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Sample records for subcortical structures involved

  1. Implications of Subcortical structures in Aphasia.

    Directory of Open Access Journals (Sweden)

    Saleh Alamri

    2015-04-01

    Taken together, the results indicate that aphasia is a common outcome after a lesion to subcortical structures. Findings show that 110 out of 394 aphasic patients with lesion in the basal ganglia exhibited comprehension deficits, while 31 participants out of 288 with thalamic aphasia. Likewise, 129 aphasics of affected basal ganglia out of 394 had impaired naming, whereas 12 participants had impaired naming out of 288 individuals with thalamic aphasia. See figure 1. Figure 1: The percentage of language impairment in two sets of aphasic patients (the thalamus and the basal ganglia. Despite contradictory results and even cases of double dissociation (for an example of absence of language deficits in the event of thalamic lesions see Cappa et al., 1986, our literature review confirms the major role of subcortical structures in language processing.

  2. Common genetic variants influence human subcortical brain structures

    OpenAIRE

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

    2015-01-01

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

  3. Physical fitness and shapes of subcortical brain structures in children.

    Science.gov (United States)

    Ortega, Francisco B; Campos, Daniel; Cadenas-Sanchez, Cristina; Altmäe, Signe; Martínez-Zaldívar, Cristina; Martín-Matillas, Miguel; Catena, Andrés; Campoy, Cristina

    2017-03-27

    A few studies have recently reported that higher cardiorespiratory fitness is associated with higher volumes of subcortical brain structures in children. It is, however, unknown how different fitness measures relate to shapes of subcortical brain nuclei. We aimed to examine the association of the main health-related physical fitness components with shapes of subcortical brain structures in a sample of forty-four Spanish children aged 9·7 (sd 0·2) years from the NUtraceuticals for a HEALthier life project. Cardiorespiratory fitness, muscular strength and speed agility were assessed using valid and reliable tests (ALPHA-fitness test battery). Shape of the subcortical brain structures was assessed by MRI, and its relationship with fitness was examined after controlling for a set of potential confounders using a partial correlation permutation approach. Our results showed that all physical fitness components studied were significantly related to the shapes of subcortical brain nuclei. These associations were both positive and negative, indicating that a higher level of fitness in childhood is related to both expansions and contractions in certain regions of the accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. Cardiorespiratory fitness was mainly associated with expansions, whereas handgrip was mostly associated with contractions in the structures studied. Future randomised-controlled trials will confirm or contrast our findings, demonstrating whether changes in fitness modify the shapes of brain structures and the extent to which those changes influence cognitive function.

  4. Dynamic brain structural changes after left hemisphere subcortical stroke.

    Science.gov (United States)

    Fan, Fengmei; Zhu, Chaozhe; Chen, Hai; Qin, Wen; Ji, Xunming; Wang, Liang; Zhang, Yujin; Zhu, Litao; Yu, Chunshui

    2013-08-01

    This study aimed to quantify dynamic structural changes in the brain after subcortical stroke and identify brain areas that contribute to motor recovery of affected limbs. High-resolution structural MRI and neurological examinations were conducted at five consecutive time points during the year following stroke in 10 patients with left hemisphere subcortical infarctions involving motor pathways. Gray matter volume (GMV) was calculated using an optimized voxel-based morphometry technique, and dynamic changes in GMV were evaluated using a mixed-effects model. After stroke, GMV was decreased bilaterally in brain areas that directly or indirectly connected with lesions, which suggests the presence of regional damage in these "healthy" brain tissues in stroke patients. Moreover, the GMVs of these brain areas were not correlated with the Motricity Index (MI) scores when controlling for time intervals after stroke, which indicates that these structural changes may reflect an independent process (such as axonal degeneration) but cannot affect the improvement of motor function. In contrast, the GMV was increased in several brain areas associated with motor and cognitive functions after stroke. When controlling for time intervals after stroke, only the GMVs in the cognitive-related brain areas (hippocampus and precuneus) were positively correlated with MI scores, which suggests that the structural reorganization in cognitive-related brain areas may facilitate the recovery of motor function. However, considering the small sample size of this study, further studies are needed to clarify the exact relationships between structural changes and recovery of motor function in stroke patients. Copyright © 2012 Wiley Periodicals, Inc.

  5. Childhood adversity impacts on brain subcortical structures relevant to depression

    NARCIS (Netherlands)

    Frodl, Thomas; Janowitz, Deborah; Schmaal, Lianne; Tozzi, Leonardo; Dobrowolny, Henrik; Stein, Dan J.; Veltman, Dick. J.; Wittfeld, Katharina; van Erp, Theo G. M.; Jahanshad, Neda; Block, Andrea; Hegenscheid, Katrin; Voelzke, Henry; Lagopoulos, Jim; Hatton, Sean N.; Hickie, Ian B.; Frey, Eva Maria; Carballedo, Angela; Brooks, Samantha J; Vuletic, Daniella; Uhlmann, Anne; Veer, Ilya M.; Walter, Henrik; Schnell, Knut; Grotegerd, Dominik; Arolt, Volker; Kugel, Harald; Schramm, Elisabeth; Konrad, Carsten; Zurowski, Bartosz; Baune, Bernhard T; van der Wee, Nic J. A.; van Tol, Marie-Jose; Penninx, Brenda W. J. H.; Thompson, Paul M.; Hibar, Derrek P.; Dannlowski, Udo; Grabe, Hans J.

    Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of

  6. Subcortical structure alterations impact language processing in individuals with schizophrenia and those at high genetic risk.

    Science.gov (United States)

    Li, Xiaobo; Black, Margaret; Xia, Shugao; Zhan, Chenyang; Bertisch, Hilary C; Branch, Craig A; DeLisi, Lynn E

    2015-12-01

    Cortical structural and functional anomalies have been found to associate with language impairments in both schizophrenia patients and genetic high risk individuals for developing schizophrenia. However, subcortical structures that contribute to language processing haven't been well studied in this population, and thus became the main objective of this study. We examined structural MRI data from 20 patients with schizophrenia, 21 individuals at genetic high risk, and 48 controls. Surface shape and volume differences of 6 subcortical structures that are involved in language processing, including nuclei pallidum, putamen, caudate, amygdala, thalamus, and hippocampus from both hemispheres, were compared between groups. Performance scores of language-associated cognitive tests were obtained to identify relationships of subcortical structures to language-related behaviors. Significantly reduced volumes of both the left and right side caudate nuclei, thalami and right side amygdala were shown in patients when compared with controls. Very interestingly, the high risk group demonstrated significantly increased correlations between volumes of left side pallidum nucleus and bilateral thalami and language-related cognitive test scores when compared to controls. This study furthers our understanding of subcortical structural alterations in schizophrenia and high risk individuals, and suggests the contribution of subcortical structures to the language impairments that may serve as an early sign for impending development of schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

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

    2015-01-01

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

  8. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

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

    2015-01-01

    textabstractThe highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate

  9. Subcortical auditory structures in the Mongolian gerbil: I. Golgi architecture.

    Science.gov (United States)

    Mylius, Judith; Brosch, Michael; Scheich, Henning; Budinger, Eike

    2013-04-15

    By means of the Golgi-Cox and Nissl methods we investigated the cyto- and fiberarchitecture as well as the morphology of neurons in the subcortical auditory structures of the Mongolian gerbil (Meriones unguiculatus), a frequently used animal model in auditory neuroscience. We describe the divisions and subdivisions of the auditory thalamus including the medial geniculate body, suprageniculate nucleus, and reticular thalamic nucleus, as well as of the inferior colliculi, nuclei of the lateral lemniscus, superior olivary complex, and cochlear nuclear complex. In this study, we 1) confirm previous results about the organization of the gerbil's subcortical auditory pathway using other anatomical staining methods (e.g., Budinger et al. [2000] Eur J Neurosci 12:2452-2474); 2) add substantially to the knowledge about the laminar and cellular organization of the gerbil's subcortical auditory structures, in particular about the orientation of their fibrodendritic laminae and about the morphology of their most distinctive neuron types; and 3) demonstrate that the cellular organization of these structures, as seen by the Golgi technique, corresponds generally to that of other mammalian species, in particular to that of rodents. Copyright © 2012 Wiley Periodicals, Inc.

  10. Fractal Dimension Analysis of Subcortical Gray Matter Structures in Schizophrenia.

    Directory of Open Access Journals (Sweden)

    Guihu Zhao

    Full Text Available A failure of adaptive inference-misinterpreting available sensory information for appropriate perception and action-is at the heart of clinical manifestations of schizophrenia, implicating key subcortical structures in the brain including the hippocampus. We used high-resolution, three-dimensional (3D fractal geometry analysis to study subtle and potentially biologically relevant structural alterations (in the geometry of protrusions, gyri and indentations, sulci in subcortical gray matter (GM in patients with schizophrenia relative to healthy individuals. In particular, we focus on utilizing Fractal Dimension (FD, a compact shape descriptor that can be computed using inputs with irregular (i.e., not necessarily smooth surfaces in order to quantify complexity (of geometrical properties and configurations of structures across spatial scales of subcortical GM in this disorder. Probabilistic (entropy-based information FD was computed based on the box-counting approach for each of the seven subcortical structures, bilaterally, as well as the brainstem from high-resolution magnetic resonance (MR images in chronic patients with schizophrenia (n = 19 and age-matched healthy controls (n = 19 (age ranges: patients, 22.7-54.3 and healthy controls, 24.9-51.6 years old. We found a significant reduction of FD in the left hippocampus (median: 2.1460, range: 2.07-2.18 vs. median: 2.1730, range: 2.15-2.23, p<0.001; Cohen's effect size, U3 = 0.8158 (95% Confidence Intervals, CIs: 0.6316, 1.0, the right hippocampus (median: 2.1430, range: 2.05-2.19 vs. median: 2.1760, range: 2.12-2.21, p = 0.004; U3 = 0.8421 (CIs: 0.5263, 1, as well as left thalamus (median: 2.4230, range: 2.40-2.44, p = 0.005; U3 = 0.7895 (CIs: 0.5789, 0.9473 in schizophrenia patients, relative to healthy individuals. Our findings provide in-vivo quantitative evidence for reduced surface complexity of hippocampus, with reduced FD indicating a less complex, less regular GM surface detected in

  11. Common genetic variants influence human subcortical brain structures

    Science.gov (United States)

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

    2015-01-01

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

  12. Bilingualism at the core of the brain. Structural differences between bilinguals and monolinguals revealed by subcortical shape analysis.

    Science.gov (United States)

    Burgaleta, Miguel; Sanjuán, Ana; Ventura-Campos, Noelia; Sebastian-Galles, Núria; Ávila, César

    2016-01-15

    Naturally acquiring a language shapes the human brain through a long-lasting learning and practice process. This is supported by previous studies showing that managing more than one language from early childhood has an impact on brain structure and function. However, to what extent bilingual individuals present neuroanatomical peculiarities at the subcortical level with respect to monolinguals is yet not well understood, despite the key role of subcortical gray matter for a number of language functions, including monitoring of speech production and language control - two processes especially solicited by bilinguals. Here we addressed this issue by performing a subcortical surface-based analysis in a sample of monolinguals and simultaneous bilinguals (N=88) that only differed in their language experience from birth. This analysis allowed us to study with great anatomical precision the potential differences in morphology of key subcortical structures, namely, the caudate, accumbens, putamen, globus pallidus and thalamus. Vertexwise analyses revealed significantly expanded subcortical structures for bilinguals compared to monolinguals, localized in bilateral putamen and thalamus, as well as in the left globus pallidus and right caudate nucleus. A topographical interpretation of our results suggests that a more complex phonological system in bilinguals may lead to a greater development of a subcortical brain network involved in monitoring articulatory processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Transcranial sonography of subcortical structures in patients with multiple sclerosis.

    Science.gov (United States)

    Puz, P; Lasek-Bal, A; Radecka, P

    2017-07-01

    Transcranial sonography may be applied to assess the basal ganglia nuclei and brain atrophy by the measurement of the width of the third ventricle. The aim of this study was to assess usefulness of transcranial sonography (TCS) in patients with multiple sclerosis (MS) by examining the echogenicity of subcortical structures and the width of the third ventricle. Transcranial sonography evaluation of substantia nigra, brain stem raphe nuclei, diameter of the third ventricle, width of the anterior horn of the lateral ventricle, thalamus, lenticular nucleus, and head of the caudate nucleus in 41 patients with relapsing-remitting MS (RRMS), 23 with secondary progressive MS (SPMS), and 20 healthy controls was compared. A potential link between the patients' age, sex, Expanded Disability Status Scale (EDSS) score, relapse index, and ultrasound parameters was assessed. The following were found in patients with MS, as compared to the control group: a greater area of the substantia nigra, a longer diameter of the third ventricle and wider frontal horns of the lateral ventricles, hypo-echogenicity of the brain stem raphe, and hyperechogenicity of the lenticular nucleus. The study group was found to have a significant correlation between the area of the substantia nigra, and the age of patients, the duration of the illness, EDSS score, and the number of relapses. There was a significant correlation between the diameter of the third ventricle and the age of patients and EDSS score. Patients with MS reveal ultrasound features of subcortical structure atrophy. Selected TCS findings show a correlation with disease progression and activity. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Improved labeling of subcortical brain structures in atlas-based segmentation of magnetic resonance images.

    Science.gov (United States)

    Yousefi, Siamak; Kehtarnavaz, Nasser; Gholipour, Ali

    2012-07-01

    Precise labeling of subcortical structures plays a key role in functional neurosurgical applications. Labels from an atlas image are propagated to a patient image using atlas-based segmentation. Atlas-based segmentation is highly dependent on the registration framework used to guide the atlas label propagation. This paper focuses on atlas-based segmentation of subcortical brain structures and the effect of different registration methods on the generated subcortical labels. A single-step and three two-step registration methods appearing in the literature based on affine and deformable registration algorithms in the ANTS and FSL algorithms are considered. Experiments are carried out with two atlas databases of IBSR and LPBA40. Six segmentation metrics consisting of Dice overlap, relative volume error, false positive, false negative, surface distance, and spatial extent are used for evaluation. Segmentation results are reported individually and as averages for nine subcortical brain structures. Based on two statistical tests, the results are ranked. In general, among four different registration strategies investigated in this paper, a two-step registration consisting of an initial affine registration followed by a deformable registration applied to subcortical structures provides superior segmentation outcomes. This method can be used to provide an improved labeling of the subcortical brain structures in MRIs for different applications.

  15. An unusual case of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy with occipital lobe involvement

    Directory of Open Access Journals (Sweden)

    Bhavesh Trikamji

    2016-01-01

    Full Text Available Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL is an autosomal dominant angiopathy caused by a mutation in the notch 3 gene on chromosome 19. Clinically, patients may be asymptomatic or can present with recurrent ischemic episodes and strokes leading to dementia, depression, pseudobulbar palsy, and hemi- or quadraplegia. Additional manifestations that have been described include migraine (mostly with aura, psychiatric disturbances, and epileptic seizures. Neuroimaging is essential to the diagnosis of CADASIL. On imaging CADASIL is characterized by symmetric involvement by confluent lesions located subcortically in the frontal and temporal lobes as well as in the insula, periventricularly, in the centrum semiovale, in the internal and external capsule, basal ganglia, and brain stem; with relative sparing of the fronto-orbital and the occipital subcortical regions. We describe a 49 year old male with CADASIL with absence of temporal lobe findings on MRI but predominant lesions within the periventricular white matter, occipital lobes with extension into the subcortical frontal lobes, corpus callosum and cerebellar white matter. Although CADASIL characteristically presents with anterior temporal lobe involvement, these findings may be absent and our case addresses the atypical imaging findings in CADASIL.

  16. Neuropsychology of subcortical dementias.

    Science.gov (United States)

    Savage, C R

    1997-12-01

    Subcortical dementias are a heterogeneous group of disorders that share primary pathology in subcortical structure and a characteristic pattern of neuropsychological impairment. This article describes the neurobiological and cognitive features of three prototypical subcortical dementias, Parkinson's disease, Huntington's disease, and progressive supranuclear palsy, concentrating of traits shared by disorders. Clinical features are also discussed, especially those which differentiate subcortical dementias from cortical dementias, such as Alzheimer's disease. The cortical-subcortical nomenclature has been criticized over the years, but it continues to provide an effective means of classifying dementia profiles in clinically and theoretically useful ways.

  17. Glucose metabolism in small subcortical structures in Parkinson's disease

    DEFF Research Database (Denmark)

    Borghammer, Per; Hansen, Søren B; Eggers, Carsten

    2012-01-01

    Evidence from experimental animal models of Parkinson's disease (PD) suggests a characteristic pattern of metabolic perturbation in discrete, very small basal ganglia structures. These structures are generally too small to allow valid investigation by conventional positron emission tomography (PET...

  18. Multi-atlas segmentation of subcortical brain structures via the AutoSeg software pipeline

    Science.gov (United States)

    Wang, Jiahui; Vachet, Clement; Rumple, Ashley; Gouttard, Sylvain; Ouziel, Clémentine; Perrot, Emilie; Du, Guangwei; Huang, Xuemei; Gerig, Guido; Styner, Martin

    2014-01-01

    Automated segmenting and labeling of individual brain anatomical regions, in MRI are challenging, due to the issue of individual structural variability. Although atlas-based segmentation has shown its potential for both tissue and structure segmentation, due to the inherent natural variability as well as disease-related changes in MR appearance, a single atlas image is often inappropriate to represent the full population of datasets processed in a given neuroimaging study. As an alternative for the case of single atlas segmentation, the use of multiple atlases alongside label fusion techniques has been introduced using a set of individual “atlases” that encompasses the expected variability in the studied population. In our study, we proposed a multi-atlas segmentation scheme with a novel graph-based atlas selection technique. We first paired and co-registered all atlases and the subject MR scans. A directed graph with edge weights based on intensity and shape similarity between all MR scans is then computed. The set of neighboring templates is selected via clustering of the graph. Finally, weighted majority voting is employed to create the final segmentation over the selected atlases. This multi-atlas segmentation scheme is used to extend a single-atlas-based segmentation toolkit entitled AutoSeg, which is an open-source, extensible C++ based software pipeline employing BatchMake for its pipeline scripting, developed at the Neuro Image Research and Analysis Laboratories of the University of North Carolina at Chapel Hill. AutoSeg performs N4 intensity inhomogeneity correction, rigid registration to a common template space, automated brain tissue classification based skull-stripping, and the multi-atlas segmentation. The multi-atlas-based AutoSeg has been evaluated on subcortical structure segmentation with a testing dataset of 20 adult brain MRI scans and 15 atlas MRI scans. The AutoSeg achieved mean Dice coefficients of 81.73% for the subcortical structures

  19. Advanced structural multimodal imaging of a patient with subcortical band heterotopia.

    Science.gov (United States)

    Kini, Lohith G; Nasrallah, Ilya M; Coto, Carlos; Ferraro, Lindsay C; Davis, Kathryn A

    2016-12-01

    Subcortical band heterotopia (SBH) is a disorder of neuronal migration most commonly due to mutations of the Doublecortin (DCX) gene. A range of phenotypes is seen, with most patients having some degree of epilepsy and intellectual disability. Advanced diffusion and structural magnetic resonance imaging (MRI) sequences may be useful in identifying heterotopias and dysplasias of different sizes in drug-resistant epilepsy. We describe a patient with SBH and drug-resistant epilepsy and investigate neurite density, neurite dispersion, and diffusion parameters as compared to a healthy control through the use of multiple advanced MRI modalities. Neurite density and dispersion in heterotopia was found to be more similar to white matter than gray matter. Neurite density and dispersion maps obtained using diffusion imaging may be able to better characterize different subtypes of heterotopia.

  20. Faster scaling of visual neurons in cortical areas relative to subcortical structures in non-human primate brains

    OpenAIRE

    Collins, C. E.; Leitch, D. B.; Wong, P.; Kaas, J. H.; Herculano-Houzel, Suzana

    2012-01-01

    Cortical expansion, both in absolute terms and in relation to subcortical structures, is considered a major trend in mammalian brain evolution with important functional implications, given that cortical computations should add complexity and flexibility to information processing. Here, we investigate the numbers of neurons that compose 4 structures in the visual pathway across 11 non-human primate species to determine the scaling relationships that apply to these structures and among them. We...

  1. Subcortical Band Heterotopia (SBH) in Rat Offspring Following Maternal Hypothyroxinemia: Structural and Functional Characteristics

    Science.gov (United States)

    Thyroid hormones (TH) play crucial roles in brain maturation, neuronal migration, and neocortical lamination. Subcortical band heterotopia (SBH) represent a class of neuronal migration errors in humans that are often associated with childhood epilepsy. We have previously reported...

  2. Central cortico-subcortical involvement: a distinct pattern of brain damage caused by perinatal and postnatal asphyxia in term infants

    NARCIS (Netherlands)

    Rademakers, R. P.; van der Knaap, M. S.; Verbeeten, B.; Barth, P. G.; Valk, J.

    1995-01-01

    The MR findings in a characteristic pattern of hypoxic-ischemic brain damage in term infants are described. The MR images of seven patients with cerebral palsy and a specific pattern of central cortico-subcortical cerebral damage were studied retrospectively and correlated with clinical findings.

  3. Development of the subcortical brain structures in the second trimester: assessment with 7.0-T MRI

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Haiwei; Geng, Hequn; Lin, Xiangtao; Feng, Lei; Liu, Shuwei [Shandong University, Research Center for Sectional and Imaging Anatomy, School of Medicine, Jinan, Shandong Province (China); Zhang, Zhonghe [Provincial Hospital Affiliated to Shandong University, Department of Medical Imaging, Jinan, Shandong (China); Teng, Gaojun; Fang, Fang; Zang, Fengchao [Southeast University School of Clinical Medicine, Department of Radiology, Zhong Da Hospital, Nanjing, Jiangsu (China)

    2012-10-15

    This study aims to obtain the signal intensity changes and quantitative measurements of the subcortical brain structures of 12-22 weeks gestational age (GA). Sixty-nine fetal specimens were selected and scanned by 7.0-T MR. The signal intensity changes of the subcortical brain structures were analyzed. The three-dimensional visualization models of the germinal matrix, caudate nucleus, lentiform nucleus, and dorsal thalamus were rebuilt with Amira 4.1, and the developmental trends between the measurements and GA were analyzed. The germinal matrix was delineated on 7.0-T MR images at 12 weeks GA, with high signals on T1-weighted images (WI). While at 16 weeks GA, the caudate nucleus, lentiform nucleus, and internal and external capsules could be distinguished. The caudate nucleus was high signal intensity on T1WI. The signal intensity of the putamen was high on T1WI during 15-17 weeks GA and was delineated as an area with uneven signal intensities. The signal intensity of the peripheral area of the putamen became higher after 18 weeks GA. The signal intensity of the globus pallidus was high on T1WI and low on T2WI after 20 weeks GA. At 18 weeks GA, the claustrum was delineated with low signals on T2WI. Measurements of the germinal matrix, caudate nucleus, lentiform nucleus, and dorsal thalamus linearly increased with the GA. Development of the subcortical brain structures during 12-22 weeks GA could be displayed with 7.0-T MRI. The measurement provides significant reference beneficial to the clinical evaluation of fetal brain development. (orig.)

  4. A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome.

    Science.gov (United States)

    des Portes, V; Pinard, J M; Billuart, P; Vinet, M C; Koulakoff, A; Carrié, A; Gelot, A; Dupuis, E; Motte, J; Berwald-Netter, Y; Catala, M; Kahn, A; Beldjord, C; Chelly, J

    1998-01-09

    X-SCLH/LIS syndrome is a neuronal migration disorder with disruption of the six-layered neocortex. It consists of subcortical laminar heterotopia (SCLH, band heterotopia, or double cortex) in females and lissencephaly (LIS) in males, leading to epilepsy and cognitive impairment. We report the characterization of a novel CNS gene encoding a 40 kDa predicted protein that we named Doublecortin and the identification of mutations in four unrelated X-SCLH/LIS cases. The predicted protein shares significant homology with the N-terminal segment of a protein containing a protein kinase domain at its C-terminal part. This novel gene is highly expressed during brain development, mainly in fetal neurons including precursors. The complete disorganization observed in lissencephaly and heterotopia thus seems to reflect a failure of early events associated with neuron dispersion.

  5. Automatic segmentation of subcortical brain structures in MR images using information fusion.

    Science.gov (United States)

    Barra, V; Boire, J Y

    2001-07-01

    This paper reports a new automated method for the segmentation of internal cerebral structures using an information fusion technique. The information is provided both by images and expert knowledge, and consists in morphological, topological, and tissue constitution data. All this ambiguous, complementary and redundant information is managed using a three-step fusion scheme based on fuzzy logic. The information is first modeled into a common theoretical frame managing its imprecision and incertitude. The models are then fused and a decision is taken in order to reduce the imprecision and to increase the certainty in the location of the structures. The whole process is illustrated on the segmentation of thalamus, putamen, and head of the caudate nucleus from expert knowledge and magnetic resonance images, in a protocol involving 14 healthy volunteers. The quantitative validation is achieved by comparing computed, manually segmented structures and published data by means of indexes assessing the accuracy of volume estimation and spatial location. Results suggest a consistent volume estimation with respect to the expert quantification and published data, and a high spatial similarity of the segmented and computed structures. This method is generic and applicable to any structure that can be defined by expert knowledge and morphological images.

  6. Toward defining deep brain stimulation targets in MNI space: A subcortical atlas based on multimodal MRI, histology and structural connectivity.

    Science.gov (United States)

    Ewert, Siobhan; Plettig, Philip; Li, Ningfei; Chakravarty, M Mallar; Collins, D Louis; Herrington, Todd M; Kühn, Andrea A; Horn, Andreas

    2017-05-20

    Three-dimensional atlases of subcortical brain structures are valuable tools to reference anatomy in neuroscience and neurology. For instance, they can be used to study the position and shape of the three most common deep brain stimulation (DBS) targets, the subthalamic nucleus (STN), internal part of the pallidum (GPi) and ventral intermediate nucleus of the thalamus (VIM) in spatial relationship to DBS electrodes. Here, we present a composite atlas based on manual segmentations of a multimodal high resolution brain template, histology and structural connectivity. In a first step, four key structures were defined on the template itself using a combination of multispectral image analysis and manual segmentation. Second, these structures were used as anchor points to coregister a detailed histological atlas into standard space. Results show that this approach significantly improved coregistration accuracy over previously published methods. Finally, a sub-segmentation of STN and GPi into functional zones was achieved based on structural connectivity. The result is a composite atlas that defines key nuclei on the template itself, fills the gaps between them using histology and further subdivides them using structural connectivity. We show that the atlas can be used to segment DBS targets in single subjects, yielding more accurate results compared to priorly published atlases. The atlas will be made publicly available and constitutes a resource to study DBS electrode localizations in combination with modern neuroimaging methods. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Cortical and Subcortical Structural Plasticity Associated with the Glioma Volumes in Patients with Cerebral Gliomas Revealed by Surface-Based Morphometry

    Directory of Open Access Journals (Sweden)

    Jinping Xu

    2017-06-01

    Full Text Available Postlesional plasticity has been identified in patients with cerebral gliomas by inducing a large functional reshaping of brain networks. Although numerous non-invasive functional neuroimaging methods have extensively investigated the mechanisms of this functional redistribution in patients with cerebral gliomas, little effort has been made to investigate the structural plasticity of cortical and subcortical structures associated with the glioma volume. In this study, we aimed to investigate whether the contralateral cortical and subcortical structures are able to actively reorganize by themselves in these patients. The compensation mechanism following contralateral cortical and subcortical structural plasticity is considered. We adopted the surface-based morphometry to investigate the difference of cortical and subcortical gray matter (GM volumes in a cohort of 14 healthy controls and 13 patients with left-hemisphere cerebral gliomas [including 1 patients with World Health Organization (WHO I, 8 WHO II, and 4 WHO III]. The glioma volume ranges from 5.1633 to 208.165 cm2. Compared to healthy controls, we found significantly increased GM volume of the right cuneus and the left thalamus, as well as a trend toward enlargement in the right globus pallidus in patients with cerebral gliomas. Moreover, the GM volumes of these regions were positively correlated with the glioma volumes of the patients. These results provide evidence of cortical and subcortical enlargement, suggesting the usefulness of surface-based morphometry to investigate the structural plasticity. Moreover, the structural plasticity might be acted as the compensation mechanism to better fulfill its functions in patients with cerebral gliomas as the gliomas get larger.

  8. Subcortical band heterotopia in rat offspring following maternal hypothyroxinaemia: structural and functional characteristics.

    Science.gov (United States)

    Gilbert, M E; Ramos, R L; McCloskey, D P; Goodman, J H

    2014-08-01

    Thyroid hormones (TH) play crucial roles in brain maturation and are important for neuronal migration and neocortical lamination. Subcortical band heterotopia (SBH) represent a class of neuronal migration errors in humans that are often associated with childhood epilepsy. We have previously reported the presence of SBH in a rodent model of low level hypothyroidism induced by maternal exposure to the goitrogen, propylthiouracil (PTU). In the present study, we report the dose-response characteristics of this developmental malformation and the connectivity of heterotopic neurones with other brain regions, as well as their functionality. Pregnant rats were exposed to varying concentrations of PTU through the drinking water (0-10 p.p.m.) beginning on gestational day 6 to produce graded levels of TH insufficiency. Dose-dependent increases in the volume of the SBH present in the corpus callosum were documented in the adult offspring, with a clear presence at concentrations of PTU that resulted in minor (< 15%) reductions in maternal serum thyroxine as measured when pups were weaned. SBH contain neurones, oligodendrocytes, astrocytes and microglia. Monoaminergic and cholinergic processes were prevalent and many of the axons were myelinated. Anatomical connectivity of SBH neurones to cortical neurones and the synaptic functionality of these anatomical connections was verified by ex vivo field potential recordings. SBH persisted in adult offspring despite a return to euthyroid status on termination of exposure and these offspring displayed an increased sensitivity to seizures. Features of this model are attractive with respect to the investigation of the molecular mechanisms of cortical development, the effectiveness of therapeutic intervention in hypothyroxinaemia during pregnancy and the impact of the very modest TH imbalance that accompanies exposure to environmental contaminants. © Published 2014. This article is a U.S. Government work and is in the public domain in the

  9. Manually segmented template library for 8-year-old pediatric brain MRI data with 16 subcortical structures.

    Science.gov (United States)

    Garg, Amanmeet; Wong, Darren; Popuri, Karteek; Poskitt, Kenneth J; Fitzpatrick, Kevin; Bjornson, Bruce; Grunau, Ruth E; Beg, Mirza Faisal

    2014-10-01

    Manual segmentation of anatomy in brain MRI data taken to be the closest to the "gold standard" in quality is often used in automated registration-based segmentation paradigms for transfer of template labels onto the unlabeled MRI images. This study presents a library of template data with 16 subcortical structures in the central brain area which were manually labeled for MRI data from 22 children (8 male, [Formula: see text]). The lateral ventricle, thalamus, caudate, putamen, hippocampus, cerebellum, third vevntricle, fourth ventricle, brainstem, and corpuscallosum were segmented by two expert raters. Cross-validation experiments with randomized template subset selection were conducted to test for their ability to accurately segment MRI data under an automated segmentation pipeline. A high value of the dice similarity coefficient ([Formula: see text], [Formula: see text], [Formula: see text]) and small Hausdorff distance ([Formula: see text], [Formula: see text], [Formula: see text]) of the automated segmentation against the manual labels was obtained on this template library data. Additionally, comparison with segmentation obtained from adult templates showed significant improvement in accuracy with the use of an age-matched library in this cohort. A manually delineated pediatric template library such as the one described here could provide a useful benchmark for testing segmentation algorithms.

  10. A Multiatlas Approach for Segmenting Subcortical Brain Structures using Local Patch Distance

    Directory of Open Access Journals (Sweden)

    Neela RAMAMOORTHI

    2015-12-01

    Full Text Available In the diagnosis and treatment of various diseases, often segmenting the brain structures from MRI data is the key step. Since there are larger variations in the anatomical structures of the brain, segmentation becomes a crucial process. Using only the intensity information is not enough to segment structures since two or more structures may share the same tissues. Recently, the use of multiple pre-labeled images called atlases or templates are used in the process of segmentation of image data. Both single atlas and multiple atlases can be used. However, using multiple atlases in the segmentation process proves a dominant method in segmenting brain structures with challenging and overlapping structures. In this paper, we propose two multi atlas segmentation methods: Local Patch Distance Segmentation (LPDS and Weighted Local Patch Distance Segmentation (WLPDS. These methods use local patch distance in the label fusion step. LPDS uses local patch distance to find the best patch match for label propagation. WLPDS uses local patch distance to calculate local weights. The brain MRI images from the MICCAI 2012 segmentation challenge are chosen for experimental purposes. These datasets are publicly available and can be downloaded from MIDAS. The proposed techniques are compared with existing fusion methods such as majority voting and weighted majority voting using the similarity measures such as Dice overlap (DC, Jaccard coefficient (JC and Kappa statistics. For 20 test data sets, LPDS gives DICE=0.95±0.05, JACCARD=0.91±0.04 and KAPPA=0.94±0.07. WLPDS gives DICE=0.98±0.02, JACCARD=0.92±0.03 and KAPPA=0.95±0.04.

  11. Baseline shape diffeomorphometry patterns of subcortical and ventricular structures in predicting conversion of mild cognitive impairment to Alzheimer's disease.

    Science.gov (United States)

    Tang, Xiaoying; Holland, Dominic; Dale, Anders M; Younes, Laurent; Miller, Michael I

    2015-01-01

    In this paper, we propose a novel predictor for the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). This predictor is based on the shape diffeomorphometry patterns of subcortical and ventricular structures (left and right amygdala, hippocampus, thalamus, caudate, putamen, globus pallidus, and lateral ventricle) of 607 baseline scans from the Alzheimer's Disease Neuroimaging Initiative database, including a total of 210 healthy control subjects, 222 MCI subjects, and 175 AD subjects. The optimal predictor is obtained via a feature selection procedure applied to all of the 14 sets of shape features via linear discriminant analysis, resulting in a combination of the shape diffeomorphometry patterns of the left hippocampus, the left lateral ventricle, the right thalamus, the right caudate, and the bilateral putamen. Via 10-fold cross-validation, we substantiate our method by successfully differentiating 77.04% (104/135) of the MCI subjects who converted to AD within 36 months and 71.26% (62/87) of the non-converters. To be specific, for the MCI-converters, we are capable of correctly predicting 82.35% (14/17) of subjects converting in 6 months, 77.5% (31/40) of subjects converting in 12 months, 74.07% (20/27) of subjects converting in 18 months, 78.13% (25/32) of subjects converting in 24 months, and 73.68% (14/19) of subject converting in 36 months. Statistically significant correlation maps were observed between the shape diffeomorphometry features of each of the 14 structures, especially the bilateral amygdala, hippocampus, lateral ventricle, and two neuropsychological test scores--the Alzheimer's Disease Assessment Scale-Cognitive Behavior Section and the Mini-Mental State Examination.

  12. Contribution of subcortical structures to cognition assessed with invasive electrophysiology in humans

    Directory of Open Access Journals (Sweden)

    Thomas F Münte

    2008-07-01

    Full Text Available Implantation of deep brain stimulation (DBS electrodes via stereotactic neurosurgery has become a standard procedure for the treatment of Parkinson’s disease. More recently, the range of neuropsychiatric conditions and the possible target structures suitable for DBS have greatly increased. The former include obsessive compulsive disease, depression, obesity, tremor, dystonia, Tourette’s syndrome and cluster-headache. In this article we argue that several of the target structures for DBS (nucleus accumbens, posterior inferior hypothalamus, nucleus subthalamicus, nuclei in the thalamus, globus pallidus internus, nucleus pedunculopontinus are located at strategic positions with brain circuits related to motivational behaviors, learning, and motor regulation. Recording from DBS electrodes either during the operation or post-operatively from externalized leads while the patient is performing cognitive tasks tapping the functions of the respective circuits provides a new window on the brain mechanisms underlying these functions. This is exemplified by a study of a patient suffering from obsessive-compulsive disease from whom we recorded in a flanker task designed to tap action monitoring processes while he received a DBS electrode in the right nucleus accumbens. Clear error-related modulations were obtained from the target structure, demonstrating a role of the nucleus accumbens in action monitoring. Based on recent conceptualizations of several different functional loops and on neuroimaging results we suggest further lines of research using this new window on brain functions.

