Research Group Study, and European Study Group

Published
1994
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10. Migraine and REM Sleep Behaviour Disorder: A Common Pathogenesis?

Author

Burcu Polat, Taskin D, Şirin Akbulut Demirci, Hanoglu L, Agargun My, Acarel E, Tavli Am, Ertugrul Eo, Yilmaz Nh, and Yavasoglu Oh

Subjects
medicine.medical_specialty, Pediatrics, Neurology, medicine.diagnostic_test, business.industry, Polysomnography, medicine.disease, Screening questionnaire, Migraine, medicine, Sleep behavior, Statistical analysis, Psychiatry, business
Abstract

Background: REM sleep behaviour disorder (RBD) and migraine are two different disorders that originate from the brainstem. Aim: To examine the relationship between the two diseases. Settings and Design: Patients attending the neurology clinics of Istanbul Medipol University, Medipol Kosuyolu Hospital and Karabuk University. Materials and Methods: The study was conducted in two parts: in the first part, migraine patients were assessed for RBD with a screening questionnaire (RBDSQ). Patients with a score of 5 or higher, meaning they were diagnosed with ‘dream-enacting behaviour’, were called on the phone and recommended to undergo a polysomnography (PSG). In the second part of the study, the patients who agreed to participate were taken a one-night PSG to assess RBD. Results: Of the 230 people who answered the RBDSQ, 51 (22.2%) scored 5 or higher. One hundred ninety-one (83%) were women and 39 (17%) were men. Eleven patients agreed to take PSG. Six (54.5%) were diagnosed with RBD. Statistical analysis: The data were evaluated with SPSS 16.0. Student’s t tests and Mann-Whitney U tests were used to compare the two independent groups and chi-square test was used to compare categorical variables. Conclusions: Among migraine sufferers, which are common in society, the prevalence of RBD is high. The problem of misdiagnosis may be due to the mild clinical symptoms of RBD in females, who are predominant among those with migraine.

Published
2017
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14. Plasma homocysteine levels in patients treated with levodopa: motor and cognitive associations

Author

Ozer, F., Meral, H., and Hanoglu, L.

Subjects
Dopa -- Research, Motor ability -- Research, Parkinson's disease -- Research -- Care and treatment, Homocysteine -- Research, Health, Care and treatment, Research
Abstract

OBJECTIVE: The aim of this study was to determine whether hyperhomocysteinemia caused by levodopa used in idiopathic Parkinson's disease (IPD) is associated with cognitive or physical impairments. The role of [...]

Published
2007

18. Surgical Outcome of Epilepsy Patients Evaluated with a Noninvasive Protocol

Author

Aysin Dervent, Lutfu Hanoglu, Filiz Onat, Cengiz Kuday, Cigdem Ozkara, Emin Ozyurt, Mine Ozmen, Esat Eşkazan, Naci Kocer, Buge Oz, Ozkara, C, Ozyurt, E, Hanoglu, L, Eskazan, E, Dervent, A, Kocer, N, Ozmen, M, Onat, F, Oz, B, and Kuday, C

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Turkey, SURGERY, LOBECTOMY, Neuropsychological Tests, Hippocampus, AMYGDALOHIPPOCAMPECTOMY, Functional Laterality, Temporal lobe, Epilepsy, amygdalo-hippocampectomy, TUMOR, TEMPORAL-LOBE EPILEPSY, medicine, Humans, Ictal, Epilepsy surgery, EEG, Child, Electrocorticography, Cerebral Cortex, Hippocampal sclerosis, ELECTROCORTICOGRAPHY, LESIONS, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Perioperative, Amygdala, medicine.disease, Magnetic Resonance Imaging, Surgery, Treatment Outcome, Neurology, hippocampal sclerosis, epilepsy surgery, Female, Neurology (clinical), SEIZURE ONSET, business, MRI
Abstract

Surgery is now an accepted treatment for some medically intractable epilepsies. Presurgical evaluation is particularly important for the localization of the epileptogenic zone, which may necessitate sophisticated imaging techniques and intracranial electroencephalogram (EEG) recordings. If patients are carefully selected, however, successful results can be achieved with noninvasive evaluation methods. Seventy-seven patients were operated on for intractable seizures. All patients underwent EEG, neuropsychological, psychiatric, and magnetic resonance imaging investigations. Ictal EEG-video recording was performed in all nonlesional and in some lesional cases that had discordant data. Selective amygdalo-hippocampectomy was performed on patients with mesial temporal lobe epilepsy (MTLE), an extended or a limited lesionectomy was performed on patients with structural lesions, and a lesionectomy with deafferentation was performed on two patients with West syndrome. Electrocorticography was not used. Temporal lobe directed surgery was performed in 63.6% of the cases. The pathological examinations of all cases showed hippocampal sclerosis (HS) in 43%, tumor or tumor-like lesions in 36%, and cortical dysplasia in 5% of patients. After a mean follow-up of 17 months (range, 2-53), 75% of the patients were seizure-free with or without aura and 15% had a marked improvement, whereas 10% did not benefit from surgery. Neuropsychological outcome of patients with MTLE and I-IS also showed worthwhile results. Our patients, who were evaluated without pre- and perioperative intracranial recordings and other sophisticated techniques, had an outcome comparable to those in other series from more experienced centers. Our experience indicates that successful results, especially for patients with MTLE-HS and lesion-related epilepsies, can be obtained at centers with limited resources if the diagnoses and evaluation procedures are performed carefully.

Published
2000
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19. Hippocampal connectivity dynamics and volumetric alterations predict cognitive status in migraine: A resting-state fMRI study.

Author

Cankaya S, Ayyildiz B, Sayman D, Duran U, Ucak D, Karaca R, Ayyildiz S, Oktem EO, Lakadamyalı H, Sayman C, Ozsimsek A, Yalçınkaya A, Hanoglu L, Velioglu HA, and Yulug B

Abstract

The etiology of cognitive decline linked to migraine remains unclear, with a growing recurrence rate and potential increased dementia risk among sufferers. Cognitive dysfunction has recently gained attention as a significant problem among migraine sufferers that can be related to alterations in hippocampal function and structure. This study explores hippocampal subfield connectivity and volume changes in migraine patients. We recruited 90 individuals from Alanya University's Neurology Department, including 49 migraine patients and 41 controls, for functional and anatomical imaging. Using the CONN toolbox and FreeSurfer, we assessed functional connectivity and subfield volumes, respectively. Montreal Cognitive Assessment (MOCA) was used to assess cognition in the entire sample. As a result, migraine patients exhibited significantly lower MOCA scores compared to controls (p<.001). Also, we found significant differences in hippocampal subfields between migraine patients and control groups in terms of functional connectivity after adjusting for years of education; here we showed that the left CA3 showed higher connectivity with right MFG and right occipitolateral cortex. Furthermore, the connectivity of left fimbria with the left temporal lobe and hippocampus and the connectivity of the right hippocampal-tail with right insula, heschl's gyrus, and frontorbital cortex were lower in the migraineurs. Additionally, volumes of specific hippocampal subfields were significantly lower in the migraineurs (whole hippocampus p = 0.004, whole hippocampus head p = 0.003, right CA1 head p = 0.006, and right HATA p = 0.005) compared to controls. In conclusion, these findings indicate that migraine-associated cognitive impairment involves significant functional and structural brain changes, particularly in the hippocampus, which may heighten dementia risk. This pioneering study unveils critical hippocampal alterations linked to cognitive function in migraine sufferers, underscoring the potential for these changes to impact dementia development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Published
2024
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20. Visuoperceptual rehabilitation with repetitive transcranial magnetic stimulation in chronic cortical blindness: a case report.