  13. Artefactual subcortical hyperperfusion in PET studies normalized to global mean: lessons from Parkinson's disease

    DEFF Research Database (Denmark)

    Borghammer, Per; Cumming, Paul; Aanerud, Joel

    2008-01-01

    AIM: Recent studies of Parkinson's disease (PD) report subcortical increases of cerebral blood flow (CBF) or cerebral metabolic rate of glucose (CMRglc), after conventional normalization to the global mean. However, if the global mean CBF or CMRglc is decreased in the PD group, this normalization...... necessarily generates artificial relative increases in regions unaffected by the disease. This potential bias may explain the reported subcortical increases in PD. To test this hypothesis, we performed simulations with manipulation and subsequently analysis of sets of quantitative CBF maps by voxel...... the global mean or to the white matter mean. RESULTS: In Simulation I, global normalization robustly created artefactual subcortical increases, irrespective of analysis methodology. Simulation II demonstrated that an increased signal from the small subcortical structures involved in PD can probably...

  14. Reassessing the causal structure of enduring involvement

    Science.gov (United States)

    Jinhee Jun; Gerard T. Kyle; James D. Absher; William E. Hammitt

    2009-01-01

    Guided by tenets of identity theory, we hypothesized a causal structure of enduring involvement suggesting that self-relevant components precede the other dimensions. We used Kyle et al.'s (2004a) Modified Involvement Scale, in which leisure involvement is conceptualized as a multidimensional construct consisting of identity affirmation, identity expression,...

  15. Discriminative analysis of early-stage Alzheimer's disease and normal aging with automatic segmentation technique in subcortical gray matter structures: a multicenter in vivo MRI volumetric and DTI study.

    Science.gov (United States)

    Li, Ya-di; He, Hui-jin; Dong, Hai-bo; Feng, Xiao-yuan; Xie, Guo-ming; Zhang, Ling-jun

    2013-12-01

    Previous studies have revealed that amyloid depositions exist in not only the hippocampus but in other subcortical gray matter structures as well. Diffusion-tensor imaging (DTI) parameters might be more sensitive measures of early degeneration in Alzheimer's disease (AD) than conventional magnetic resonance imaging (MRI) techniques. To evaluate the significance of the volumes and the mean diffusivity (MD) values of subcortical gray matter structures in discrimination between early-stage AD and normal subjects using the Integrated Registration and Segmentation Tool in FMRIB's Software Library. Fifty-three cases of early-stage AD and 30 normal aging volunteers from two hospitals were scanned with 3D-FSPGRIR and SSSE-EPI sequences using two similar 1.5T MR systems. The mean relative volumes and mean MD values of subcortical gray matter structures were compared between early-stage AD and control groups. Binary logistic regression analysis and receiver-operating characteristic (ROC) curves were applied to assess the diagnostic significance of every structure's relative volume, MD value, and combination of both. The relative volumes of the left hippocampus, right amygdala, bilateral thalamus, right caudate, left putamen, and bilateral pallidum were significantly lower in the early-stage AD group than in the control group (P early-stage AD group (P early-stage AD. Diffusive imaging has great diagnostic significance in early-stage AD. The combination of both imaging modalities can lead to better discrimination between early-stage AD and normal aging.

  16. Subcortical correlates of individual differences in aptitude.

    Science.gov (United States)

    Jung, Rex E; Ryman, Sephira G; Vakhtin, Andrei A; Carrasco, Jessica; Wertz, Chris; Flores, Ranee A

    2014-01-01

    The study of individual differences encompasses broad constructs including intelligence, creativity, and personality. However, substantially less research is devoted to the study of specific aptitudes in spite of their importance to educational, occupational, and avocational success. We sought to determine subcortical brain structural correlates of several broad aptitudes including Math, Vocabulary, Foresight, Paper Folding, and Inductive Reasoning in a large (N = 107), healthy, young (age range  = 16-29) cohort. Subcortical volumes were measured using an automated technique (FreeSurfer) across structures including bilateral caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus, amygdala, and five equal regions of the corpus callosum. We found that performance on measures of each aptitude was predicted by different subcortical structures: Math--higher right nucleus accumbens volume; Vocabulary--higher left hippocampus volume; Paper Folding--higher right thalamus volume; Foresight--lower right thalamus and higher mid anterior corpus callosum volume; Inductive Reasoning--higher mid anterior corpus callosum volume. Our results support general findings, within the cognitive neurosciences, showing lateralization of structure-function relationships, as well as more specific relationships between individual structures (e.g., left hippocampus) and functions relevant to particular aptitudes (e.g., Vocabulary).

  17. Subcortical correlates of individual differences in aptitude.

    Directory of Open Access Journals (Sweden)

    Rex E Jung

    Full Text Available The study of individual differences encompasses broad constructs including intelligence, creativity, and personality. However, substantially less research is devoted to the study of specific aptitudes in spite of their importance to educational, occupational, and avocational success. We sought to determine subcortical brain structural correlates of several broad aptitudes including Math, Vocabulary, Foresight, Paper Folding, and Inductive Reasoning in a large (N = 107, healthy, young (age range  = 16-29 cohort. Subcortical volumes were measured using an automated technique (FreeSurfer across structures including bilateral caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus, amygdala, and five equal regions of the corpus callosum. We found that performance on measures of each aptitude was predicted by different subcortical structures: Math--higher right nucleus accumbens volume; Vocabulary--higher left hippocampus volume; Paper Folding--higher right thalamus volume; Foresight--lower right thalamus and higher mid anterior corpus callosum volume; Inductive Reasoning--higher mid anterior corpus callosum volume. Our results support general findings, within the cognitive neurosciences, showing lateralization of structure-function relationships, as well as more specific relationships between individual structures (e.g., left hippocampus and functions relevant to particular aptitudes (e.g., Vocabulary.

  18. Gap junctions mediate large-scale Turing structures in a mean-field cortex driven by subcortical noise

    Science.gov (United States)

    Steyn-Ross, Moira L.; Steyn-Ross, D. A.; Wilson, M. T.; Sleigh, J. W.

    2007-07-01

    One of the grand puzzles in neuroscience is establishing the link between cognition and the disparate patterns of spontaneous and task-induced brain activity that can be measured clinically using a wide range of detection modalities such as scalp electrodes and imaging tomography. High-level brain function is not a single-neuron property, yet emerges as a cooperative phenomenon of multiply-interacting populations of neurons. Therefore a fruitful modeling approach is to picture the cerebral cortex as a continuum characterized by parameters that have been averaged over a small volume of cortical tissue. Such mean-field cortical models have been used to investigate gross patterns of brain behavior such as anesthesia, the cycles of natural sleep, memory and erasure in slow-wave sleep, and epilepsy. There is persuasive and accumulating evidence that direct gap-junction connections between inhibitory neurons promote synchronous oscillatory behavior both locally and across distances of some centimeters, but, to date, continuum models have ignored gap-junction connectivity. In this paper we employ simple mean-field arguments to derive an expression for D2 , the diffusive coupling strength arising from gap-junction connections between inhibitory neurons. Using recent neurophysiological measurements reported by Fukuda [J. Neurosci. 26, 3434 (2006)], we estimate an upper limit of D2≈0.6cm2 . We apply a linear stability analysis to a standard mean-field cortical model, augmented with gap-junction diffusion, and find this value for the diffusive coupling strength to be close to the critical value required to destabilize the homogeneous steady state. Computer simulations demonstrate that larger values of D2 cause the noise-driven model cortex to spontaneously crystalize into random mazelike Turing structures: centimeter-scale spatial patterns in which regions of high-firing activity are intermixed with regions of low-firing activity. These structures are consistent with the

  19. Subcortical shape and volume abnormalities in an elderly HIV+ cohort

    Science.gov (United States)

    Wade, Benjamin S. C.; Valcour, Victor; Busovaca, Edgar; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H.; Wang, Yalin; Thompson, Paul M.

    2015-03-01

    Over 50% of HIV+ individuals show significant impairment in psychomotor functioning, processing speed, working memory and attention [1, 2]. Patients receiving combination antiretroviral therapy may still have subcortical atrophy, but the profile of HIV-associated brain changes is poorly understood. With parametric surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV+ subjects (4 female; age=65.35 ± 2.21) and 31 uninfected elderly controls (2 female; age=64.68 ± 4.57) scanned with MRI as part of a San Francisco Bay Area study of elderly people with HIV. We also investigated whether morphometry was associated with nadir CD4+ (T-cell) counts, viral load and illness duration among HIV+ participants. FreeSurfer was used to segment the thalamus, caudate, putamen, pallidum, hippocampus, amygdala, accumbens, brainstem, callosum and ventricles from brain MRI scans. To study subcortical shape, we analyzed: (1) the Jacobian determinant (JD) indexed over structures' surface coordinates and (2) radial distances (RD) of structure surfaces from a medial curve. A JD less than 1 reflects regional tissue atrophy and greater than 1 reflects expansion. The volumes of several subcortical regions were found to be associated with HIV status. No regional volumes showed detectable associations with CD4 counts, viral load or illness duration. The shapes of numerous subcortical regions were significantly linked to HIV status, detectability of viral RNA and illness duration. Our results show subcortical brain differences in HIV+ subjects in both shape and volumetric domains.

  20. Comparative neuropsychology of cortical and subcortical dementia.

    Science.gov (United States)

    Freedman, M; Oscar-Berman, M

    1986-11-01

    The terms "cortical" and "subcortical" dementia are controversial; however, the clinical distinction between them is real. For example, although Alzheimer's and Parkinson's disease (prototypical of cortical and subcortical dementia, respectively) share clinical features, they differ in the presence of aphasia, apraxia, and agnosia in Alzheimer's disease but not in Parkinson's dementia. We review our studies aimed at clarifying the mechanisms underlying the differences between these neurological disorders. Experimental paradigms adopted from animal models were used to study the functional anatomy and neuropsychological characteristics of Alzheimer's and Parkinson's disease. The tasks administered include delayed alternation (DA) and delayed response (DR), which are sensitive to frontal system damage, and tactile discrimination learning (TOL) and reversal (TRL) paradigms sensitive to parietal system damage. Alzheimer's patients were significantly impaired on all tasks whereas Parkinsonians with dementia were impaired only on DR and TRL. Consideration of neuroanatomical and neuropsychological mechanisms involved in DA, DR, TOL, and TRL appears to have sharpened the distinction between Alzheimer's and Parkinson's dementia. Dementia in Alzheimer's disease may involve dorsolateral frontal, orbitofrontal and parietal systems. In contrast, dementia in Parkinson's disease may involve prominent dorsolateral frontal system damage.

  1. Mapping Subcortical Brain Maturation during Adolescence: Evidence of Hemisphere-and Sex-Specific Longitudinal Changes

    Science.gov (United States)

    Dennison, Meg; Whittle, Sarah; Yücel, Murat; Vijayakumar, Nandita; Kline, Alexandria; Simmons, Julian; Allen, Nicholas B.

    2013-01-01

    Early to mid-adolescence is an important developmental period for subcortical brain maturation, but longitudinal studies of these neurodevelopmental changes are lacking. The present study acquired repeated magnetic resonance images from 60 adolescent subjects (28 female) at ages 12.5 and 16.5 years to map changes in subcortical structure volumes.…

  2. Subcortical biophysical abnormalities in patients with mood disorders.

    Science.gov (United States)

    Kumar, A; Yang, S; Ajilore, O; Wu, M; Charlton, R; Lamar, M

    2014-06-01

    Cortical-subcortical circuits have been implicated in the pathophysiology of mood disorders. Structural and biochemical abnormalities have been identified in patients diagnosed with mood disorders using magnetic resonance imaging-related approaches. In this study, we used magnetization transfer (MT), an innovative magnetic resonance approach, to study biophysical changes in both gray and white matter regions in cortical-subcortical circuits implicated in emotional regulation and behavior. Our study samples comprised 28 patients clinically diagnosed with major depressive disorder (MDD) and 31 non-depressed subjects of comparable age and gender. MT ratio (MTR), representing the biophysical integrity of macromolecular proteins within key components of cortical-subcortical circuits-the caudate, thalamic, striatal, orbitofrontal, anterior cingulate and dorsolateral regions-was the primary outcome measure. In our study, the MTR in the head of the right caudate nucleus was significantly lower in the MDD group when compared with the comparison group. MTR values showed an inverse relationship with age in both groups, with more widespread relationships observed in the MDD group. These data indicate that focal biophysical abnormalities in the caudate nucleus may be central to the pathophysiology of depression and critical to the cortical-subcortical abnormalities that underlie mood disorders. Depression may also accentuate age-related changes in the biophysical properties of cortical and subcortical regions. These observations have broad implications for the neuronal circuitry underlying mood disorders across the lifespan.

  3. Cortical and subcortical mapping of language areas: correlation of functional MRI and tractography in a 3T scanner with intraoperative cortical and subcortical stimulation in patients with brain tumors located in eloquent areas.

    Science.gov (United States)

    Jiménez de la Peña, M; Gil Robles, S; Recio Rodríguez, M; Ruiz Ocaña, C; Martínez de Vega, V

    2013-01-01

    To describe the detection of cortical areas and subcortical pathways involved in language observed in MRI activation studies and tractography in a 3T MRI scanner and to correlate the findings of these functional studies with direct intraoperative cortical and subcortical stimulation. We present a series of 14 patients with focal brain tumors adjacent to eloquent brain areas. All patients underwent neuropsychological evaluation before and after surgery. All patients underwent MRI examination including structural sequences, perfusion imaging, spectroscopy, functional imaging to determine activation of motor and language areas, and 3D tractography. All patients underwent cortical mapping through cortical and subcortical stimulation during the operation to resect the tumor. Postoperative follow-up studies were done 24 hours after surgery. The correlation of motor function and of the corticospinal tract determined by functional MRI and tractography with intraoperative mapping of cortical and subcortical motor areas was complete. The eloquent brain areas of language expression and reception were strongly correlated with intraoperative cortical mapping in all but two cases (a high grade infiltrating glioma and a low grade glioma located in the frontal lobe). 3D tractography identified the arcuate fasciculus, the lateral part of the superior longitudinal fasciculus, the subcallosal fasciculus, the inferior fronto-occipital fasciculus, and the optic radiations, which made it possible to mark the limits of the resection. The correlation with the subcortical mapping of the anatomic arrangement of the fasciculi with respect to the lesions was complete. The best treatment for brain tumors is maximum resection without associated deficits, so high quality functional studies are necessary for preoperative planning. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

  4. Reassessing the structure of enduring leisure involvement

    Science.gov (United States)

    Jinhee Jun; Gerard T. Kyle; Symeon P. Vlachopoulos; Nicholas D. Theodorakis; James D. Absher; William E. Hammitt

    2012-01-01

    Using data collected from U.S. and Greek respondents, we tested an alternate conceptualization of enduring leisure involvement where identity was considered a key driver of other affective and conative outcomes. Rather than existing on the same temporal plane, as has been the tradition in the leisure literature, we observed that identity was an antecedent of the other...

  5. Involvement of intraocular structures in disseminated histoplasmosis.

    Science.gov (United States)

    Ala-Kauhaluoma, Marianne; Aho, Inka; Ristola, Matti; Karma, Anni

    2010-06-01

    To describe ocular involvement and response to treatment in a patient with human immunodeficiency virus (HIV) infection with severe progressive disseminated histoplasmosis (PDH). We report a 35-year-old HIV-infected patient seen in our clinics over a period of 4 years. During antiretroviral treatment (ART), the HIV load became undetectable at 3 months; however, CD4 T-cell count increased slowly and rose to 100 cells/microl. Histoplasma capsulatum was cultured from skin pustules, cerebrospinal fluid (CF) and aqueous humour. The patient developed central nervous system (CNS) involvement 2 months and panuveitis in both eyes 4 months after the initiation of ART. With intravenous liposomal amphotericin B followed by oral voricanozole, the chorioretinal lesions of the right eye (RE) became inactivated and magnetic resonance imaging (MRI) lesions of CNS disappeared. Relapse of the inflammation in the anterior segment of the left eye (LE) resulted in a total closure of the chamber angle and severe glaucoma. Despite medical therapy, two cyclophotocoagulations, total vitrectomy and repeated intravitreal amphotericin B injections, LE became blind. Histoplasma capsulatum was cultured from the aqueous humour after antifungal therapy of 16 months' duration. PDH with intraocular and CNS manifestations was probably manifested by an enhanced immune response against a previous subclinical disseminated infection. It seems difficult to eradicate H. capsulatum from the anterior segment of the eye in an immunocompromised patient.

  6. Common behavioral clusters and subcortical anatomy in stroke

    Science.gov (United States)

    Corbetta, Maurizio; Ramsey, Lenny; Callejas, Alicia; Baldassarre, Antonello; Hacker, Carl D.; Siegel, Joshua S.; Astafiev, Serguei V.; Rengachary, Jennifer; Zinn, Kristina; Lang, Catherine E.; Connor, Lisa Tabor; Fucetola, Robert; Strube, Michael; Carter, Alex R.; Shulman, Gordon L.

    2015-01-01

    SUMMARY A long-held view is that stroke causes many distinct neurological syndromes due to damage of specialized cortical and subcortical centers. However, it is unknown if a syndrome-based description is helpful in characterizing behavioral deficits across a large number of patients. We studied a large prospective sample of first-time stroke patients with heterogeneous lesions at 1–2 weeks post-stroke. We measured behavior over multiple domains and lesion anatomy with structural MRI and a probabilistic atlas of white matter pathways. Multivariate methods estimated the percentage of behavioral variance explained by structural damage. A few clusters of behavioral deficits spanning multiple functions explained neurological impairment. Stroke topography was predominantly subcortical, and disconnection of white matter tracts critically contributed to behavioral deficits and their correlation. The locus of damage explained more variance for motor and language than memory or attention deficits. Our findings highlight the need for better models of white matter damage on cognition. PMID:25741721

  7. Male brain ages faster: the age and gender dependence of subcortical volumes.

    Science.gov (United States)

    Király, András; Szabó, Nikoletta; Tóth, Eszter; Csete, Gergő; Faragó, Péter; Kocsis, Krisztián; Must, Anita; Vécsei, László; Kincses, Zsigmond Tamás

    2016-09-01

    Effects of gender on grey matter (GM) volume differences in subcortical structures of the human brain have consistently been reported. Recent research evidence suggests that both gender and brain size influences volume distribution in subcortical areas independently. The goal of this study was to determine the effects of the interplay between brain size, gender and age contributing to volume differences of subcortical GM in the human brain. High-resolution T1-weighted images were acquired from 53 healthy males and 50 age-matched healthy females. Total GM volume was determined using voxel-based morphometry. We used model-based subcortical segmentation analysis to measure the volume of subcortical nuclei. Main effects of gender, brain volume and aging on subcortical structures were examined using multivariate analysis of variance. No significant difference was found in total brain volume between the two genders after correcting for total intracranial volume. Our analysis revealed significantly larger hippocampus volume for females. Additionally, GM volumes of the caudate nucleus, putamen and thalamus displayed a significant age-related decrease in males as compared to females. In contrast to this only the thalamic volume loss proved significant for females. Strikingly, GM volume decreases faster in males than in females emphasizing the interplay between aging and gender on subcortical structures. These findings might have important implications for the interpretation of the effects of unalterable factors (i.e. gender and age) in cross-sectional structural MRI studies. Furthermore, the volume distribution and changes of subcortical structures have been consistently related to several neuropsychiatric disorders (e.g. Parkinson's disease, attention deficit hyperactivity disorder, etc.). Understanding these changes might yield further insight in the course and prognosis of these disorders.

  8. Large-scale cortico-subcortical functional networks in focal epilepsies: The role of the basal ganglia

    Directory of Open Access Journals (Sweden)

    Eva Výtvarová

    2017-01-01

    Significance: Focal epilepsies affect large-scale brain networks beyond the epileptogenic zones. Cortico-subcortical functional connectivity disturbance was displayed in LTLE, FLE, and POLE. Significant changes in the resting-state functional connectivity between cortical and subcortical structures suggest an important role of the BG and thalamus in focal epilepsies.

  9. Sparsity enables estimation of both subcortical and cortical activity from MEG and EEG.

    Science.gov (United States)

    Krishnaswamy, Pavitra; Obregon-Henao, Gabriel; Ahveninen, Jyrki; Khan, Sheraz; Babadi, Behtash; Iglesias, Juan Eugenio; Hämäläinen, Matti S; Purdon, Patrick L

    2017-11-14

    Subcortical structures play a critical role in brain function. However, options for assessing electrophysiological activity in these structures are limited. Electromagnetic fields generated by neuronal activity in subcortical structures can be recorded noninvasively, using magnetoencephalography (MEG) and electroencephalography (EEG). However, these subcortical signals are much weaker than those generated by cortical activity. In addition, we show here that it is difficult to resolve subcortical sources because distributed cortical activity can explain the MEG and EEG patterns generated by deep sources. We then demonstrate that if the cortical activity is spatially sparse, both cortical and subcortical sources can be resolved with M/EEG. Building on this insight, we develop a hierarchical sparse inverse solution for M/EEG. We assess the performance of this algorithm on realistic simulations and auditory evoked response data, and show that thalamic and brainstem sources can be correctly estimated in the presence of cortical activity. Our work provides alternative perspectives and tools for characterizing electrophysiological activity in subcortical structures in the human brain. Copyright © 2017 the Author(s). Published by PNAS.

  10. Glutamate concentration in the medial prefrontal cortex predicts resting-state cortical-subcortical functional connectivity in humans.

    Directory of Open Access Journals (Sweden)

    Niall W Duncan

    Full Text Available Communication between cortical and subcortical regions is integral to a wide range of psychological processes and has been implicated in a number of psychiatric conditions. Studies in animals have provided insight into the biochemical and connectivity processes underlying such communication. However, to date no experiments that link these factors in humans in vivo have been carried out. To investigate the role of glutamate in individual differences in communication between the cortex--specifically the medial prefrontal cortex (mPFC--and subcortical regions in humans, a combination of resting-state fMRI, DTI and MRS was performed. The subcortical target regions were the nucleus accumbens (NAc, dorsomedial thalamus (DMT, and periaqueductal grey (PAG. It was found that functional connectivity between the mPFC and each of the NAc and DMT was positively correlated with mPFC glutamate concentrations, whilst functional connectivity between the mPFC and PAG was negatively correlated with glutamate concentration. The correlations involving mPFC glutamate and FC between the mPFC and each of the DMT and PAG were mirrored by correlations with structural connectivity, providing evidence that the glutamatergic relationship may, in part, be due to direct connectivity. These results are in agreement with existing results from animal studies and may have relevance for MDD and schizophrenia.

  11. Fast synaptic subcortical control of hippocampal circuits.

    Science.gov (United States)

    Varga, Viktor; Losonczy, Attila; Zemelman, Boris V; Borhegyi, Zsolt; Nyiri, Gábor; Domonkos, Andor; Hangya, Balázs; Holderith, Noémi; Magee, Jeffrey C; Freund, Tamás F

    2009-10-16

    Cortical information processing is under state-dependent control of subcortical neuromodulatory systems. Although this modulatory effect is thought to be mediated mainly by slow nonsynaptic metabotropic receptors, other mechanisms, such as direct synaptic transmission, are possible. Yet, it is currently unknown if any such form of subcortical control exists. Here, we present direct evidence of a strong, spatiotemporally precise excitatory input from an ascending neuromodulatory center. Selective stimulation of serotonergic median raphe neurons produced a rapid activation of hippocampal interneurons. At the network level, this subcortical drive was manifested as a pattern of effective disynaptic GABAergic inhibition that spread throughout the circuit. This form of subcortical network regulation should be incorporated into current concepts of normal and pathological cortical function.

  12. Formulaic language in cortical and subcortical disease: Evidence of the dual process model.

    Directory of Open Access Journals (Sweden)

    Kelly Bridges

    2014-04-01

    of formulaic language is at least partially modulated by the intact subcortical region, supporting the dual process model. Subcortical disease: Parkinson’s disease and recited speech Evidence of the involvement of subcortical structures in the production of formulaic language also comes from studies of subcortical injury. An examination of the spontaneous speech of people with basal ganglia stroke found fewer formulaic expressions than healthy adults or people with left hemisphere lesions (Sidtis et al., 2009; Illes et al., 1988. Similarly, a case study of a man post-subcortical stroke described deficits in the ability to recite prayers, a longer form of formulaic language (Speedie et al., 1993. A study of individuals with Parkinson’s disease (PD, a progressive disease causing dysfunction of the basal ganglia circuitry, sought to extend Speedie et al.’s (1993 findings with group data (Bridges et al., 2013b. Two groups of people with PD (M age = 60.9, 6 with deep brain stimulation of the subthalamic nucleus (STN-DBS, and 7 without STN-DBS, and another 7 healthy participants (HC were asked to recite familiar poems, prayers and rhymes (Humpty Dumpty, Twinkle Twinkle Little Star, Mary Had a Little Lamb, Jack and Jill, Roses are Red, Sticks and Stones, The Lord’s Prayer, and The Pledge of Allegiance. Groups were compared for the percent of error words produced (out of all non-target words produced during the task. The STN-DBS group in the OFF condition (a more severe state of subcortical dysfunction produced significantly more error words (37.13% than HCs (17.44%. The STN-DBS group in the ON condition (33.34% and the PD group without STN-DBS (21.53% fell between the STN-DBS OFF condition and HCs. These results provide further support for the dual process model of language production, as individuals with the most severe state of subcortical dysfunction perform poorly on recited speech tasks when compared to healthy adults, indicating the importance of intact

  13. The role of the thalamus in the human subcortical vestibular system.

    Science.gov (United States)

    Conrad, Julian; Baier, Bernhard; Dieterich, Marianne

    2014-01-01

    Most of our knowledge concerning central vestibular pathways is derived from animal studies while evidence of the functional importance and localization of these pathways in humans is less well defined. The termination of these pathways at the thalamic level in humans is even less known. In this review we summarize the findings concerning the central subcortical vestibular pathways in humans and the role of these structures in the central vestibular system with regard to anatomical localization and function. Also, we review the role of the thalamus in the pathogenesis of higher order sensory deficits such as spatial neglect, pusher syndrome or thalamic astasia and the correlation of these phenomena with findings of a vestibular tone imbalance at the thalamic level. By highlighting thalamic structures involved in vestibular signal processing and relating the different nomenclatures we hope to provide a base for future studies on thalamic sensory signal processing.

  14. Modulation of Cortical-subcortical Networks in Parkinson’s Disease by Applied Field Effects

    Directory of Open Access Journals (Sweden)

    Christopher William Hess

    2013-09-01

    Full Text Available Studies suggest that endogenous field effects may play a role in neuronal oscillations and communication. Non-invasive transcranial electrical stimulation with low-intensity currents can also have direct effects on the underlying cortex as well as distant network effects. While Parkinson's disease (PD is amenable to invasive neuromodulation in the basal ganglia by deep brain stimulation, techniques of non-invasive neuromodulation like transcranial direct current stimulation (tDCS and transcranial alternating current stimulation (tACS are being investigated as possible therapies. tDCS and tACS have the potential to influence the abnormal cortical-subcortical network activity that occurs in PD through sub-threshold changes in cortical excitability or through entrainment or disruption of ongoing rhythmic cortical activity. This may allow for the targeting of specific features of the disease involving abnormal oscillatory activity, as well as the enhancement of potential cortical compensation for basal ganglia dysfunction and modulation of cortical plasticity in neurorehabilitation. However, little is currently known about how cortical stimulation will affect subcortical structures, the size of any effect, and the factors of stimulation that will influence these effects.

  15. [Subcortical dementia in HTLV-I tropical spastic paraparesis. Study of 43 cases].

    Science.gov (United States)

    Cartier, L; Gormaz, A

    1999-04-01

    Central nervous system damage associated to HTLV-I does not limit itself to the spinal cord, but also involves subcortical structures, producing cognitive impairment and behavioral changes which eventually could conform a new form of subcortical dementia. To study cognitive changes in patients with HTLV-I associated myelopathy. Forty three patients (31 female) with Tropical Spastic Paraparesis, aged 52 years old as a mean and with a disease lasting a mean of 7.5 years, were studied. The diagnosis was based on clinical, radiological and neurophysiological changes. The virus was identified with ELISA, indirect immunofluorescence, Western Blot or proviral DNA identification. Cognitive assessment was done using the Wechler Adult Intelligence Scale (WAIS) and Benton Visual Retention Test (form D). Patients were grouped according to their motor disability in; 23 patients with independent spastic gait, 11 patients that needed support to walk and 9 patients unable to walk. WAIS test demonstrated cognitive impairment with special deficit in some subtests such as Digit Span, Digit Symbol, Picture Arrangement and Object Assembly. Benton Test also disclosed cognitive impairment. There was a positive relationship between cognitive and motor performance. At least 50% of patients with Tropical Spastic Paraparesis have certain degree of intellectual and affective impairment.

  16. Cortical and subcortical networks in human secondarily generalized tonic–clonic seizures

    Science.gov (United States)

    Varghese, G. I.; Purcaro, M.J.; Motelow, J.E.; Enev, M.; McNally, K. A.; Levin, A.R.; Hirsch, L. J.; Tikofsky, R.; Zubal, I. G.; Paige, A. L.; Spencer, S. S.

    2009-01-01

    Generalized tonic–clonic seizures are among the most dramatic physiological events in the nervous system. The brain regions involved during partial seizures with secondary generalization have not been thoroughly investigated in humans. We used single photon emission computed tomography (SPECT) to image cerebral blood flow (CBF) changes in 59 secondarily generalized seizures from 53 patients. Images were analysed using statistical parametric mapping to detect cortical and subcortical regions most commonly affected in three different time periods: (i) during the partial seizure phase prior to generalization; (ii) during the generalization period; and (iii) post-ictally. We found that in the pre-generalization period, there were focal CBF increases in the temporal lobe on group analysis, reflecting the most common region of partial seizure onset. During generalization, individual patients had focal CBF increases in variable regions of the cerebral cortex. Group analysis during generalization revealed that the most consistent increase occurred in the superior medial cerebellum, thalamus and basal ganglia. Post-ictally, there was a marked progressive CBF increase in the cerebellum which spread to involve the bilateral lateral cerebellar hemispheres, as well as CBF increases in the midbrain and basal ganglia. CBF decreases were seen in the fronto-parietal association cortex, precuneus and cingulate gyrus during and following seizures, similar to the ‘default mode’ regions reported previously to show decreased activity in seizures and in normal behavioural tasks. Analysis of patient behaviour during and following seizures showed impaired consciousness at the time of SPECT tracer injections. Correlation analysis across patients demonstrated that cerebellar CBF increases were related to increases in the upper brainstem and thalamus, and to decreases in the fronto-parietal association cortex. These results reveal a network of cortical and subcortical structures that

  17. Cortical and subcortical networks in human secondarily generalized tonic-clonic seizures.

    Science.gov (United States)

    Blumenfeld, H; Varghese, G I; Purcaro, M J; Motelow, J E; Enev, M; McNally, K A; Levin, A R; Hirsch, L J; Tikofsky, R; Zubal, I G; Paige, A L; Spencer, S S

    2009-04-01

    Generalized tonic-clonic seizures are among the most dramatic physiological events in the nervous system. The brain regions involved during partial seizures with secondary generalization have not been thoroughly investigated in humans. We used single photon emission computed tomography (SPECT) to image cerebral blood flow (CBF) changes in 59 secondarily generalized seizures from 53 patients. Images were analysed using statistical parametric mapping to detect cortical and subcortical regions most commonly affected in three different time periods: (i) during the partial seizure phase prior to generalization; (ii) during the generalization period; and (iii) post-ictally. We found that in the pre-generalization period, there were focal CBF increases in the temporal lobe on group analysis, reflecting the most common region of partial seizure onset. During generalization, individual patients had focal CBF increases in variable regions of the cerebral cortex. Group analysis during generalization revealed that the most consistent increase occurred in the superior medial cerebellum, thalamus and basal ganglia. Post-ictally, there was a marked progressive CBF increase in the cerebellum which spread to involve the bilateral lateral cerebellar hemispheres, as well as CBF increases in the midbrain and basal ganglia. CBF decreases were seen in the fronto-parietal association cortex, precuneus and cingulate gyrus during and following seizures, similar to the 'default mode' regions reported previously to show decreased activity in seizures and in normal behavioural tasks. Analysis of patient behaviour during and following seizures showed impaired consciousness at the time of SPECT tracer injections. Correlation analysis across patients demonstrated that cerebellar CBF increases were related to increases in the upper brainstem and thalamus, and to decreases in the fronto-parietal association cortex. These results reveal a network of cortical and subcortical structures that are most

  18. Structuring User Involvement in Panel-Based Living Labs

    Directory of Open Access Journals (Sweden)

    Lieven De Marez

    2012-09-01

    Full Text Available A shift towards open innovation approaches with systematic user involvement has occurred within media and ICT. One of the emerging frameworks structuring these initiatives is the "living lab" approach. Despite the growing evidence of the beneficial nature of customer involvement in product development, research into specific user characteristics for innovation is still scarce, particularly in living labs, with the notable exception of literature on lead users. Especially within the context of living labs for ICT and media innovation, an application of the lead-user framework looks promising as a way to structure and facilitate user involvement. This article is based on the experiences of three Flemish living lab initiatives with a panel-based approach and provides a customer characteristics framework that guides user involvement in living labs.

  19. Safety of eptifibatide for subcortical stroke progression.

    Science.gov (United States)

    Martin-Schild, Sheryl; Shaltoni, Hashem; Abraham, Anitha T; Barreto, Andrew D; Hallevi, Hen; Gonzales, Nicole R; Grotta, James C; Savitz, Sean I

    2009-01-01

    There is no proven treatment for stroke progression in patients with subcortical infarcts. Eptifibatide, a glycoprotein IIb/IIIa inhibitor, might halt stroke progression by improving flow in the microcirculation. We conducted a retrospective analysis of patients with subcortical stroke who experienced deterioration and were treated with eptifibatide (loading dose 180 microg/kg; infusion 2 m microg/kg/min) for 24-48 h. Oral antiplatelet agents were started 6 h before discontinuation of eptifibatide. Twenty-four patients with subcortical strokes were treated. The median admission NIHSS score was 5.0, which worsened to 8.5 (motor 5.0) before starting eptifibatide. The median NIHSS score 24 h after starting eptifibatide was 5.5. At 24 h, 42% had motor NIHSS scores less than or equal to pre-deterioration scores (50% for total NIHSS), and 50% had improved at least 1 motor point compared to pre-eptifibatide scores, which was sustained until hospital discharge. At discharge, the median total NIHSS score was 4.5. Ninety-two percent of patients were discharged home or to inpatient rehabilitation. Treatment was stopped early in 1 case due to a platelet drop Eptifibatide infusion may be safe in patients with subcortical ischemic strokes. Future studies are needed to test the safety and potential efficacy of this agent in subcortical stroke progression. Copyright (c) 2009 S. Karger AG, Basel.

  20. Impact of an Invasive Longhorned Beetle, Tetropium fuscum (Coleoptera: Cerambycidae), on Community Structure of Subcortical and Wood-Associated Insects in Eastern Canada.

    Science.gov (United States)

    Heustis, Allyson; Moise, Eric R D; Johns, Rob; Pureswaran, Deepa S; Heard, Stephen B

    2017-12-29

    Tetropium fuscum (Fabricius) (Coleoptera: Cerambycidae), a phloem-feeding and wood-boring beetle introduced from Eurasia, attacks spruce in eastern Canada alongside its native congener Tetropium cinnamopterum Kirby. We reared phloem- and wood-feeding insects (and their predators) from bolts of red and Norway spruce (Picea rubens and Picea abies) in Nova Scotia, comparing insect communities between bolts with added eggs of T. fuscum or T. cinnamopterum and bolts without added Tetropium (controls). We tested for impacts of each Tetropium on insect community structure (Simpson's diversity, richness, and evenness). We also asked whether, consistent with Darwin's Naturalization Hypothesis, Tetropium spp. would have greater impacts on emergence of its closer relatives (which might be most likely to compete and/or share natural enemies). Addition of Tetropium eggs (either species) to bolts lowered insect diversity in both host trees. Both richness and evenness components of diversity were always lower in +Tetropium treatments, although different components reached statistical significance in different Tetropium species × host combinations. Addition of Tetropium spp. significantly reduced emergence of some species: Evodinus monticola (Randall) (Coleoptera: Cerambycidae) was reduced by T. fuscum on both hosts and by T. cinnamopterum on Norway spruce; Hylobius congener Dalla Torre, Schenkling, and Marshall was reduced by T. fuscum on red spruce; and Xylophagus sp. (Diptera: Xylophagidae) was reduced by T. cinnamopterum on Norway spruce. However, there was no relationship between Tetropium's impact on a community member and their phylogenetic relatedness, and the overall impacts of Tetropium presence were not very different between T. fuscum and T. cinnamopterum. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Partly segregated cortico-subcortical pathways support phonologic and semantic verbal fluency: A lesion study.

    Science.gov (United States)

    Chouiter, Leila; Holmberg, Josefina; Manuel, Aurelie L; Colombo, Françoise; Clarke, Stephanie; Annoni, Jean-Marie; Spierer, Lucas

    2016-08-04

    Verbal fluency refers to the ability to generate as many words as possible in a limited time interval, without repetition and according to either a phonologic (each word begins with a given letter) or a semantic rule (each word belongs to a given semantic category). While current literature suggests the involvement of left fronto-temporal structures in fluency tasks, whether the same or distinct brain areas are necessary for each type of fluency remains unclear. We tested the hypothesis for an involvement of partly segregated cortico-subcortical structures between phonologic and semantic fluency by examining with a voxel-based lesion symptom mapping approach the effects of brain lesions on fluency scores corrected for age and education level in a group of 191 unselected brain-damaged patients with a first left or right hemispheric lesion. There was a positive correlation between the scores to the two types of fluency, suggesting that common mechanisms underlie the word generation independent of the production rule. The lesion-symptom mapping revealed that lesions to left basal ganglia impaired both types of fluency and that left superior temporal, supramarginal and rolandic operculum lesions selectively impaired phonologic fluency and left middle temporal lesions impaired semantic fluency. Our results corroborate current neurocognitive models of word retrieval and production, and refine the role of cortical-subcortical interaction in lexical search by highlighting the common executive role of basal ganglia in both types of verbal fluency and the preferential involvement of the ventral and dorsal language pathway in semantic and phonologic fluency, respectively. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Effect of a structured course involving goal management training

    NARCIS (Netherlands)

    Van Hooren, Susan; Valentijn, Susanne; Bosma, Hans; Ponds, Rudolf; Van Boxtel, Martin; Levine, Brian; Robertson, Ian; Jolles, Jelle

    2010-01-01

    Objective: The objective of this study was to investigate the effects of a structured 6-week neuropsychological course on the executive functioning of older adults with cognitive complaints. Methods: A randomised controlled design was used involving 69 community dwelling individuals aged 55 years

  3. Cognitively Engaging Activity is Associated with Greater Cortical and Subcortical Volumes

    Directory of Open Access Journals (Sweden)

    Talia R. Seider

    2016-05-01

    Full Text Available As the population ages and dementia becomes a growing healthcare concern, it is increasingly important to identify targets for intervention to delay or attenuate cognitive decline. Research has shown that the most successful interventions aim at altering lifestyle factors. Thus, this study examined how involvement in physical, cognitive, and social activity is related to brain structure in older adults. Sixty-five adults (mean age = 71.4 years, standard deviation = 8.9 received the Community Healthy Activities Model Program for Seniors (CHAMPS, a questionnaire that polls everyday activities in which older adults may be involved, and also underwent structural magnetic resonance imaging. Stepwise regression with backwards selection was used to predict weekly time spent in either social, cognitive, light physical, or heavy physical activity from the volume of one of the cortical or subcortical regions of interest (corrected by intracranial volume as well as age, education, and gender as control variables. Regressions revealed that more time spent in cognitive activity was associated with greater volumes of all brain regions studied: total cortex (β = .289, p = .014, frontal (β = .276, p = .019, parietal (β = .305, p = .009, temporal (β = .275, p = .020, and occipital (β = .256, p = .030 lobes, and thalamus (β = .310, p = .010, caudate (β = .233, p = .049, hippocampus (β = .286, p = .017, and amygdala (β = .336, p = .004. These effects remained even after accounting for the positive association between cognitive activity and education. No other activity variable was associated with brain volumes. Results indicate that time spent in cognitively engaging activity is associated with greater cortical and subcortical brain volume. Findings suggest that interventions aimed at increasing levels of cognitive activity may delay cognitive consequences of aging and decrease the risk of developing dementia.

  4. Different structures involved during ictal and interictal epileptic activity in malformations of cortical development: an EEG-fMRI study.

    Science.gov (United States)

    Tyvaert, L; Hawco, C; Kobayashi, E; LeVan, P; Dubeau, F; Gotman, J

    2008-08-01

    Malformations of cortical development (MCDs) are commonly complicated by intractable focal epilepsy. Epileptogenesis in these disorders is not well understood and may depend on the type of MCD. The cellular mechanisms involved in interictal and ictal events are notably different, and could be influenced independently by the type of pathology. We evaluated the relationship between interictal and ictal zones in eight patients with different types of MCD in order to better understand the generation of these activities: four had nodular heterotopia, two focal cortical dysplasia and two subcortical band heterotopia (double-cortex). We used the non-invasive EEG-fMRI technique to record simultaneously all cerebral structures with a high spatio-temporal resolution. We recorded interictal and ictal events during the same session. Ictal events were either electrical only or clinical with minimal motion. BOLD changes were found in the focal cortical dysplasia during interictal and ictal epileptiform events in the two patients with this disorder. Heterotopic and normal cortices were involved in BOLD changes during interictal and ictal events in the two patients with double cortex, but the maximum BOLD response was in the heterotopic band in both patients. Only two of the four patients with nodular heterotopia showed involvement of a nodule during interictal activity. During seizures, although BOLD changes affected the lesion in two patients, the maximum was always in the overlying cortex and never in the heterotopia. For two patients intracranial recordings were available and confirm our findings. The dysplastic cortex and the heterotopic cortex of band heterotopia were involved in interictal and seizure processes. Even if the nodular gray matter heterotopia may have the cellular substrate to produce interictal events, the often abnormal overlying cortex is more likely to be involved during the seizures. The non-invasive BOLD study of interictal and ictal events in MCD

  5. Dysphagia Post Subcortical and Supratentorial Stroke.

    Science.gov (United States)

    Wan, Ping; Chen, Xuhui; Zhu, Lequn; Xu, Shuangjin; Huang, Li; Li, Xiangcui; Ye, Qing; Ding, Ruiying

    2016-01-01

    Studies have recognized that the damage in the subcortical and supratentorial regions may affect voluntary and involuntary aspects of the swallowing function. The current study attempted to explore the dysphagia characteristics in patients with subcortical and supratentorial stroke. Twelve post first or second subcortical and supratentorial stroke patients were included in the study. The location of the stroke was ascertained by computed tomography and magnetic resonance imaging. The characteristics of swallowing disorder were assessed by video fluoroscopic swallowing assessment/fiberoptic endoscopic evaluation of swallowing. The following main parameters were analyzed: oral transit time, pharyngeal delay time, presence of cricopharyngeal muscle achalasia (CMA), distance of laryngeal elevation, the amounts of vallecular residue and pyriform sinus residue (PSR), and the extent of pharyngeal contraction. Eighty-three percent of the 12 patients were found suffering from pharyngeal dysphagia, with 50% having 50%-100% PSRs, 50% having pharyngeal delay, and 41.6% cases demonstrating CMA. Simple regression analysis showed PSRs were most strongly associated with CMA. Pharyngeal delay in the study can be caused by infarcts of basal ganglia/thalamus, infarcts of sensory tract, infarcts of swallowing motor pathways in the centrum semiovale, or a combination of the three. Subcortical and supratentorial stroke may result in pharyngeal dysphagia such as PSR and pharyngeal delay. PSR was mainly caused by CMA. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  6. Hippocampal atrophy in subcortical vascular dementia

    NARCIS (Netherlands)

    van de Pol, L.A.; Gertz, H.J.; Scheltens, P.; Wolf, H

    2011-01-01

    Background and Purpose: New research criteria for subcortical vascular dementia (SVaD) have been suggested to define a more homogeneous subgroup of vascular dementia. Hippocampal (Hc) atrophy is a hallmark of Alzheimer's disease (AD), but it also occurs in other dementia disorders including vascular

  7. Subcortical Facilitation of Behavioral Responses to Threat.

    Science.gov (United States)

    Vida, Mark D; Behrmann, Marlene

    2017-10-12

    Behavioral responses to threat are critical to survival. Several cortical and subcortical brain regions respond selectively to threat. However, the relation of these neural responses and their underlying representations to behavior is unclear. We examined the contribution of lower-order subcortical representations to behavioral responses to threat in adult humans. In Experiments 1 and 2, participants viewed pairs of images presented to the same eye or to different eyes. We observed a monocular advantage, which indicates subcortical facilitation, for ancestral threats (snakes, spiders), but not for modern threats, positive images, or neutral images. In Experiment 3, we presented pairs of snakes or neutral images into the temporal or nasal hemifield. For snakes only, we observed a temporal hemifield advantage, which indicates facilitation by the retino-tectal subcortical pathway. These results advance the current understanding of processing of threat by adult humans by revealing the characteristics of behaviors driven by a lower-order neural mechanism that is specialized for the processing of ancestral threats. The results also contribute to ongoing debates concerning the biological generality of neural mechanisms for processing of complex, emotionally-relevant stimuli by providing evidence for conservation of lower-order neural mechanisms for processing of ancestral threats across both ontogeny and phylogeny.

  8. An Allometric Analysis of Sex and Sex Chromosome Dosage Effects on Subcortical Anatomy in Humans

    Science.gov (United States)

    Clasen, Liv; Giedd, Jay N.; Blumenthal, Jonathan; Lerch, Jason P.; Chakravarty, M. Mallar; Raznahan, Armin

    2016-01-01

    Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings. SIGNIFICANCE STATEMENT Sex and sex-chromosome dosage (SCD) are known to modulate human brain size and cortical anatomy, but very little is known regarding their impact on subcortical structures that work with the cortex to subserve a range of behaviors in health and disease. Moreover

  9. Family structure, nonresident father involvement, and adolescent eating patterns.

    Science.gov (United States)

    Stewart, Susan D; Menning, Chadwick L

    2009-08-01

    To examine the relationship between family structure, nonresident father involvement, and adolescent eating patterns. Analyses were performed on data from Waves 1 and 2 of the National Longitudinal Study of Adolescent Health (Wave 1, N = approximately 15,550; Wave 2, N = approximately 11,540), and a subsample of adolescents from each wave who had a nonresident father (Wave 1, N = approximately 3,745; Wave 2, N = 2,358). Multivariate regression provides estimates of the independent effects of family structure and nonresident father involvement on adolescent eating patterns while controlling for potentially confounding sociodemographic characteristics. Compared with children in traditional households (i.e., two biological or adoptive parents), adolescents in nontraditional family households (single parent, step-parent, no parent) were more likely to display unhealthy eating habits such as skipping breakfast and lunch, eating fewer vegetables, consuming more fast food, and had less parental monitoring of meals. Nonresident father involvement was associated with an increased frequency of eating breakfast and lunch and increased consumption of vegetables (Wave 1) but did not affect adolescents' consumption of fast food. Child support was positively associated with the odds that adolescents would consume dinner. Adolescents in living in nontraditional families were more likely than adolescents living with two biological/adoptive parents to display unhealthy eating habits. Nonresident father involvement was generally associated with healthier eating patterns. Health professionals should keep in mind that children's and adolescents' living arrangements can be complex and have the potential to affect what and how they eat.

  10. Subcortical regional morphology correlates with fluid and spatial intelligence.

    Science.gov (United States)

    Burgaleta, Miguel; MacDonald, Penny A; Martínez, Kenia; Román, Francisco J; Álvarez-Linera, Juan; Ramos González, Ana; Karama, Sherif; Colom, Roberto

    2014-05-01

    Neuroimaging studies have revealed associations between intelligence and brain morphology. However, researchers have focused primarily on the anatomical features of the cerebral cortex, whereas subcortical structures, such as the basal ganglia (BG), have often been neglected despite extensive functional evidence on their relation with higher-order cognition. Here we performed shape analyses to understand how individual differences in BG local morphology account for variability in cognitive performance. Structural MRI was acquired in 104 young adults (45 men, 59 women, mean age = 19.83, SD = 1.64), and the outer surface of striatal structures (caudate, nucleus accumbens, and putamen), globus pallidus, and thalamus was estimated for each subject and hemisphere. Further, nine cognitive tests were used to measure fluid (Gf), crystallized (Gc), and spatial intelligence (Gv). Latent scores for these factors were computed by means of confirmatory factor analysis and regressed vertex-wise against subcortical shape (local displacements of vertex position), controlling for age, sex, and adjusted for brain size. Significant results (FDR intelligence-related prefrontal areas. Copyright © 2013 Wiley Periodicals, Inc.

  11. A case of generalized auditory agnosia with unilateral subcortical brain lesion.

    Science.gov (United States)

    Suh, Hyee; Shin, Yong-Il; Kim, Soo Yeon; Kim, Sook Hee; Chang, Jae Hyeok; Shin, Yong Beom; Ko, Hyun-Yoon

    2012-12-01

    The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. Auditory agnosia is a deficit of auditory object processing defined as a disability to recognize spoken languages and/or nonverbal environmental sounds and music despite adequate hearing while spontaneous speech, reading and writing are preserved. Usually, either the bilateral or unilateral temporal lobe, especially the transverse gyral lesions, are responsible for auditory agnosia. Subcortical lesions without cortical damage rarely causes auditory agnosia. We present a 73-year-old right-handed male with generalized auditory agnosia caused by a unilateral subcortical lesion. He was not able to repeat or dictate but to perform fluent and comprehensible speech. He could understand and read written words and phrases. His auditory brainstem evoked potential and audiometry were intact. This case suggested that the subcortical lesion involving unilateral acoustic radiation could cause generalized auditory agnosia.

  12. Gray matter volume changes in chronic subcortical stroke: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Qingqing Diao

    2017-01-01

    Full Text Available This study aimed to investigate the effects of lesion side and degree of motor recovery on gray matter volume (GMV difference relative to healthy controls in right-handed subcortical stroke. Structural MRI data were collected in 97 patients with chronic subcortical ischemic stroke and 79 healthy controls. Voxel-wise GMV analysis was used to investigate the effects of lesion side and degree of motor recovery on GMV difference in right-handed chronic subcortical stroke patients. Compared with healthy controls, right-lesion patients demonstrated GMV increase (P < 0.05, voxel-wise false discovery rate correction in the bilateral paracentral lobule (PCL and supplementary motor area (SMA and the right middle occipital gyrus (MOG; while left-lesion patients did not exhibit GMV difference under the same threshold. Patients with complete and partial motor recovery showed similar degree of GMV increase in right-lesion patients. However, the motor recovery was correlated with the GMV increase in the bilateral SMA in right-lesion patients. These findings suggest that there exists a lesion-side effect on GMV difference relative to healthy controls in right-handed patients with chronic subcortical stroke. The GMV increase in the SMA may facilitate motor recovery in subcortical stroke patients.

  13. Delayed visual maturation: pupillary responses implicate subcortical and cortical visual systems.

    Science.gov (United States)

    Cocker, K D; Moseley, M J; Stirling, H F; Fielder, A R

    1998-03-01

    Vision in very early infancy is probably subserved by subcortical pathways, with many cortical processes only fully emerging by 3 months of age. The improvement of vision in delayed visual maturation (DVM) occurs around this time, and this has given rise to the suggestion that the condition may have a subcortical basis that resolves with the appearance of cortical function. To explore further the role of cortical and subcortical visual systems in DVM we studied the visual development in identical twins, one of whom had type 1b DVM. Two non-invasive methods of investigating visual pathway function were employed: the acuity card procedure (a behavioural response) and luminance and grating pupillometry. While the former reflects both subcortical and cortical function and can be detected at birth, pupil responses to gratings reflect cortical activity alone and normally become measurable at 1 month of age. Development of both behavioural and pupillary responses was delayed in DVM, indicating that although the underlying defect is primarily subcortical, secondarily it delays the emergence of cortically mediated responses. The observed rapidity of improvement--over a very few days and within a narrow age range--suggests a discrete rather than a widespread structural abnormality, the improvement of which is closely linked to postmenstrual age.

  14. Neuropsychological performance in patients with subcortical stroke

    Directory of Open Access Journals (Sweden)

    Silviane Pinheiro Campos de Andrade

    2012-05-01

    Full Text Available Vascular cognitive impairment (VCI is characterized by cognitive compromise predominantly of executive dysfunction. OBJECTIVES: To assess cognitive functions in VCI, focusing on executive functions, to observe functional losses in relation to activities of daily living (ADLs and to detect early symptoms prior to the onset of dementia. METHODS: We evaluated healthy subjects matched for gender, education and age to patients with diagnosis of subcortical vascular disease who had a stroke classified into three groups: 1 vascular lesions and no impairment; 2 vascular cognitive impairment with no dementia (VCIND; 3 vascular dementia (VaD. RESULTS AND DISCUSSION: The performance on neuropsychological tests differed among groups, worsening with increased impairment level. The probable VaD group demonstrated impaired performance in memory, processing speed and verbal production, while the VCIND group showed attention deficits. CONCLUSION: Impairment in executive functions and difficulties in ADLs allow us to differentiate levels of impairment in groups of subcortical vascular disease.

  15. Subcortical cerebral infarctions in sickle cell trait.

    OpenAIRE

    Reyes, M G

    1989-01-01

    At necropsy, two patients with sickle cell trait and progressive motor and visual deficits, lethargy and coma showed infarctions of the deep cerebral white matter and brain stem. The findings in these patients and another reported in the literature suggest that subcortical infarctions may be more common in sickle cell trait than has been recognised and should be suspected in any patient with sickle cell trait who presents with an unusual neurological illness.

  16. Tumor suppressor CADM1 is involved in epithelial cell structure.

    Science.gov (United States)

    Sakurai-Yageta, Mika; Masuda, Mari; Tsuboi, Yumi; Ito, Akihiko; Murakami, Yoshinori

    2009-12-18

    The tumor suppressor, CADM1, is involved in cell adhesion and preferentially inactivated in invasive cancer. We have previously reported that CADM1 associates with an actin-binding protein, 4.1B/DAL-1, and a scaffold protein, membrane protein palmitoylated 3 (MPP3)/DLG3. However, underlying mechanism of tumor suppression by CADM1 is not clarified yet. Here, we demonstrate that MPP1/p55 and MPP2/DLG2, as well as MPP3, interact with both CADM1 and 4.1B, forming a tripartite complex. We then examined cell biological roles of CADM1 and its complex in epithelia using HEK293 cells. Among MPP1-3, MPP2 is recruited to the CADM1-4.1B complex in the early process of adhesion in HEK293 cells. By suppression of CADM1 expression using siRNA, HEK293 lose epithelia-like structure and show flat morphology with immature cell adhesion. 4.1B and MPP2, as well as E-cadherin and ZO-1, are mislocalized from the membrane by depletion of CADM1 in HEK293. Mislocalization of MPP2 is also observed in several cancer cells lacking CADM1 expression with the transformed morphology. These findings suggest that CADM1 is involved in the formation of epithelia-like cell structure with 4.1B and MPP2, while loss of its function could cause morphological transformation of cancer cells.

  17. Magnetisation transfer measurements of the subcortical grey and white matter in Parkinson's disease with and without dementia and in progressive supranuclear palsy

    Energy Technology Data Exchange (ETDEWEB)

    Hanyu, H.; Asano, T.; Sakurai, H.; Takasaki, M. [Dept. of Geriatric Medicine, Tokyo Medical University (Japan); Shindo, H.; Abe, K. [Dept. of Radiology, Tokyo Medical University (Japan)

    2001-07-01

    We measured the magnetisation transfer ratio (MTR) in the subcortical grey and white matter of 11 patients with idiopathic Parkinson's disease (PD) without dementia, six with PD with dementia (PDD), six with progressive supranuclear palsy (PSP), and 12 elderly control subjects to assess regional differences in structural brain damage. There were no significant differences in MTR in any region between PD and controls. However, patients with PDD had significantly lower MTR in the subcortical white matter, including the frontal white matter and the genu of the corpus callosum than the controls, whereas PSP had significantly lower MTR in the subcortical grey matter, including the putamen, globus pallidus and thalamus, in addition to the subcortical white matter. This suggests that regional patterns of structural brain damage can be detected using the magnetisation transfer technique. Measurement of MTR in the subcortical grey and white matter may be useful in differential diagnosis. (orig.)

  18. Cortical and subcortical mechanisms of brain-machine interfaces.

    Science.gov (United States)

    Marchesotti, Silvia; Martuzzi, Roberto; Schurger, Aaron; Blefari, Maria Laura; Del Millán, José R; Bleuler, Hannes; Blanke, Olaf

    2017-06-01

    Technical advances in the field of Brain-Machine Interfaces (BMIs) enable users to control a variety of external devices such as robotic arms, wheelchairs, virtual entities and communication systems through the decoding of brain signals in real time. Most BMI systems sample activity from restricted brain regions, typically the motor and premotor cortex, with limited spatial resolution. Despite the growing number of applications, the cortical and subcortical systems involved in BMI control are currently unknown at the whole-brain level. Here, we provide a comprehensive and detailed report of the areas active during on-line BMI control. We recorded functional magnetic resonance imaging (fMRI) data while participants controlled an EEG-based BMI inside the scanner. We identified the regions activated during BMI control and how they overlap with those involved in motor imagery (without any BMI control). In addition, we investigated which regions reflect the subjective sense of controlling a BMI, the sense of agency for BMI-actions. Our data revealed an extended cortical-subcortical network involved in operating a motor-imagery BMI. This includes not only sensorimotor regions but also the posterior parietal cortex, the insula and the lateral occipital cortex. Interestingly, the basal ganglia and the anterior cingulate cortex were involved in the subjective sense of controlling the BMI. These results inform basic neuroscience by showing that the mechanisms of BMI control extend beyond sensorimotor cortices. This knowledge may be useful for the development of BMIs that offer a more natural and embodied feeling of control for the user. Hum Brain Mapp 38:2971-2989, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  19. Motor recovery and microstructural change in rubro-spinal tract in subcortical stroke.

    Science.gov (United States)

    Takenobu, Yohei; Hayashi, Takuya; Moriwaki, Hiroshi; Nagatsuka, Kazuyuki; Naritomi, Hiroaki; Fukuyama, Hidenao

    2014-01-01

    The mechanism of motor recovery after stroke may involve reorganization of the surviving networks. However, details of adaptive changes in structural connectivity are not well understood. Here, we show long-term changes in white matter microstructure that relate to motor recovery in stroke patients. We studied ten subcortical ischemic stroke patients who showed motor hemiparesis at the initial clinical examination and an infarcted lesion centered in the posterior limb of internal capsule of the unilateral hemisphere at the initial diffusion-weighted magnetic resonance imaging scan. The participants underwent serial diffusion tensor imaging and motor function assessments at three consecutive time points; within 2 weeks, and at 1 and 3 months after the onset. Fractional anisotropy (FA) was analyzed for regional differences between hemispheres and time points, as well as for correlation with motor recovery using a tract-based spatial statistics analysis. The results showed significantly increased FA in the red nucleus and dorsal pons in the ipsi-lesional side at 3 months, and significantly decreased FA in the ipsi-lesional internal capsule at all time points, and in the cerebral peduncle, corona radiata, and corpus callosum at 3 months. In the correlation analysis, FA values of clusters in the red nucleus, dorsal pons, midbody of corpus callosum, and cingulum were positively correlated with recovery of motor function. Our study suggests that changes in white matter microstructure in alternative descending motor tracts including the rubro-spinal pathway, and interhemispheric callosal connections may play a key role in compensating for motor impairment after subcortical stroke.

  20. Cortical and subcortical processing of short duration speech stimuli in trained rock musicians: a pilot study.

    Science.gov (United States)

    Kumar, Prawin; Anil, Sam Publius; Grover, Vibhu; Sanju, Himanshu Kumar; Sinha, Sachchidanand

    2017-02-01

    Most trained musicians are actively involved in rigorous practice from several years to achieve a high level of proficiency. Therefore, musicians are best group to research changes or modification in brain structures and functions across several information processing systems. This study aimed to investigate cortical and subcortical processing of short duration speech stimuli in trained rock musicians and non-musicians. Two groups of participant (experimental and control groups) in the age range of 18-25 years were selected for the study. Experimental group includes 15 rock musicians who had minimum professional training of 5 years of rock music, and each member had to be a regular performer of rock music for at least 15 h a week. Further age-matched 15 participants who were not having any formal training of any music served as non-musicians, in the control group. The speech-evoked ABR (S-ABR) and speech-evoked ALLR (S-LLR) with short duration speech 'synthetic /da/' was elicited in both groups. Different measures were analyzed for S-ABR and S-LLR. For S-ABR, MANOVA revealed significant main effect of groups on latencies of wave V, wave A, and amplitude of wave V/A slope. Similarly, Kruskal-Wallis test showed significantly higher F 0 amplitude in rock musicians compared with non-musicians. For S-LLR, MANOVA showed statistically significant differences observed for latencies of wave P2 and N2 and amplitude measures of P2-N2 amplitude. This study indicated better neural processing of short duration speech stimuli at subcortical as well as cortical level among rock musicians when compared with non-musicians.

  1. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

    NARCIS (Netherlands)

    Guadalupe, Tulio; Mathias, Samuel R.; Vanerp, Theo G. M.; Whelan, Christopher D.; Zwiers, Marcel P.; Abe, Yoshinari; Abramovic, Lucija; Agartz, Ingrid; Andreassen, Ole A.; Arias-Vasquez, Alejandro; Aribisala, Benjamin S.; Armstrong, Nicola J.; Arolt, Volker; Artiges, Eric; Ayesa-Arriola, Rosa; Baboyan, Vatche G.; Banaschewski, Tobias; Barker, Gareth; Bastin, Mark E.; Baune, Bernhard T.; Blangero, John; Bokde, Arun L. . W.; Boedhoe, Premika S. . W.; Bose, Anushree; Brem, Silvia; Brodaty, Henry; Bromberg, Uli; Brooks, Samantha; Buechel, Christian; Buitelaar, Jan; Calhoun, Vince D.; Cannon, Dara M.; Cattrell, Anna; Cheng, Yuqi; Conrod, Patricia J.; Conzelmann, Annette; Corvin, Aiden; Crespo-Facorro, Benedicto; Crivello, Fabrice; Dannlowski, Udo; De Zubicaray, Greig I.; De Zwarte, Sonja M. C.; Deary, Ian J.; Desrivieres, Sylvane; Doan, Nhat Trung; Donohoe, Gary; Dorum, Erlend S.; Ehrlich, Stefan; Espeseth, Thomas; Fernandez, Guillen; Flor, Herta; Fouche, Jean-Paul; Frouin, Vincent; Fukunaga, Masaki; Gallinat, Jurgen; Garavan, Hugh; Gill, Michael; Suarez, Andrea Gonzalez; Gowland, Penny; Grabe, Hans J.; Grotegerd, Dominik; Gruber, Oliver; Hagenaars, Saskia; Hashimoto, Ryota; Hauser, Tobias U.; Heinz, Andreas; Hibar, Derrek P.; Hoekstra, Pieter J.; Hoogman, Martine; Howells, Fleur M.; Hu, Hao; Pol, Hilleke E. Hulshoff; Huyser, Chaim; Ittermann, Bernd; Jahanshad, Neda; Jonsson, Erik G.; Jurk, Sarah; Kahn, Rene S.; Kelly, Sinead; Kraemer, Bernd; Kugel, Harald; Kwon, Jun Soo; Lemaitre, Herve; Lesch, Klaus-Peter; Lochner, Christine; Luciano, Michelle; Marquand, Andre F.; Martin, Nicholas G.; Martinez-Zalacain, Ignacio; Martinot, Jean-Luc; Mataix-Cols, David; Mather, Karen; McDonald, Colm; McMahon, Katie L.; Medland, Sarah E.; Menchon, Jose M.; Morris, Derek W.; Mothersill, Omar; Maniega, Susana Munoz; Mwangi, Benson; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswaamy, Janardhanan C.; Nees, Frauke; Nordvik, Jan E.; Onnink, A. Marten H.; Opel, Nils; Ophoff, Roel; Martinot, Marie-Laure Paillere; Orfanos, Dimitri Papadopoulos; Pauli, Paul; Paus, Tomas; Poustka, Luise; Reddy, Janardhan Y. C.; Renteria, Miguel E.; Roiz-Santianez, Roberto; Roos, Annerine; Royle, Natalie A.; Sachdev, Perminder; Sanchez-Juan, Pascual; Schmaal, Lianne; Schumann, Gunter; Shumskaya, Elena; Smolka, Michael N.; Soares, Jair C.; Soriano-Mas, Carles; Stein, Dan J.; Strike, Lachlan T.; Toro, Roberto; Turner, Jessica A.; Tzourio-Mazoyer, Nathalie; Uhlmann, Anne; Hernandez, Maria Valdes; Van den Heuvel, Odile A.; Van der Meer, Dennis; Van Haren, Neeltje E. M.; Veltman, Dick J.; Venkatasubramanian, Ganesan; Vetter, Nora C.; Vuletic, Daniella; Walitza, Susanne; Walter, Henrik; Walton, Esther; Wang, Zhen; Wardlaw, Joanna; Wen, Wei; Westlye, Lars T.; Whelan, Robert; Wittfeld, Katharina; Wolfers, Thomas; Wright, Margaret J.; Xu, Jian; Xu, Xiufeng; Yun, Je-Yeon; Zhao, JingJing; Franke, Barbara; Thompson, Paul M.; Glahn, David C.; Mazoyer, Bernard; Fisher, Simon E.; Francks, Clyde

    2017-01-01

    The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain

  2. Examining the subcortical infarcts in the era of acute multimodality CT imaging

    Directory of Open Access Journals (Sweden)

    Mindy Tan

    2016-12-01

    Full Text Available Background: Lacunar infarcts have been characterized as small subcortical infarcts, resulting from in situ microatheroma or lipohyalinosis in small vessels. Based on this hypothesis, such infarcts should not be associated with large areas of perfusion deficits extending beyond subcortical regions to involve cortical regions. By contrast, selected small subcortical infarcts, as defined by MR imaging in the subacute or chronic stage, may initially have large perfusion deficits or related large vessel occlusions. These infarcts with ‘lacunar’ phenotype may also be caused by disease in the parent vessel and may have very different stroke mechanisms from small vessel disease. Our aim was to describe differences in imaging characteristics between patients with small subcortical infarction with ‘lacunar phenotype’ from those with lacunar mechanism. Methods: Patients undergoing acute CT Perfusion/angiography (CTP/CTA within 6 hours of symptom onset and follow-up magnetic resonance imaging (MRI for ischaemic stroke were included (2009-2013. A lacunar infarct was defined as a single subcortical infarct (SSI ≤20 mm on follow-up MRI. Presence of perfusion deficits, vessel occlusion and infarct dimensions were compared between lacunar infarcts and other topographical infarct types. Results: Overall, 182 patients (mean age 66.4±15.3 years, 66% male were included. SSI occurred in 31 (17% patients. Of these, 12 (39% patients had a perfusion deficit compared with those with any cortical infarction (120/142, 67%, and the smallest SSI with a perfusion deficit had a diameter of <5mm. The majority of patients with SSI (8/12, 66.7% had a relevant vessel occlusion. A quarter of SSIs had a large-artery stroke mechanism evident on acute CTP/CTA. Lacunar mechanism was present in 3/8 patients with corona radiata, 5/10 lentiform nucleus, 5/6 posterior limb of internal capsule PLIC, 3/5 thalamic infarcts and 1/2 miscellaneous locations. There was a trend toward

  3. Preserved episodic memory in subcortical band heterotopia.

    Science.gov (United States)

    Janzen, Laura; Sherman, Elisabeth; Langfitt, John; Berg, Michel; Connolly, Mary

    2004-05-01

    Neuropsychological profiles of four patients with subcortical band heterotopia (SBH) are presented to delineate further the phenotype of this disorder. Standardized, norm-referenced measures of cognitive functioning, including intelligence, processing speed, attention, language, visuomotor skills, memory, and fine motor ability were administered to four patients with magnetic resonance imaging evidence of SBH. Despite intellectual impairment and other severe cognitive deficits, all four patients displayed relatively intact episodic memory. This selective sparing of memory functions has not been previously reported in individuals with SBH and suggests that doublecortin does not play a role in the development of memory systems in the mesial temporal region, which tend to be spared in SBH.

  4. Diffusion tractography of the subcortical auditory system in a postmortem human brain

    OpenAIRE

    Sitek, Kevin

    2017-01-01

    The subcortical auditory system is challenging to identify with standard human brain imaging techniques: MRI signal decreases toward the center of the brain as well as at higher resolution, both of which are necessary for imaging small brainstem auditory structures.Using high-resolution diffusion-weighted MRI, we asked:Can we identify auditory structures and connections in high-resolution ex vivo images?Which structures and connections can be mapped in vivo?

  5. The developing human brain: age-related changes in cortical, subcortical, and cerebellar anatomy.

    Science.gov (United States)

    Sussman, Dafna; Leung, Rachel C; Chakravarty, M Mallar; Lerch, Jason P; Taylor, Margot J

    2016-04-01

    This study is the first to characterize normal development and sex differences across neuroanatomical structures in cortical, subcortical, and cerebellar brain regions in a single large cohort. One hundred and ninety-two magnetic resonance images were examined from 96 typically developing females and 96 age-matched typically developing males from 4 to 18 years of age. Image segmentation of the cortex was conducted with CIVET, while that of the cerebellum, hippocampi, thalamus, and basal ganglia were conducted using the MAGeT algorithm. Cortical thickness analysis revealed that most cortical regions decrease linearly, while surface area increases linearly with age. Volume relative to total cerebrum followed a quadratic trend with age, with only the left supramarginal gyrus showing sexual dimorphism. Hippocampal relative volume increased linearly, while the thalamus, caudate, and putamen decreased linearly, and the cerebellum did not change with age. The relative volumes of several subcortical subregions followed inverted U-shaped trends that peaked at ~12 years of age. Many subcortical structures were found to be larger in females than in males, independently of age, while others showed a sex-by-age interaction. This study provides a comprehensive assessment of cortical, subcortical, and cerebellar growth patterns during normal development, and draws attention to the role of sex on neuroanatomical maturation throughout childhood and adolescence.

  6. Crystal structures of two eukaryotic nucleases involved in RNA metabolism

    DEFF Research Database (Denmark)

    Jonstrup, Anette Thyssen; Midtgaard, Søren Fuglsang; Van, Lan Bich

    as well as the controlled turnover of these in response to changing surrounding conditions is of vital importance to ensure optimal fitness of a cell. Central to both these processes is the degradation of RNA, either as a means of decreasing the level of particular RNAs or as a way to get rid of aberrant...... form the 3'-end of mRNA, is normally the first and also rate-limiting step in cellular mRNA degradation and therefore a key process in the control of eukaryotic mRNA turnover. Since Ccr4p is believed to be the main deadenylase the precise role of Pop2p in the complex is less clear. Nevertheless, Pop2p....... In the nucleus Rrp6p associates with the exosome and participates in the degradation of improperly processed precursor mRNAs and trimming of stable RNAs. The crystal structure of S. cerevisiae Rrp6p presented here displays a conserved DEDD nuclease core with a flanking HRDC domain believed to be involved in RNA...

  7. Subcortical intelligence: caudate volume predicts IQ in healthy adults.

    Science.gov (United States)

    Grazioplene, Rachael G; G Ryman, Sephira; Gray, Jeremy R; Rustichini, Aldo; Jung, Rex E; DeYoung, Colin G

    2015-04-01

    This study examined the association between size of the caudate nuclei and intelligence. Based on the central role of the caudate in learning, as well as neuroimaging studies linking greater caudate volume to better attentional function, verbal ability, and dopamine receptor availability, we hypothesized the existence of a positive association between intelligence and caudate volume in three large independent samples of healthy adults (total N = 517). Regression of IQ onto bilateral caudate volume controlling for age, sex, and total brain volume indicated a significant positive correlation between caudate volume and intelligence, with a comparable magnitude of effect across each of the three samples. No other subcortical structures were independently associated with IQ, suggesting a specific biological link between caudate morphology and intelligence. © 2014 Wiley Periodicals, Inc.