Author

Erkan Ogul O, Yılmaz S, Duz OA, Senturk F, and Hanoglu L

Subjects
Aged, Humans, Chronic Disease, Visual Fields physiology, Visual Perception physiology, Blindness, Cortical rehabilitation, Blindness, Cortical etiology, Neurological Rehabilitation methods, Transcranial Magnetic Stimulation
Abstract

This study aims to reveal the effect of visuoperceptual rehabilitation combined with neuromodulation on visual impairment recovery in chronic cortical blindness. A 71-year-old patient with cortical blindness was assessed using perimetry, pattern electroretinogram (pERG), Canadian Occupational Performance Measurement (COPM), and Montreal Cognitive Assessment (MoCA) at baseline and after treatment. After 12 rTMS sessions and 50 visual perceptual rehabilitation sessions, perimetry, pERG, COPM, and MoCA significantly improved the visual field and daily functioning. Both COPM-MoCA scores exceeded clinical significance. The results indicate that combining vision therapy with rTMS may improve vision field, daily function, and satisfaction in a chronic blindness case.

Published
2024
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21. Multi-omics analysis reveals the key factors involved in the severity of the Alzheimer's disease.

Author

Meng L, Jin H, Yulug B, Altay O, Li X, Hanoglu L, Cankaya S, Coskun E, Idil E, Nogaylar R, Ozsimsek A, Shoaie S, Turkez H, Nielsen J, Zhang C, Borén J, Uhlén M, and Mardinoglu A

Subjects
Humans, Female, Male, Aged, Severity of Illness Index, Artificial Intelligence, Aged, 80 and over, Biomarkers blood, Metagenomics methods, Multiomics, Alzheimer Disease genetics, Alzheimer Disease microbiology, Alzheimer Disease metabolism, Alzheimer Disease blood, Proteomics, Metabolomics methods, Gastrointestinal Microbiome
Abstract

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder with a global impact, yet its pathogenesis remains poorly understood. While age, metabolic abnormalities, and accumulation of neurotoxic substances are potential risk factors for AD, their effects are confounded by other factors. To address this challenge, we first utilized multi-omics data from 87 well phenotyped AD patients and generated plasma proteomics and metabolomics data, as well as gut and saliva metagenomics data to investigate the molecular-level alterations accounting the host-microbiome interactions. Second, we analyzed individual omics data and identified the key parameters involved in the severity of the dementia in AD patients. Next, we employed Artificial Intelligence (AI) based models to predict AD severity based on the significantly altered features identified in each omics analysis. Based on our integrative analysis, we found the clinical relevance of plasma proteins, including SKAP1 and NEFL, plasma metabolites including homovanillate and glutamate, and Paraprevotella clara in gut microbiome in predicting the AD severity. Finally, we validated the predictive power of our AI based models by generating additional multi-omics data from the same group of AD patients by following up for 3 months. Hence, we observed that these results may have important implications for the development of potential diagnostic and therapeutic approaches for AD patients., (© 2024. Crown.)

Published
2024
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22. Parietal memory network and memory encoding versus retrieval impairments in PD-MCI patients: A hippocampal volume and cortical thickness study.

Author

Sahin S, Velioglu HA, Yulug B, Bayraktaroglu Z, Yildirim S, and Hanoglu L

Subjects
Humans, Male, Female, Aged, Middle Aged, Parietal Lobe pathology, Parietal Lobe diagnostic imaging, Atrophy pathology, Cerebral Cortex diagnostic imaging, Cerebral Cortex pathology, Brain Cortical Thickness, Hippocampus pathology, Hippocampus diagnostic imaging, Parkinson Disease pathology, Parkinson Disease diagnostic imaging, Parkinson Disease complications, Cognitive Dysfunction pathology, Cognitive Dysfunction diagnostic imaging, Cognitive Dysfunction physiopathology, Cognitive Dysfunction etiology, Mental Recall physiology, Memory Disorders etiology, Memory Disorders pathology, Memory Disorders diagnostic imaging, Magnetic Resonance Imaging
Abstract

Objective: The pathophysiology behind memory impairment in Parkinson's Disease Mild Cognitive Impairment (PD-MCI) is unclear. This study aims to investigate the hippocampal and cortical atrophy patterns in PD-MCI patients with different types of memory impairments, categorized as Retrieval Failure (RF) and Encoding Failure (EF)., Methods: The study included 16 healthy controls (HC) and 34 PD-MCI patients, divided into RF (N = 18) and EF (N = 16) groups based on their Verbal Memory Processes Test (VMPT) scores, including spontaneous recall, recognition, and Index of Sensitivity to Cueing (ISC). Hippocampal subfields and cortical thicknesses were measured using the FreeSurfer software for automatic segmentation., Results: Compared to the HC group, the EF group exhibited significant atrophy in the left lateral occipital region and the right caudal middle frontal, superior temporal, and inferior temporal regions (p⟨0.05). The RF group displayed significant atrophy in the left lateral occipital, middle temporal, and precentral regions, as well as the right pars orbitalis and superior frontal regions (p⟨0.05). Hippocampal subfield analysis revealed distinct volume differences between HC-EF and RF-EF groups, with significant reductions in the CA1, CA3, and CA4 subregions in the EF group, but no differences between HC and RF groups (p > 0.05)., Conclusion: Gray matter atrophy patterns differ in PD-MCI patients with encoding and retrieval memory impairments. The significant hippocampal atrophy in the EF group, particularly in the CA subregions, highlights its potential role in disease progression and memory decline. Additionally, the convergence of atrophy in the lateral occipital cortex across both RF and EF groups suggests the involvement of the Parietal Memory Network (PMN) in PD-related memory impairment., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Published
2024
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23. Smoking affects global and regional brain entropy in depression patients regardless of depression: Preliminary findings.

Author

Velioglu HA, Yıldız S, Ozdemir-Oktem E, Cankaya S, Lundmark AK, Ozsimsek A, Hanoglu L, and Yulug B

Subjects
Humans, Male, Female, Adult, Middle Aged, Entropy, Nerve Net diagnostic imaging, Nerve Net physiopathology, Young Adult, Depressive Disorder, Major physiopathology, Depressive Disorder, Major diagnostic imaging, Magnetic Resonance Imaging, Smoking epidemiology, Brain diagnostic imaging, Brain physiopathology
Abstract

Objective: This study examines the effect of smoking on global and regional brain entropy in patients with Major Depressive Disorder (MDD), aiming to elucidate the relationship between smoking habits and brain network complexity in depression., Methods: The study enrolled 24 MDD patients, divided into smokers and non-smokers, from Alanya Alaaddin Keykubat University and Istanbul Medipol University. Resting-state fMRI data were acquired and processed. The complexity of neuronal activity was assessed using dispersion entropy, with statistical significance determined by a suite of tests including Kolmogorov-Smirnov, Student's t-test, and Mann-Whitney U test., Results: The smoking cohort exhibited higher global brain entropy compared to the non-smoking group (p = 0.033), with significant differences in various brain networks, indicating that smoking may alter global brain activity and network dynamics in individuals with MDD., Conclusion: The study provides evidence that smoking is associated with increased brain entropy in MDD patients, suggesting that chronic smoking may influence cognitive and emotional networks. This underscores the importance of considering smoking history in the treatment and prognosis of MDD. The findings call for further research to understand the mechanistic links between smoking, brain entropy, and depression., Competing Interests: Declaration of competing interest All contributing authors have declared no potential conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Published
2024
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25. The functional role of the pulvinar in discriminating between objective and subjective cognitive impairment in major depressive disorder.

Author

Yulug B, Ayyildiz S, Sayman D, Karaca R, Ipek L, Cankaya S, Salar AB, Ayyildiz B, Mikuta C, Yagci N, Oktem EO, Ozsimsek A, Velioglu HA, and Hanoglu L

Abstract

Introduction: Emotionally driven cognitive complaints represent a major diagnostic challenge for clinicians and indicate the importance of objective confirmation of the accuracy of depressive patients' descriptions of their cognitive symptoms., Methods: We compared cognitive status and structural and functional brain connectivity changes in the pulvinar and hippocampus between patients with total depression and healthy controls. The depressive group was also classified as "amnestic" or "nonamnestic," based on the members' subjective reports concerning their forgetfulness. We then sought to determine whether these patients would differ in terms of objective neuroimaging and cognitive findings., Results: The right pulvinar exhibited altered connectivity in individuals with depression with objective cognitive impairment, a finding which was not apparent in depressive patients with subjective cognitive impairment., Discussion: The pulvinar may play a role in depression-related cognitive impairments. Connectivity network changes may differ between objective and subjective cognitive impairment in depression and may play a role in the increased risk of dementia in patients with depression., Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the Supporting information., (© 2024 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Published
2024
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26. rTMS reduces delta and increases theta oscillations in Alzheimer's disease: A visual-evoked and event-related potentials study.

Author

Velioglu HA, Dudukcu EZ, Hanoglu L, Guntekin B, Akturk T, and Yulug B

Subjects
Humans, Longitudinal Studies, Evoked Potentials physiology, Electroencephalography, Transcranial Magnetic Stimulation, Alzheimer Disease therapy
Abstract

Background: Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative therapy for Alzheimer's disease (AD) due to its ability to modulate neural networks and enhance cognitive function. This treatment offers the unique advantage of enabling real-time monitoring of immediate cognitive effects and dynamic brain changes through electroencephalography (EEG)., Objective: This study focused on exploring the effects of left parietal rTMS stimulation on visual-evoked potentials (VEP) and visual event-related potentials (VERP) in AD patients., Methods: Sixteen AD patients were recruited for this longitudinal study. EEG data were collected within a Faraday cage both pre- and post-rTMS to evaluate its impact on potentials., Results: Significant alterations were found in both VEP and VERP oscillations. Specifically, delta power in VEP decreased, while theta power in VERP increased post-rTMS, indicating a modulation of brain activities., Discussion: These findings confirm the positive modulatory impact of rTMS on brain activities in AD, evidenced by improved cognitive scores. They align with previous studies highlighting the potential of rTMS in managing hyperexcitability and oscillatory disturbances in the AD cortex., Conclusion: Cognitive improvements post-rTMS endorse its potential as a promising neuromodulatory treatment for cognitive enhancement in AD, thereby providing critical insights into the neurophysiological anomalies in AD and possible therapeutic avenues., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Published
2024
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27. Functional neural networks stratify Parkinson's disease patients across the spectrum of cognitive impairment.

Author

Hajebrahimi F, Budak M, Saricaoglu M, Temel Z, Demir TK, Hanoglu L, Yildirim S, and Bayraktaroglu Z

Subjects
Humans, Cross-Sectional Studies, Magnetic Resonance Imaging, Brain diagnostic imaging, Parkinson Disease complications, Parkinson Disease diagnostic imaging, Cognitive Dysfunction diagnostic imaging, Cognitive Dysfunction etiology
Abstract

Introduction: Cognitive impairment (CI) is a significant non-motor symptoms in Parkinson's disease (PD) that often precedes the emergence of motor symptoms by several years. Patients with PD hypothetically progress from stages without CI (PD-normal cognition [NC]) to stages with Mild CI (PD-MCI) and PD dementia (PDD). CI symptoms in PD are linked to different brain regions and neural pathways, in addition to being the result of dysfunctional subcortical regions. However, it is still unknown how functional dysregulation correlates to progression during the CI. Neuroimaging techniques hold promise in discriminating CI stages of PD and further contribute to the biomarker formation of CI in PD. In this study, we explore disparities in the clinical assessments and resting-state functional connectivity (FC) among three CI stages of PD., Methods: We enrolled 88 patients with PD and 26 healthy controls (HC) for a cross sectional clinical study and performed intra- and inter-network FC analysis in conjunction with comprehensive clinical cognitive assessment., Results: Our findings underscore the significance of several neural networks, namely, the default mode network (DMN), frontoparietal network (FPN), dorsal attention network, and visual network (VN) and their inter-intra-network FC in differentiating between PD-MCI and PDD. Additionally, our results showed the importance of sensory motor network, VN, DMN, and salience network (SN) in the discriminating PD-NC from PDD. Finally, in comparison to HC, we found DMN, FPN, VN, and SN as pivotal networks for further differential diagnosis of CI stages of PD., Conclusion: We propose that resting-state networks (RSN) can be a discriminating factor in distinguishing the CI stages of PD and progressing from PD-NC to MCI or PDD. The integration of clinical and neuroimaging data may enhance the early detection of PD in clinical settings and potentially prevent the disease from advancing to more severe stages., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Published
2024
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28. Low frequency oscillations during hand laterality judgment task with and without personal perspectives: a preliminary study.

Author

Dilek B, Yildirim E, and Hanoglu L

Abstract

Sense of personal perspective is crucial for understanding in attentional mechanisms of the perception in "self" or "other's" body. In a hand laterality judgment (HLJ) task, perception of perspective can be assessed by arranging angular orientations and depths of images. A total of 11 healthy, right-handed participants (8 females, mean age: 38.36 years, education: 14 years) were included in the study. The purpose of this study was to investigate behavioural and cortical responses in low-frequency cortical rhythms during a HLJ task. A total of 80-visual hand stimuli were presented through the experiment. Hand visuals were categorized in the way of side (right vs. left) and perspective (1st vs. 3rd personal perspective). Both behavioural outcomes and brain oscillatory characteristics (i.e., frequency and amplitude) of the Electroencephalography were analysed. All reaction time and incorrect answers for 3rd person perspective were higher than the ones for 1st person perspective. Location effect was statistically significant in event-related theta responses confirming the dominant activity of theta frequency in spatial memory tasks on parietal and occipital areas. In addition, we found there were increasing in delta power and phase in hand visuals with 1st person perspective and increasing theta phase in hand visuals with 3rd person perspective ( p  < 0.05). Accordingly, a clear dissociation in the perception of perspectives in low-frequency bands was revealed. These different cortical strategy in the perception of hand visual with and without perspectives may be interpreted as delta activity may be related in self-body perception, whereas theta activity may be related in allocentric perception., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Published
2023
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29. The effects of cognitive, physical, and somatosensory rehabilitation after right temporo-parietal tumor resection on cognitive, motor, somatosensory, and electrophysiological parameters: A case report.

Author

Saricaoglu M, Hanoglu L, Guntekin B, and Ozkara C

Subjects
Humans, Young Adult, Adult, Parietal Lobe surgery, Parietal Lobe physiology, Hand, Electroencephalography, Cognition, Neoplasms, Transcutaneous Electric Nerve Stimulation
Abstract

Introduction: This report examines the effects of a multimodal rehabilitation program which includes cognitive, physical, and somatosensory rehabilitation after right temporo-parietal tumor resection on cognitive, motor, somatosensory, and electrophysiological parameters., Case Description: A 22-year-old patient presented with sensory loss in the dominant left hand and reduced writing ability after right temporo-parietal lobe resection. Cognitive, motor, and sensory evaluations were carried out pre and post-treatment. The patient's spontaneous electroencephalo-gram (EEG) and an EEG during application of transcutaneous electrical nerve stimulation (TENS) (TENS EEG) were recorded. As a reference for the patient's electrophysiological values, EEGs of 4 healthy individuals were also taken. Over a period of 1 year, the patient received multimodal rehabilitation which includes cognitive, physical, and somato-sensory rehabilitation on 2 days each week., Outcomes: An improvement of the patient's cognitive capacities, motor strength, superficial, deep and cortical sensations was achieved. After rehabilitation, an increase in parietal and occipital alpha activity as well as in frontal and parietal beta activity was seen both in spontaneous EEG and in TENS EEG. With increasing TENS intensity, alpha and beta power increased as well., Conclusion: Our findings suggest that a multimodal rehabilitation program may improve cognitive, sensory, and motor effects after resection due to tumor surgery.