  8. Early neurone loss in Alzheimer's disease: cortical or subcortical?

    Science.gov (United States)

    Arendt, Thomas; Brückner, Martina K; Morawski, Markus; Jäger, Carsten; Gertz, Hermann-Josef

    2015-02-10

    Alzheimer's disease (AD) is a degenerative disorder where the distribution of pathology throughout the brain is not random but follows a predictive pattern used for pathological staging. While the involvement of defined functional systems is fairly well established for more advanced stages, the initial sites of degeneration are still ill defined. The prevailing concept suggests an origin within the transentorhinal and entorhinal cortex (EC) from where pathology spreads to other areas. Still, this concept has been challenged recently suggesting a potential origin of degeneration in nonthalamic subcortical nuclei giving rise to cortical innervation such as locus coeruleus (LC) and nucleus basalis of Meynert (NbM). To contribute to the identification of the early site of degeneration, here, we address the question whether cortical or subcortical degeneration occurs more early and develops more quickly during progression of AD. To this end, we stereologically assessed neurone counts in the NbM, LC and EC layer-II in the same AD patients ranging from preclinical stages to severe dementia. In all three areas, neurone loss becomes detectable already at preclinical stages and is clearly manifest at prodromal AD/MCI. At more advanced AD, cell loss is most pronounced in the NbM > LC > layer-II EC. During early AD, however, the extent of cell loss is fairly balanced between all three areas without clear indications for a preference of one area. We can thus not rule out that there is more than one way of spreading from its site of origin or that degeneration even occurs independently at several sites in parallel.

  9. Frontal-subcortical volumetric deficits in single episode, medication-naive depressed patients and the effects of 8 weeks fluoxetine treatment: a VBM-DARTEL study.

    Directory of Open Access Journals (Sweden)

    Lingtao Kong

    Full Text Available BACKGROUND: Convergent studies suggest that morphological abnormalities of frontal-subcortical circuits which involved with emotional and cognitive processing may contribute to the pathophysiology of major depressive disorder (MDD. Antidepressant treatment which has been reported to reverse the functional abnormalities of frontal-subcortical circuits in MDD may have treating effects to related brain morphological abnormalities. In this study, we used voxel-based morphometry method to investigate whole brain structural abnormalities in single episode, medication-naïve MDD patients. Furthermore, we investigated the effects of an 8 weeks pharmacotherapy with fluoxetine. METHODS: 28 single episode, medication-naïve MDD participants and 28 healthy controls (HC acquired the baseline high-resolution structural magnetic resonance imaging (sMRI scan. 24 MDD participants acquired a follow-up sMRI scan after 8 weeks antidepressant treatment. Gray matter volumetric (GMV difference between groups was examined. RESULTS: Medication-naïve MDD had significantly decreased GMV in the right dorsolateral prefrontal cortex and left middle frontal gyrus as well as increased GMV in the left thalamus and right insula compared to HC (P<0.05, corrected. Moreover, treated MDD had significantly increased GMV in the left middle frontal gyrus and right orbitofrontal cortex compared to HC (P<0.05, corrected. No difference on GMV was detected between medication-naïve MDD group and treated MDD group. CONCLUSIONS: This study of single episode, medication-naïve MDD subjects demonstrated structural abnormalities of frontal-subcortical circuitsin the early stage of MDD and the effects of 8 weeks successful antidepressant treatment, suggesting these abnormalities may play an important role in the neuropathophysiology of MDD at its onset.

  10. Distinct subcortical volume alterations in pediatric and adult OCD

    Science.gov (United States)

    Boedhoe, Premika S.W.; Schmaal, Lianne; Abe, Yoshinari; Ameis, Stephanie H.; Arnold, Paul D.; Batistuzzo, Marcelo C.; Benedetti, Francesco; Beucke, Jan C.; Bollettini, Irene; Bose, Anushree; Brem, Silvia; Calvo, Anna; Cheng, Yuqi; Cho, Kang Ik K.; Dallaspezia, Sara; Denys, Damiaan; Fitzgerald, Kate D.; Fouche, Jean-Paul; Giménez, Mònica; Gruner, Patricia; Hanna, Gregory L.; Hibar, Derrek P.; Hoexter, Marcelo Q.; Huyser, Chaim; Ikari, Keisuke; Jahanshad, Neda; Kathmann, Norbert; Kaufmann, Christian; Koch, Kathrin; Kwon, Jun Soo; Lazaro, Luisa; Liu, Yanni; Lochner, Christine; Marsh, Rachel; Martínez-Zalacaín, Ignacio; Mataix-Cols, David; Menchón, José M.; Minuzzii, Luciano; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswamy, Janardhanan C.; Piras, Fabrizio; Piras, Federica; Pittenger, Christopher; Reddy, Y.C. Janardhan; Sato, Joao R.; Simpson, H. Blair; Soreni, Noam; Soriano-Mas, Carles; Spalletta, Gianfranco; Stevens, Michael C.; Szeszko, Philip R.; Tolin, David F.; Venkatasubramanian, Ganesan; Walitza, Susanne; Wang, Zhen; van Wingen, Guido A.; Xu, Jian; Xu, Xiufeng; Yun, Je-Yeon; Zhao, Qing; Thompson, Paul M.; Stein, Dan J.; van den Heuvel, Odile A.

    2016-01-01

    Objective Structural brain imaging studies in Obsessive-Compulsive Disorder (OCD) have produced inconsistent findings. This may be partially due to limited statistical power from relatively small samples and clinical heterogeneity related to variation in disease profile and developmental stage. Methods To address these limitations, we conducted a meta- and mega-analysis of data from OCD sites worldwide. T1 images from 1,830 OCD patients and 1,759 controls were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ in OCD patients and healthy controls. We additionally examined potential modulating effects of clinical characteristics on morphological differences in OCD patients. Results The meta-analysis indicated that adult patients had significantly smaller hippocampal volumes (Cohen’s d=−0.13; p=5.1x10−3, % difference −2.80) and larger pallidum volumes (d=0.16; p=1.6x10−3, % difference 3.16) compared to adult controls. Both effects were stronger in medicated patients compared to controls (d=−0.29; p=2.4x10−5, % difference −4.18 and d=0.29; p=1.2x10−5, % difference 4.38, respectively). Unmedicated pediatric patients had larger thalamic volumes (d=0.38, p=2.1x10−3) compared to pediatric controls. None of these findings were mediated by sample characteristics such as mean age or field strength. Overall the mega-analysis yielded similar results. Conclusion Our study indicates a different pattern of subcortical abnormalities in pediatric versus adult OCD patients. The pallidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. This highlights the potential importance of neurodevelopmental alterations in OCD, and suggests that further research on neuroplasticity in OCD may be useful. PMID:27609241

  11. Gait and Equilibrium in Subcortical Vascular Dementia

    Directory of Open Access Journals (Sweden)

    Rita Moretti

    2011-01-01

    Full Text Available Subcortical vascular dementia is a clinical entity, widespread, even challenging to diagnose and correctly treat. Patients with this diagnosis are old, frail, often with concomitant pathologies, and therefore, with many drugs in therapy. We tried to diagnose and follow up for three years more than 600 patients. Study subjects were men and women, not bedridden, aged 68–94 years, outpatients, recruited from June, 1st 2007 to June, 1st 2010. We examined them clinically, neurologically, with specific consideration on drug therapies. Our aim has been to define gait and imbalance problem, if eventually coexistent with the pathology of white matter and/or with the worsening of the deterioration. Drug intake interference has been detected and considered.

  12. Anatomical distance affects cortical-subcortical connectivity in first-episode, drug-naive somatization disorder.

    Science.gov (United States)

    Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Li, Lehua; Zhang, Zhikun; Chen, Huafu; Zhao, Jingping

    2017-08-01

    Brain structural and functional alterations in the cortical-subcortical circuits have been observed in somatization disorder (SD). However, whether and how anatomical distance affects the cortical-subcortical connectivity in SD remain unclear. This study aims to examine whether anatomical distance affects the cortical-subcortical in first-episode, drug-naive SD. Twenty-five first-episode, drug-naive patients with SD and twenty-eight healthy controls were recruited for a resting-state scan. Regional functional connectivity strength (FCS) was calculated for each voxel in the brain, which was further divided into short- and long-range FCSs. Correlation analyses were conducted between abnormal FCS and clinical/cognitive variables in the patients. Compared with the controls, the patients showed increased short-range positive FCS (spFCS) in the right superior frontal gyrus (SFG) and decreased spFCS in the left pallidum, and increased long-range positive FCS (lpFCS) in the left middle frontal gyrus and right inferior temporal gyrus (ITG). Positive correlations were observed between the spFCS values in the right SFG and Eysenck Personality Questionnaire psychoticism scores (r=0.441, p=0.027, uncorrected) and between the lpFCS values in the right ITG and scores of digit symbol-coding of Wechsler Adult Intelligence Scale (r=0.416, p=0.039, uncorrected) in the patients CONCLUSIONS: The patients exhibited increased spFCS/lpFCS in the cortical regions and decreased spFCS in the subcortical regions. The left pallidum is first reported here to show decreased spFCS in SD. The present results suggest that abnormal cortical-subcortical circuits may play an important role in SD neurobiology. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Disruptions in cortico-subcortical covariance networks associated with anxiety in new-onset childhood epilepsy

    Directory of Open Access Journals (Sweden)

    Camille Garcia-Ramos

    2016-01-01

    Full Text Available Anxiety disorders represent a prevalent psychiatric comorbidity in both adults and children with epilepsy for which the etiology remains controversial. Neurobiological contributions have been suggested, but only limited evidence suggests abnormal brain volumes particularly in children with epilepsy and anxiety. Since the brain develops in an organized fashion, covariance analyses between different brain regions can be investigated as a network and analyzed using graph theory methods. We examined 46 healthy children (HC and youth with recent onset idiopathic epilepsies with (n = 24 and without (n = 62 anxiety disorders. Graph theory (GT analyses based on the covariance between the volumes of 85 cortical/subcortical regions were investigated. Both groups with epilepsy demonstrated less inter-modular relationships in the synchronization of cortical/subcortical volumes compared to controls, with the epilepsy and anxiety group presenting the strongest modular organization. Frontal and occipital regions in non-anxious epilepsy, and areas throughout the brain in children with epilepsy and anxiety, showed the highest centrality compared to controls. Furthermore, most of the nodes correlating to amygdala volumes were subcortical structures, with the exception of the left insula and the right frontal pole, which presented high betweenness centrality (BC; therefore, their influence in the network is not necessarily local but potentially influencing other more distant regions. In conclusion, children with recent onset epilepsy and anxiety demonstrate large scale disruptions in cortical and subcortical brain regions. Network science may not only provide insight into the possible neurobiological correlates of important comorbidities of epilepsy, but also the ways that cortical and subcortical disruption occurs.

  14. Cortical and subcortical brain alterations in Juvenile Absence Epilepsy

    Directory of Open Access Journals (Sweden)

    Manuela Tondelli

    2016-01-01

    Full Text Available Despite the common assumption that genetic generalized epilepsies are characterized by a macroscopically normal brain on magnetic resonance imaging, subtle structural brain alterations have been detected by advanced neuroimaging techniques in Childhood Absence Epilepsy syndrome. We applied quantitative structural MRI analysis to a group of adolescents and adults with Juvenile Absence Epilepsy (JAE in order to investigate micro-structural brain changes using different brain measures. We examined grey matter volumes, cortical thickness, surface areas, and subcortical volumes in 24 patients with JAE compared to 24 healthy controls; whole-brain voxel-based morphometry (VBM and Freesurfer analyses were used. When compared to healthy controls, patients revealed both grey matter volume and surface area reduction in bilateral frontal regions, anterior cingulate, and right mesial-temporal lobe. Correlation analysis with disease duration showed that longer disease was correlated with reduced surface area in right pre- and post-central gyrus. A possible effect of valproate treatment on brain structures was excluded. Our results indicate that subtle structural brain changes are detectable in JAE and are mainly located in anterior nodes of regions known to be crucial for awareness, attention and memory.

  15. Structure and function of enzymes involved in the anaerobic ...

    Indian Academy of Sciences (India)

    In the recent past, extensive structural and biochemical studies have been carried out on these enzymes by various groups. Besides detailed structural and functional insights, these studies have also shown the similarities and differences between the other related enzymes present in the metabolic network. In this paper, we ...

  16. Cortical and subcortical anatomy of chronic spatial neglect following vascular damage

    Directory of Open Access Journals (Sweden)

    Schnider Armin

    2008-09-01

    Full Text Available Abstract Background The role of the inferior parietal lobule (IPL and superior temporal gyrus (STG or subcortical pathways as possible anatomical correlates of spatial neglect is currently intensely discussed. Some of the conflicting results might have arisen because patients were examined in the acute stage of disease. Methods We examined the anatomical basis of spatial neglect in a sample of patients examined in the post-acute stage following right-hemispheric vascular brain damage. Lesions of 28 patients with chronic spatial neglect were contrasted to lesions of 22 control patients without neglect using lesion subtraction techniques and voxel-wise comparisons. Results The comparisons identified the temporo-parietal junction (TPJ with underlying white matter, the supramarginal gyrus, the posterior STG, and the insula as brain regions damaged significantly more often in neglect compared to non-neglect patients. In a subgroup of neglect patients showing particularly large cancellation bias together with small errors on line bisection damage was prevalent deep in the frontal lobe while damage of patients with the reverse pattern was located in the white matter of the TPJ. Conclusion Considering our results and the findings of previous studies, spatial neglect appears to be associated with a network of regions involving the TPJ, inferior IPL, posterior STG, the insular cortex, and posterior-frontal projections. Frontal structures or projections may be of particular relevance for spatial exploration, while the IPL may be important for object-based attention as required for line bisection.

  17. Genetic influences on schizophrenia and subcortical brain volumes:large-scale proof of concept

    OpenAIRE

    Franke, Barbara; Stein, Jason L.; Ripke, Stephan; Anttila, Verneri; Hibar, Derrek P.; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W.; Nichols, Thomas E.; Neale, Michael C.; Mcintosh, Andrew M.; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel

    2016-01-01

    Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain...

  18. Structural proteins involved in emergence of microbial aerial hyphae

    NARCIS (Netherlands)

    Wosten, HAB; Willey, JM

    1999-01-01

    Filamentous fungi and filamentous bacteria (i.e., the streptomycetes) belong to different kingdoms that diverged early in evolution, Yet, they adopted similar lifestyles, After a submerged feeding mycelium has been established, hyphae grow into the air and form aerial structures from which (a)sexual

  19. Development of strongly coupled FSI technology involving thin walled structures

    CSIR Research Space (South Africa)

    Suliman, Ridhwaan

    2011-01-01

    Full Text Available A strongly coupled finite volume-finite element fluid-structure interaction (FSI) scheme is developed. Both an edge-based finite volume and Galerkin finite element scheme are implemented and evaluated for modelling the mechanics of solids...

  20. Towards the structural characterization of proteins involved in peptidoglycan biosynthesis

    NARCIS (Netherlands)

    Nikolaidis, I.|info:eu-repo/dai/nl/330830260

    2015-01-01

    The cell wall is an essential structure for bacterial survival and unique to bacteria. It is responsible for maintenance of cellular shape and allows the bacterium to withstand high differences in osmotic pressure between the inner and outer leaflet of the cell. Consequently, the bacterial cell wall

  1. Pathophysiology of language switching and mixing in an early bilingual child with subcortical aphasia.

    Science.gov (United States)

    Mariën, Peter; Abutalebi, Jubin; Engelborghs, Sebastiaan; De Deyn, Peter P

    2005-12-01

    Acquired aphasia after circumscribed vascular subcortical lesions has not been reported in bilingual children. We report clinical and neuroimaging findings in an early bilingual boy who incurred equally severe transcortical sensory aphasia in his first language (L1) and second language (L2) after a posterior left thalamic hemorrhage. Following recurrent bleeding of the lesion the aphasic symptoms substantially aggravated. Spontaneous pathological language switching and mixing were found in both languages. Remission of these phenomena was reflected on brain perfusion SPECT revealing improved perfusion in the left frontal lobe and left caudate nucleus. The parallelism between the evolution of language symptoms and the SPECT findings may demonstrate that a subcortical left frontal lobe circuity is crucially involved in language switching and mixing.

  2. Subcortical frontal lesions on MRI in patients with motor neurone disease

    Energy Technology Data Exchange (ETDEWEB)

    Andreadou, E.; Sgouropoulos, P.; Varelas, P.; Papageorgiou, C. [Eginition Hospital, Athens (Greece); Gouliamos, A. [Department of Radiology, CT/MRI Unit, Areteion Hospital, University of Athens (Greece)

    1998-05-01

    MRI was performed in 32 patients with motor neurone disease (26 men and 6 women, aged 40-77 years) and in a control group of 21 subjects. Of the patients studied, 19 had definite and 11 probable amyotrophic lateral sclerosis (ALS) and two had progressive bulbar palsy. In 10 patients there were asymmetrical bilateral foci of increased signal intensity on proton-density and T{sub 2}-weighted images, confined to the white matter. Two patients had only cortical frontal atrophy and slightly increased ventricular size, whereas 20 had normal MRI. The focal lesions were not confined to corticospinal tracts, but were also observed in subcortical frontal areas. While the lesions along the corticospinal tracts correspond to pyramidal tract degeneration, the subcortical foci correlate with degeneration of the frontal bundles and indicate generalised involvement of the central nervous system. (orig.) With 3 figs., 2 tabs., 25 refs.

  3. The influence of puberty on subcortical brain development.

    Science.gov (United States)

    Goddings, Anne-Lise; Mills, Kathryn L; Clasen, Liv S; Giedd, Jay N; Viner, Russell M; Blakemore, Sarah-Jayne

    2014-03-01

    Puberty is characterized by hormonal, physical and psychological transformation. The human brain undergoes significant changes between childhood and adulthood, but little is known about how puberty influences its structural development. Using a longitudinal sample of 711 magnetic resonance imaging scans from 275 individuals aged 7-20years, we examined how subcortical brain regions change in relation to puberty. Our regions of interest included the amygdala, hippocampus and corpus striatum including the nucleus accumbens (NA), caudate, putamen and globus pallidus (GP). Pubertal development was significantly related to structural volume in all six regions in both sexes. Pubertal development and age had both independent and interactive influences on volume for the amygdala, hippocampus and putamen in both sexes, and the caudate in females. There was an interactive puberty-by-age effect on volume for the NA and GP in both sexes, and the caudate in males. These findings suggest a significant role for puberty in structural brain development. © 2013. Published by Elsevier Inc. All rights reserved.

  4. Precursor Events Involving Plasmas Structures Around Collapsing Black Holes Binaries

    Science.gov (United States)

    Medvedev, M.; Coppi, B.

    2017-10-01

    The plasma structures that can exist around black hole binaries can sustain intrinsic plasma collective modes that have characteristic low frequencies related to the particle rotation frequencies around the binary system. As the collapse approaches, with the loss of angular momentum by emission of gravitational waves from the binary system we have suggested that the frequency of the fluctuating component of the gravitational potential can go through that of the intrinsic modes of the surrounding plasma structure and lead to a sharp amplification of them. Then the precursor to the event reported in Ref., tentatively identified by the Agile X- γ-ray observatory may be associated with the high energy radiation emission due to the fields produced by excitation of the proposed plasma modes. M. Tavani is thanked for bringing Ref. to our attention while Ref. was being completed. Sponsored in part by the U.S. DoE.

  5. Regulation of the fear network by mediators of stress: Norepinephrine alters the balance between Cortical and Subcortical afferent excitation of the Lateral Amygdala

    Directory of Open Access Journals (Sweden)

    Luke R Johnson

    2011-05-01

    Full Text Available Pavlovian auditory fear conditioning crucially involves the integration of information about and acoustic conditioned stimulus (CS and an aversive unconditioned stimulus (US in the lateral nucleus of the amygdala (LA. The auditory CS reaches the LA subcortically via a direct connection from the auditory thalamus and also from the auditory association cortex itself. How neural modulators, especially those activated during stress, such as norepinephrine (NE, regulate synaptic transmission and plasticity in this network is poorly understood. Here we show that NE inhibits synaptic transmission in both the subcortical and cortical input pathway but that sensory processing is biased towards the subcortical pathway. In addition binding of NE to β-adrenergic receptors further dissociates sensory processing in the LA. These findings suggest a network mechanism that shifts sensory balance towards the faster but more primitive subcortical input.

  6. Double Cortex Syndrome (Subcortical Band Heterotopia): A Case Report

    National Research Council Canada - National Science Library

    Momen, Ali Akbar; Momen, Mehdi

    2015-01-01

    .... Many congenital or acquired brain anomalies are revealed with MRIs. Although the majority of these abnormalities are sporadic but patients with subcortical band heterotopia or double cortex syndrome have sex-linked inheritance...

  7. Patient preference for involvement, experienced involvement, decisional conflict, and satisfaction with physician: a structural equation model test.

    Science.gov (United States)

    Hölzel, Lars P; Kriston, Levente; Härter, Martin

    2013-06-25

    A comprehensive model of the relationships among different shared decision-making related constructs and their effects on patient-relevant outcomes is largely missing. Objective of our study was the development of a model linking decision-making in medical encounters to an intermediate and a long-term endpoint. The following hypotheses were tested: physicians are more likely to involve patients who have a preference for participation and are willing to take responsibility in the medical decision-making process, increased patient involvement decreases decisional conflict, and lower decisional conflict favourably influences patient satisfaction with the physician. This model was tested in a German primary care sample (N = 1,913). Psychometrically tested instruments were administered to assess the following: patients' preference for being involved in medical decision-making, patients' experienced involvement in medical decision-making, decisional conflict, and satisfaction with the primary care provider. Structural equation modelling was used to explore multiple associations. The model was tested and adjusted in a development sub-sample and cross-validated in a confirmatory sample. Demographic and clinical characteristics were accounted for as possible confounders. Local and global indexes suggested an acceptable fit between the theoretical model and the data. Increased patient involvement was strongly associated with decreased decisional conflict (standardised regression coefficient Β = -.73). Both high experienced involvement (Β = .34) and low decisional conflict (B = -.28) predicted higher satisfaction with the physician. Patients' preference for involvement was negatively associated with the experienced involvement (B = -.24). Altogether, our model could be largely corroborated by the collected empirical data except the unexpected negative association between preference for involvement and experienced involvement. Future research on the

  8. Quantity language speakers show enhanced subcortical processing.

    Science.gov (United States)

    Dawson, Caitlin; Aalto, Daniel; Šimko, Juraj; Putkinen, Vesa; Tervaniemi, Mari; Vainio, Martti

    2016-07-01

    The complex auditory brainstem response (cABR) can reflect language-based plasticity in subcortical stages of auditory processing. It is sensitive to differences between language groups as well as stimulus properties, e.g. intensity or frequency. It is also sensitive to the synchronicity of the neural population stimulated by sound, which results in increased amplitude of wave V. Finnish is a full-fledged quantity language, in which word meaning is dependent upon duration of the vowels and consonants. Previous studies have shown that Finnish speakers have enhanced behavioural sound duration discrimination ability and larger cortical mismatch negativity (MMN) to duration change compared to German and French speakers. The next step is to find out whether these enhanced duration discrimination abilities of quantity language speakers originate at the brainstem level. Since German has a complementary quantity contrast which restricts the possible patterns of short and long vowels and consonants, the current experiment compared cABR between nonmusician Finnish and German native speakers using seven short complex stimuli. Finnish speakers had a larger cABR peak amplitude than German speakers, while the peak onset latency was only affected by stimulus intensity and spectral band. The results suggest that early cABR responses are better synchronised for Finns, which could underpin the enhanced duration sensitivity of quantity language speakers. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Early Developmental Gene Enhancers Affect Subcortical Volumes in the Adult Human Brain

    Science.gov (United States)

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P.; Renteria, Miguel E.; Stein, Jason L.; Thompson, Paul M.; Francks, Clyde; Vernes, Sonja C.; Fisher, Simon E.

    2016-01-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype–phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. PMID:26890892

  10. Identification of genetic and epigenetic marks involved in population structure.

    Directory of Open Access Journals (Sweden)

    Jingyu Liu

    2010-10-01

    Full Text Available Population structure is well known as a prevalent and important factor in genetic studies, but its relevance in epigenetics is unclear. Very little is known about the affected epigenetic markers and their connections with genetics. In this study we assessed the impact of population diversity on genome wide single nucleotide polymorphisms (SNPs and DNA methylation levels in 196 participants from five ethnic groups, using principle and independent component analyses. Three population stratification factors (PSFs were identified in the genomic SNP dataset, accounting for a relatively large portion of total variance (6%. In contrast, only one PSF was identified in genomic methylation dataset accounting for 0.2% of total variance. This methylation PSF, however, was significantly correlated with the largest SNP PSF (r = 0.72, p<1E-23. We then investigated the top contributing markers in these two linked PSFs. The SNP PSF predominantly consists of 8 SNPs from three genes, SLC45A2, HERC2 and CTNNA2, known to encode skin/hair/eye color. The methylation PSF includes 48 methylated sites in 44 genes coding for basic molecular functions, including transcription regulation, DNA binding, cytokine, and transferase activity. Among them, 8 sites are either hypo- or hyper-methylated correlating to minor alleles of SNPs in the SNP PSF. We found that the genes in SNP and methylation PSFs share common biological processes including sexual/multicellular organism reproduction, cell-cell signaling and cytoskeleton organization. We further investigated the transcription regulatory network operating at these genes and identified that most of genes closely interact with ID2, which encodes for a helix-loop-helix inhibitor of DNA binding. Overall, our results show a significant correlation between genetic and epigenetic population stratification, and suggest that the interrelationship between genetic and epigenetic population structure is mediated via complex multiple

  11. Graph theory analysis of cortical-subcortical networks in late-life depression.

    Science.gov (United States)

    Ajilore, Olusola; Lamar, Melissa; Leow, Alex; Zhang, Aifeng; Yang, Shaolin; Kumar, Anand

    2014-02-01

    Late-life major depression (LLD) is characterized by distinct epidemiologic and psychosocial factors, as well as medical comorbidities that are associated with specific neuroanatomical differences. The purpose of this study was to use interregional correlations of cortical and subcortical volumes to examine cortical-subcortical structural network properties in subjects with LLD compared with healthy comparison subjects. This was a cross-sectional neuroimaging study conducted in the general community. We recruited 73 healthy elderly comparison subjects and 53 subjects with LLD who volunteered in response to advertisements. Brain network connectivity measures were generated by correlating regional volumes after controlling for age, gender, and intracranial volume by using the Brain Connectivity Toolbox. Results for overall network strength revealed that LLD networks showed a greater magnitude of associations for both positive and negative correlation weights compared with healthy elderly networks. LLD networks also demonstrated alterations in brain network structure compared with healthy comparison subjects. LLD networks were also more vulnerable to targeted attacks compared with healthy elderly comparison subjects, and this vulnerability was attenuated when controlling for white matter alterations. Overall, this study demonstrates that cortical-subcortical network properties are altered in LLD and may reflect the underlying neuroanatomical vulnerabilities of the disorder. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. The dysexecutive syndrome associated with ischaemic vascular disease and related subcortical neuropathology: a Boston process approach.

    Science.gov (United States)

    Lamar, Melissa; Price, Cate C; Giovannetti, Tania; Swenson, Rod; Libon, David J

    2010-01-01

    The introduction of diagnostic criteria for vascular dementia has helped to re-define the impact of various subcortical neuropathologies on aging; however, state-of-the-art neuroimaging techniques and autopsy studies suggest that not all structural brain alterations associated with vascular dementia are exclusive to this neurodegenerative process alone. Thus, a detailed analysis of the cognitive phenotype associated with ischaemic vascular disease is key to our understanding of subcortical neuropathology and its associated behaviors. Over the past twenty years, we have operationally defined this cognitive phenotype using the Boston Process Approach to neuropsychological assessment. This has led to both an empirical, as well as a theoretical understanding of three core constructs related to the dysexecutive syndrome associated with ischaemic vascular disease affecting periventricular and deep white matter as well as subcortical structures connecting these regions with the prefrontal cortex. Thus, difficulties with mental set, cognitive control and mental manipulation negatively impact executive functioning. This review will outline the subtle markers underlying this prefrontal dysfunction, i.e., the dysexecutive phenotype, associated with ischaemic vascular disease and relate it to fundamental impairments of gating subserved by basal ganglia-thalamic pathways within and across various dementia syndromes.

  13. The Dysexecutive Syndrome Associated with Ischaemic Vascular Disease and Related Subcortical Neuropathology: A Boston Process Approach

    Directory of Open Access Journals (Sweden)

    Melissa Lamar

    2010-01-01

    Full Text Available The introduction of diagnostic criteria for vascular dementia has helped to re-define the impact of various subcortical neuropathologies on aging; however, state-of-the-art neuroimaging techniques and autopsy studies suggest that not all structural brain alterations associated with vascular dementia are exclusive to this neurodegenerative process alone. Thus, a detailed analysis of the cognitive phenotype associated with ischaemic vascular disease is key to our understanding of subcortical neuropathology and its associated behaviors. Over the past twenty years, we have operationally defined this cognitive phenotype using the Boston Process Approach to neuropsychological assessment. This has led to both an empirical, as well as a theoretical understanding of three core constructs related to the dysexecutive syndrome associated with ischaemic vascular disease affecting periventricular and deep white matter as well as subcortical structures connecting these regions with the prefrontal cortex. Thus, difficulties with mental set, cognitive control and mental manipulation negatively impact executive functioning. This review will outline the subtle markers underlying this prefrontal dysfunction, i.e., the dysexecutive phenotype, associated with ischaemic vascular disease and relate it to fundamental impairments of gating subserved by basal ganglia-thalamic pathways within and across various dementia syndromes.

  14. Hippocampal-cortical interaction during periods of subcortical silence.

    Science.gov (United States)

    Logothetis, N K; Eschenko, O; Murayama, Y; Augath, M; Steudel, T; Evrard, H C; Besserve, M; Oeltermann, A

    2012-11-22

    Hippocampal ripples, episodic high-frequency field-potential oscillations primarily occurring during sleep and calmness, have been described in mice, rats, rabbits, monkeys and humans, and so far they have been associated with retention of previously acquired awake experience. Although hippocampal ripples have been studied in detail using neurophysiological methods, the global effects of ripples on the entire brain remain elusive, primarily owing to a lack of methodologies permitting concurrent hippocampal recordings and whole-brain activity mapping. By combining electrophysiological recordings in hippocampus with ripple-triggered functional magnetic resonance imaging, here we show that most of the cerebral cortex is selectively activated during the ripples, whereas most diencephalic, midbrain and brainstem regions are strongly and consistently inhibited. Analysis of regional temporal response patterns indicates that thalamic activity suppression precedes the hippocampal population burst, which itself is temporally bounded by massive activations of association and primary cortical areas. These findings suggest that during off-line memory consolidation, synergistic thalamocortical activity may be orchestrating a privileged interaction state between hippocampus and cortex by silencing the output of subcortical centres involved in sensory processing or potentially mediating procedural learning. Such a mechanism would cause minimal interference, enabling consolidation of hippocampus-dependent memory.

  15. Binge drinking differentially affects cortical and subcortical microstructure.

    Science.gov (United States)

    Morris, Laurel S; Dowell, Nicholas G; Cercignani, Mara; Harrison, Neil A; Voon, Valerie

    2017-01-20

    Young adult binge drinkers represent a model for endophenotypic risk factors for alcohol misuse and early exposure to repeated binge cycles. Chronic or harmful alcohol use leads to neurochemical, structural and morphological neuroplastic changes, particularly in regions associated with reward processing and motivation. We investigated neural microstructure in 28 binge drinkers compared with 38 matched healthy controls. We used a recently developed diffusion magnetic resonance imaging acquisition and analysis, which uses three-compartment modelling (of intracellular, extracellular and cerebrospinal fluid) to determine brain tissue microstructure features including neurite density and orientation dispersion index (ODI). Binge drinkers had reduced ODI, a proxy of neurite complexity, in frontal cortical grey matter and increased ODI in parietal grey matter. Neurite density was higher in cortical white matter in adjacent regions of lower ODI in binge drinkers. Furthermore, binge drinkers had higher ventral striatal grey matter ODI that was positively correlated with binge score. Healthy volunteers showed no such relationships. We demonstrate disturbed dendritic complexity of higher-order prefrontal and parietal regions, along with higher dendritic complexity of a subcortical region known to mediate reward-related motivation. The findings illustrate novel microstructural abnormalities that may reflect an infnce of alcohol bingeing on critical neurodevelopmental processes in an at-risk young adult group. © 2017 The Authors.Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

  16. Ego Strength Development of Adolescents Involved in Adult-Sponsored Structured Activities.

    Science.gov (United States)

    Markstrom, Carol A.; Li, Xaioming; Blackshire, Shana L.; Wilfong, Juanita J.

    2005-01-01

    A psychosocial conception of ego strengths is presented in relation to adolescent involvement in adult-sponsored structured youth activities. Five-hundred and seventeen high school students completed measures on their involvement in structured activities and on 8 ego strengths. Gender, age, and SES were controlled in a MANCOVA procedure and it was…

  17. The effect of duration of illness and antipsychotics on subcortical volumes in schizophrenia: Analysis of 778 subjects.

    Science.gov (United States)

    Hashimoto, Naoki; Ito, Yoichi M; Okada, Naohiro; Yamamori, Hidenaga; Yasuda, Yuka; Fujimoto, Michiko; Kudo, Noriko; Takemura, Ariyoshi; Son, Shuraku; Narita, Hisashi; Yamamoto, Maeri; Tha, Khin Khin; Katsuki, Asuka; Ohi, Kazutaka; Yamashita, Fumio; Koike, Shinsuke; Takahashi, Tsutomu; Nemoto, Kiyotaka; Fukunaga, Masaki; Onitsuka, Toshiaki; Watanabe, Yoshiyuki; Yamasue, Hidenori; Suzuki, Michio; Kasai, Kiyoto; Kusumi, Ichiro; Hashimoto, Ryota

    2018-01-01

    The effect of duration of illness and antipsychotic medication on the volumes of subcortical structures in schizophrenia is inconsistent among previous reports. We implemented a large sample analysis utilizing clinical data from 11 institutions in a previous meta-analysis. Imaging and clinical data of 778 schizophrenia subjects were taken from a prospective meta-analysis conducted by the COCORO consortium in Japan. The effect of duration of illness and daily dose and type of antipsychotics were assessed using the linear mixed effect model where the volumes of subcortical structures computed by FreeSurfer were used as a dependent variable and age, sex, duration of illness, daily dose of antipsychotics and intracranial volume were used as independent variables, and the type of protocol was incorporated as a random effect for intercept. The statistical significance of fixed-effect of dependent variable was assessed. Daily dose of antipsychotics was positively associated with left globus pallidus volume and negatively associated with right hippocampus. It was also positively associated with laterality index of globus pallidus. Duration of illness was positively associated with bilateral globus pallidus volumes. Type of antipsychotics did not have any effect on the subcortical volumes. A large sample size, uniform data collection methodology and robust statistical analysis are strengths of the current study. This result suggests that we need special attention to discuss about relationship between subcortical regional brain volumes and pathophysiology of schizophrenia because regional brain volumes may be affected by antipsychotic medication.

  18. Association between subcortical volumes and verbal memory in unmedicated depressed patients and healthy controls.

    Science.gov (United States)

    Turner, Arlener D; Furey, Maura L; Drevets, Wayne C; Zarate, Carlos; Nugent, Allison C

    2012-07-01

    Research has shown poor performance on verbal memory tasks in patients with major depressive disorder relative to healthy controls, as well as structural abnormalities in the subcortical structures that form the limbic-cortical-striatal-pallidal-thalamic circuitry. Few studies, however, have attempted to link the impairments in learning and memory in depression with these structural abnormalities, and of those which have done so, most have included patients medicated with psychotropic agents likely to influence cognitive performance. This study thus examines the relationship between subcortical structural abnormalities and verbal memory using the California Verbal Learning Test (CVLT) in unmedicated depressed patients. A T1 weighted magnetic resonance imaging scan and the CVLT were obtained on 45 subjects with major depressive disorder and 44 healthy controls. Using the FMRIB's Integrated Registration and Segmentation Tool (FIRST) volumes of selected subcortical structures were segmented and correlated with CVLT performance. Depressed participants showed significantly smaller right thalamus and right hippocampus volumes than healthy controls. Depressed participants also showed impaired performance on global verbal learning ability, and appeared to depend upon an inferior memory strategy (serial clustering). Measures of serial clustering were correlated significantly with right hippocampal volumes in depressed participants. Our findings indicate that depressed participants and healthy controls differ in the memory strategies they employ, and that while depressed participants had a smaller hippocampal volume, there was a positive correlation between volume and use of an inferior memory strategy. This suggests that larger hippocampal volume is related to better memory recall in depression, but specifically with regard to utilizing an inferior memory strategy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Black grandmothers in multigenerational households: diversity in family structure and parenting involvement in the Woodlawn community.

    Science.gov (United States)

    Pearson, J L; Hunter, A G; Ensminger, M E; Kellam, S G

    1990-04-01

    We report here the frequency of black grandmothers' coresidence in households with first-grade children, their patterns of involvement in parenting, and the degree to which family structure and employment affected the grandmothers' parenting involvement in a 1966/1967 community-defined population. Coresidence between grandmothers and their target first-grade grandchildren was found in 10% of the households. The 130 grandmothers' parenting involvement was substantial, second only to mother involvement, and was characterized by 2 parenting activity patterns: control and punishment, and support and punishment. The degree of grandmothers' parenting involvement differed by family structure, with grandmothers in mother-absent homes most likely to be involved. Grandmothers' employment did not moderate their engagement in parenting behaviors. These findings are consistent with previous reports of significant parenting involvement by black extended family members.

  20. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof-of-concept and roadmap for future studies

    Science.gov (United States)

    Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Shugart, Yin Yao; Ho, Yvonne YW; Martin, Nicholas G; Wright, Margaret J

    2016-01-01

    Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between schizophrenia cases and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. The current study provides proof-of-concept (albeit based on a limited set of structural brain measures), and defines a roadmap for future studies investigating the genetic covariance between structural/functional brain phenotypes and risk for psychiatric disorders. PMID:26854805

  1. Ten-Structure as Strategy of Addition 1-20 by Involving Spatial Structuring Ability for First Grade Students

    Science.gov (United States)

    Salmah, Ummy; Putri, Ratu Ilma Indra; Somakim

    2015-01-01

    The aim of this study is to design learning activities that can support students to develop strategies for the addition of number 1 to 20 in the first grade by involving students' spatial structuring ability. This study was conducted in Indonesia by involving 27 students. In this paper, one of three activities is discussed namely ten-box activity.…

  2. Distribution and initiation of seizure activity in a rat brain with subcortical band heterotopia.

    Science.gov (United States)

    Chen, Z F; Schottler, F; Bertram, E; Gall, C M; Anzivino, M J; Lee, K S

    2000-05-01

    Misplaced (heterotopic) cortical neurons are a common feature of developmental epilepsies. To better understand seizure disorders associated with cortical heterotopia, the sites of aberrant discharge activity were investigated in vivo and in vitro in a seizure-prone mutant rat (tish) exhibiting subcortical band heterotopia. Depth electrode recordings and postmortem assessment of regional c-fos mRNA levels were used to characterize the distribution of aberrant discharge activity during spontaneous seizures in vivo. Electrophysiologic recordings of spontaneous and evoked activity also were performed by using in vitro brain slices from the tish rat treated with proconvulsant drugs (penicillin and 4-aminopyridine). Depth electrode recordings demonstrate that seizure activity begins almost simultaneously in the normotopic and heterotopic areas of the tish neocortex. Spontaneous seizures induce c-fos mRNA in normotopic and heterotopic neocortical areas, and limbic regions. The threshold concentrations of proconvulsant drugs for inducing epileptiform spiking were similar in the normotopic and heterotopic areas of tish brain slices. Manipulations that blocked communication between the normotopic and heterotopic areas of the cortex inhibited spiking in the heterotopic, but not the normotopic, area of the cortex. These findings indicate that aberrant discharge activity occurs in normotopic and heterotopic areas of the neocortex, and in certain limbic regions during spontaneous seizures in the tish rat. Normotopic neurons are more prone to exhibit epileptiform activity than are heterotopic neurons in the tish cortex, and heterotopic neurons are recruited into spiking by activity initiated in normotopic neurons. The findings indicate that seizures in the tish brain primarily involve telencephalic structures, and suggest that normotopic neurons are responsible for initiating seizures in the dysplastic neocortex.

  3. The Development of a Structural Equation Model to Demonstrate the Correlations between Marijuana Use and Involvement

    Science.gov (United States)

    Borcherding, Matthew J.

    2017-01-01

    This quantitative study examined the effects of marijuana on academic and social involvement in undergraduates using a structural equation model. The study was conducted at a midsized comprehensive community college in the Midwest and was guided by Astin's (1985) theory of student involvement. A survey link was e-mailed to all 4,527 eligible…

  4. Phonemic Characteristics of Apraxia of Speech Resulting from Subcortical Hemorrhage

    Science.gov (United States)

    Peach, Richard K.; Tonkovich, John D.

    2004-01-01

    Reports describing subcortical apraxia of speech (AOS) have received little consideration in the development of recent speech processing models because the speech characteristics of patients with this diagnosis have not been described precisely. We describe a case of AOS with aphasia secondary to basal ganglia hemorrhage. Speech-language symptoms…

  5. Automated localization of periventricular and subcortical white matter lesions

    Science.gov (United States)

    van der Lijn, Fedde; Vernooij, Meike W.; Ikram, M. Arfan; Vrooman, Henri A.; Rueckert, Daniel; Hammers, Alexander; Breteler, Monique M. B.; Niessen, Wiro J.

    2007-03-01

    It is still unclear whether periventricular and subcortical white matter lesions (WMLs) differ in etiology or clinical consequences. Studies addressing this issue would benefit from automated segmentation and localization of WMLs. Several papers have been published on WML segmentation in MR images. Automated localization however, has not been investigated as much. This work presents and evaluates a novel method to label segmented WMLs as periventricular and subcortical. The proposed technique combines tissue classification and registration-based segmentation to outline the ventricles in MRI brain data. The segmented lesions can then be labeled into periventricular WMLs and subcortical WMLs by applying region growing and morphological operations. The technique was tested on scans of 20 elderly subjects in which neuro-anatomy experts manually segmented WMLs. Localization accuracy was evaluated by comparing the results of the automated method with a manual localization. Similarity indices and volumetric intraclass correlations between the automated and the manual localization were 0.89 and 0.95 for periventricular WMLs and 0.64 and 0.89 for subcortical WMLs, respectively. We conclude that this automated method for WML localization performs well to excellent in comparison to the gold standard.

  6. Neuropsychological Profile of Children with Subcortical Band Heterotopia

    Science.gov (United States)

    Spencer-Smith, Megan; Leventer, Richard; Jacobs, Rani; De Luca, Cinzia; Anderson, Vicki

    2009-01-01

    Aim: Subcortical band heterotopia (SBH) or "double cortex" is a malformation of cortical development resulting from impaired neuronal migration. So far, research has focused on the neurological, neuroimaging, and genetic correlates of SBH. More recently, clinical reports and small sample studies have documented neuropsychological dysfunction in…

  7. Cortical and subcortical functional neuroanatomy for low-grade glioma surgery.

    Science.gov (United States)

    Chenin, L; Lefranc, M; Velut, S; Foulon, P; Havet, E; Peltier, J

    2017-06-01

    Knowledge of the encephalon anatomy is crucial for neurosurgical practice, especially the main cortical functional structures and their connections. General organisation of the encephalon is presented with frontal, parietal, occipital, temporal, limbic and insular lobes and their Brodmann correspondence. Secondly, subcortical anatomy will be presented with main white matter fasciculi in three separated categories: association, commissural and projection fibers. Main association fibers are inferior occipitofrontal fasciculus, superior longitudinal fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, uncinate fasciculus, and cingulum. Commissural fibers include anterior commissure, corpus callosum and fornix. Projection fibers are internal capsule and optic radiations. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. 21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted intracerebral/subcortical stimulator for... Devices § 882.5840 Implanted intracerebral/subcortical stimulator for pain relief. (a) Identification. An implanted intracerebral/subcortical stimulator for pain relief is a device that applies electrical current...

  9. Morphologic characteristics of subcortical heterotopia: MR imaging study.

    Science.gov (United States)

    Barkovich, A J

    2000-02-01

    Gray matter heterotopia have been divided into three groups based on clinical and imaging characteristics: subependymal, subcortical, and band heterotopia. Nonetheless, subcortical heterotopia can have variable morphologic findings. The purpose of this study was to perform a morphologic analysis of a series of cases of subcortical heterotopia based on MR images, to correlate the morphologic appearance with clinical characteristics, and to speculate about the embryologic implications of our results. The MR imaging studies and clinical records of 24 patients with subcortical heterotopia were retrospectively reviewed. The morphologic findings of the heterotopia were recorded along with presence and type of associated malformations. These results were correlated with available data on development and neurologic status. Analysis revealed that, in six cases, the heterotopia were composed exclusively of multiple nodules, in 13, they appeared primarily as curvilinear ribbons of cortex extending into the white matter, and in five, they had deep nodular regions with curvilinear areas more peripherally. All of the curvilinear regions were contiguous with the cerebral cortex in at least two locations. In eight cases, curvilinear heterotopia contained curvilinear areas of flow void that were thought to be blood vessels; in 10, they contained fluid resembling CSF. No difference in developmental or neurologic manifestations was noted among patients with heterotopia of different morphologic appearances. Subcortical heterotopia can have nodular or curvilinear morphologic appearances. Although no difference was found in the clinical conditions of the patients with differing morphologic appearances, additional analysis of these patients or studies of animal models of these malformations may further our understanding of normal and abnormal brain development.

  10. Intraosseous migration of tendinous calcifications: cortical erosions, subcortical migration and extensive intramedullary diffusion, a SIMS series

    Energy Technology Data Exchange (ETDEWEB)

    Malghem, Jacques; Omoumi, Patrick; Lecouvet, Frederic; Berg, Bruno vande [Universite Catholique de Louvain, Departement de radiologie et d' imagerie medicale, Bruxelles (Belgium)

    2015-10-15

    Calcium hydroxyapatite crystal deposition is a common disorder, which sometimes causes acute pain as calcifications dissolve and migrate into adjacent soft tissue. Intraosseous calcium penetration has also been described. We illustrate the appearance of these lesions using a series of 35 cases compiled by members of the French Society of Musculoskeletal Imaging (Societe d'Imagerie Musculo-Squelettique, SIMS). The first group in our series (7 cases) involved calcification-related cortical erosions of the humeral and femoral diaphyses, in particular at the pectoralis major and gluteus maximus insertions. A second group (28 cases) involved the presence of calcium material in subcortical areas. The most common site was the greater tubercle of the humerus, accompanying a calcifying tendinopathy of the supraspinatus. In addition, an extensive intramedullary diffusion of calcium deposits was observed in four of these cases, associated with cortical erosion in one case and subcortical lesions in three cases. Cortical erosions and intraosseous migration of calcifications associated with calcific tendinitis may be confused with neoplasm or infection. It is important to recognize atypical presentations of hydroxyapatite deposition to avoid unnecessary investigation or surgery. (orig.)

  11. The structure of parental involvement and relations to disease management for youth with type 1 diabetes.

    Science.gov (United States)

    Palmer, Debra L; Osborn, Peter; King, Pamela S; Berg, Cynthia A; Butler, Jorie; Butner, Jonathan; Horton, Dwayne; Wiebe, Deborah J

    2011-06-01

    To test structural models of parental involvement in type 1 diabetes and to examine associations of parental involvement with adherence and metabolic control. Two hundred and fifty-two young adolescents (10-14 years) completed reports of adherence and parents' involvement: acceptance, independence encouragement, communication, general and diabetes-specific monitoring, frequency of help, and intrusive support. HbA(1c) values came from medical records. A model of relationship quality, behavioral involvement, and monitoring as three separate yet interrelated factors best fit the data. Higher reports of mothers' and fathers' monitoring and fathers' relationship quality uniquely related to better adherence, whereas higher reports of fathers' behavioral involvement uniquely related to poorer adherence. Higher reports of paternal monitoring were related to lower HbA(1c). Adolescent perceptions of components of parental involvement are interrelated, yet separate constructs for both mothers and fathers. Parental monitoring was an important predictor of management of type 1 diabetes during adolescence.

  12. Customer involvement in greening the supply chain: an interpretive structural modeling methodology

    Science.gov (United States)

    Kumar, Sanjay; Luthra, Sunil; Haleem, Abid

    2013-04-01

    The role of customers in green supply chain management needs to be identified and recognized as an important research area. This paper is an attempt to explore the involvement aspect of customers towards greening of the supply chain (SC). An empirical research approach has been used to collect primary data to rank different variables for effective customer involvement in green concept implementation in SC. An interpretive structural-based model has been presented, and variables have been classified using matrice d' impacts croises- multiplication appliqué a un classement analysis. Contextual relationships among variables have been established using experts' opinions. The research may help practicing managers to understand the interaction among variables affecting customer involvement. Further, this understanding may be helpful in framing the policies and strategies to green SC. Analyzing interaction among variables for effective customer involvement in greening SC to develop the structural model in the Indian perspective is an effort towards promoting environment consciousness.

  13. Relative activity of cerebral subcortical gray matter in varying states of attention and awareness in normal subjects and patient studies

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, M.; Chen, C.T.; Levy, J.; Wagner, N.; Spire, J.P.; Jacobsen, J.; Meltzer, H.; Metz, J.; Beck, R.N.

    1985-05-01

    An important aspect of the study of brain function involves measurement of the relationships; between activities in the subcortical gray matter of the caudate and of the thalamus; and between these structures and functional cortical areas. The authors have studied these relationships in 22 subjects under different conditions of activation, sleep and sensory deprivation using a PET VI system and F-18-2DG to determine regional cerebral metabolism. Subject activating conditions were maintained throughout the period of equilibration of F-18-2DG and E.E.G.'s were monitored. Multiple tomographic slices of 1-2 million counts were obtained simultaneously with slice separation of 14mm and each plane parallel to the cantho-meatal line. In activated and non-activated awake conditions for normal subjects, left and right thalmus-to-caudate ratios were similar and greater than unity. This relationship was maintained in non-REM sleep, but was reversed and divergent in REM sleep and sensory deprivation; this was also evident in 3/4 narcoleptics awake and asleep in non-REM and REM and 2/3 schizophrenics and affective disorder, subjects. This approach appears to have potential for characterizating normal and disordered regional cerebral function.

  14. Regional brain differences in cortical thickness, surface area and subcortical volume in individuals with Williams syndrome.

    Directory of Open Access Journals (Sweden)

    Shashwath A Meda

    Full Text Available Williams syndrome (WS is a rare genetic neurodevelopmental disorder characterized by increased non-social anxiety, sensitivity to sounds and hypersociability. Previous studies have reported contradictory findings with regard to regional brain variation in WS, relying on only one type of morphological measure (usually volume in each study. The present study aims to contribute to this body of literature and perhaps elucidate some of these discrepancies by examining concurrent measures of cortical thickness, surface area and subcortical volume between WS subjects and typically-developing (TD controls. High resolution MRI scans were obtained on 31 WS subjects and 50 typically developing control subjects. We derived quantitative regional estimates of cortical thickness, cortical surface area, and subcortical volume using FreeSurfer software. We evaluated between-group ROI differences while controlling for total intracranial volume. In post-hoc exploratory analyses within the WS group, we tested for correlations between regional brain variation and Beck Anxiety Inventory scores. Consistent with our hypothesis, we detected complex patterns of between-group cortical variation, which included lower surface area in combination with greater thickness in the following cortical regions: post central gyrus, cuneus, lateral orbitofrontal cortex and lingual gyrus. Additional cortical regions showed between-group differences in one (but not both morphological measures. Subcortical volume was lower in the basal ganglia and the hippocampus in WS versus TD controls. Exploratory correlations revealed that anxiety scores were negatively correlated with gray matter surface area in insula, OFC, rostral middle frontal, superior temporal and lingual gyrus. Our results were consistent with previous reports showing structural alterations in regions supporting the socio-affective and visuospatial impairments in WS. However, we also were able to effectively capture novel and

  15. Motivational climate, achievement goals, perceived sport competence, and involvement in physical activity: structural and mediator models.

    Science.gov (United States)

    Skjesol, Knut; Halvari, Hallgeir

    2005-04-01

    Students (N=231) were tested on involvement in physical activity, motivational climate, perceived sport competence, and goal orientations. Multiple regression, partial correlation, and LISREL analyses indicated that mastery goal adoption is positively correlated with a mastery climate. Performance-approach goal adoption is positively correlated with a performance climate. Mastery climate, mastery goal, and perceived sport competence are all positively correlated with involvement in physical activity. LISREL analyses supported three mediational hypotheses: (I) the positive correlation between the performance-approach goal and involvement in physical activity is mediated by (high) perceived sport competence, (II) the negative correlation between the performance-avoidance goal and involvement in physical activity is mediated by (low) perceived sport competence, (III) the positive correlation between mastery climate and involvement in physical activity is mediated by (high) mastery goal orientation. An alternative structural model with perceived competence as the last latent construct in the path was also tested.

  16. Subcortical encoding of sound is enhanced in bilinguals and relates to executive function advantages

    Science.gov (United States)

    Krizman, Jennifer; Marian, Viorica; Shook, Anthony; Skoe, Erika; Kraus, Nina

    2012-01-01

    Bilingualism profoundly affects the brain, yielding functional and structural changes in cortical regions dedicated to language processing and executive function [Crinion J, et al. (2006) Science 312:1537–1540; Kim KHS, et al. (1997) Nature 388:171–174]. Comparatively, musical training, another type of sensory enrichment, translates to expertise in cognitive processing and refined biological processing of sound in both cortical and subcortical structures. Therefore, we asked whether bilingualism can also promote experience-dependent plasticity in subcortical auditory processing. We found that adolescent bilinguals, listening to the speech syllable [da], encoded the stimulus more robustly than age-matched monolinguals. Specifically, bilinguals showed enhanced encoding of the fundamental frequency, a feature known to underlie pitch perception and grouping of auditory objects. This enhancement was associated with executive function advantages. Thus, through experience-related tuning of attention, the bilingual auditory system becomes highly efficient in automatically processing sound. This study provides biological evidence for system-wide neural plasticity in auditory experts that facilitates a tight coupling of sensory and cognitive functions. PMID:22547804

  17. [The CADASIL syndrome: a model of subcortical-cortical disconnection].

    Science.gov (United States)

    Blanco Menéndez, R; Aguado Balsas, A M; Blanco, E; Lobo Rodríguez, B; Vera De La Puente, E

    CADASIL syndrome (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarts and Leukoencephalopathy) includes some neurological signs and symptoms (gait disturbances, epileptic seizures, pseudobulbar palsy, migraines, etc.), as well as neuropsychological dysfunctions (cognitive and executive impairment, emotional disorders and, frequently, dementia). This syndrome is a good model of white matter damage and potential disconnection syndromes. In this article, the neuropsychological profile of a 47 year-old woman diagnosed of CADASIL is investigated and thoroughly discussed. Results show the presence of a moderate cognitive and executive impairment, specially of memory, psychomotor abilities, executive functions and verbal fluency, but not dementia, overall suggesting the presence of a temporal-frontal-subcortical disfunction. This clinical pattern is an illuminating example of the neuropsychological consequences of the partial disconnection of prefrontal cortex from the thalamus and basal ganglia.

  18. Sum rules across the unpolarized Compton processes involving generalized polarizabilities and moments of nucleon structure functions

    OpenAIRE

    Lensky, Vadim; Hagelstein, Franziska; Pascalutsa, Vladimir; Vanderhaeghen, Marc

    2017-01-01

    We derive two new sum rules for the unpolarized doubly-virtual Compton scattering (VVCS) process on a nucleon, which establish novel low-$Q^2$ relations involving the so-called generalized polarizabilities (GPs) and moments of the nucleon's unpolarized structure functions $F_1$ and $F_2(x,Q^2)$. These relations facilitate the determination of some structure constants which can only be accessed in off-forward VVCS, not experimentally accessible at present. We perform an empirical determination...

  19. The implication of subcortical motor centers in voluntary human activities

    OpenAIRE

    Queralt Blasco, Ana

    2009-01-01

    The main objective of the present dissertation was to analyse the subcortical implications in the preparation and execution of complex voluntary movements. Three different tasks were selected on purpose. They all are everyday activities which although functionally related have differential characteristics. The first task was the sit-to-stand manoeuvre. Simple ballistic movements are executed faster in reaction time task paradigms when the imperative signal is accompanied by a startling audito...

  20. Double Cortex Syndrome (Subcortical Band Heterotopia): A Case Report

    OpenAIRE

    Momen, Ali Akbar; Momen, Mehdi

    2015-01-01

    AbstractObjectiveApproximately 5–10% of preschool age children are considered developmentally disabled. Brain Magnetic Resonance Imaging (MRI) plays a key role in the diagnostic evaluation in these children. Many congenital or acquired brain anomalies are revealed with MRIs. Although the majority of these abnormalities are sporadic but patients with subcortical band heterotopia or double cortex syndrome have sex-linked inheritance. We are going to present the first case in Iran from Ahvaz cit...

  1. Clinical presentation and outcome of geriatric depression in subcortical ischemic vascular disease.

    Science.gov (United States)

    Bella, R; Pennisi, G; Cantone, M; Palermo, F; Pennisi, M; Lanza, G; Zappia, M; Paolucci, S

    2010-01-01

    Vascular damage of frontal-subcortical circuits involved in mood regulation and cognition might be the main contributor to the pathogenesis of late-life depression, and it is linked to poor response to treatment. To investigate the relationship between executive dysfunction and outcome of depressive symptoms among elderly patients with subcortical ischemic vascular disease. Ninety-two elderly patients with white matter lesions (WMLs) or lacunar infarcts (LAs) on brain MRI and depressive symptomatology were consecutively recruited. Depression was rated with the Hamilton Depression Rating Scale (HDRS). Evaluation of executive functions by means of the Stroop color-word test was performed at entry of the study, and WMLs were categorized into mild, moderate or severe. Mood was reevaluated by means of HDRS after the 12th week of pharmacological treatment. Psychomotor retardation, difficulties at work, apathy, and lack of insight were the predominant symptoms. Fifty-six patients (62.8%) had a neuroradiological picture of WMLs, while the remaining 33 (37.1%) had LAs. Executive dysfunctions significantly and independently predict poor outcome of depressive symptoms. Patients with the severest WMLs showed not only a greater executive dysfunction, but also a minor response to antidepressant treatment. This study supports the vascular depression hypothesis. WMLs are of crucial clinical relevance as they are linked with cognitive symptoms and poor antidepressant outcome. 2009 S. Karger AG, Basel.

  2. Neurolinguistic and follow-up study of an unusual pattern of recovery from bilingual subcortical aphasia.

    Science.gov (United States)

    Aglioti, S; Beltramello, A; Girardi, F; Fabbro, F

    1996-10-01

    We report on the neuropsychological and neurolinguistic features of a bilingual patient, E.M., who presented with an uncommon pattern of aphasic deficit consequent to subcortical lesions mainly involving the left basal ganglia. Not only are reports of bilingual subcortical aphasia rare, but E.M.'s deficit is particularly uncommon for it concerns the most used mother tongue (Venetian) much more than a less practiced second language (standard Italian). In this patient, the linguistic deficit in mother tongue production has been observed in spontaneous speech and in cross language translation tasks, where an asymmetrical paradoxical performance has been revealed. Indeed, unlike neurologically intact subjects, E.M. has more difficulties when translating into her mother tongue than into her second language. Although E.M.'s mother tongue is prevalently an oral language, the asymmetrical translation pattern is similar in written and oral translation tasks, thus ruling out the possibility that the deficit simply reflects differences between written and oral language codes. Finally, another remarkable feature of E.M.'s impairment is its stability over almost 5 years from the stroke. We propose that this unusual type of recovery in E.M. is related to the higher degree of automatization of the first language with respect to the second one. This proposal fits with the role of basal ganglia in automatized motor and cognitive performance.

  3. Mapping abnormal subcortical brain morphometry in an elderly HIV+ cohort

    Directory of Open Access Journals (Sweden)

    Benjamin S.C. Wade

    2015-01-01

    Full Text Available Over 50% of HIV+ individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV+ participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD and radial distances (RD defined on each region's surfaces. We also investigated effects of nadir CD4+ T-cell counts, viral load, time since diagnosis (TSD and cognition on subcortical morphology. Lastly, we explored whether HIV+ participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF model. The model was validated with 2-fold cross-validation. Volumes of HIV+ participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV+ people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV+ participants vs. controls, our RF model attained an area under the curve of 72%.

  4. Pigmentary mosaicism, subcortical band heterotopia, and brain cystic lesions.

    Science.gov (United States)

    Ruggieri, Martino; Roggini, Mario; Spalice, Alberto; Addis, Maria; Iannetti, Paola

    2009-05-01

    A 10-year-old boy presented with a severe and diffuse mosaic skin hypopigmentation running (in narrow bands) along the lines of Blaschko associated with mosaic areas of alopecia, facial dysmorphism with midface hypoplasia, bilateral punctate cataract, microretrognathia, short neck, pectus excavatum, joint hypermobility, mild muscular hypotonia, generalized seizures, and mild mental retardation. Cranial magnetic resonance imaging revealed hypoplastic corpus callosum (primarily posterior), subcortical band heterotopia, and diffuse subcortical, periventricular cystic-like lesions. Similar dysmorphic features were observed in the child's mother, but with no imaging abnormalities. The facial phenotype coupled with the cysts in the brain was strongly reminiscent of the oculocerebrorenal Lowe syndrome. Full chromosome studies in the parents and the proband and mutation analysis on peripheral blood lymphocytes (and on skin cultured fibroblasts from affected and unaffected skin areas in the child) in the genes for subcortical band heterotopia (DCX (Xq22.3-q23)], lissencephaly (PAFAH1B1, alias LIS1, at 17p13.3), and oculocerebrorenal syndrome of Lowe (OCRL at Xq23-q24)] were unrevealing. This constellation of multiple congenital anomalies including skin hypopigmentation and eye, musculoskeletal, and nervous system abnormalities was sufficiently characterized to be regarded as a novel example of pigmentary mosaicism of the Ito type (i.e., hypomelanosis of Ito).

  5. Relationships among Adolescents' Leisure Motivation, Leisure Involvement, and Leisure Satisfaction: A Structural Equation Model

    Science.gov (United States)

    Chen, Ying-Chieh; Li, Ren-Hau; Chen, Sheng-Hwang

    2013-01-01

    The purpose of this cross-sectional study was to test a cause-and-effect model of factors affecting leisure satisfaction among Taiwanese adolescents. A structural equation model was proposed in which the relationships among leisure motivation, leisure involvement, and leisure satisfaction were explored. The study collected data from 701 adolescent…

  6. Altered Functional Connectivity in Patients with Subcortical Vascular Cognitive Impairment--A Resting-State Functional Magnetic Resonance Imaging Study.

    Directory of Open Access Journals (Sweden)

    Weina Ding

    Full Text Available Recent neuroimaging studies have shown that people with subcortical vascular cognitive impairment (sVCI have structural and functional abnormalities in the frontal lobe and subcortical brain sites. In this study, we used seed-based resting-state functional connectivity (rsFC analysis and voxel-mirrored homotopic connectivity (VMHC techniques to investigate the alteration of rsFC in patients with sVCI. rsFC and structural magnetic resonance images were acquired for 51 patients with subcortical cerebrovascular disease. All patients were subdivided based on cognitive status into 29 with sVCI and 22 controls; patient characteristics were matched. rsFC of the posterior cingulate cortex (PCC and VMHC were calculated separately, and rsFC of the PCC and VMHC between the two groups were compared. The regions showing abnormal rsFC of the PCC or VMHC in sVCI patients were adopted as regions of interest for correlation analyses. Our results are as follows: The patients with sVCI exhibited increases in rsFC in the left middle temporal lobe, right inferior temporal lobe and left superior frontal gyrus, and significant decreases in rsFC of the left thalamus with the PCC. sVCI patients showed a significant deficit in VMHC between the bilateral lingual gyrus, putamen, and precentral gyrus. Additionally, the z-memory score was significantly positively associated with connectivity between the left thalamus and the PCC (r = 0.41, p = 0.03, uncorrected in the sVCI group. Our findings suggest that the frontal lobe and subcortical brain sites play an important role in the pathogenesis of sVCI. Furthermore, rsFC between the left thalamus and the PCC might indicate the severity of sVCI.

  7. Thyroid Hormone-Dependent Formation of a Subcortical Band Heterotopia (SBH) in the Neonatal Brain is not Exacerbated Under Conditions of Low Dietary Iron

    Science.gov (United States)

    Thyroid hormones (TH) are critical for brain development. Modest TH insufficiency in pregnant rats induced by propylthiouracil (PTU) results in formation of a structural abnormality, a subcortical band heterotopia (SBH), in brains of offspring. PTU reduces TH by inhibiting the s...

  8. Isolated posterior fossa involvement of progressive multifocal ...

    African Journals Online (AJOL)

    2017-11-14

    Nov 14, 2017 ... Open Access frontal lobe. Supratentorial lesions typically involve the subcortical white matter with a scalloping appearance.2. White matter of the posterior fossa is the next common area of involvement; however, isolated cerebellar white matter or isolated medullary involvement is less common.2. One study ...

  9. Malignant transformation in a case of megalencephalic leukoencephalopathy with subcortical cysts: An extreme rarity in a rare disorder.

    Science.gov (United States)

    Jain, Rajendra Singh; Gupta, Pankaj Kumar; Kumar, Sunil; Agrawal, Rakesh

    2016-01-01

    Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive inherited disorder characterized by macrocephaly, progressive motor disability, seizures, mild cognitive decline, slow progression, and typical magnetic resonance imaging (MRI) findings. Age of onset of symptoms is described from birth to 25 years. Late onset presentation is very rare, only few cases have been reported worldwide. Most important clue for diagnosis is the characteristic MRI changes that include diffuse involvement of subcortical white matter mainly in frontoparietal region with relative sparing of central white matter along with subcortical cysts mostly in anterior temporal region. Cysts are usually benign and slowly progressive. Malignant transformation of cysts has not been reported as yet. We herein report a very unusual and probably the first case of MLC who presented to us in a unique manner with late onset and malignant transformation of cyst in left temporal region leading to rapid neurological decline. This case report highlights a possible life-threatening complication of a previously known slowly progressive disease warranting urgent neurosurgical intervention.

  10. Intraoperative subcortical stimulation mapping of language pathways in a consecutive series of 115 patients with Grade II glioma in the left dominant hemisphere.

    Science.gov (United States)

    Duffau, Hugues; Peggy Gatignol, S T; Mandonnet, Emmanuel; Capelle, Laurent; Taillandier, Luc

    2008-09-01

    Despite better knowledge of cortical language organization, its subcortical anatomofunctional connectivity remains poorly understood. The authors used intraoperative subcortical stimulation in awake patients undergoing operation for a glioma in the left dominant hemisphere to map the language pathways and to determine the contribution of such a method to surgical results. One hundred fifteen patients harboring a World Health Organization Grade II glioma within language areas underwent operation after induction of local anesthesia, using direct electrical stimulation to perform online cortical and subcortical language mapping throughout the resection. After detection of cortical language sites, the authors identified 1 or several of the following subcortical language pathways in all patients: 1) arcuate fasciculus, eliciting phonemic paraphasia when stimulated; 2) inferior frontooccipital fasciculus, generating semantic paraphasia when stimulated; 3) subcallosal fasciculus, inducing transcortical motor aphasia during stimulation; 4) frontoparietal phonological loop, eliciting speech apraxia during stimulation; and 5) fibers coming from the ventral premotor cortex, inducing anarthria when stimulated. These structures were preserved, representing the limits of the resection. Despite a transient immediate postoperative worsening, all but 2 patients (98%) returned to baseline or better. On control MR imaging, 83% of resections were total or subtotal. These results represent the largest experience with human subcortical language mapping ever reported. The use of intraoperative cortical and subcortical stimulation gives a unique opportunity to perform an accurate and reliable real-time anatomofunctional study of language connectivity. Such knowledge of the individual organization of language networks enables practitioners to optimize the benefit-to-risk ratio of surgery for Grade II glioma within the left dominant hemisphere.

  11. Aspects of Subcortical Ischaemic Vascular Disease : Early clinical manifestations and associations with Type 2 diabetes mellitus

    OpenAIRE

    Harten, van, B.

    2006-01-01

    Summary Subcortical ischaemic vascular disease (SIVD) is an important cause of cognitive impairment in elderly patients. Screening and diagnostic tests are needed to identify these patients. The HIV dementia scale (HDS) is a reliable and quantitative scale for identifying HIV dementia1. The cognitive profile of HIV dementia has subcortical features that resemble subcortical ischaemic vascular disease (SIVD). The clinical syndrome is characterized by early impairment of attention and executive...

  12. A structural model of customer satisfaction and trust in vendors involved in mobile commerce

    OpenAIRE

    Suki, N.M.

    2011-01-01

    The purpose of this paper is to provide an explanation of factors influencing customer satisfaction and trust in vendors involved in mobile commerce (m-commerce). The study sample consists of 200 respondents. Data were analyzed by employing structural equation modelling (SEM) supported by AMOS 5.0 with maximum likelihood estimation in order to test the proposed hypotheses. The proposed model was empirically tested and results confirmed that users’ satisfaction with vendors in m-commerce was n...

  13. The Anthropic Principle and numerical coincidences involving the cosmological, gravitational and fine structure constants

    CERN Document Server

    Eaves, Laurence

    2014-01-01

    Christian Beck has proposed a set of Shannon-Khinchin axioms to derive a formula for the cosmological constant, {\\Lambda}. We discuss this result in relation to numerical coincidences involving the measured values of {\\Lambda} and the gravitational and fine structure constants, G and {\\alpha}. The empirical formulae that inter-relate the three constants suggest that the measured values of G and {\\Lambda} are consistent with the apparent anthropic fine-tuning of {\\alpha}.

  14. Conduction aphasia in a 3-year-old with a left posterior cortical/subcortical abscess.

    Science.gov (United States)

    Nass, R; Leventhal, F; Levine, B; Lebron, D; Maxfield, C; McCaul, P; George, A; Allen, J

    1998-03-01

    A 3-year-old, right-handed girl developed a conduction-type aphasia following a second generalized seizure in the setting of a developing abscess involving left subcortical and cortical angular gyrus and arcuate fasciculus, and the posterior corpus callosum. The language disorder was fluent, characterized by age appropriate mean length of utterance and syntax, but with markedly reduced spontaneity of output, rapid rate of speech and mild dysarthria. Comprehension was relatively, but not completely spared. Naming, repetition, and reading (letters) were initially markedly impaired. Improvements in naming and repetition were associated with both literal and semantic paraphasias. Writing skills in the form of drawing were spared, but a mild apraxia to verbal command and imitation was initially present. Despite her young age, this child's fluent conduction aphasia and lesion localization were adult-like. Multimodal memory difficulties appeared to underlie what is best described as conduction aphasia.

  15. Mosaic DCX deletion causes subcortical band heterotopia in males.

    Science.gov (United States)

    Quélin, Chloé; Saillour, Yoann; Souville, Isabelle; Poirier, Karine; N'guyen-Morel, Marie Ange; Vercueil, Laurent; Millisher-Bellaiche, Anne Elodie; Boddaert, Nathalie; Dubois, Fanny; Chelly, Jamel; Beldjord, Cherif; Bahi-Buisson, Nadia

    2012-11-01

    Subcortical band heterotopia (SBH) is a neuronal migration disorder usually described in females carrying heterozygous mutations in the X-linked doublecortin (DCX) gene. Hemizygous DCX mutations in males result in lissencephaly. Recently, exonic deletions of DCX resulting in a severer form of agyria have been reported. Nevertheless, rare male patients with SBH have been described with somatic mosaicism of point mutations. Here, we identified a somatic mosaicism for a deletion of exon 4 in the DCX gene in a male patient with SBH detected prenatally. This finding points to the possible implication of mosaic deletions in the DCX gene in unexplained forms of SBH and may allow for detection of SBH prenatally.

  16. Filovirus proteins for antiviral drug discovery: Structure/function of proteins involved in assembly and budding.

    Science.gov (United States)

    Martin, Baptiste; Reynard, Olivier; Volchkov, Viktor; Decroly, Etienne

    2018-02-01

    There are no approved medications for the treatment of Marburg or Ebola virus infection. In two previous articles (Martin et al., 2016, Martin et al., 2017), we reviewed surface glycoprotein and replication proteins structure/function relationship to decipher the molecular mechanisms of filovirus life cycle and identify antiviral strategies. In the present article, we recapitulate knowledge about the viral proteins involved in filovirus assembly and budding. First we describe the structural data available for viral proteins associated with virus assembly and virion egress and then, we integrate the structural features of these proteins in the functional context of the viral replication cycle. Finally, we summarize recent advances in the development of innovative antiviral strategies to target filovirus assembly and egress. The development of such prophylactic or post-exposure treatments could help controlling future filovirus outbreaks. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. The gender gap in student engagement: The role of teachers' autonomy support, structure, and involvement.