Published
2023
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30. Infection with COVID-19 is no longer a public emergency: But what about degenerative dementia?

Author

Yulug B, Ayyıldız B, Ayyıldız S, Sayman D, Salar AB, Cankaya S, Ozdemir Oktem E, Ozsimsek A, Kurt CC, Lakadamyalı H, Akturk A, Altay Ö, Hanoglu L, Velioglu HA, and Mardinoglu A

Subjects
Humans, Hippocampus, Public Health, COVID-19 complications, Alzheimer Disease epidemiology, Cognition Disorders
Abstract

Although no longer considered a public health threat, post-COVID cognitive syndrome continues to impact on a considerable proportion of individuals who were infected with COVID-19. Recent studies have also suggested that COVID may be represent a critical risk factor for the development of Alzheimer's disease (AD). We compared 17 COVID patients with 20 controls and evaluated the effects of COVID-19 on general cognitive performance, hippocampal volume, and connections using structural and seed-based connectivity analysis. We showed that COVID patients exhibited considerably worse cognitive functioning and increased hippocampal connectivity supported by the strong correlation between hippocampal connectivity and cognitive scores. Our findings of higher hippocampal connectivity with no observable hippocampal morphological changes even in mild COVID cases may be represent evidence of a prestructural compensatory mechanism for stimulating additional neuronal resources to combat cognitive dysfunction as recently shown for the prodromal stages of degenerative cognitive disorders. Our findings may be also important in light of recent data showing that other viral infections as well as COVID may constitute a critical risk factor for the development of AD. To our knowledge, this is the first study that investigated network differences in COVID patients, with a particular focus on compensatory hippocampal connectivity., (© 2023 Wiley Periodicals LLC.)

Published
2023
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31. A structural and resting-state functional connectivity investigation of the pulvinar in elderly individuals and Alzheimer's disease patients.

Author

Velioglu HA, Ayyildiz B, Ayyildiz S, Sutcubasi B, Hanoglu L, Bayraktaroglu Z, and Yulug B

Subjects
Humans, Aged, Brain, Gray Matter, Magnetic Resonance Imaging, Alzheimer Disease, Pulvinar diagnostic imaging, Cognition Disorders, Cognitive Dysfunction
Abstract

In Alzheimer's disease (AD), structural and functional changes in the brain may give rise to disruption of specific cognitive functions. The aim of this study is to investigate the functional connectivity alterations in the pulvinar's subdivisions and total pulvinar voxel-based morphometry (VBM) changes in individuals with AD and healthy controls. A seed-based functional connectivity analysis was applied to the anterior, inferior, lateral, and medial pulvinar in each hemisphere. Furthermore, VBM analysis was carried out to compare gray matter (GM) volume differences in the pulvinar and thalamus between the two groups. Connectivity analysis revealed that the pulvinar subdivisions had decreased connectivity in individuals with AD. In addition, the pulvinar and thalamus in each hemisphere were significantly smaller in the AD group. The pulvinar may have a role in AD-related cognitive impairments and the intrinsic connectivity network changes and GM loss in pulvinar subdivisions suggest the cognitive deterioration occurring in those with AD. HIGHLIGHTS: The pulvinar may play a role in pathophysiology of cognitive impairments in those with Alzheimer's disease (AD). Decreased structural volume and functional connectivity were found in patients with AD. The inferior pulvinar is functionally the most affected subdivision by AD compared to the others., (© 2022 the Alzheimer's Association.)

Published
2023
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32. Brain temperature in healthy and diseased conditions: A review on the special implications of MRS for monitoring brain temperature.

Author

Yulug B, Velioglu HA, Sayman D, Cankaya S, and Hanoglu L

Subjects
Humans, Temperature, Brain metabolism, Cognition, Amyloid beta-Peptides metabolism, Alzheimer Disease
Abstract

Brain temperature determines not only an individual's cognitive functionality but also the prognosis and mortality rates of many brain diseases. More specifically, brain temperature not only changes in response to different physiological events like yawning and stretching, but also plays a significant pathophysiological role in a number of neurological and neuropsychiatric illnesses. Here, we have outlined the function of brain hyperthermia in both diseased and healthy states, focusing particularly on the amyloid beta aggregation in Alzheimer's disease., Competing Interests: Conflict of interest statement We declare that we have no known financial interest or any relationships that could have to affect the work reported in this paper., (Copyright © 2023. Published by Elsevier Masson SAS.)

Published
2023
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33. Differentiation of claustrum resting-state functional connectivity in healthy aging, Alzheimer's disease, and Parkinson's disease.

Author

Ayyildiz S, Velioglu HA, Ayyildiz B, Sutcubasi B, Hanoglu L, Bayraktaroglu Z, Yildirim S, Atasever A, and Yulug B

Subjects
Humans, Aged, Gray Matter diagnostic imaging, Magnetic Resonance Imaging methods, Alzheimer Disease, Parkinson Disease, Claustrum, Healthy Aging
Abstract

The claustrum is a sheet-like of telencephalic gray matter structure whose function is poorly understood. The claustrum is considered a multimodal computing network due to its reciprocal connections with almost all cortical areas as well as subcortical structures. Although the claustrum has been involved in several neurodegenerative diseases, specific changes in connections of the claustrum remain unclear in Alzheimer's disease (AD), and Parkinson's disease (PD). Resting-state fMRI and T1-weighted structural 3D images from healthy elderly (n = 15), AD (n = 16), and PD (n = 12) subjects were analyzed. Seed-based FC analysis was performed using CONN FC toolbox and T1-weighted images were analyzed with the Computational Anatomy Toolbox for voxel-based morphometry analysis. While we observed a decreased FC between the left claustrum and sensorimotor cortex, auditory association cortex, and cortical regions associated with social cognition in PD compared with the healthy control group (HC), no significant difference was found in alterations in the FC of both claustrum comparing the HC and AD groups. In the AD group, high FC of claustrum with regions of sensorimotor cortex and cortical regions related to cognitive control, including cingulate gyrus, supramarginal gyrus, and insular cortex were demonstrated. In addition, the structural results show significantly decreased volume in bilateral claustrum in AD and PD compared with HC. There were no significant differences in the claustrum volumes between PD and AD groups so the FC may offer more precise findings in distinguishing changes for claustrum in AD and PD., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Published
2023
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34. The effects of repetitive transcranial magnetic stimulation and aerobic exercise on cognition, balance and functional brain networks in patients with Alzheimer's disease.

Author

Budak M, Bayraktaroglu Z, and Hanoglu L

Abstract

The purpose of this study was to investigate the effects of high-frequency repetitive Transcranial Magnetic Stimulation (rTMS) and aerobic exercises (AE) in addition to the pharmacological therapy (PT) in Alzheimer's Disease (AD). Twenty-seven patients with AD aged ≥ 60 years were included in the study and divided into 3 groups (rTMS, AE and control). All groups received PT. rTMS group (n = 10) received 20 Hz rTMS over dorsolateral prefrontal cortex (dlPFC) bilaterally and AE group (n = 9) received the structured moderate-intensity AE for 5 consecutive days/week over 2 weeks. Control group (n = 8) only received PT. Cognition, balance, mobility, quality of life (QoL), and resting state functional brain activity were evaluated one week before and one week after the interventions. (ClinicalTrials.gov ID:NCT05102045). Significant improvements were found in executive functions, behavior, and QoL in the rTMS group, in balance and mobility in the AE group, and in the visual memory and behavior in the control group ( p  < 0.05). Significant differences were found in the behavior in favor of the rTMS group, and balance in favor of the AE group ( p  < 0.05). There was a significant increase in activation on middle temporal gyrus, intra calcarine, central opercular cortex, superior parietal lobule, and paracingulate cortex in Default Mode Network (DMN) in the rTMS group ( p  < 0.05). High-frequency rTMS over bilateral dlPFC may improve executive functions and behavior and lead to increased activation in DMN, structured moderate-intensity AE may improve balance and mobility, and PT may improve memory and behaviour compared to pretreatment in AD., Competing Interests: Conflict of interestNone., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022.)