    Science.gov (United States)

    Lietaert, Sofie; Roorda, Debora; Laevers, Ferre; Verschueren, Karine; De Fraine, Bieke

    2015-12-01

    The gender gap in education in favour of girls is a widely known phenomenon. Boys generally have higher dropout rates, obtain lower grades, and show lower engagement. Insight into factors related to these academic outcomes could help to address the gender gap. This study investigated, for Dutch language classes, (1) how boys and girls differ in behavioural engagement, (2) which teacher support dimensions (autonomy support, structure, involvement) may explain gender differences in engagement (mediation hypothesis), and (3) whether and which of these teacher support dimensions matter more for boys' as opposed to girls' engagement (moderation or differential effects hypothesis). A total of 385 Grade 7 students and their 15 language teachers participated in this study. Teacher support was assessed through student reports. Student engagement was measured using student, teacher, and observer reports. By means of structural equation modelling, the mediating role of the teacher support dimensions for gender differences in behavioural engagement was tested. The potential differential role of the teacher support dimensions for boys' and girls' engagement was investigated through multigroup analysis. Boys were less engaged than girls and reported lower support from their teacher. Autonomy support and involvement partially mediated the relationship between gender and behavioural engagement. Autonomy support was demonstrated to be a protective factor for boys' engagement but not for girls'. Structure and involvement contributed equally to engagement for both sexes. Although involvement and autonomy support partly explained the gender gap in engagement (mediation hypothesis), more support was found for differential effects of autonomy support on boys' versus girls' engagement (differential effects hypothesis). © 2015 The British Psychological Society.

  18. Regulation of genes involved in cell wall synthesis and structure during Ustilago maydis dimorphism.

    Science.gov (United States)

    Robledo-Briones, Mariana; Ruiz-Herrera, José

    2013-02-01

    The cell wall is the structure that provides the shape to fungal cells and protects them from the difference in osmotic pressure existing between the cytosol and the external medium. Accordingly, changes in structure and composition of the fungal wall must occur during cell differentiation, including the dimorphic transition of fungi. We analyzed, by use of microarrays, the transcriptional regulation of the 639 genes identified to be involved in cell wall synthesis and structure plus the secretome of the Basidiomycota species Ustilago maydis during its dimorphic transition induced by a change in pH. Of these, 189 were differentially expressed during the process, and using as control two monomorphic mutants, one yeast like and the other mycelium constitutive, 66 genes specific of dimorphism were identified. Most of these genes were up-regulated in the mycelial phase. These included CHS genes, genes involved in β-1,6-glucan synthesis, N-glycosylation, and proteins containing a residue of glycosylphosphatidylinositol, and a number of genes from the secretome. The possible significance of these data on cell wall plasticity is discussed. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  19. In-silico bonding schemes to encode chemical bonds involving sharing of electrons in molecular structures.

    Science.gov (United States)

    Punnaivanam, Sankar; Sathiadhas, Jerome Pastal Raj; Panneerselvam, Vinoth

    2016-05-01

    Encoding of covalent and coordinate covalent bonds in molecular structures using ground state valence electronic configuration is achieved. The bonding due to electron sharing in the molecular structures is described with five fundamental bonding categories viz. uPair-uPair, lPair-uPair, uPair-lPair, vPair-lPair, and lPair-lPair. The involvement of lone pair electrons and the vacant electron orbitals in chemical bonding are explained with bonding schemes namely "target vacant promotion", "source vacant promotion", "target pairing promotion", "source pairing promotion", "source cation promotion", "source pairing double bond", "target vacant occupation", and "double pairing promotion" schemes. The bonding schemes are verified with a chemical structure editor. The bonding in the structures like ylides, PCl5, SF6, IF7, N-Oxides, BF4(-), AlCl4(-) etc. are explained and encoded unambiguously. The encoding of bonding in the structures of various organic compounds, transition metals compounds, coordination complexes and metal carbonyls is accomplished. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 3D fully convolutional networks for subcortical segmentation in MRI: A large-scale study.

    Science.gov (United States)

    Dolz, Jose; Desrosiers, Christian; Ben Ayed, Ismail

    2017-04-24

    This study investigates a 3D and fully convolutional neural network (CNN) for subcortical brain structure segmentation in MRI. 3D CNN architectures have been generally avoided due to their computational and memory requirements during inference. We address the problem via small kernels, allowing deeper architectures. We further model both local and global context by embedding intermediate-layer outputs in the final prediction, which encourages consistency between features extracted at different scales and embeds fine-grained information directly in the segmentation process. Our model is efficiently trained end-to-end on a graphics processing unit (GPU), in a single stage, exploiting the dense inference capabilities of fully CNNs. We performed comprehensive experiments over two publicly available datasets. First, we demonstrate a state-of-the-art performance on the ISBR dataset. Then, we report a large-scale multi-site evaluation over 1112 unregistered subject datasets acquired from 17 different sites (ABIDE dataset), with ages ranging from 7 to 64 years, showing that our method is robust to various acquisition protocols, demographics and clinical factors. Our method yielded segmentations that are highly consistent with a standard atlas-based approach, while running in a fraction of the time needed by atlas-based methods and avoiding registration/normalization steps. This makes it convenient for massive multi-site neuroanatomical imaging studies. To the best of our knowledge, our work is the first to study subcortical structure segmentation on such large-scale and heterogeneous data. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Structure of glycerol-3-phosphate dehydrogenase, an essential monotopic membrane enzyme involved in respiration and metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Joanne I.; Chinte, Unmesh; Du, Shoucheng (Pitt)

    2008-04-02

    Sn-glycerol-3-phosphate dehydrogenase (GlpD) is an essential membrane enzyme, functioning at the central junction of respiration, glycolysis, and phospholipid biosynthesis. Its critical role is indicated by the multitiered regulatory mechanisms that stringently controls its expression and function. Once expressed, GlpD activity is regulated through lipid-enzyme interactions in Escherichia coli. Here, we report seven previously undescribed structures of the fully active E. coli GlpD, up to 1.75 {angstrom} resolution. In addition to elucidating the structure of the native enzyme, we have determined the structures of GlpD complexed with substrate analogues phosphoenolpyruvate, glyceric acid 2-phosphate, glyceraldehyde-3-phosphate, and product, dihydroxyacetone phosphate. These structural results reveal conformational states of the enzyme, delineating the residues involved in substrate binding and catalysis at the glycerol-3-phosphate site. Two probable mechanisms for catalyzing the dehydrogenation of glycerol-3-phosphate are envisioned, based on the conformational states of the complexes. To further correlate catalytic dehydrogenation to respiration, we have additionally determined the structures of GlpD bound with ubiquinone analogues menadione and 2-n-heptyl-4-hydroxyquinoline N-oxide, identifying a hydrophobic plateau that is likely the ubiquinone-binding site. These structures illuminate probable mechanisms of catalysis and suggest how GlpD shuttles electrons into the respiratory pathway. Glycerol metabolism has been implicated in insulin signaling and perturbations in glycerol uptake and catabolism are linked to obesity in humans. Homologs of GlpD are found in practically all organisms, from prokaryotes to humans, with >45% consensus protein sequences, signifying that these structural results on the prokaryotic enzyme may be readily applied to the eukaryotic GlpD enzymes.

  2. Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Klausen, Mikkel; Aaes-Jorgensen, A.; Molin, Søren

    2003-01-01

    development, we have performed an investigation with time-lapse confocal laser scanning microscopy of biofilms formed by various combinations of colour-coded P. aeruginosa wild type and motility mutants. We show that mushroom-shaped multicellular structures in P. aeruginosa biofilms can form in a sequential...... process involving a non-motile bacterial subpopulation and a migrating bacterial subpopulation. The non-motile bacteria form the mushroom stalks by growth in certain foci of the biofilm. The migrating bacteria form the mushroom caps by climbing the stalks and aggregating on the tops in a process which...

  3. Structural domains in NADPH: Protochlorophyllide oxidoreductases involved in catalysis and substrate binding. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Timko, Michael P.

    1999-09-24

    Until recently little direct information was available about specific structural determinants within the light-dependent NADPH: protochlorophyllide oxidoreductases (PORs) required for substrate and cofactor binding, catalytic activity, and thylakoid membrane localization. Based on our previous DOE-funded studies, during the past year we brought to fruition a number of ongoing experiments, initiated several new avenues of investigations, and overall have made considerable progress towards establishing the basic structural parameters governing POR function. Our studies to date have defined residues and domains involved in substrate and cofactor binding and catalysis, and elaborated on the mechanism for membrane localization of POR in developing plastids. Our results and their significance, as well as our work in progress, are detailed.

  4. Striatal dopaminergic innervation regulates subthalamic beta-oscillations and cortical-subcortical coupling during movements: evidence in three subjects with Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Andrea Canessa

    2016-12-01

    Full Text Available Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remain unclear. We recorded local field potential activity from the subthalamic nucleus and high-density electroencephalography signals in four patients with Parkinson’s disease off dopaminergic medication during a multi-joint motor task performed with their dominant and non-dominant hand. Recordings were performed by means of a fully-implantable deep brain stimulation device at four months after surgery. Three patients also performed a single-photon computed tomography with 123IN-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenylnortropane to assess striatal dopaminergic innervation. Unilateral movement execution led to event-related desynchronization followed by a rebound after movement termination (event-related synchronization of oscillatory beta activity in the subthalamic nucleus and primary sensorimotor cortex of both hemispheres. Dopamine deficiency directly influenced movement-related beta-modulation, with greater beta-suppression in the most dopamine-depleted hemisphere for both ipsi- and contralateral hand movements. Cortical-subcortical, but not interhemispheric subcortical coherencies were modulated by movement and influenced by striatal dopaminergic innervation, being stronger in the most dopamine-depleted hemisphere. The data are consistent with a role of dopamine in shielding subcortical structures from an excessive cortical entrapment and cross-hemispheric coupling, thus allowing fine-tuning of movement.

  5. Structural analysis of SgvP involved in carbon-sulfur bond formation during griseoviridin biosynthesis.

    Science.gov (United States)

    Li, Qin; Chen, Yan; Zhang, Guiqin; Zhang, Huaidong

    2017-05-01

    Griseoviridin (GV) is a broad-spectrum antibiotic with antibacterial and antifungal activity. In the GV biosynthetic pathway, SgvP catalyzes formation of the carbon-sulfur bond in GV. Herein, we report the recombinant expression and characterization of SgvP from Streptomyces griseoviridis NRRL2427. We also present the 2.6 Å crystal structure of SgvP, which is the first structure of a cytochrome P450 involved in carbon-sulfur bond formation in GV. Structural analysis indicates that Pro237 in the I-helix of SgvP may play a critical role in dioxygen binding and proton transfer during the catalytic cycle. Of the three channels we observed in SgvP, channel 3 may be essential for substrate ingress and egress from the active site, while channels 1 and 2 may be the solvent and water pathway, respectively. Coordinate and structure factor were deposited in the Protein Data Bank database under the accession number 4MM0. © 2017 Federation of European Biochemical Societies.

  6. Alveolar Antral Artery: Review of Surgical Techniques Involving this Anatomic Structure

    Directory of Open Access Journals (Sweden)

    Amin Rahpeyma

    2014-04-01

    Full Text Available Introduction: The horizontal bony canal in the lateral maxillary wall is the site of anastomosis between the arterial branches from the posterior superior alveolar artery (PSAa and the infraorbital artery. This anatomic structure is known as the ‘alveolar antral artery’.   Materials and Methods: We performed a literature review. The anatomic location of the alveolar antral artery in the lateral maxillary sinus wall was researched and its importance in surgical procedures routinely performed on this bony wall discussed.   Results: This artery can be accidentally involved during surgical procedures on the lateral maxillary sinus wall, such as open sinus lift surgery, horizontal osteotomy of the maxilla, Le Fort I fracture treatment, and Caldwell-Luc surgeries.   Conclusion: The alveolar antral artery is an important anatomic structure in the lateral maxillary sinus wall. A preoperative cone beam computed tomography (CBCT scan can be used as a good diagnostic procedure to reduce surgical complications in suspected cases as well as conditions that may involve this artery. 

  7. Basement-involved faults and deep structures in the West Philippine Basin: constrains from gravity field

    Science.gov (United States)

    Wang, Gang; Jiang, Suhua; Li, Sanzhong; Zhang, Huixuan; Lei, Jianping; Gao, Song; Zhao, Feiyu

    2017-06-01

    To reveal the basement-involved faults and deep structures of the West Philippine Basin (WPB), the gravitational responses caused by these faults are observed and analyzed based on the latest spherical gravity model: WGM2012 Model. By mapping the free-air and Bouguer gravity anomalies, several main faults and some other linear structures are located and observed in the WPB. Then, by conducting a 2D discrete multi-scale wavelet decomposition, the Bouguer anomalies are decomposed into the first- to eighth-order detail and approximation fields (the first- to eighth-order Details and Approximations). The first- to third-order Details reflect detailed and localized geological information of the crust at different depths, and of which the higher-order reflects gravity field of the deeper depth. The first- to fourth-order Approximations represent the regional gravity fields at different depths of the crust, respectively. The fourth-order Approximation represents the regional gravity fluctuation caused by the density inhomogeneity of Moho interface. Therefore, taking the fourth-order Approximation as input, and adopting Parker-Oldenburg interactive inversion, We calculated the depth of Moho interface in the WPB. Results show that the Moho interface depth in the WPB ranges approximately from 8 to 12 km, indicating that there is typical oceanic crust in the basin. In the Urdaneta Plateau and the Benham Rise, the Moho interface depths are about 14 and 16 km, respectively, which provides a piece of evidence to support that the Banham Rise could be a transitional crust caused by a large igneous province. The second-order vertical derivative and the horizontal derivatives in direction 0° and 90° are computed based on the data of the third-order Detail, and most of the basement-involved faults and structures in the WPB, such as the Central Basin Fault Zone, the Gagua Ridge, the Luzon-Okinawa Fault Zone, and the Mindanao Fault Zone are interpreted by the gravity derivatives.

  8. Subcortical processing of speech regularities underlies reading and music aptitude in children

    Science.gov (United States)

    2011-01-01

    Background Neural sensitivity to acoustic regularities supports fundamental human behaviors such as hearing in noise and reading. Although the failure to encode acoustic regularities in ongoing speech has been associated with language and literacy deficits, how auditory expertise, such as the expertise that is associated with musical skill, relates to the brainstem processing of speech regularities is unknown. An association between musical skill and neural sensitivity to acoustic regularities would not be surprising given the importance of repetition and regularity in music. Here, we aimed to define relationships between the subcortical processing of speech regularities, music aptitude, and reading abilities in children with and without reading impairment. We hypothesized that, in combination with auditory cognitive abilities, neural sensitivity to regularities in ongoing speech provides a common biological mechanism underlying the development of music and reading abilities. Methods We assessed auditory working memory and attention, music aptitude, reading ability, and neural sensitivity to acoustic regularities in 42 school-aged children with a wide range of reading ability. Neural sensitivity to acoustic regularities was assessed by recording brainstem responses to the same speech sound presented in predictable and variable speech streams. Results Through correlation analyses and structural equation modeling, we reveal that music aptitude and literacy both relate to the extent of subcortical adaptation to regularities in ongoing speech as well as with auditory working memory and attention. Relationships between music and speech processing are specifically driven by performance on a musical rhythm task, underscoring the importance of rhythmic regularity for both language and music. Conclusions These data indicate common brain mechanisms underlying reading and music abilities that relate to how the nervous system responds to regularities in auditory input

  9. Subcortical processing of speech regularities underlies reading and music aptitude in children.

    Science.gov (United States)

    Strait, Dana L; Hornickel, Jane; Kraus, Nina

    2011-10-17

    Neural sensitivity to acoustic regularities supports fundamental human behaviors such as hearing in noise and reading. Although the failure to encode acoustic regularities in ongoing speech has been associated with language and literacy deficits, how auditory expertise, such as the expertise that is associated with musical skill, relates to the brainstem processing of speech regularities is unknown. An association between musical skill and neural sensitivity to acoustic regularities would not be surprising given the importance of repetition and regularity in music. Here, we aimed to define relationships between the subcortical processing of speech regularities, music aptitude, and reading abilities in children with and without reading impairment. We hypothesized that, in combination with auditory cognitive abilities, neural sensitivity to regularities in ongoing speech provides a common biological mechanism underlying the development of music and reading abilities. We assessed auditory working memory and attention, music aptitude, reading ability, and neural sensitivity to acoustic regularities in 42 school-aged children with a wide range of reading ability. Neural sensitivity to acoustic regularities was assessed by recording brainstem responses to the same speech sound presented in predictable and variable speech streams. Through correlation analyses and structural equation modeling, we reveal that music aptitude and literacy both relate to the extent of subcortical adaptation to regularities in ongoing speech as well as with auditory working memory and attention. Relationships between music and speech processing are specifically driven by performance on a musical rhythm task, underscoring the importance of rhythmic regularity for both language and music. These data indicate common brain mechanisms underlying reading and music abilities that relate to how the nervous system responds to regularities in auditory input. Definition of common biological underpinnings

  10. Subcortical processing of speech regularities underlies reading and music aptitude in children

    Directory of Open Access Journals (Sweden)

    Strait Dana L

    2011-10-01

    Full Text Available Abstract Background Neural sensitivity to acoustic regularities supports fundamental human behaviors such as hearing in noise and reading. Although the failure to encode acoustic regularities in ongoing speech has been associated with language and literacy deficits, how auditory expertise, such as the expertise that is associated with musical skill, relates to the brainstem processing of speech regularities is unknown. An association between musical skill and neural sensitivity to acoustic regularities would not be surprising given the importance of repetition and regularity in music. Here, we aimed to define relationships between the subcortical processing of speech regularities, music aptitude, and reading abilities in children with and without reading impairment. We hypothesized that, in combination with auditory cognitive abilities, neural sensitivity to regularities in ongoing speech provides a common biological mechanism underlying the development of music and reading abilities. Methods We assessed auditory working memory and attention, music aptitude, reading ability, and neural sensitivity to acoustic regularities in 42 school-aged children with a wide range of reading ability. Neural sensitivity to acoustic regularities was assessed by recording brainstem responses to the same speech sound presented in predictable and variable speech streams. Results Through correlation analyses and structural equation modeling, we reveal that music aptitude and literacy both relate to the extent of subcortical adaptation to regularities in ongoing speech as well as with auditory working memory and attention. Relationships between music and speech processing are specifically driven by performance on a musical rhythm task, underscoring the importance of rhythmic regularity for both language and music. Conclusions These data indicate common brain mechanisms underlying reading and music abilities that relate to how the nervous system responds to

  11. Cortical thickness and hippocampal shape in pure vascular mild cognitive impairment and dementia of subcortical type.

    Science.gov (United States)

    Kim, H J; Ye, B S; Yoon, C W; Noh, Y; Kim, G H; Cho, H; Jeon, S; Lee, J M; Kim, J-H; Seong, J-K; Kim, C-H; Choe, Y S; Lee, K H; Kim, S T; Kim, J S; Park, S E; Kim, J-H; Chin, J; Cho, J; Kim, C; Lee, J H; Weiner, M W; Na, D L; Seo, S W

    2014-05-01

    The progression pattern of brain structural changes in patients with isolated cerebrovascular disease (CVD) remains unclear. To investigate the role of isolated CVD in cognitive impairment patients, patterns of cortical thinning and hippocampal atrophy in pure subcortical vascular mild cognitive impairment (svMCI) and pure subcortical vascular dementia (SVaD) patients were characterized. Forty-five patients with svMCI and 46 patients with SVaD who were negative on Pittsburgh compound B (PiB) positron emission tomography imaging and 75 individuals with normal cognition (NC) were recruited. Compared with NC, patients with PiB(-) svMCI exhibited frontal, language and retrieval type memory dysfunctions, which in patients with PiB(-) SVaD were further impaired and accompanied by visuospatial and recognition memory dysfunctions. Compared with NC, patients with PiB(-) svMCI exhibited cortical thinning in the frontal, perisylvian, basal temporal and posterior cingulate regions. This atrophy was more prominent and extended further toward the lateral parietal and medial temporal regions in patients with PiB(-) SVaD. Compared with NC subjects, patients with PiB(-) svMCI exhibited hippocampal shape deformities in the lateral body, whilst patients with PiB(-) SVaD exhibited additional deformities within the lateral head and inferior body. Our findings suggest that patients with CVD in the absence of Alzheimer's disease pathology can be demented, showing cognitive impairment in multiple domains, which is consistent with the topography of cortical thinning and hippocampal shape deformity. © 2014 The Author(s) European Journal of Neurology © 2014 EFNS.

  12. Subcortical band heterotopia with simplified gyral pattern and syndactyly.

    Science.gov (United States)

    Sicca, Federico; Silengo, Margherita; Parrini, Elena; Ferrero, Giovanni B; Guerrini, Renzo

    2003-06-01

    We describe a girl with an unusual form of subcortical band heterotopia (SBH) and a complex malformation syndrome. SBH had an irregular inner margin, organized in contiguous fascicles of migrating neurons, sometimes giving the appearance of many small contiguous gyri. The true cortex had decreased thickness and showed a simplified gyral pattern with decreased number of gyri, which were usually of increased width, and shallow sulci. The cerebellum was hypoplastic. Additional features included epicanthal folds, hypertelorism, small nose with hypoplastic nares, bilateral syndactyly of the toes, pulmonary valve stenosis, atrial and ventricular septal defects. At the age of 1 year the patient had severe developmental delay and epilepsy. Chromosome studies and mutation analysis of the DCX and LIS1 genes gave negative results. This observation delineates a new multiple congenital abnormalities mental retardation syndrome and confirms genetic heterogeneity of SBH. Copyright 2003 Wiley-Liss, Inc.

  13. Lissencephaly and subcortical band heterotopia: molecular basis and diagnosis.

    Science.gov (United States)

    Leventer, R J; Pilz, D T; Matsumoto, N; Ledbetter, D H; Dobyns, W B

    2000-07-01

    Magnetic resonance imaging is now used routinely in the evaluation of developmental and neurological disorders and provides exquisite images of the living human brain. Consequently, it is evident that cortical malformations are more common than previously thought. Among the most severe is classical lissencephaly, in which the cortex lacks the complex folding that characterizes the normal human brain. Lissencephaly includes agyria and pachygyria, and merges with subcortical band heterotopia. Current molecular genetic techniques combined with the identification of affected patients have enabled the detection of two of the genes responsible: LIS1 (PAFAH1B1) on chromosome 17 and DCX (doublecortin) on the X chromosome. This review highlights the discovery of these genes and discusses the advances made in understanding the molecular basis of cortical development and improvements in diagnosis and genetic counseling.

  14. Functions of gamma-band synchronization in cognition: from single circuits to functional diversity across cortical and subcortical systems.

    Science.gov (United States)

    Bosman, Conrado A; Lansink, Carien S; Pennartz, Cyriel M A

    2014-06-01

    Gamma-band activity (30-90 Hz) and the synchronization of neural activity in the gamma-frequency range have been observed in different cortical and subcortical structures and have been associated with different cognitive functions. However, it is still unknown whether gamma-band synchronization subserves a single universal function or a diversity of functions across the full spectrum of cognitive processes. Here, we address this question reviewing the mechanisms of gamma-band oscillation generation and the functions associated with gamma-band activity across several cortical and subcortical structures. Additionally, we raise a plausible explanation of why gamma rhythms are found so ubiquitously across brain structures. Gamma band activity originates from the interplay between inhibition and excitation. We stress that gamma oscillations, associated with this interplay, originate from basic functional motifs that conferred advantages for low-level system processing and multiple cognitive functions throughout evolution. We illustrate the multifunctionality of gamma-band activity by considering its role in neural systems for perception, selective attention, memory, motivation and behavioral control. We conclude that gamma-band oscillations support multiple cognitive processes, rather than a single one, which, however, can be traced back to a limited set of circuit motifs which are found universally across species and brain structures. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. Crystal structure of a bicupin protein HutD involved in histidine utilization in Pseudomonas.

    Science.gov (United States)

    Gerth, M L; Liu, Y; Jiao, W; Zhang, X-X; Baker, E N; Lott, J S; Rainey, P B; Johnston, J M

    2017-08-01

    Cupins form one of the most functionally diverse superfamilies of proteins, with members performing a wide range of catalytic, non-catalytic, and regulatory functions. HutD is a predicted bicupin protein that is involved in histidine utilization (Hut) in Pseudomonas species. Previous genetic analyses have suggested that it limits the upper level of Hut pathway expression, but its mechanism of action is unknown. Here, we have determined the structure of PfluHutD at 1.74 Å resolution in several crystallization conditions, and identified N-formyl-l-glutamate (FG, a Hut pathway intermediate) as a potential ligand in vivo. Proteins 2017; 85:1580-1588. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Anatomical pathways involved in generating and sensing rhythmic whisker movements.

    Science.gov (United States)

    Bosman, Laurens W J; Houweling, Arthur R; Owens, Cullen B; Tanke, Nouk; Shevchouk, Olesya T; Rahmati, Negah; Teunissen, Wouter H T; Ju, Chiheng; Gong, Wei; Koekkoek, Sebastiaan K E; De Zeeuw, Chris I

    2011-01-01

    The rodent whisker system is widely used as a model system for investigating sensorimotor integration, neural mechanisms of complex cognitive tasks, neural development, and robotics. The whisker pathways to the barrel cortex have received considerable attention. However, many subcortical structures are paramount to the whisker system. They contribute to important processes, like filtering out salient features, integration with other senses, and adaptation of the whisker system to the general behavioral state of the animal. We present here an overview of the brain regions and their connections involved in the whisker system. We do not only describe the anatomy and functional roles of the cerebral cortex, but also those of subcortical structures like the striatum, superior colliculus, cerebellum, pontomedullary reticular formation, zona incerta, and anterior pretectal nucleus as well as those of level setting systems like the cholinergic, histaminergic, serotonergic, and noradrenergic pathways. We conclude by discussing how these brain regions may affect each other and how they together may control the precise timing of whisker movements and coordinate whisker perception.

  17. Fluid-structure interaction involving large deformations: 3D simulations and applications to biological systems

    Science.gov (United States)

    Tian, Fang-Bao; Dai, Hu; Luo, Haoxiang; Doyle, James F.; Rousseau, Bernard

    2014-02-01

    Three-dimensional fluid-structure interaction (FSI) involving large deformations of flexible bodies is common in biological systems, but accurate and efficient numerical approaches for modeling such systems are still scarce. In this work, we report a successful case of combining an existing immersed-boundary flow solver with a nonlinear finite-element solid-mechanics solver specifically for three-dimensional FSI simulations. This method represents a significant enhancement from the similar methods that are previously available. Based on the Cartesian grid, the viscous incompressible flow solver can handle boundaries of large displacements with simple mesh generation. The solid-mechanics solver has separate subroutines for analyzing general three-dimensional bodies and thin-walled structures composed of frames, membranes, and plates. Both geometric nonlinearity associated with large displacements and material nonlinearity associated with large strains are incorporated in the solver. The FSI is achieved through a strong coupling and partitioned approach. We perform several validation cases, and the results may be used to expand the currently limited database of FSI benchmark study. Finally, we demonstrate the versatility of the present method by applying it to the aerodynamics of elastic wings of insects and the flow-induced vocal fold vibration.

  18. Protein Machineries Involved in the Attachment of Heme to Cytochrome c: Protein Structures and Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Carlo Travaglini-Allocatelli

    2013-01-01

    Full Text Available Cytochromes c (Cyt c are ubiquitous heme-containing proteins, mainly involved in electron transfer processes, whose structure and functions have been and still are intensely studied. Surprisingly, our understanding of the molecular mechanism whereby the heme group is covalently attached to the apoprotein (apoCyt in the cell is still largely unknown. This posttranslational process, known as Cyt c biogenesis or Cyt c maturation, ensures the stereospecific formation of the thioether bonds between the heme vinyl groups and the cysteine thiols of the apoCyt heme binding motif. To accomplish this task, prokaryotic and eukaryotic cells have evolved distinctive protein machineries composed of different proteins. In this review, the structural and functional properties of the main maturation apparatuses found in gram-negative and gram-positive bacteria and in the mitochondria of eukaryotic cells will be presented, dissecting the Cyt c maturation process into three functional steps: (i heme translocation and delivery, (ii apoCyt thioreductive pathway, and (iii apoCyt chaperoning and heme ligation. Moreover, current hypotheses and open questions about the molecular mechanisms of each of the three steps will be discussed, with special attention to System I, the maturation apparatus found in gram-negative bacteria.

  19. A new structural arrangement in proteins involving lysine NH3+ group and carbonyl.

    Science.gov (United States)

    Rogacheva, Olga N; Izmailov, Sergei A; Slipchenko, Lyudmila V; Skrynnikov, Nikolai R

    2017-11-27

    Screening of the Protein Data Bank led to identification of a recurring structural motif where lysine NH3+ group interacts with backbone carbonyl. This interaction is characterized by linear atom arrangement, with carbonyl O atom positioned on the three-fold symmetry axis of the NH3+ group (angle Cε-Nζ-O close to 180°, distance Nζ-O ca. 2.7-3.0 Å). Typically, this linear arrangement coexists with three regular hydrogen bonds formed by lysine NH3+ group (angle Cε-Nζ-acceptor atom close to 109°, distance Nζ-acceptor atom ca. 2.7-3.0 Å). Our DFT calculations using polarizable continuum environment suggest that this newly identified linear interaction makes an appreciable contribution to protein's energy balance, up to 2 kcal/mol. In the context of protein structure, linear interactions play a role in capping the C-termini of α-helices and 310-helices. Of note, linear interaction involving conserved lysine is consistently found in the P-loop of numerous NTPase domains, where it stabilizes the substrate-binding conformation of the P-loop. Linear interaction NH3+ - carbonyl represents an interesting example of ion-dipole interactions that has so far received little attention compared to ion-ion interactions (salt bridges) and dipole-dipole interactions (hydrogen bonds), but nevertheless represents a distinctive element of protein architecture.

  20. Combined Invasive Subcortical and Non-invasive Surface Neurophysiological Recordings for the Assessment of Cognitive and Emotional Functions in Humans.

    Science.gov (United States)

    Trenado, Carlos; Elben, Saskia; Petri, David; Hirschmann, Jan; Groiss, Stefan J; Vesper, Jan; Schnitzler, Alfons; Wojtecki, Lars

    2016-05-19

    In spite of the success in applying non-invasive electroencephalography (EEG), magneto-encephalography (MEG) and functional magnetic resonance imaging (fMRI) for extracting crucial information about the mechanism of the human brain, such methods remain insufficient to provide information about physiological processes reflecting cognitive and emotional functions at the subcortical level. In this respect, modern invasive clinical approaches in humans, such as deep brain stimulation (DBS), offer a tremendous possibility to record subcortical brain activity, namely local field potentials (LFPs) representing coherent activity of neural assemblies from localized basal ganglia or thalamic regions. Notwithstanding the fact that invasive approaches in humans are applied only after medical indication and thus recorded data correspond to altered brain circuits, valuable insight can be gained regarding the presence of intact brain functions in relation to brain oscillatory activity and the pathophysiology of disorders in response to experimental cognitive paradigms. In this direction, a growing number of DBS studies in patients with Parkinson's disease (PD) target not only motor functions but also higher level processes such as emotions, decision-making, attention, memory and sensory perception. Recent clinical trials also emphasize the role of DBS as an alternative treatment in neuropsychiatric disorders ranging from obsessive compulsive disorder (OCD) to chronic disorders of consciousness (DOC). Consequently, we focus on the use of combined invasive (LFP) and non-invasive (EEG) human brain recordings in assessing the role of cortical-subcortical structures in cognitive and emotional processing trough experimental paradigms (e.g. speech stimuli with emotional connotation or paradigms of cognitive control such as the Flanker task), for patients undergoing DBS treatment.

  1. Subcortical surgical anatomy of the lateral frontal region: human white matter dissection and correlations with functional insights provided by intraoperative direct brain stimulation: laboratory investigation.

    Science.gov (United States)

    De Benedictis, Alessandro; Sarubbo, Silvio; Duffau, Hugues

    2012-12-01

    Recent neuroimaging and surgical results support the crucial role of white matter in mediating motor and higher-level processing within the frontal lobe, while suggesting the limited compensatory capacity after damage to subcortical structures. Consequently, an accurate knowledge of the anatomofunctional organization of the pathways running within this region is mandatory for planning safe and effective surgical approaches to different diseases. The aim of this dissection study was to improve the neurosurgeon's awareness of the subcortical anatomofunctional architecture for a lateral approach to the frontal region, to optimize both resection and postoperative outcome. Ten human hemispheres (5 left, 5 right) were dissected according to the Klingler technique. Proceeding lateromedially, the main association and projection tracts as well as the deeper basal structures were identified. The authors describe the anatomy and the relationships among the exposed structures in both a systematic and topographical surgical perspective. Structural results were also correlated to the functional responses obtained during resections of infiltrative frontal tumors guided by direct cortico-subcortical electrostimulation with patients in the awake condition. The eloquent boundaries crucial for a safe frontal lobectomy or an extensive lesionectomy are as follows: 1) the motor cortex; 2) the pyramidal tract and premotor fibers in the posterior and posteromedial part of the surgical field; 3) the inferior frontooccipital fascicle and the superior longitudinal fascicle posterolaterally; and 4) underneath the inferior frontal gyrus, the head of the caudate nucleus, and the tip of the frontal horn of the lateral ventricle in the depth. Optimization of results following brain surgery, especially within the frontal lobe, requires a perfect knowledge of functional anatomy, not only at the cortical level but also with regard to subcortical white matter connectivity.

  2. Giant subcortical high-frequency SEPs in idiopathic generalized epilepsy: a protective mechanism against seizures?

    Science.gov (United States)

    Restuccia, Domenico; Valeriani, Massimiliano; Della Marca, Giacomo

    2007-01-01

    Recently, we found that high-frequency somatosensory evoked potentials (HF-SEPs), which are modulated by arousal-related structures, were abnormally enhanced during N-REM sleep in two seizure-free IGE patients [Restuccia D, Rubino M, Valeriani M, Della Marca G. Increase of brainstem high-frequency SEP subcomponents during light sleep in seizure-free epileptic patients. Clin Neurophysiol 2005; 116: 1774-1778]. Here, we aimed at verifying whether similar HF-SEP abnormalities were significantly correlated to the clinical outcome in a larger population of untreated IGE patients. Patients were classified as Juvenile Myoclonic epilepsy (JME; six patients) and Childhood or Juvenile Absence epilepsy (CAE and JAE, six patients). They were untreated because newly diagnosed, or because seizure-free. HF-SEPs from patients were compared with those obtained from 21 healthy volunteers. HF-SEPs were abnormally enhanced in all seizure-free CAE-JAE patients, whereas they were normal in all JME patients and in CAE-JAE patients with frequent seizures. Not only scalp distribution, but also dipolar source analysis suggested a subcortical origin for these enhanced subcomponents, possibly in the brainstem. The enhancement of HF-SEPs might reflect the hyperactivity of arousal-related brainstem structures; such an enhancement was found in all seizure-free CAE-JAE patients, while it was never observed in JME patients. We speculate that the hyperactivity of arousal-related brainstem structures might account for the different clinical outcome among IGE subsyndromes.

  3. Assessing cortical and subcortical changes in a western diet mouse model using spectral/Fourier domain OCT (Conference Presentation)

    Science.gov (United States)

    Bernucci, Marcel T.; Norman, Jennifer E.; Merkle, Conrad W.; Aung, Hnin H.; Rutkowsky, Jennifer; Rutledge, John C.; Srinivasan, Vivek J.

    2017-02-01

    The Western diet, causative in the development of atherosclerotic cardiovascular disease, has recently been associated with the development of diffuse white matter disease (WMD) and other subcortical changes. Yet, little is known about the pathophysiological mechanisms by which a high-fat diet can cause WMD. Mechanistic studies of deep brain regions in mice have been challenging due to a lack of non-invasive, high-resolution, and deep imaging technologies. Here we used Optical Coherence Tomography to study mouse cortical/subcortical structures noninvasively and in vivo. To better understand the role of Western Diet in the development of WMD, intensity and Doppler flow OCT images, obtained using a 1300 nm spectral / Fourier domain OCT system, were used to observe the structural and functional alterations in the cortex and corpus callosum of Western Diet and control diet mouse models. Specifically, we applied segmentation to the OCT images to identify the boundaries of the cortex/corpus callosum, and further quantify the layer thicknesses across animals between the two diet groups. Furthermore, microvasculature alterations such as changes in spatiotemporal flow profiles within diving arterioles, arteriole diameter, and collateral tortuosity were analyzed. In the current study, while the arteriole vessel diameters between the two diet groups was comparable, we show that collateral tortuosity was significantly higher in the Western diet group, compared to control diet group, possibly indicating remodeling of brain vasculature due to dietary changes. Moreover, there is evidence showing that the corpus callosum is thinner in Western diet mice, indicative of tissue atrophy.

  4. Fluid-structure interaction involving dynamic wetting: 2D modeling and simulations

    Science.gov (United States)

    Liu, Hao-Ran; Gao, Peng; Ding, Hang

    2017-11-01

    In this paper, we propose a hybrid model to compute the capillary force acting on moving solid objects, and combine it with the diffuse-interface immersed-boundary method in Liu and Ding (2015) [18] to simulate fluid-structure interaction (FSI) involving dynamic wetting. Dynamic wetting is very important in the dynamic interaction between fluid-fluid interfaces and small moving objects. Numerical simulations of these flow problems require accurate computation of the capillary force acting on the structure, which depends on the instantaneous position of and the effective surface tension at the moving contact line. In order to achieve this, we use the diffuse-interface immersed-boundary method to simulate the dynamic wetting on moving objects, and propose a hybrid model to compute the effective surface tension at the contact line. Specifically, a diffuse interface model is used for the interface profile out of equilibrium, e.g. at the onset of formation or detachment of contact lines, and a sharp interface model is used for the interface profile at equilibrium. The performance of the method is examined by a variety of numerical experiments. We simulate the sinking of a circular cylinder due to gravity, and study the capillarity-dominated impact dynamics of a solid sphere on a water pool. In both cases the numerical results are quantitatively compared against the experimental data, and good agreements have been achieved. The momentum conservation of the system is carefully checked by studying head-on collision between a drop and a solid sphere. Finally, we apply the method to the self-assembly process of multiple floating cylinders on water surface.

  5. SEORious business: structural proteins in sieve tubes and their involvement in sieve element occlusion.

    Science.gov (United States)

    Knoblauch, Michael; Froelich, Daniel R; Pickard, William F; Peters, Winfried S

    2014-04-01

    The phloem provides a network of sieve tubes for long-distance translocation of photosynthates. For over a century, structural proteins in sieve tubes have presented a conundrum since they presumably increase the hydraulic resistance of the tubes while no potential function other than sieve tube or wound sealing in the case of injury has been suggested. Here we summarize and critically evaluate current speculations regarding the roles of these proteins. Our understanding suffers from the suggestive power of images; what looks like a sieve tube plug on micrographs may not actually impede translocation very much. Recent reports of an involvement of SEOR (sieve element occlusion-related) proteins, a class of P-proteins, in the sealing of injured sieve tubes are inconclusive; various lines of evidence suggest that, in neither intact nor injured plants, are SEORs determinative of translocation stoppage. Similarly, the popular notion that P-proteins serve in the defence against phloem sap-feeding insects is unsupported by empirical facts; it is conceivable that in functional sieve tubes, aphids actually could benefit from inducing a plug. The idea that rising cytosolic Ca(2+) generally triggers sieve tube blockage by P-proteins appears widely accepted, despite lacking experimental support. Even in forisomes, P-protein assemblages restricted to one single plant family and the only Ca(2+)-responsive P-proteins known, the available evidence does not unequivocally suggest that plug formation is the cause rather than a consequence of translocation stoppage. We conclude that the physiological roles of structural P-proteins remain elusive, and that in vivo studies of their dynamics in continuous sieve tube networks combined with flow velocity measurements will be required to (hopefully) resolve this scientific roadblock.

  6. Potential gray matter unpruned in adolescents and young adults dependent on dextromethorphan-containing cough syrups: evidence from cortical and subcortical study.

    Science.gov (United States)

    Qiu, Ying-Wei; Lv, Xiao-Fei; Jiang, Gui-Hua; Su, Huan-Huan; Ma, Xiao-Fen; Tian, Jun-Zhang; Zhuo, Fu-Zhen

    2017-10-01

    Adolescence is a unique period in neurodevelopment. Dextromethorphan (DXM)-containing cough syrups are new addictive drugs used by adolescents and young adults. The effects of chronic DXM abuse on neurodevelopment in adolescents and young adults are still unknown. The aim of this study was to investigate the differences in cortical thickness and subcortical gray matter volumes between DXM-dependent adolescents and young adults and healthy controls, and to explore relationships between alternations in cortical thickness/subcortical volume and DXM duration, initial age of DXM use, as well as impulsive behavior in DXM-dependent adolescents and young adults. Thirty-eight DXM-dependent adolescents and young adults and 18 healthy controls underwent magnetic resonance imaging scanning, and cortical thickness across the continuous cortical surface was compared between the groups. Subcortical volumes were compared on a structure-by-structure basis. DXM-dependent adolescents and young adults exhibited significantly increased cortical thickness in the bilateral precuneus (PreC), left dorsal lateral prefrontal cortex (DLPFC. L), left inferior parietal lobe (IPL. L), right precentral gyrus (PreCG. R), right lateral occipital cortex (LOC. R), right inferior temporal cortex (ITC. R), right lateral orbitofrontal cortex (lOFC. R) and right transverse temporal gyrus (TTG. R) (all p adolescents dependent on DXM. These structural changes might explain the neurobiological mechanism of impulsive behavior in adolescent DXM users.

  7. Intermittent cortical involvement in the preservation of tremor in essential tremor

    NARCIS (Netherlands)

    Sharifi, Sarvi; Luft, Frauke; Verhagen, Rens; Heida, Tjitske; Speelman, Johannes D.; Bour, Lo J.; van Rootselaar, Anne-Fleur

    2017-01-01

    Cortical involvement in essential tremor, an involuntary action tremor supposedly of subcortical origin, is uncertain. Conflicting results of corticomuscular coherence studies in essential tremor suggest an intermittent corticomuscular coupling. On the basis of the literature, we hypothesized that

  8. Eight novel mutations in MLC1 from 18 Iranian patients with megalencephalic leukoencephalopathy with subcortical cysts

    NARCIS (Netherlands)

    Kariminejad, Ariana; Rajaee, Ahmad; Ashrafi, Mahmoud Reza; Alizadeh, Houman; Tonekaboni, Seyed Hasan; Malamiri, Reza Azizi; Ghofrani, Mohamad; Karimzadeh, Parvaneh; Mohammadi, Mohsen Molla; Baghalshooshtari, Ali; Bozorgmehr, Bita; Kariminejad, Mohamad Hasan; Postma, N.; Abbink, Truus E. M.; van der Knaap, Marjo S.

    2015-01-01

    Megalencephalic leukoencephalopathy with subcortical cysts (MLC) (MIM #604004) is a rare autosomal recessive neurological disorder characterized by macrocephaly, motor and cognitive decline, ataxia, spasticity and occasional seizures. Magnetic resonance imaging (MRI) shows diffusely abnormal and

  9. [Subcortical laminal heterotopia and lissencephaly: cerebral malformations of X-linked inheritance].

    Science.gov (United States)

    Pinard, J M; Desguerre, I; Motte, J; Dulac, O; Ponsot, G

    1995-03-01

    Subcortical laminar heterotopia (band heterotopia) is a brain malformation now recognized by MRI. We report 3 families (2 previously described) in which several members had subcortical laminar heterotopia or a more severe malformation (agyria/pachygyria). In these families, subcortical laminar heterotopia were observed in women and were associated with epilepsy or slight mental retardation depending on the extend of heterotopia. Males had lissencephaly with refractory epilepsy and severe mental retardation. The pedigrees of these families demonstrate that these 2 malformations originate from a single genetic origin. A single X-linked dominant gene is postulated. Diagnosis of subcortical laminar heterotopia in a female or lissencephaly in a male (except in the case of Miller-Dieker syndrome) requires appropriate genetic counselling in the family: brain imaging should be performed in relatives.

  10. Genotype-phenotype correlation in lissencephaly and subcortical band heterotopia: the key questions answered.

    Science.gov (United States)

    Leventer, Richard Jacob

    2005-04-01

    Lissencephaly and subcortical band heterotopia are closely related cortical malformations and are true disorders of neuronal migration. The genetic basis of approximately 70% of classic lissencephaly and 80% of typical subcortical band heterotopia is known. Most are due to abnormalities within the LIS1 or DCX genes, with abnormalities ranging from single basepair substitutions to contiguous gene deletions. Understanding the genetic basis of these disorders has led to the elucidation of the molecular and developmental mechanisms that are adversely affected. There is a robust correlation between many of the clinical aspects of lissencephaly or subcortical band heterotopia and the type and location of mutations in the affected gene. Using this knowledge, the clinician can predict with some accuracy which gene is likely to be affected based on the clinical and imaging features. This review answers some of the key questions regarding the genotype-phenotype correlation for lissencephaly and subcortical band heterotopia.

  11. Delayed visual maturation: pupillary responses implicate subcortical and cortical visual systems

    National Research Council Canada - National Science Library

    Cocker, K D; Moseley, M J; Stirling, H F; Fielder, A R

    1998-01-01

    .... The improvement of vision in delayed visual maturation (DVM) occurs around this time, and this has given rise to the suggestion that the condition may have a subcortical basis that resolves with the appearance of cortical function...

  12. Association of father involvement and neighborhood quality with kindergartners' physical activity: a multilevel structural equation model.

    Science.gov (United States)

    Beets, Michael W; Foley, John T

    2008-01-01

    Examine the effects of father-child involvement and neighborhood characteristics with young children's physical activity (PA) within a multilevel framework. Cross-sectional analysis of the Early Childhood Longitudinal Study-Kindergarten Cohort 1998. Nationally representative sample. Data were available for 10,694 kindergartners (5-6 years; 5240 girls) living in 1053 neighborhoods. Parental report of child's PA level, father characteristics (e.g., time spent with child, age, education, socioeconomic status, hours worked), family time spent doing sports/ activities together, and neighborhood quality (e.g., safety, presence of crime violence, garbage). Child weight status, motor skills, ethnicity, and television viewing were used as covariates. Multilevel structural equation modeling with children nested within neighborhoods. At the child level father-child time and family time doing sports together were positively associated with children's PA. At the neighborhood level parental perception of a neighborhood's safety for children to play outside fully mediated the effect of neighborhood quality on children's PA. Overall 19.1% and 7.6% of the variance in PA was explained at the child and neighborhood levels, respectively. Family-based interventions for PA should consider father-child time, with this contributing to a child's overall PA level. Further, neighborhood quality is an important predictor of PA only to the extent by which parents perceive it to be unsafe for their child to play outdoors.

  13. A structural model of customer satisfaction and trust in vendors involved in mobile commerce

    Directory of Open Access Journals (Sweden)

    Suki, N.M.

    2011-01-01

    Full Text Available The purpose of this paper is to provide an explanation of factors influencing customer satisfaction and trust in vendors involved in mobile commerce (m-commerce. The study sample consists of 200 respondents. Data were analyzed by employing structural equation modelling (SEM supported by AMOS 5.0 with maximum likelihood estimation in order to test the proposed hypotheses. The proposed model was empirically tested and results confirmed that users’ satisfaction with vendors in m-commerce was not significantly influenced by two antecedents of the vendor’s website quality: interactivity and customisation, and also two antecedents of mobile technology quality: usefulness and ease-of-use. Meanwhile, users’ trust towards the vendor in m-commerce is affected by users’ satisfaction with the vendor. Interestingly, vendor quality dimensions such as responsiveness and brand image influence customer satisfaction with vendors in m-commerce. Based on the findings, vendors in m-commerce should focus on the factors which generate more satisfaction and trust among customers. For vendors in general, the results can help them to better develop customer trust in m-commerce. Vendors of m-commerce can provide a more satisfying experience for customers.

  14. Structural myocardial involvement in adult patients with type 1 myotonic dystrophy

    Directory of Open Access Journals (Sweden)

    Upinder K. Dhand

    2013-03-01

    Full Text Available Myotonic dystrophy type 1 (DM1 is the commonest muscular dystrophy in adults, affecting multiple organs in addition to skeletal muscles. Cardiac conduction system abnormalities are well recognized as an important component of DM1 phenotype; however, primary structural myocardial abnormalities, which may predispose these patients to congestive heart failure, are not as well characterized. We reviewed the retrospective analysis of the clinical and echocardiographic findings in adult patients with DM1. Among 27 patients (16 male; age 19-61 years with DM1, the echocardiogram (ECHO was abnormal in 10 (37% including one of 6 patients (16% with congenital myotonic dystrophy. Reduced left ventricular ejection fraction (LVEF ≤50% was noted in 5, diastolic dysfunction in 4, left atrial dilatation in 3, left ventricular hypertrophy in 2, apical hypokinesia in 1 and mitral valve prolapse in 3 patients. One patient had paradoxical septal movement in the setting of left bundle branch block. Echocardiographic abnormalities significantly correlated with older age; however, patients with systolic dysfunction on echocardiogram ranged in age from 27 to 52 years including 2 patients aged 27 and 34 years. We can conclude that echocardiographic abnormalities are frequent in adult patients with DM1. The incidence is similar in the classical and congenital type of DM1. Overall, echocardiographic abnormalities in DM1 correlate with increasing age; however, reduced LVEF is observed even at young age. Cardiac assessment and monitoring in adult patients with DM1 should include evaluation for primary myocardial involvement.

  15. Extra-hippocampal subcortical limbic involvement predicts episodic recall performance in multiple sclerosis.

    Science.gov (United States)

    Dineen, Robert A; Bradshaw, Christopher M; Constantinescu, Cris S; Auer, Dorothee P

    2012-01-01

    Episodic memory impairment is a common but poorly-understood phenomenon in multiple sclerosis (MS). We aim to establish the relative contributions of reduced integrity of components of the extended hippocampal-diencephalic system to memory performance in MS patients using quantitative neuroimaging. 34 patients with relapsing-remitting MS and 24 healthy age-matched controls underwent 3 T MRI including diffusion tensor imaging and 3-D T1-weighted volume acquisition. Manual fornix regions-of-interest were used to derive fornix fractional anisotropy (FA). Normalized hippocampal, mammillary body and thalamic volumes were derived by manual segmentation. MS subjects underwent visual recall, verbal recall, verbal recognition and verbal fluency assessment. Significant differences between MS patients and controls were found for fornix FA (0.38 vs. 0.46, means adjusted for age and fornix volume, Pvisual recall (R(2) = .31, P = .003, P = .006), and thalamic volume as predictive of verbal recall (R(2) = .37, Precall in MS patients with mild memory dysfunction.

  16. Two cases with megalencephalic leukoencephalopathy with subcortical cysts and MLC1 mutations in the Turkish population.

    Science.gov (United States)

    Yiş, Uluç; Scheper, Gert C; Uran, Nedret; Unalp, Aycan; Cakmakçi, Handan; Hiz-Kurul, Semra; Dirik, Eray; van der Knaap, Marjo S

    2010-01-01

    Megalencephalic leukoencephalopathy with subcortical cysts is a rare leukodystrophy that is characterized by macrocephaly and a slowly progressive clinical course. It is one of the most commonly reported leukoencephalopathies in Turkey. Mutations in the MLC1 gene are the main cause of the disease. We report two patients with megalencephalic leukoencephalopathy with subcortical cysts with confirmed mutations in the MLC1 gene. The mutation in the second patient was novel. We also review identified mutations in the Turkish population.

  17. Comparative Study of Subcortical Atrophy in Patients with Frontotemporal Dementia and Dementia with Extrapyramidal Signs

    Science.gov (United States)

    Caixeta, Leonardo; Vieira, Renata Teles; Paes, Flávia; Carta, Mauro Giovanni; Nardi, Antonio Egidio; Arias-Carrión, Oscar; Rocha, Nuno B. F; Budde, Henning; Machado, Sergio

    2015-01-01

    Objectives : To investigate the severity of subcortical atrophy in frontotemporal dementia (FTD) without extrapyramidal symptoms (EPS) and dementia with EPS. In addition, we aim to verify if there is correlation between demographic and clinical characteristics and subcortical atrophy in the groups. Methodology : The sample was composed of 21 patients with dementia and EPS as well as 19 patients with FTD without EPS. A linear assessment was conducted in order to identify the degree of subcortical atrophy (i.e., bifrontal index - BFI) using MRI. Moreover, the Mini-Mental State Examination (MMSE), Pfeffer Functional Activities Questionnaire (FAQ) and the Clinical Dementia Rating (CDR) were used to investigate clinical aspects. Results : It was verified that patients with dementia and EPS was older than the patients with FTD (p=0.01). The severity of cognitive deficits was associated with BFI, as well as the dementia severity in the EPS group. Conclusion : FTD group presented mean BFI scores above the cutoff for normal elderly population, indicating the presence of subcortical atrophy in this group. Mean BFI was higher (although not statistically significant) in FTD group than in dementia with EPS, which can suggest at least that subcortical pathology in FTD may be as important as in the dementia with EPS group. Subcortical atrophy is a good biological marker for cognitive deterioration in FTD and in dementia with EPS. PMID:25870648

  18. The subcortical hidden side of focal motor seizures: evidence from micro-recordings and local field potentials.

    Science.gov (United States)

    Devergnas, Annaelle; Piallat, Brigitte; Prabhu, Shivadatta; Torres, Napoleon; Louis Benabid, Alim; David, Olivier; Chabardès, Stephan

    2012-07-01

    cortical activity throughout the seizure. In putamen, the synchronization appeared only by the end of seizures and for the two output structures, despite some increase of the oscillatory activity, the synchronization with the cortex was not significant. Our results suggest that the subthalamo-(external)-pallidal pathway is the main subcortical route involved during ictal motor seizures. Surprisingly, ictal activity did not propagate to the output structure of basal ganglia in that model. This finding may be important for clinical decisions of targeting when considering anti-epileptic neuromodulation in human beings suffering from disabling, drug resistant motor epilepsy.

  19. Cortical Thickness, Surface Area and Subcortical Volume Differentially Contribute to Cognitive Heterogeneity in Parkinson's Disease.

    Directory of Open Access Journals (Sweden)

    Niels J H M Gerrits

    Full Text Available Parkinson's disease (PD is often associated with cognitive deficits, although their severity varies considerably between patients. Recently, we used voxel-based morphometry (VBM to show that individual differences in gray matter (GM volume relate to cognitive heterogeneity in PD. VBM does, however, not differentiate between cortical thickness (CTh and surface area (SA, which might be independently affected in PD. We therefore re-analyzed our cohort using the surface-based method FreeSurfer, and investigated (i CTh, SA, and (subcortical GM volume differences between 93 PD patients and 45 matched controls, and (ii the relation between these structural measures and cognitive performance on six neuropsychological tasks within the PD group. We found cortical thinning in PD patients in the left pericalcarine gyrus, extending to cuneus, precuneus and lingual areas and left inferior parietal cortex, bilateral rostral middle frontal cortex, and right cuneus, and increased cortical surface area in the left pars triangularis. Within the PD group, we found negative correlations between (i CTh of occipital areas and performance on a verbal memory task, (ii SA and volume of the frontal cortex and visuospatial memory performance, and, (iii volume of the right thalamus and scores on two verbal fluency tasks. Our primary findings illustrate that i CTh and SA are differentially affected in PD, and ii VBM and FreeSurfer yield non-overlapping results in an identical dataset. We argue that this discrepancy is due to technical differences and the subtlety of the PD-related structural changes.

  20. Temporal Lobe and Frontal-Subcortical Dissociations in Non-Demented Parkinson's Disease with Verbal Memory Impairment.

    Science.gov (United States)

    Tanner, Jared J; Mareci, Thomas H; Okun, Michael S; Bowers, Dawn; Libon, David J; Price, Catherine C

    2015-01-01

    The current investigation examined verbal memory in idiopathic non-dementia Parkinson's disease and the significance of the left entorhinal cortex and left entorhinal-retrosplenial region connections (via temporal cingulum) on memory impairment in Parkinson's disease. Forty non-demented Parkinson's disease patients and forty non-Parkinson's disease controls completed two verbal memory tests--a wordlist measure (Philadelphia repeatable Verbal Memory Test) and a story measure (Logical Memory). All participants received T1-weighted and diffusion magnetic resonance imaging (3T; Siemens) sequences. Left entorhinal volume and left entorhinal-retrosplenial connectivity (temporal cingulum edge weight) were the primary imaging variables of interest with frontal lobe thickness and subcortical structure volumes as dissociating variables. Individuals with Parkinson's disease showed worse verbal memory, smaller entorhinal volumes, but did not differ in entorhinal-retrosplenial connectivity. For Parkinson's disease entorhinal-retrosplenial edge weight had the strongest associations with verbal memory. A subset of Parkinson's disease patients (23%) had deficits (z-scores frontal-subcortical gray or frontal white matter regions. These findings argue for additional investigation into medial temporal lobe gray and white matter connectivity for understanding memory in Parkinson's disease.

  1. The Impact of Parental Involvement on a Structured Youth Program Experience: A Qualitative Inquiry

    Directory of Open Access Journals (Sweden)

    Mat D. Duerden

    2013-12-01

    Full Text Available Parental involvement is an often proposed, but rarely researched, key element of youth programs. Questions remain regarding the impact of parental involvement on program processes and outcomes. Qualitative data were collected over a one-year period with youth participants (n=46, parents (n=26, and teachers (n=5 associated with an international immersion/service learning program for adolescents. Three main research questions guided the data analysis: (1 what role does parental involvement play in the youths’ experience in the program; (2 how does parental involvement in the program influence the parent/child relationship; and (3 what role does parental involvement play in terms of the program’s long-term impact on the youth participants? Findings suggest a relationship between parental involvement in youth programs and improved parent/child communication, bonding, and perceptions of one another. Findings also suggest that having a common ground experience prolonged the experience’s positive post-participation effects.

  2. Vestibular and Attractor Network Basis of the Head Direction Cell Signal in Subcortical Circuits

    Directory of Open Access Journals (Sweden)

    Benjamin J Clark

    2012-03-01

    Full Text Available Accurate navigation depends on a network of neural systems that encode the moment-to-moment changes in an animal’s directional orientation and location in space. Within this navigation system are head direction (HD cells, which fire persistently when an animal’s head is pointed in a particular direction (Sharp et al., 2001a; Taube, 2007. HD cells are widely thought to underlie an animal’s sense of spatial orientation, and research over the last 25+ years has revealed that this robust spatial signal is widely distributed across subcortical and cortical limbic areas. Much of this work has been directed at understanding the functional organization of the HD cell circuitry, and precisely how this signal is generated from sensory and motor systems. The purpose of the present review is to summarize some of the recent studies arguing that the HD cell circuit is largely processed in a hierarchical fashion, following a pathway involving the dorsal tegmental nuclei → lateral mammillary nuclei → anterior thalamus → parahippocampal and retrosplenial cortical regions. We also review recent work identifying bursting cellular activity in the HD cell circuit after lesions of the vestibular system, and relate these observations to the long held view that attractor network mechanisms underlie HD signal generation. Finally, we summarize the work to date suggesting that this network architecture may reside within the tegmento-mammillary circuit.

  3. Technical, Anatomical, and Functional Study after Removal of a Symptomatic Cavernous Angioma Located in Deep Wernicke’s Territories with Cortico-Subcortical Awake Mapping

    Directory of Open Access Journals (Sweden)

    Silvio Sarubbo

    2013-01-01

    Full Text Available Introduction. The subcortical region underneath Wernicke’s area (WA is a critical crossing of the eloquent language pathways involved in all semantic, phonological, syntactic, and working memory elaboration. We report the resection of a CA located underneath the dominant WA discussing the functional and anatomical evidence provided by fMRI, dissections with Klingler’s technique, and intraoperative mapping during awake surgery. Case Report. A 64-year-old right-handed female affected by daily complex focal seizures underwent f-MRI, showing language activations in the middle and inferior temporal gyri and an unusual free entry zone in the “classical” WA. The cortical intraoperative mapping partially confirmed the f-MRI results, and we approached the lesion directly through WA. Subcortical DES allowed the identification of the eloquent language pathways and the radical resection of the perilesional gliotic rim. The patient did not report deficits and she is seizures and drug free after 1-year surgery. Discussion. Cortical DES demonstrated the variability of the eloquent areas within the cortex of the dominant temporal lobe. The subcortical DES confirmed the crucial role in language elaboration and the anatomical course of the bundles underneath WA. Conclusions. Awake surgery with DES represents a reliable and dynamic technique also for safer and functional-customized resection of CAs.

  4. Double Cortex Syndrome (Subcortical Band Heterotopia): A Case Report.

    Science.gov (United States)

    Momen, Ali Akbar; Momen, Mehdi

    2015-01-01

    Objective Approximately 5-10% of preschool age children are considered developmentally disabled. Brain Magnetic Resonance Imaging (MRI) plays a key role in the diagnostic evaluation in these children. Many congenital or acquired brain anomalies are revealed with MRIs. Although the majority of these abnormalities are sporadic but patients with subcortical band heterotopia or double cortex syndrome have sex-linked inheritance. We are going to present the first case in Iran from Ahvaz city, which was presented with status epilepticus associated with developmental delay and finally diagnosed as double cortex syndrome, because band heterotopia cases especially for continuous or generalized form is rare. A 4.5-year-old developmentally delayed girl was admitted for generalized tonic clonic seizure attack of 1 hr, upward gaze, locked mouth, and urinary incontinence (status epilepticus) in the child neurology ward. She had a history of recurrent seizures that started as febrile seizures since she was 12 months of age and had frequent admissions for having recurrent seizure attacks. She was the only child of consanguineous parents with negative family history of any neurologic problems. She was a product of uneventful term pregnancy, vaginal delivery with a low Apgar score at birth who was admitted for six days in the neonatal ward for hypotonia and cyanosis. At 4.5 years of age, she had HC: 45cm (band heterotopia, and polymicrogyria. She was discharged home with oral valproate and regular outpatient follow-ups. In the diagnostic evaluation of developmentally delayed and epileptic children, a brain MRI is strongly recommended for accurate diagnosis of anomalies such as neuronal migration disorders (band heterotopia) and others, because appropriate therapeutic management, prognosis, prevention, and genetic counseling for prenatal diagnosis are dependent on definite diagnosis of the proband case.

  5. Cortical and Subcortical Coordination of Visual Spatial Attention Revealed by Simultaneous EEG-fMRI Recording.

    Science.gov (United States)

    Green, Jessica J; Boehler, Carsten N; Roberts, Kenneth C; Chen, Ling-Chia; Krebs, Ruth M; Song, Allen W; Woldorff, Marty G

    2017-08-16

    Visual spatial attention has been studied in humans with both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) individually. However, due to the intrinsic limitations of each of these methods used alone, our understanding of the systems-level mechanisms underlying attentional control remains limited. Here, we examined trial-to-trial covariations of concurrently recorded EEG and fMRI in a cued visual spatial attention task in humans, which allowed delineation of both the generators and modulators of the cue-triggered event-related oscillatory brain activity underlying attentional control function. The fMRI activity in visual cortical regions contralateral to the cued direction of attention covaried positively with occipital gamma-band EEG, consistent with activation of cortical regions representing attended locations in space. In contrast, fMRI activity in ipsilateral visual cortical regions covaried inversely with occipital alpha-band oscillations, consistent with attention-related suppression of the irrelevant hemispace. Moreover, the pulvinar nucleus of the thalamus covaried with both of these spatially specific, attention-related, oscillatory EEG modulations. Because the pulvinar's neuroanatomical geometry makes it unlikely to be a direct generator of the scalp-recorded EEG, these covariational patterns appear to reflect the pulvinar's role as a regulatory control structure, sending spatially specific signals to modulate visual cortex excitability proactively. Together, these combined EEG/fMRI results illuminate the dynamically interacting cortical and subcortical processes underlying spatial attention, providing important insight not realizable using either method alone.SIGNIFICANCE STATEMENT Noninvasive recordings of changes in the brain's blood flow using functional magnetic resonance imaging and electrical activity using electroencephalography in humans have individually shown that shifting attention to a location in space

  6. Cortical and Subcortical Grey and White Matter Atrophy in Myotonic Dystrophies Type 1 and 2 Is Associated with Cognitive Impairment, Depression and Daytime Sleepiness.

    Directory of Open Access Journals (Sweden)

    Christiane Schneider-Gold

    Full Text Available Central nervous system involvement is one important clinical aspect of myotonic dystrophy type 1 and 2 (DM1 and DM2. We assessed CNS involvement DM1 and DM2 by 3T MRI and correlated clinical and neuocognitive symptoms with brain volumetry and voxel-based morphometry (VBM.12 patients with juvenile or classical DM1 and 16 adult DM2 patients underwent 3T MRI, a thorough neurological and neuropsychological examination and scoring of depression and daytime sleepiness. Volumes of brain, ventricles, cerebellum, brainstem, cervical cord, lesion load and VBM results of the patient groups were compared to 33 matched healthy subjects.Clinical symptoms were depression (more pronounced in DM2, excessive daytime sleepiness (more pronounced in DM1, reduced attention and flexibility of thinking, and deficits of short-term memory and visuo-spatial abilities in both patient groups. Both groups showed ventricular enlargement and supratentorial GM and WM atrophy, with prevalence for more GM atrophy and involvement of the motor system in DM1 and more WM reduction and affection of limbic structures in DM2. White matter was reduced in DM1 in the splenium of the corpus callosum and in left-hemispheric WM adjacent to the pre- and post-central gyrus. In DM2, the bilateral cingulate gyrus and subgyral medio-frontal and primary somato-sensory WM was affected. Significant structural-functional correlations of morphological MRI findings (global volumetry and VBM with clinical findings were found for reduced flexibility of thinking and atrophy of the left secondary visual cortex in DM1 and of distinct subcortical brain structures in DM2. In DM2, depression was associated with brainstem atrophy, Daytime sleepiness correlated with volume decrease in the middle cerebellar peduncles, pons/midbrain and the right medio-frontal cortex.GM and WM atrophy was significant in DM1 and DM2. Specific functional-structural associations related morphological changes to cognitive impairment

  7. Frequency and pathogenesis of silent subcortical brain infarction in acute first-ever ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Tomohide; Kobayashi, Shotai; Yamaguchi, Shuhei [Shimane Medical Univ., Izumo (Japan)

    2002-02-01

    We have often observed silent subcortical brain lesions on CT or MRI in first-ever ischemic stroke, but there is little published information on the relationship of these lesions to stroke subtypes. Here, we describe the incidence of MRI-detected silent subcortical brain lesions, including infarctions and white matter lesions, in a series of patients with first-ever ischemic stroke classified according to stroke subtypes. We also discuss the pathogenesis of these silent subcortical lesions. We evaluated 171 patients with acute first-ever ischemic stroke. The subjects were divided into three groups: lacunar, atherothrombotic and cardioembolic infarction groups. We evaluated silent subcortical brain infarction (SSBI), enlargement of perivascular space (EPS), and other white-matter lesions using MRI. Hypertension was observed in 67.6% of lacunar infarction, 57.1% of atherosclerotic infarction, and 54.1% of cardioembolic infarction. SSBI was more frequently observed in lacunar infarction than the others (lacunar vs. atherothrombotic vs. cardiogenic infarction, 81.5% vs. 44.4% vs. 42.1%, p=0.006). High-grade EPS (grade 2 or higher) was also observed more frequently in lacunar infarction than in the others (lacunar vs. atherothrombotic vs. cardiogenic infarction, 63.3% vs. 24.2% vs. 0%, p<0.001). Scheltens' score of silent subcortical lesions was significantly higher in lacunar infarction than in the others. The frequency of silent subcortical ischemic brain lesions was significantly higher in lacunar infarction than in atherosclerotic or cardioembolic infarction. We suggest that the pathogenesis of silent subcortical ischemic brain lesions is common to that of lacunar infarction, that is, small-vessel vasculopathy. (author)

  8. A translational study on looming-evoked defensive response and the underlying subcortical pathway in autism.

    Science.gov (United States)

    Hu, Yu; Chen, Zhuoming; Huang, Lu; Xi, Yue; Li, Bingxiao; Wang, Hong; Yan, Jiajian; Lee, Tatia M C; Tao, Qian; So, Kwok-Fai; Ren, Chaoran

    2017-11-07

    Rapidly approaching objects indicating threats can induce defensive response through activating a subcortical pathway comprising superior colliculus (SC), lateral posterior nucleus (LP), and basolateral amygdala (BLA). Abnormal defensive response has been reported in autism, and impaired synaptic connections could be the underlying mechanism. Whether the SC-LP-BLA pathway processes looming stimuli abnormally in autism is not clear. Here, we found that looming-evoked defensive response is impaired in a subgroup of the valproic acid (VPA) mouse model of autism. By combining the conventional neurotracer and transneuronal rabies virus tracing techniques, we demonstrated that synaptic connections in the SC-LP-BLA pathway were abnormal in VPA mice whose looming-evoked defensive responses were absent. Importantly, we further translated the finding to children with autism and observed that they did not present looming-evoked defensive response. Furthermore, the findings of the DTI with the probabilistic tractography showed that the structural connections of SC-pulvinar-amygdala in autism children were weak. The pulvinar is parallel to the LP in a mouse. Because looming-evoked defensive response is innate in humans and emerges much earlier than do social and language functions, the absence of defensive response could be an earlier sign of autism in children.

  9. Altered Spontaneous Brain Activity in Cortical and Subcortical Regions in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Jie Xiang

    2016-01-01

    Full Text Available Purpose. The present study aimed to explore the changes of amplitude of low-frequency fluctuations (ALFF at rest in patients with Parkinson’s disease (PD. Methods. Twenty-four PD patients and 22 healthy age-matched controls participated in the study. ALFF was measured on the whole brain of all participants. A two-sample t-test was then performed to detect the group differences with age, gender, education level, head motion, and gray matter volume as covariates. Results. It was showed that PD patients had significantly decreased ALFF in the left thalamus/caudate and right insula/inferior prefrontal gyrus, whereas they had increased ALFF in the right medial prefrontal cortex (BA 8/6 and dorsolateral prefrontal cortex (BA 9/10. Conclusions. Our results indicated that significant alterations of ALFF in the subcortical regions and prefrontal cortex have been detected in PD patients, independent of age, gender, education, head motion, and structural atrophy. The current findings further provide insights into the biological mechanism of the disease.

  10. Decreased centrality of subcortical regions during the transition to adolescence: a functional connectivity study.

    Science.gov (United States)

    Sato, João Ricardo; Salum, Giovanni Abrahão; Gadelha, Ary; Vieira, Gilson; Zugman, André; Picon, Felipe Almeida; Pan, Pedro Mario; Hoexter, Marcelo Queiroz; Anés, Mauricio; Moura, Luciana Monteiro; Del'Aquilla, Marco Antonio Gomes; Crossley, Nicolas; Amaro Junior, Edson; Mcguire, Philip; Lacerda, Acioly L T; Rohde, Luis Augusto; Miguel, Euripedes Constantino; Jackowski, Andrea Parolin; Bressan, Rodrigo Affonseca

    2015-01-01

    Investigations of brain maturation processes are a key step to understand the cognitive and emotional changes of adolescence. Although structural imaging findings have delineated clear brain developmental trajectories for typically developing individuals, less is known about the functional changes of this sensitive development period. Developmental changes, such as abstract thought, complex reasoning, and emotional and inhibitory control, have been associated with more prominent cortical control. The aim of this study is to assess brain networks connectivity changes in a large sample of 7- to 15-year-old subjects, testing the hypothesis that cortical regions will present an increasing relevance in commanding the global network. Functional magnetic resonance imaging (fMRI) data were collected in a sample of 447 typically developing children from a Brazilian community sample who were submitted to a resting state acquisition protocol. The fMRI data were used to build a functional weighted graph from which eigenvector centrality (EVC) was extracted. For each brain region (a node of the graph), the age-dependent effect on EVC was statistically tested and the developmental trajectories were estimated using polynomial functions. Our findings show that angular gyrus become more central during this maturation period, while the caudate; cerebellar tonsils, pyramis, thalamus; fusiform, parahippocampal and inferior semilunar lobe become less central. In conclusion, we report a novel finding of an increasing centrality of the angular gyrus during the transition to adolescence, with a decreasing centrality of many subcortical and cerebellar regions. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Neuroanatomical characterization of the cellular and axonal architecture of subcortical band heterotopia in the BXD29-Tlr4lps-2J/J mouse cortex.