Published
2023
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35. Combined metabolic activators improve metabolic functions in the animal models of neurodegenerative diseases.

Author

Turkez H, Altay O, Yildirim S, Li X, Yang H, Bayram C, Bolat I, Oner S, Tozlu OO, Arslan ME, Arif M, Yulug B, Hanoglu L, Cankaya S, Lam S, Velioglu HA, Coskun E, Idil E, Nogaylar R, Ozsimsek A, Hacimuftuoglu A, Shoaie S, Zhang C, Nielsen J, Borén J, Uhlén M, and Mardinoglu A

Subjects
Humans, Animals, Rats, Mitochondria metabolism, Models, Animal, Disease Models, Animal, Neurodegenerative Diseases metabolism, Parkinson Disease metabolism, Alzheimer Disease metabolism
Abstract

Background: Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), are associated with metabolic abnormalities. Integrative analysis of human clinical data and animal studies have contributed to a better understanding of the molecular and cellular pathways involved in the progression of NDDs. Previously, we have reported that the combined metabolic activators (CMA), which include the precursors of nicotinamide adenine dinucleotide and glutathione can be utilized to alleviate metabolic disorders by activating mitochondrial metabolism., Methods: We first analysed the brain transcriptomics data from AD patients and controls using a brain-specific genome-scale metabolic model (GEM). Then, we investigated the effect of CMA administration in animal models of AD and PD. We evaluated pathological and immunohistochemical findings of brain and liver tissues. Moreover, PD rats were tested for locomotor activity and apomorphine-induced rotation., Findings: Analysis of transcriptomics data with GEM revealed that mitochondrial dysfunction is involved in the underlying molecular pathways of AD. In animal models of AD and PD, we showed significant damage in the high-fat diet groups' brain and liver tissues compared to the chow diet. The histological analyses revealed that hyperemia, degeneration and necrosis in neurons were improved by CMA administration in both AD and PD animal models. These findings were supported by immunohistochemical evidence of decreased immunoreactivity in neurons. In parallel to the improvement in the brain, we also observed dramatic metabolic improvement in the liver tissue. CMA administration also showed a beneficial effect on behavioural functions in PD rats., Interpretation: Overall, we showed that CMA administration significantly improved behavioural scores in parallel with the neurohistological outcomes in the AD and PD animal models and is a promising treatment for improving the metabolic parameters and brain functions in NDDs., Competing Interests: Declaration of competing interest AM, JB and MU are the founder and shareholders of ScandiBio Therapeutics. The other authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2023
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36. Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial.

Author

Yulug B, Altay O, Li X, Hanoglu L, Cankaya S, Lam S, Velioglu HA, Yang H, Coskun E, Idil E, Nogaylar R, Ozsimsek A, Bayram C, Bolat I, Oner S, Tozlu OO, Arslan ME, Hacimuftuoglu A, Yildirim S, Arif M, Shoaie S, Zhang C, Nielsen J, Turkez H, Borén J, Uhlén M, and Mardinoglu A

Subjects
Animals, Rats, Treatment Outcome, Cognition, Double-Blind Method, Alzheimer Disease metabolism
Abstract

Background: Alzheimer's disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress., Methods: Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients., Results: We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment., Conclusion: Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis. Trial registration ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131., (© 2023. The Author(s).)

Published
2023
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37. The Savant Syndrome: a Gift or a Disability? A Deeper Look into Metabolic Correlates of Hidden Cognitive Capacity.

Author

Onin I, Hanoglu L, and Yulug B

Subjects
Humans, Child, Cognition, Brain, Aptitude, Transcranial Direct Current Stimulation
Abstract

Savant syndrome is a rare and unusual condition that occurs in the presence of severe developmental disabilities, disorders, and injuries. The syndrome can be congenital from birth to childhood or acquired as a result of a brain injury or damage to the central nervous system. There are several findings that indicate that savant syndrome usually occurs with significant brain metabolism alterations resulting in critical brain network changes. These types of changes in the brain are usually explained by the "tyranny of the left hemisphere" theory, which indicates the inhibition of the left hemisphere to allow the right hemisphere to develop savant abilities. Another way to temporarily simulate these types of changes in the brain can be through different neuromodulation techniques such as transcranial magnetic stimulation and transcranial direct current stimulation. Such neuromodulation techniques might help us discover the "hidden talent" potential through modulating the brain network metabolism. We herein discussed the types of savant syndrome along with its relation to specific neurometabolic network alterations. Furthermore, we provide a perspective on how newly developed neuromodulation and cognitive rehabilitation techniques can help simulate savant syndrome in healthy individuals through modulating the brain network activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Published
2023
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38. The effect of Electromyography (EMG)-driven Robotic Treatment on the recovery of the hand Nine years after stroke.

Author

Ogul OE, Coskunsu DK, Akcay S, Akyol K, Hanoglu L, and Ozturk N

Subjects
Humans, Electromyography, Treatment Outcome, Canada, Upper Extremity, Recovery of Function physiology, Robotic Surgical Procedures, Stroke Rehabilitation, Stroke complications
Abstract

Objective: To investigate the effect of electromyography (EMG)-driven robotic therapy on the recovery of the hand in a stroke case lasting 9 years., Case: An 18-year-old patient with hemiparesis due to the ischemic lesion was admitted to our clinic with hand impairment. Fifteen sessions (5 weeks x 3 times) of robotic rehabilitation were applied with the Hand of Hope. Average EMG (mV) of flexor digitorum superficialis (FDS) muscle, average force (N) and the rate of force development (RFD)(N/s) were also assessed before and after the treatment following the 5th and 10th sessions and at the end of treatment. Also, Fugl-Meyer Assessment of Upper Extremity Scale (FMU-UE), Motor Activity Log (MAL), Canadian Occupational Performance Score (COPM) and Visual Analog Scale (VAS) were used for assessment before and after the treatment., Results: The average EMG measured from FDS increased from 0.093-0.133 mV. The average force and average RFD increased from 45.6-97.7 and from 135.6-172.6 respectively. While affected and/or unaffected side force ratio increased dramatically from 54%-82%, the FMA-UE score increased from 56-59. The MAL quality of use score increased from 3.93-4.13. Performance and satisfaction scores of COPM changed from 5.25-7.25 and 4.5-8.25 respectively. VAS score for fatigue changed from 6 to 4., Discussion: The improvement achieved 9 years later with 15 sessions of rehabilitation suggests that improvement may be possible for chronic stroke patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2023
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39. Neuroimaging-Guided Transcranial Magnetic and Direct Current Stimulation in MCI: Toward an Individual, Effective and Disease-Modifying Treatment.

Author

Hanoglu L, Velioglu HA, Hanoglu T, and Yulug B

Subjects
Humans, Electroencephalography, Neuroimaging, Magnetic Phenomena, Transcranial Magnetic Stimulation methods, Cognitive Dysfunction therapy
Abstract

The therapeutic approaches currently applied in Alzheimer's disease (AD) and similar neurodegenerative diseases are essentially based on pharmacological strategies. However, despite intensive research, the effectiveness of these treatments is limited to transient symptomatic effects, and they are still far from exhibiting a true therapeutic effect capable of altering prognosis. The lack of success of such pharmacotherapy-based protocols may be derived from the cases in the majority of trials being too advanced to benefit significantly in therapeutic terms at the clinical level. For neurodegenerative diseases, mild cognitive impairment (MCI) may be an early stage of the disease continuum, including Alzheimer's. Noninvasive brain stimulation (NIBS) techniques have been developed to modulate plasticity in the human cortex in the last few decades. NIBS techniques have made it possible to obtain unique findings concerning brain functions, and design novel approaches to treat various neurological and psychiatric conditions. In addition, its synaptic and cellular neurobiological effects, NIBS is an attractive treatment option in the early phases of neurodegenerative diseases, such as MCI, with its beneficial modifying effects on cellular neuroplasticity. However, there is still insufficient evidence about the potential positive clinical effects of NIBS on MCI. Furthermore, the huge variability of the clinical effects of NIBS limits its use. In this article, we reviewed the combined approach of NIBS with various neuroimaging and electrophysiological methods. Such methodologies may provide a new horizon to the path for personalized treatment, including a more individualized pathophysiology approach which might even define new specific targets for specific symptoms of neurodegenerations.

Published
2023
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40. Screening for Alzheimer's disease using prefrontal resting-state functional near-infrared spectroscopy.

Author

Keles HO, Karakulak EZ, Hanoglu L, and Omurtag A

Abstract

Introduction: Alzheimer's disease (AD) is neurodegenerative dementia that causes neurovascular dysfunction and cognitive impairment. Currently, 50 million people live with dementia worldwide, and there are nearly 10 million new cases every year. There is a need for relatively less costly and more objective methods of screening and early diagnosis., Methods: Functional near-infrared spectroscopy (fNIRS) systems are a promising solution for the early Detection of AD. For a practical clinically relevant system, a smaller number of optimally placed channels are clearly preferable. In this study, we investigated the number and locations of the best-performing fNIRS channels measuring prefrontal cortex activations. Twenty-one subjects diagnosed with AD and eighteen healthy controls were recruited for the study., Results: We have shown that resting-state fNIRS recordings from a small number of prefrontal locations provide a promising methodology for detecting AD and monitoring its progression. A high-density continuous-wave fNIRS system was first used to verify the relatively lower hemodynamic activity in the prefrontal cortical areas observed in patients with AD. By using the episode averaged standard deviation of the oxyhemoglobin concentration changes as features that were fed into a Support Vector Machine; we then showed that the accuracy of subsets of optical channels in predicting the presence and severity of AD was significantly above chance. The results suggest that AD can be detected with a 0.76 sensitivity score and a 0.68 specificity score while the severity of AD could be detected with a 0.75 sensitivity score and a 0.72 specificity score with ≤5 channels., Discussion: These scores suggest that fNIRS is a viable technology for conveniently detecting and monitoring AD as well as investigating underlying mechanisms of disease progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Keles, Karakulak, Hanoglu and Omurtag.)

Published
2022
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41. Chemogenetic inhibition of MCH neurons does not alter memory performance in mice.

Author

Mutlu-Burnaz O, Yulug B, Oncul M, Celik E, Atasoy NS, Cankaya S, Hanoglu L, and Velioglu HA

Subjects
Animals, Mice, Pituitary Hormones physiology, Sleep, REM, Melanins, Neurons physiology, Hypothalamic Hormones physiology
Abstract

Memory storage in the brain is one of the most extensively studied subjects in neuroscience. However, due to the highly complex structure of the memory-related systems in the brain, the mystery remains unsolved. Consolidation is one of the most important parts of the memory process, and one that can be affected by numerous neurodegenerative diseases. Hypothalamic melanin-concentrating hormone (MCH) neuronal activity has been of particular interest to researchers in terms of the association between sleep, neurodegenerative diseases, and memory consolidation. We used Pmch-Cre animals to investigate the role of MCH neuronal activity in memory consolidation. In order to observe the differences in memory consolidation, we chemogenetically inhibited MCH neurons using the DREADD method and measured hippocampus-dependent memory performance with a novel object recognition test applicable to early memory impairment in Alzheimer's disease. Our results revealed no significant improvement or worsening with MCH inhibition, suggesting that the role of MCH should now be evaluated in a wider setting., Competing Interests: Conflict of interest statement None., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Published
2022
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42. Predicting the Effects of Repetitive Transcranial Magnetic Stimulation on Cognitive Functions in Patients With Alzheimer's Disease by Automated EEG Analysis.

Author

Kayasandik CB, Velioglu HA, and Hanoglu L

Abstract

Alzheimer's disease (AD) is a progressive, neurodegenerative brain disorder that generally affects the elderly. Today, after the limited benefit of the pharmacological treatment strategies, numerous noninvasive brain stimulation techniques have been developed. Transcranial magnetic stimulation (TMS), based on electromagnetic stimulation, is one of the most widely used methods. The main problem in the use of TMS is the existence of large individual variability in the results. This causes a waste of money, time, and more importantly, a burden for delicate patients. Hence, it is a necessity to form an efficient and personalized TMS application protocol. In this paper, we performed a machine-learning analysis to see whether it is possible to predict the responses of patients with AD to TMS by analyzing their electroencephalography (EEG) signals. For that purpose, we analyzed both the EEG signals collected before and after the TMS application (EEG1 and EEG2, respectively). Through correlating EEG1 and repetitive transcranial magnetic stimulation (rTMS) outcomes, we tried to see whether it is possible to predict patients' responses before the treatment application. On the other hand, by EEG2 analysis, we investigated TMS impacts on EEG, more importantly if this impact is correlated with patients' response to the treatment. We used the support vector machine (SVM) classifier due to its multiple advantages for the current task with feature selection processes by stepwise linear discriminant analysis (SWLDA) and SVM. However, to justify our numerical analysis framework, we examined and compared the performances of different feature selection and classification techniques. Since we have a limited sample number, we used the leave-one-out method for the validation with the Monte Carlo technique to eliminate bias by a small sample size. In the conclusion, we observed that the correlation between rTMS outcomes and EEG2 is stronger than EEG1, since we observed, respectively, 93 and 79% of accuracies during our data analysis. Besides the informative features of EEG2 are focused on theta band, it indicates that TMS is characterizing the theta band signals in patients with AD in direct relation to patients' response to rTMS. This shows that it is more possible to determine patients' benefit from the TMS at the early stages of the treatment, which would increase the efficiency of rTMS applications in patients with Alzheimer's disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kayasandik, Velioglu and Hanoglu.)

Published
2022
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43. Clinical evaluation and resting state fMRI analysis of virtual reality based training in Parkinson's disease through a randomized controlled trial.

Author

Hajebrahimi F, Velioglu HA, Bayraktaroglu Z, Helvaci Yilmaz N, and Hanoglu L

Subjects
Exercise Therapy methods, Humans, Magnetic Resonance Imaging, Neuropsychological Tests, Parkinson Disease diagnostic imaging, Parkinson Disease therapy, Virtual Reality
Abstract

There are few studies investigating the short-term effects of Virtual Reality based Exergaming (EG) on motor and cognition simultaneously and pursue the brain functional activity changes after these interventions in patients with Parkinson's Disease (PD). The purpose of this study was to investigate the synergistic therapeutic effects of Virtual Reality based EG on motor and cognitive symptoms in PD and its possible effects on neuroplasticity. Eligible patients with the diagnosis of PD were randomly assigned to one of the two study groups: (1) an experimental EG group, (2) an active control Exercise Therapy (ET) group. All patients participated in a 4-week exercise program consisting of 12 treatment sessions. Every session lasted 60 min. Participants underwent a motor evaluation, extensive neuropsychological assessment battery and rs-fMRI before and after the interventions. Thirty patients fulfilled the inclusion criteria and were randomly assigned to the EG and ET groups. After the dropouts, 23 patients completed the assessments and interventions (11 in EG, 13 in ET). Within group analysis showed significant improvements in both groups. Between group comparisons considering the interaction of group × time effect, showed superiority of EG in terms of general cognition, delayed visual recall memory and Boston Naming Test. These results were consistent in the within-group and between-group analysis. Finally, rs-fMRI analysis showed increased activity in the precuneus region in the time × group interaction in the favor of EG group. EG can be an effective alternative in terms of motor and cognitive outcomes in patients with PD. Compared to ET, EG may affect brain functional connectivity and can have beneficial effects on patients' cognitive functions and motor symptoms. Whenever possible, using EG and ET in combination, may have the better effects on patients daily living and patients can benefit from the advantages of both interventions., (© 2022. The Author(s).)

Published
2022
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44. Axillary Microbiota Is Associated with Cognitive Impairment in Parkinson's Disease Patients.

Author

Arikan M, Yildiz Z, Kahraman Demir T, Yilmaz NH, Sen A, Hanoglu L, and Yildirim S

Subjects
Aged, Bacteria classification, Bacteria genetics, Cognitive Dysfunction etiology, Female, Humans, Male, Middle Aged, Parkinson Disease microbiology, Parkinson Disease psychology, Phylogeny, Axilla microbiology, Bacteria isolation & purification, Cognitive Dysfunction microbiology, Microbiota, Parkinson Disease complications
Abstract

Cognitive impairment (CI) is among the most common non-motor symptoms of Parkinson's disease (PD), with a substantially negative impact on patient management and outcome. The development and progression of CI exhibits high interindividual variability, which requires better diagnostic and monitoring strategies. PD patients often display sweating disorders resulting from autonomic dysfunction, which has been associated with CI. Because the axillary microbiota is known to change with humidity level and sweat composition, we hypothesized that the axillary microbiota of PD patients shifts in association with CI progression, and thus can be used as a proxy for classification of CI stages in PD. We compared the axillary microbiota compositions of 103 PD patients (55 PD patients with dementia [PDD] and 48 PD patients with mild cognitive impairment [PD-MCI]) and 26 cognitively normal healthy controls (HC). We found that axillary microbiota profiles differentiate HC, PD-MCI, and PDD groups based on differential ranking analysis, and detected an increasing trend in the log ratio of Corynebacterium to Anaerococcus in progression from HC to PDD. In addition, phylogenetic factorization revealed that the depletion of the Anaerococcus, Peptoniphilus , and W5053 genera is associated with PD-MCI and PDD. Moreover, functional predictions suggested significant increases in myo-inositol degradation, ergothioneine biosynthesis, propionate biosynthesis, menaquinone biosynthesis, and the proportion of aerobic bacteria and biofilm formation capacity, in parallel to increasing CI. Our results suggest that alterations in axillary microbiota are associated with CI in PD. Thus, axillary microbiota has the potential to be exploited as a noninvasive tool in the development of novel strategies. IMPORTANCE Parkinson's disease (PD) is the second most common neurodegenerative disease. Cognitive impairment (CI) in PD has significant negative impacts on life quality of patients. The emergence and progression of cognitive impairment shows high variability among PD patients, and thus requires better diagnostic and monitoring strategies. Recent findings indicate a close link between autonomic dysfunction and cognitive impairment. Since thermoregulatory dysfunction and skin changes are among the main manifestations of autonomic dysfunction in PD, we hypothesized that alterations in the axillary microbiota may be useful for tracking cognitive impairment stages in PD. To our knowledge, this the first study characterizing the axillary microbiota of PD patients and exploring its association with cognitive impairment stages in PD. Future studies should include larger cohorts and multicenter studies to validate our results and investigate potential biological mechanisms.

Published
2022
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45. Therapeutic Role of Repetitive Transcranial Magnetic Stimulation in Alzheimer's and Parkinson's Disease: Electroencephalography Microstate Correlates.

Author

Hanoglu L, Toplutas E, Saricaoglu M, Velioglu HA, Yildiz S, and Yulug B

Abstract

Introduction: The microstate analysis is a method to convert the electrical potentials on the multi-channel electrode array to topographical electroencephalography (EEG) data. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method that can modulate brain networks. This study explores the pathophysiological changes through microstate analysis in two different neurodegenerative diseases, Alzheimer's (AD) and Parkinson's disease (PD), characterized by motor and cognitive symptoms and analysis the effect of rTMS on the impaired cognitive and motor functions., Materials and Methods: We included 18 AD, 8 PD patients, and 13 age-matched controls. For both groups, we applied 5 Hz rTMS on the left pre-SMA in PD patients while 20 Hz rTMS on the left lateral parietal region in AD patients. Each patient was re-evaluated 1 week after the end of the sessions, which included a detailed clinical evaluation and measurement of EEG microstates., Results: At the baseline, the common findings between our AD and PD patients were altered microstate (MS) B, MS D durations and transition frequencies between MS A-MS B, MS C-MS D while global explained variance (GEV) ratio and the extent and frequency of occurrence of MS A, MS B, and MS D were separately altered in AD patients. Although no specific microstate parameter adequately differentiated between AD and PD patients, we observed significant changes in MS B and MS D parameters in PD patients. Further, we observed that Mini-Mental State Examination (MMSE) performances were associated with the transition frequencies between MS A-MS B and MS C-MS D and GEV ratio. After left parietal rTMS application, we have observed significantly increased visual memory recognition and clock drawing scores after left parietal rTMS application associated with improved microstate conditions prominent, especially in the mean duration of MS C in AD patients. Also, pre-SMA rTMS resulted in significant improvement in motor scores and frequency of transitions from MS D to MS C in PD patients., Conclusion: This study shows that PD and AD can cause different and similar microstate changes that can be modulated through rTMS, suggesting the role of MS parameters and rTMS as a possible combination in monitoring the treatment effect in neurodegenerative diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hanoglu, Toplutas, Saricaoglu, Velioglu, Yildiz and Yulug.)

Published
2022
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46. The Multifactorial Role of Pre-supplementary Motor Area Stimulation in the Freezing of Gait: An Alternative Strategy to the Classical Drug-Target Approach.

Author

Saricaoglu M, Hanoglu L, Toprak G, Yilmaz NH, and Yulug B

Subjects
Female, Gait physiology, Humans, Male, Transcranial Magnetic Stimulation methods, Gait Disorders, Neurologic diagnosis, Gait Disorders, Neurologic etiology, Gait Disorders, Neurologic therapy, Motor Cortex, Parkinson Disease complications, Parkinson Disease therapy
Abstract

Introduction: The pre-supplementary motor area (Pre-SMA) plays a pivotal role in the control of voluntary motor control and freezing of gait (FOG) pathophysiological mechanism. Here, we aimed to modulate if the pre-SMA would have beneficial effects on motor and behavioural outcomes in freezing of gait. To test this hypothesis, we examined the left pre-SMA stimulating effect of repetitive Transcranial Magnetic Stimulation (rTMS) on motor, cognitive and behavioural parameters in Parkinson's patients with FOG., Methods: The study included 20 Parkinson's patients with FOG (3 females, 17 males) who received the left Pre-SMA rTMS procedure. The clinical assessments were performed on all patients at the baseline and the patients were re-evaluated under the same clinical conditions one week after the end of the sessions., Results & Discussion: We found significant improvements in motor, cognitive and behavioural symptoms (p<0.05). The main finding of our study is that Pre-SMA is an attractive stimulation area leading to critical improvement of symptoms of Parkinson's patients with FOG., Conclusion: The high-frequency rTMS stimulation over the left preSMA has a restorative effect on the motor, cognitive and behavioural symptoms of Parkinson's patients with FOG., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Published
2022
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47. DLPF Targeted Repetitive Transcranial Magnetic Stimulation Improves Brain Glucose Metabolism Along with the Clinical and Electrophysiological Parameters in CBD Patients.

Author

Toprak G, Hanoglu L, Cakir T, Guntekin B, Velioglu HA, and Yulug B

Subjects
Brain pathology, Female, Glucose, Humans, Male, Transcranial Magnetic Stimulation methods, Corticobasal Degeneration, Neurodegenerative Diseases pathology
Abstract

Background: Corticobasal Degeneration (CBD) is a rare neurological disease caused by the pathological accumulation of tau protein. The primary pathological features of CBD include progressive neurodegenerative processes resulting in remarkable frontoparietal and basal ganglia atrophy., Objective: Like in many other neurodegenerative disorders, there is still no effective disease-modifying drug therapy in CBD. Therefore, the development of new treatment methods is of great importance. In this study, we aimed to assess the stimulating effects of high-frequency DLPFC rTMS on the motor, cognitive and behavioral disturbances in four CBD patients., Methods: Four (three females, one male) CBD patients who had been diagnosed as CBD were enrolled in this study. Patients were evaluated before and after the rTMS procedure regarding the motor, neuropsychometric and behavioral tests. The results of statistical analysis of behavioral and neuropsychometric evaluation were assessed via SPSS 18.0 package program. Data are expressed as mean, standard deviation. Before and after values of the groups were compared with the Wilcoxon sign rank test, and p<0.05 was considered significant., Results: We have provided strong preliminary evidence that the improvement in clinical parameters was associated with the normalizations of the theta activity and glucose metabolism., Conclusion: Our current results are consistent with some previous trials showing a strong association between DLPFC targeted rTMS and electrophysiological normalizations in the left DLPFC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Published
2022
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48. The correlation of non-motor symptoms and sleep on balance in Parkinson's disease patients with normal cognition and mild cognitive impairment.

Author

Saricaoglu M, Yilmaz NH, Ozer FF, and Hanoglu L

Subjects
Cognition, Humans, Quality of Life, Sleep, Cognitive Dysfunction etiology, Parkinson Disease complications
Abstract

Background: Parkinson's disease (PD) is characterized by non-motor symptoms (NMS) as well as by motor symptoms. Together with the impairment of cognitive functions, NMS and sleep also affect motor symptoms negatively. The aim of our study is to examine the correlation of NMS and sleep on balance in PD patients with normal cognition (PD-NC) and with mild cognitive impairment (PD-MCI)., Methods: A total of 69 patients were included in our study. Using the Standardized Mini-Mental State Examination, participants were divided into 2 groups, PD-NC and PD-MCI. Patients were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), the Berg Balance Scale (BBS), the Tinetti Balance Assessment Tool (TBAT), the Non-Motor Symptoms Questionnaire (NMSQ), and the Parkinson's Disease Questionnaire (PDQ-39)., Results: PD-MCI patients had statistically significant worse motor symptoms and more balance disorder compared to PD-NC (UPDRS: p = 0.009; BBS: p = 0.010; TBAT: p = 0.004). PD-MCI patients had greater severity of non-motor symptoms and worse sleep quality than the PD-NC group (NMSQ-total: p = 0.02; NMSQ-sleep total: p = 0.01). The evaluation has shown that with a diagnosis of MCI, NMS, and sleeping problems were correlated, and the correlation was associated with impairment of the balance function. While being more pronounced in the PD-MCI group, quality of life was affected in both groups (p < 0.05)., Conclusion: Our data demonstrate a negative effect on the balance function in patients with cognitive impairment suffering increased NMS and sleeping disorders. Treatment of these patients needs to concentrate on NMS and cognitive functions as much as on motor symptoms., (© 2021. Royal Academy of Medicine in Ireland.)

Published
2021
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49. Left lateral parietal rTMS improves cognition and modulates resting brain connectivity in patients with Alzheimer's disease: Possible role of BDNF and oxidative stress.

Author

Velioglu HA, Hanoglu L, Bayraktaroglu Z, Toprak G, Guler EM, Bektay MY, Mutlu-Burnaz O, and Yulug B

Subjects
Aged, Alzheimer Disease physiopathology, Brain physiopathology, Female, Functional Neuroimaging, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways diagnostic imaging, Neural Pathways physiopathology, Sulfhydryl Compounds blood, Alzheimer Disease diagnostic imaging, Brain diagnostic imaging, Brain-Derived Neurotrophic Factor blood, Oxidative Stress, Parietal Lobe, Transcranial Magnetic Stimulation methods
Abstract

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulation technique which is increasingly used for cognitive impairment in Alzheimer's Disease (AD). Although rTMS has been shown to modify Brain-Derived Neurotrophic Factor (BDNF) and oxidative stress levels in many neurological and psychiatric diseases, there is still no study evaluating the relationship between memory performance, BDNF, oxidative stress, and resting brain connectivity following rTMS in Alzheimer's patients. Furthermore, there are increasing clinical data showing that the stimulation of strategic brain regions may lead to more robust improvements in memory functions compared to conventional rTMS. In this study, we aimed to evaluate the possible disease-modifying effects of rTMS on the lateral parietal cortex in AD patients who have the highest connectivity with the hippocampus. To fill the mentioned research gaps, we have evaluated the relationships between resting-state Functional Magnetic Resonance Imaging (fMRI), cognitive scores, blood BDNF levels, and total oxidative/antioxidant status to explain the therapeutic and potential disease-modifying effects of rTMS which has been applied at 20 Hz frequencies for two weeks. Our results showed significantly increased visual recognition memory functions and clock drawing test scores which were associated with elevated peripheral BDNF levels, and decreased oxidant status after two weeks of left lateral parietal TMS stimulation. Clinically our findings suggest that the left parietal region targeted rTMS application leads to significant improvement in familiarity-based cognition associated with the network connections between the left parietal region and the hippocampus., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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50. Topological network mechanisms of clinical response to antidepressant treatment in drug-naive major depressive disorder.

Author

Uykur AB, Yıldız S, Velioglu HA, Ozsimsek A, Oktem EO, Bayraktaroglu Z, Ergun T, Lakadamyali H, Hanoglu L, Cankaya S, Saatçi Ö, and Yulug B

Subjects
Adult, Brain physiopathology, Citalopram therapeutic use, Cross-Sectional Studies, Duloxetine Hydrochloride pharmacology, Duloxetine Hydrochloride therapeutic use, Female, Humans, Image Interpretation, Computer-Assisted methods, Magnetic Resonance Imaging methods, Male, Nerve Net physiopathology, Antidepressive Agents therapeutic use, Brain drug effects, Depressive Disorder, Major drug therapy, Depressive Disorder, Major physiopathology, Nerve Net drug effects
Abstract

Aim: There is rapidly increasing evidence that remission of MDD is associated with substantial changes in functional brain connectivity. These New data have provided a holistic view on the mechanism of antidepressants on multiple levels that goes beyond their conventional effects on neurotransmitters., Method: The study was approved by the Local Ethics Committee of Istanbul Medipol University (10840098-604.01.01-E.65129) and followed the Helsinki Declaration principles. In our study, we have evaluated the effect of six weeks of treatment with antidepressants (escitalopram and duloxetine), and tested the underlying brain functional connectivity through a Graph analysis approach in a well-defined first-episode, drug-naive, and non-comorbid population with MDD., Results: Beyond indicating that there was a significant correlation between the antidepressant response and topological characteristics of the brain, our results suggested that global rather than regional network alterations may be implicated in the antidepressant effect., Conclusion: Despite the small-sample size and non-controlled study design, our study provides important and relevant clinical data regarding the underlying mechanisms of the antidepressants on topological dynamics in the human brain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Published
2021
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