    Science.gov (United States)

    Ramos, Raddy L; Toia, Alyssa R; Pasternack, Daniel M; Dotzler, Timothy P; Cuoco, Joshua A; Esposito, Anthony W; Le, Megan M; Parker, Alexander K; Goodman, Jeffrey H; Sarkisian, Matthew R

    2016-11-19

    Subcortical band heterotopia (SBH) are malformations of the human cerebral cortex typically associated with epilepsy and cognitive delay/disability. Rodent models of SBH have demonstrated strong face validity as they are accompanied by both cognitive deficits and spontaneous seizures or reduced seizure threshold. BXD29-Tlr4lps-2J/J recombinant inbred mice display striking bilateral SBH, partial callosal agenesis, morphological changes in subcortical structures of the auditory pathway, and display sensory deficits in behavioral tests (Rosen et al., 2013; Truong et al., 2013, 2015). Surprisingly, these mice show no cognitive deficits and have a higher seizure threshold to chemi-convulsive treatment (Gabel et al., 2013) making them different than other rodent SBH models described previously. In the present report, we perform a detailed characterization of the cellular and axonal constituents of SBH in BXD29-Tlr4lps-2J/J mice and demonstrate that various types of interneurons and glia as well as cortical and subcortical projections are found in SBH. In addition, the length of neuronal cilia was reduced in SBH compared to neurons in the overlying and adjacent normotopic cortex. Finally, we describe additional and novel malformations of the hippocampus and neocortex present in BXD29-Tlr4lps-2J/J mice. Together, our findings in BXD29-Tlr4lps-2J/J mice are discussed in the context of the known neuroanatomy and phenotype of other SBH rodent models. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. The antidepressant efficacy of subanesthetic-dose ketamine does not correlate with baseline subcortical volumes in a replication sample with major depressive disorder.

    Science.gov (United States)

    Niciu, Mark J; Iadarola, Nicolas D; Banerjee, Dipavo; Luckenbaugh, David A; Park, Minkyung; Lener, Marc; Park, Lawrence; Ionescu, Dawn F; Ballard, Elizabeth D; Brutsche, Nancy E; Akula, Nirmala; McMahon, Francis J; Machado-Vieira, Rodrigo; Nugent, Allison C; Zarate, Carlos A

    2017-12-01

    This study sought to reproduce, in a larger sample, previous findings of a correlation between smaller raw 3-Tesla (3T) hippocampal volumes and improved antidepressant efficacy of ketamine in individuals with major depressive disorder (MDD). A secondary analysis stratified subjects according to functional BDNF rs6265 (val66met) genotype. Unmedicated subjects with treatment-resistant MDD ( n=55) underwent baseline structural 3T MRI. Data processing was conducted with FSL/FIRST and Freesurfer software. The amygdala, hippocampus, and thalamus were selected a priori for analysis. All subjects received a single 0.5mg/kg × 40-minute ketamine infusion. Pearson correlations were performed with subcortical volumes and percent change in MADRS score (from baseline to 230 minutes, 1 day, and 1 week post-infusion). Raw and corrected subcortical volumes did not correlate with antidepressant response at any timepoint. In val/val subjects ( n=23), corrected left and right thalamic volume positively correlated with antidepressant response to ketamine at 230 minutes post-infusion but did not reach statistical significance. In met carriers ( n=14), corrected left and right thalamic volume negatively correlated with antidepressant response to ketamine. Baseline subcortical volumes implicated in MDD did not correlate with ketamine's antidepressant efficacy. Baseline thalamic volume and BDNF genotype may be a combinatorial rapid antidepressant response biomarker.

  13. Cortical and Subcortical Brain Morphometry Differences Between Patients With Autism Spectrum Disorder and Healthy Individuals Across the Lifespan: Results From the ENIGMA ASD Working Group.

    Science.gov (United States)

    van Rooij, Daan; Anagnostou, Evdokia; Arango, Celso; Auzias, Guillaume; Behrmann, Marlene; Busatto, Geraldo F; Calderoni, Sara; Daly, Eileen; Deruelle, Christine; Di Martino, Adriana; Dinstein, Ilan; Duran, Fabio Luis Souza; Durston, Sarah; Ecker, Christine; Fair, Damien; Fedor, Jennifer; Fitzgerald, Jackie; Freitag, Christine M; Gallagher, Louise; Gori, Ilaria; Haar, Shlomi; Hoekstra, Liesbeth; Jahanshad, Neda; Jalbrzikowski, Maria; Janssen, Joost; Lerch, Jason; Luna, Beatriz; Martinho, Mauricio Moller; McGrath, Jane; Muratori, Filippo; Murphy, Clodagh M; Murphy, Declan G M; O'Hearn, Kirsten; Oranje, Bob; Parellada, Mara; Retico, Alessandra; Rossa, Pedro; Rubia, Katya; Shook, Devon; Taylor, Margot; Thompson, Paul M; Tosetti, Michela; Wallace, Gregory L; Zhou, Fengfeng; Buitelaar, Jan K

    2017-11-17

    Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group. The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach. The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions. The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different

  14. Striatal Dopaminergic Innervation Regulates Subthalamic Beta-Oscillations and Cortical-Subcortical Coupling during Movements: Preliminary Evidence in Subjects with Parkinson’s Disease

    Science.gov (United States)

    Canessa, Andrea; Pozzi, Nicolò G.; Arnulfo, Gabriele; Brumberg, Joachim; Reich, Martin M.; Pezzoli, Gianni; Ghilardi, Maria F.; Matthies, Cordula; Steigerwald, Frank; Volkmann, Jens; Isaias, Ioannis U.

    2016-01-01

    Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remains unclear. We recorded local field potential (LFP) activity from the subthalamic nucleus (STN) and high-density electroencephalography (EEG) signals in four patients with Parkinson’s disease (PD) off dopaminergic medication during a multi-joint motor task performed with their dominant and non-dominant hand. Recordings were performed by means of a fully-implantable deep brain stimulation (DBS) device at 4 months after surgery. Three patients also performed a single-photon computed tomography (SPECT) with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT) to assess striatal dopaminergic innervation. Unilateral movement execution led to event-related desynchronization (ERD) followed by a rebound after movement termination event-related synchronization (ERS) of oscillatory beta activity in the STN and primary sensorimotor cortex of both hemispheres. Dopamine deficiency directly influenced movement-related beta-modulation, with greater beta-suppression in the most dopamine-depleted hemisphere for both ipsi- and contralateral hand movements. Cortical-subcortical, but not interhemispheric subcortical coherencies were modulated by movement and influenced by striatal dopaminergic innervation, being stronger in the most dopamine-depleted hemisphere. The data are consistent with a role of dopamine in shielding subcortical structures from an excessive cortical entrapment and cross-hemispheric coupling, thus allowing fine-tuning of movement. PMID:27999534

  15. Striatal Dopaminergic Innervation Regulates Subthalamic Beta-Oscillations and Cortical-Subcortical Coupling during Movements: Preliminary Evidence in Subjects with Parkinson's Disease.

    Science.gov (United States)

    Canessa, Andrea; Pozzi, Nicolò G; Arnulfo, Gabriele; Brumberg, Joachim; Reich, Martin M; Pezzoli, Gianni; Ghilardi, Maria F; Matthies, Cordula; Steigerwald, Frank; Volkmann, Jens; Isaias, Ioannis U

    2016-01-01

    Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remains unclear. We recorded local field potential (LFP) activity from the subthalamic nucleus (STN) and high-density electroencephalography (EEG) signals in four patients with Parkinson's disease (PD) off dopaminergic medication during a multi-joint motor task performed with their dominant and non-dominant hand. Recordings were performed by means of a fully-implantable deep brain stimulation (DBS) device at 4 months after surgery. Three patients also performed a single-photon computed tomography (SPECT) with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT) to assess striatal dopaminergic innervation. Unilateral movement execution led to event-related desynchronization (ERD) followed by a rebound after movement termination event-related synchronization (ERS) of oscillatory beta activity in the STN and primary sensorimotor cortex of both hemispheres. Dopamine deficiency directly influenced movement-related beta-modulation, with greater beta-suppression in the most dopamine-depleted hemisphere for both ipsi- and contralateral hand movements. Cortical-subcortical, but not interhemispheric subcortical coherencies were modulated by movement and influenced by striatal dopaminergic innervation, being stronger in the most dopamine-depleted hemisphere. The data are consistent with a role of dopamine in shielding subcortical structures from an excessive cortical entrapment and cross-hemispheric coupling, thus allowing fine-tuning of movement.

  16. Intraoperative subcortical motor evoked potential stimulation: how close is the corticospinal tract?

    Science.gov (United States)

    Shiban, Ehab; Krieg, Sandro M; Haller, Bernhard; Buchmann, Niels; Obermueller, Thomas; Boeckh-Behrens, Tobias; Wostrack, Maria; Meyer, Bernhard; Ringel, Florian

    2015-09-01

    Subcortical stimulation is a method used to evaluate the distance from the stimulation site to the corticospinal tract (CST) and to decide whether the resection of an adjacent lesion should be terminated to prevent damage to the CST. However, the correlation between stimulation intensity and distance to the CST has not yet been clearly assessed. The objective of this study was to investigate the appropriate correlation between the subcortical stimulation pattern and the distance to the CST. Monopolar subcortical motor evoked potential (MEP) mapping was performed in addition to continuous MEP monitoring in 37 consecutive patients with lesions located in motor-eloquent locations. The proximity of the resection cavity to the CST was identified by subcortical MEP mapping. At the end of resection, the point at which an MEP response was still measurable with minimal subcortical MEP intensity was marked with a titanium clip. At this location, different stimulation paradigms were executed with cathodal or anodal stimulation at 0.3-, 0.5-, and 0.7-msec pulse durations. Postoperatively, the distance between the CST as defined by postoperative diffusion tensor imaging fiber tracking and the titanium clip was measured. The correlation between this distance and the subcortical MEP electrical charge was calculated. Subcortical MEP mapping was successful in all patients. There were no new permanent motor deficits. Transient new postoperative motor deficits were observed in 14% (5/36) of cases. Gross-total resection was achieved in 75% (27/36) and subtotal resection (> 80% of tumor mass) in 25% (9/36) of cases. Stimulation intensity with various pulse durations as well as current intensity was plotted against the measured distance between the CST and the titanium clip on postoperative MRI using diffusion-weighted imaging fiberitracking tractography. Correlational and regression analyses showed a nonlinear correlation between stimulation intensity and the distance to the CST

  17. A novel mutation of the doublecortin gene in Japanese patients with X-linked lissencephaly and subcortical band heterotopia.

    Science.gov (United States)

    Kato, M; Kimura, T; Lin, C; Ito, A; Kodama, S; Morikawa, T; Soga, T; Hayasaka, K

    1999-04-01

    The doublecortin (DCX) gene was recently found to be involved in patients with X-linked lissencephaly and subcortical band heterotopia or double cortex syndrome. We have studied the coding regions of the DCX gene in 11 Japanese patients with cortical dysplasia and have identified three different mutations (R186C in exon 3, R272X and R303X in exon 5) in four sporadic female cases. R272X, which has been detected in two unrelated cases, is a novel mutation. Although the number of cases studied remains limited, exon 5 may be a common mutational site in Japanese patients in contrast to many previous reports concerning exons 2 and 3.

  18. Structures of the first representatives of Pfam family PF06938 (DUF1285) reveal a new fold with repeated structural motifs and possible involvement in signal transduction.

    Science.gov (United States)

    Han, Gye Won; Bakolitsa, Constantina; Miller, Mitchell D; Kumar, Abhinav; Carlton, Dennis; Najmanovich, Rafael J; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L; Chen, Connie; Chiu, Hsiu Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C; Duan, Lian; Ernst, Dustin; Feuerhelm, Julie; Grant, Joanna C; Grzechnik, Anna; Jaroszewski, Lukasz; Jin, Kevin K; Johnson, Hope A; Klock, Heath E; Knuth, Mark W; Kozbial, Piotr; Krishna, S Sri; Marciano, David; McMullan, Daniel; Morse, Andrew T; Nigoghossian, Edward; Okach, Linda; Reyes, Ron; Rife, Christopher L; Sefcovic, Natasha; Tien, Henry J; Trame, Christine B; van den Bedem, Henry; Weekes, Dana; Xu, Qingping; Hodgson, Keith O; Wooley, John; Elsliger, Marc André; Deacon, Ashley M; Godzik, Adam; Lesley, Scott A; Wilson, Ian A

    2010-10-01

    The crystal structures of SPO0140 and Sbal_2486 were determined using the semiautomated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). The structures revealed a conserved core with domain duplication and a superficial similarity of the C-terminal domain to pleckstrin homology-like folds. The conservation of the domain interface indicates a potential binding site that is likely to involve a nucleotide-based ligand, with genome-context and gene-fusion analyses additionally supporting a role for this family in signal transduction, possibly during oxidative stress.

  19. Decreased activation of subcortical brain areas in the motor fatigue state: an fMRI study

    Directory of Open Access Journals (Sweden)

    Lijuan Hou

    2016-08-01

    Full Text Available One aspect of motor fatigue is the exercise-induced reduction of neural activity to voluntarily drive the muscle or muscle group. Functional magnetic resonance imaging provides access to investigate the neural activation on the whole brain level and studies observed changes of activation intensity after exercise-induced motor fatigue in the sensorimotor cortex. However, in human, little evidence exists to demonstrate the role of subcortical brain regions in motor fatigue, which is contradict to abundant researches in rodent indicating that during simple movement, the activity of the basal ganglia is modulated by the state of motor fatigue. Thus, in present study, we explored the effect of motor fatigue on subcortical areas in human. A series of fMRI data were collected from 11 healthy subjects while they were executing simple motor tasks in two conditions: before and under the motor fatigue state. The results showed that in both conditions, movements evoked activation volumes in the sensorimotor areas, SMA, cerebellum, thalamus and basal ganglia. Of primary importance are the results that the intensity and size of activation volumes in the subcortical areas (i.e. thalamus and basal ganglia areas are significantly decreased during the motor fatigue state, implying that motor fatigue disturbs the motor control processing in a way that both sensorimotor areas and subcortical brain areas are less active. Further study is needed to clarify how subcortical areas contribute to the overall decreased activity of CNS during motor fatigue state.

  20. A structured PBL tutorial involving small teams for teaching the human nervous system.

    Science.gov (United States)

    Cardozo, David Lopes; Raymond, Laurie; White, Benjamin

    2012-01-01

    The Human Nervous System and Behavior course at Harvard Medical School (HMS) incorporates a hybrid model of problem-based learning. Student preparation for and participation in the tutorial seemed to be insufficient. We sought to increase student engagement in tutorial by creating a structured approach, which included assigned roles for students, weekly testing, formal cornerstone presentations, and a weekly self-assessment exercise. We wished to determine the students' and tutors' satisfaction with this structured approach as compared with the more traditional tutorial experienced in other courses at HMS. For the first 4 years of the course, students (n = 160) were surveyed concerning their impressions of the quality of the structured approach in comparison with the traditional tutorial. In addition, they were surveyed concerning the cornerstone presentations and the self-assessment exercise. Tutors (n = 10) who had taught in both the traditional and structured tutorial formats were surveyed about their impressions of student performance as well as their own enjoyment in the structured format. Students and tutors found the structured approach superior to the previous method. Both groups noted increased student preparation, participation, and accountability. Tutors preferred teaching in the structured format. The structured approach increased student accountability, preparation, and participation. Students and tutors preferred this tutorial experience over the previous approach.

  1. Structural changes induced by daily music listening in the recovering brain after middle cerebral artery stroke: a voxel-based morphometry study

    OpenAIRE

    Teppo eSärkämö; Pablo eRipollés; Henna eVepsäläinen; Taina eAutti; Silvennoinen, Heli M.; Eero eSalli; Sari eLaitinen; Anita eForsblom; Seppo eSoinila; Antoni eRodríguez-Fornells

    2014-01-01

    Music is a highly complex and versatile stimulus for the brain that engages many temporal, frontal, parietal, cerebellar, and subcortical areas involved in auditory, cognitive, emotional, and motor processing. Regular musical activities have been shown to effectively enhance the structure and function of many brain areas, making music a potential tool also in neurological rehabilitation. In our previous randomized controlled study, we found that listening to music on a daily basis can improve...

  2. Effect of repeated contact on adhesion measurements involving polydimethylsiloxane structural material

    Energy Technology Data Exchange (ETDEWEB)

    Kroner, E; Arzt, E [INM-Leibniz Institute for New Materials, Campus D2 2, 66125 Saarbruecken (Germany); Maboudian, R, E-mail: elmar.kroner@inm-gmbh.de [Department of Chem. Eng., 201 Gilman Hall, University of California, Berkeley, CA 94720-1462 (United States)

    2009-09-15

    During the last few years several research groups have focused on the fabrication of artificial gecko inspired adhesives. For mimicking these structures, different polymers are used as structure material, such as polydimethylsiloxanes (PDMS), polyurethanes (PU), and polypropylene (PP). While these polymers can be structured easily and used for artificial adhesion systems, the effects of repeated adhesion testing have never been investigated closely. In this paper we report on the effect of repeated adhesion measurements on the commercially available poly(dimethylsiloxane) polymer kit Sylgard 184 (Dow Corning). We show that the adhesion force decreases as a function of contact cycles. The rate of change and the final value of adhesion are found to depend on the details of the PDMS synthesis and structuring.

  3. Comparison between Alzheimer's disease and subcortical vascular dementia: attentional cortex study in functional magnetic resonance imaging.

    Science.gov (United States)

    Li, C; Zheng, J; Wang, J; Gui, L

    2011-01-01

    Blood oxygen level dependent functional magnetic resonance imaging (fMRI) and the Stroop test were used to assess attentional cortex activation in patients with Alzheimer's disease, subcortical vascular dementia, and normal control subjects. Patients with Alzheimer's disease and subcortical vascular dementia demonstrated similar locations of cortical activation, including the bilateral middle and inferior frontal gyri, anterior cingulate and inferior parietal lobule in response to Stroop colour word stimuli. This activation was distinctly decreased in patients with dementia compared with normal control subjects. Different regions of the brain were activated in patients with Alzheimer's disease and subcortical vascular dementia compared with normal controls. fMRI is a useful tool for the study of dementia in humans and has some potential diagnostic value. Further studies with larger numbers of participants are required.

  4. Focal cortical dysplasia type IIb: completeness of cortical, not subcortical, resection is necessary for seizure freedom.

    Science.gov (United States)

    Wagner, Jan; Urbach, Horst; Niehusmann, Pitt; von Lehe, Marec; Elger, Christian E; Wellmer, Jörg

    2011-08-01

    Focal cortical dysplasia type IIb (FCD IIb) lesions are highly epileptogenic and frequently cause pharmacoresistant epilepsy. Complete surgical resection leads to seizure freedom in most cases. However, the term "complete" resection is controversial with regard to the necessity of performing resections of the subcortical zone, which is frequently seen in these lesions on magnetic resonance imaging (MRI). We retrospectively analyzed 50 epilepsy patients with histologically proven FCD IIb. The extent of surgical resection was determined by SPM5-based coregistration of the preoperative and postoperative MRI scans. Postoperative outcome was analyzed with regard to (1) the completeness of the resection of the cortical abnormality and (2) the completeness of the resection of the subcortical abnormality. Complete resection of the cortical abnormality led to postoperative seizure freedom (Engel class Ia) in 34 of 37 patients (92%), whereas incomplete cortical resection achieved this in only one of 13 patients (8%, p < 0.001). Among the patients with complete cortical resection, 36 had FCDs with a subcortical hyperintensity according to MRI. In this group, complete resection of the subcortical abnormality did not result in a better postoperative outcome than incomplete resection (90% vs. 93% for Engel class Ia, n.s.). Complete resection of the MRI-documented cortical abnormality in FCD IIb is crucial for a favorable postoperative outcome. However, resection of the subcortical hyperintense zone is not essential for seizure freedom. Therefore, sparing of the subcortical white matter may reduce the surgical risk of encroaching on relevant fiber tracts. In addition, these findings give an interesting insight into the epileptogenic propensity of different parts of these lesions. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

  5. A Rapid Subcortical Amygdala Route for Faces Irrespective of Spatial Frequency and Emotion.

    Science.gov (United States)

    McFadyen, Jessica; Mermillod, Martial; Mattingley, Jason B; Halász, Veronika; Garrido, Marta I

    2017-04-05

    There is significant controversy over the existence and function of a direct subcortical visual pathway to the amygdala. It is thought that this pathway rapidly transmits low spatial frequency information to the amygdala independently of the cortex, and yet the directionality of this function has never been determined. We used magnetoencephalography to measure neural activity while human participants discriminated the gender of neutral and fearful faces filtered for low or high spatial frequencies. We applied dynamic causal modeling to demonstrate that the most likely underlying neural network consisted of a pulvinar-amygdala connection that was uninfluenced by spatial frequency or emotion, and a cortical-amygdala connection that conveyed high spatial frequencies. Crucially, data-driven neural simulations revealed a clear temporal advantage of the subcortical connection over the cortical connection in influencing amygdala activity. Thus, our findings support the existence of a rapid subcortical pathway that is nonselective in terms of the spatial frequency or emotional content of faces. We propose that that the "coarseness" of the subcortical route may be better reframed as "generalized." SIGNIFICANCE STATEMENT The human amygdala coordinates how we respond to biologically relevant stimuli, such as threat or reward. It has been postulated that the amygdala first receives visual input via a rapid subcortical route that conveys "coarse" information, namely, low spatial frequencies. For the first time, the present paper provides direction-specific evidence from computational modeling that the subcortical route plays a generalized role in visual processing by rapidly transmitting raw, unfiltered information directly to the amygdala. This calls into question a widely held assumption across human and animal research that fear responses are produced faster by low spatial frequencies. Our proposed mechanism suggests organisms quickly generate fear responses to a wide range

  6. Quantitative analysis of [{sup 18}F]FDDNP PET using subcortical white matter as reference region

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Koon-Pong; Shao, Weber; Dahlbom, Magnus; Kepe, Vladimir; Liu, Jie; Satyamurthy, Nagichettiar; Barrio, Jorge R. [David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States); Wardak, Mirwais; Huang, Sung-Cheng [David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States); David Geffen School of Medicine at UCLA, Department of Biomathematics, Los Angeles, CA (United States); Small, Gary W. [David Geffen School of Medicine at UCLA, Department of Psychiatry and Biobehavioral Sciences, Los Angeles, CA (United States); David Geffen School of Medicine at UCLA, Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA (United States); David Geffen School of Medicine at UCLA, UCLA Center on Aging, Los Angeles, CA (United States); Mary S. Easton Center for Alzheimer' s Disease Research, Los Angeles, CA (United States)

    2010-03-15

    Subcortical white matter is known to be relatively unaffected by amyloid deposition in Alzheimer's disease (AD). We investigated the use of subcortical white matter as a reference region to quantify [{sup 18}F]FDDNP binding in the human brain. Dynamic [{sup 18}F]FDDNP PET studies were performed on 7 control subjects and 12 AD patients. Population efflux rate constants (k{sup '}{sub 2}) from subcortical white matter (centrum semiovale) and cerebellar cortex were derived by a simplified reference tissue modeling approach incorporating physiological constraints. Regional distribution volume ratio (DVR) estimates were derived using Logan and simplified reference tissue approaches, with either subcortical white matter or cerebellum as reference input. Discriminant analysis with cross-validation was performed to classify control subjects and AD patients. The population estimates of k{sup '}{sub 2} in subcortical white matter did not differ significantly between control subjects and AD patients but the variability of individual estimates of k{sup '}{sub 2} determined in white matter was lower than that in cerebellum. Logan DVR showed dependence on the efflux rate constant in white matter. The DVR estimates in the frontal, parietal, posterior cingulate, and temporal cortices were significantly higher in the AD group (p<0.01). Incorporating all these regional DVR estimates as predictor variables in discriminant analysis yielded accurate classification of control subjects and AD patients with high sensitivity and specificity, and the results agreed well with those using the cerebellum as the reference region. Subcortical white matter can be used as a reference region for quantitative analysis of [{sup 18}F]FDDNP with the Logan method which allows more accurate and less biased binding estimates, but a population efflux rate constant has to be determined a priori. (orig.)

  7. Brain regions involved in the recognition of happiness and sadness in music.

    Science.gov (United States)

    Khalfa, Stéphanie; Schon, Daniele; Anton, Jean-Luc; Liégeois-Chauvel, Catherine

    2005-12-19

    Here, we used functional magnetic resonance imaging to test for the lateralization of the brain regions specifically involved in the recognition of negatively and positively valenced musical emotions. The manipulation of two major musical features (mode and tempo), resulting in the variation of emotional perception along the happiness-sadness axis, was shown to principally involve subcortical and neocortical brain structures, which are known to intervene in emotion processing in other modalities. In particular, the minor mode (sad excerpts) involved the left orbito and mid-dorsolateral frontal cortex, which does not confirm the valence lateralization model. We also show that the recognition of emotions elicited by variations of the two perceptual determinants rely on both common (BA 9) and distinct neural mechanisms.

  8. From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study.

    Science.gov (United States)

    Aghakhanyan, Gayane; Bonanni, Paolo; Randazzo, Giovanna; Nappi, Sara; Tessarotto, Federica; De Martin, Lara; Frijia, Francesca; De Marchi, Daniele; De Masi, Francesco; Kuppers, Beate; Lombardo, Francesco; Caramella, Davide; Montanaro, Domenico

    2016-01-01

    Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS.

  9. From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study.

    Directory of Open Access Journals (Sweden)

    Gayane Aghakhanyan

    Full Text Available Angelman syndrome (AS is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM method to investigate disease-related changes in the cortical/subcortical grey matter (GM structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM. Principal component analysis (PCA was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS.

  10. From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study

    Science.gov (United States)

    Aghakhanyan, Gayane; Bonanni, Paolo; Randazzo, Giovanna; Nappi, Sara; Tessarotto, Federica; De Martin, Lara; Frijia, Francesca; De Marchi, Daniele; De Masi, Francesco; Kuppers, Beate; Lombardo, Francesco; Caramella, Davide; Montanaro, Domenico

    2016-01-01

    Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS. PMID:27626634

  11. Pea border cell maturation and release involve complex cell wall structural dynamics

    DEFF Research Database (Denmark)

    Mravec, Jozef; Guo, Xiaoyuan; Hansen, Aleksander Riise

    2017-01-01

    of hydrolytic activities, transmission electron microscopy (TEM) and immunolocalization of cell wall components. Using this integrated glycobiology approach, we identified multiple novel modes of cell wall structural and compositional rearrangement during root cap growth and the release of border cells. Our...

  12. Structure of a Bacterial ABC Transporter Involved in the Import of an Acidic Polysaccharide Alginate.

    Science.gov (United States)

    Maruyama, Yukie; Itoh, Takafumi; Kaneko, Ai; Nishitani, Yu; Mikami, Bunzo; Hashimoto, Wataru; Murata, Kousaku

    2015-09-01

    The acidic polysaccharide alginate represents a promising marine biomass for the microbial production of biofuels, although the molecular and structural characteristics of alginate transporters remain to be clarified. In Sphingomonas sp. A1, the ATP-binding cassette transporter AlgM1M2SS is responsible for the import of alginate across the cytoplasmic membrane. Here, we present the substrate-transport characteristics and quaternary structure of AlgM1M2SS. The addition of poly- or oligoalginate enhanced the ATPase activity of reconstituted AlgM1M2SS coupled with one of the periplasmic solute-binding proteins, AlgQ1 or AlgQ2. External fluorescence-labeled oligoalginates were specifically imported into AlgM1M2SS-containing proteoliposomes in the presence of AlgQ2, ATP, and Mg(2+). The crystal structure of AlgQ2-bound AlgM1M2SS adopts an inward-facing conformation. The interaction between AlgQ2 and AlgM1M2SS induces the formation of an alginate-binding tunnel-like structure accessible to the solvent. The translocation route inside the transmembrane domains contains charged residues suitable for the import of acidic saccharides. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Paths of water entry and structures involved in the breaking of seed dormancy of Lupinus.

    Science.gov (United States)

    Robles-Díaz, Erika; Flores, Joel; Yáñez-Espinosa, Laura

    2016-03-15

    Physical dormancy is the water impermeability of the seed coat caused by one or more palisade cell layer(s) called macrosclereids. The specialised structure for water entry sites is the water gap, which serves as a detector of environmental cues for germination. In Fabaceae, the water gap is the lens, although another seed structure for water entry could exist. In this study, we identified the initial site of water entry, observed the hydration of a cushion-like structure near the radicle, described the anatomy of the water gap, and analysed the association of anatomical seed traits with the initial site of water entry and the imbibition velocity of six species of Lupinus from the state of Jalisco, Mexico. Dye tracking with a toluidine blue solution was used to identify the initial site of water entry. The anatomical description was performed using conventional microtechnique and a light microscope. The entry of the toluidine solution into seeds of L. montanus was observed after 6h, followed by L. exaltatus and L. mexicanus after 18h and L. elegans, L. reflexus and L. rotundiflorus after 48h. The site of water entry was the lens in L. elegans, L. exaltatus, L. reflexus and L. rotundiflorus and the micropyle in L. mexicanus and L. montanus. The cushion-like structure was responsible for water accumulation in embryo imbibition. Significant differences among anatomical seed traits such as thickness in the hilar region, the counter-palisade layer, cushion-like structure, epidermis, hypodermis, and innermost parenchyma layer were found among the species. Copyright © 2016 Elsevier GmbH. All rights reserved.

  14. The Crystal Structure of CREG, a secreted Glycoprotein Involved in Cellular Growth and Differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Sacher,M.; Di Bacco, A.; Lunin, V.; Ye, Z.; Wagner, J.; Gill, G.; Cygler, M.

    2005-01-01

    The cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein that inhibits proliferation and enhances differentiation of human embryonal carcinoma cells. CREG binds to the cation-independent mannose 6-phosphate (M6P)/insulin-like growth factor II (IGF2) receptor (IGF2R) (M6P/IGF2R), and this receptor has been shown to be required for CREG-induced growth suppression. To better understand CREG function in cellular growth and differentiation, we solved the 3D crystal structure of this protein to 1.9-Angstrom resolution. CREG forms a tight homodimeric complex, and CREG monomers display a {beta}-barrel fold. The three potential glycosylation sites on CREG map to a confined patch opposite the dimer interface. Thus, dimerization of glycosylated CREG likely presents a bivalent ligand for the M6P/IGF2R. Closely related structural homologs of CREG are FMN-binding split-barrel fold proteins that bind flavin mononucleotide. Our structure shows that the putative flavin mononucleotide-binding pocket in CREG is sterically blocked by a loop and several key bulky residues. A mutant of CREG lacking a part of this loop maintained overall structure and dimerization, as well as M6P/IGF2R binding, but lost the growth suppression activity of WT CREG. Thus, analysis of a structure-based mutant of CREG revealed that binding to M6P/IGF2R, while necessary, is not sufficient for CREG-induced growth suppression. These findings indicate that CREG utilizes a known fold.

  15. Subcortical contribution to late TMS-induced I-waves in intact humans

    Science.gov (United States)

    Cirillo, John; Perez, Monica A.

    2015-01-01

    Paired-pulse transcranial magnetic stimulation (TMS) of the human motor cortex results in consecutive facilitatory motor evoked potential (MEP) peaks in surface electromyography. It has been proposed that early and late MEP peaks involve different mechanisms of action; however, little is known about the characteristics of the later peaks. Using paired-pulse TMS over the hand motor cortex at different test (S1) and conditioning (S2) interstimulus intervals and intensities we examined early (first) and late (second and third) MEP peaks in a resting finger muscle. We demonstrate that the third peak had reduced amplitude and duration compared with the second, regardless of the S1 intensity. Higher S2 intensity increased the amplitude of the third but not the second peak, suggesting that the third peak had a higher threshold. The interval between the second and third peak was longer than between the first and second peak in all conditions even though all peaks had a similar latency dispersion. No differences were found in the amplitude, duration, and threshold of the first and second peaks. A threshold electrical S2 over the cervicomedullary junction facilitated the second and third but not the first peak similarly to TMS. Our results indicate that the third MEP peak is smaller and has higher threshold than the second peak and the similarities between the first and second peak suggest that this is less likely explained by a reduced effectiveness in recruitment. We argue that subcortical pathways might contribute to differences found between late TMS-induced peaks in intact humans. PMID:26069470

  16. Symmetrical retrograde actin flow in the actin fusion structure is involved in osteoclast fusion

    Directory of Open Access Journals (Sweden)

    Jiro Takito

    2017-07-01

    Full Text Available The aim of this study was to elucidate the role of the zipper-like structure (ZLS, a podosome-related structure that transiently appears at the cell contact zone, in osteoclast fusion. Live-cell imaging of osteoclasts derived from RAW264.7 cells transfected with EGFP-actin revealed consistent symmetrical retrograde actin flow in the ZLS, but not in the podosome cluster, the podosome ring or the podosome belt. Confocal imaging showed that the distributions of F-actin, vinculin, paxillin and zyxin in the ZLS were different from those in the podosome belt. Thick actin filament bundles running outside the ZLS appeared to recruit non-muscle myosin IIA. The F-actin-rich domain of the ZLS contained actin-related protein 2/3 complex (Arp2/3. Inhibition of Arp2/3 activity disorganized the ZLS, disrupted actin flow, deteriorated cell-cell adhesion and inhibited osteoclast hypermultinucleation. In contrast, ML-7, an inhibitor of myosin light chain kinase, had little effect on the structure of ZLS and promoted osteoclast hypermultinucleation. These results reveal a link between actin flow in the ZLS and osteoclast fusion. Osteoclast fusion was promoted by branched actin elongation and negatively regulated by actomyosin contraction.

  17. Crystal Structure of a Phenol-coupling P450 Monooxygenase Involved in Teicoplanin Biosynthesis

    Science.gov (United States)

    Li, Zhi; Rupasinghe, Sanjeewa G.; Schuler, Mary A.; Nair, Satish K.

    2011-01-01

    The lipoglycopeptide antibiotic teicoplanin has proven efficacy against gram-positive pathogens. Teicoplanin is distinguished from the vancomycin-type glycopeptide antibiotics, by the presence of an additional cross-link between the aromatic amino acids 1 and 3 that is catalyzed by the cytochrome P450 monooxygenase Orf6* (CYP165D3). As a goal towards understanding the mechanism of this phenol-coupling reaction, we have characterized recombinant Orf6* and determined its crystal structure to 2.2 Å resolution. Although the structure of Orf6* reveals the core fold common to other P450 monooxygenases, there are subtle differences in the disposition of secondary structure elements near the active site cavity necessary to accommodate its complex heptapeptide substrate. Specifically, the orientation of the F and G helices in Orf6* results in a more closed active site than found in the vancomycin oxidative enzymes OxyB and OxyC. In addition, Met226 in the I helix replaces the more typical Gly/Ala residue that is positioned above the heme porphyrin ring, where it forms a hydrogen bond with a heme iron-bound water molecule. Sequence comparisons with other phenol-coupling P450 monooxygenases suggest that Met226 plays a role in determining the substrate regiospecificity of Orf6*. These features provide further insights into the mechanism of the cross-linking mechanisms that occur during glycopeptide antibiotics biosynthesis. PMID:21445994

  18. Crystal structure of a phenol-coupling P450 monooxygenase involved in teicoplanin biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhi; Rupasinghe, Sanjeewa G.; Schuler, Mary A.; Nair, Satish K. (UIUC)

    2012-02-08

    The lipoglycopeptide antibiotic teicoplanin has proven efficacy against gram-positive pathogens. Teicoplanin is distinguished from the vancomycin-type glycopeptide antibiotics, by the presence of an additional cross-link between the aromatic amino acids 1 and 3 that is catalyzed by the cytochrome P450 monooxygenase Orf6* (CYP165D3). As a goal towards understanding the mechanism of this phenol-coupling reaction, we have characterized recombinant Orf6* and determined its crystal structure to 2.2-{angstrom} resolution. Although the structure of Orf6* reveals the core fold common to other P450 monooxygenases, there are subtle differences in the disposition of secondary structure elements near the active site cavity necessary to accommodate its complex heptapeptide substrate. Specifically, the orientation of the F and G helices in Orf6* results in a more closed active site than found in the vancomycin oxidative enzymes OxyB and OxyC. In addition, Met226 in the I helix replaces the more typical Gly/Ala residue that is positioned above the heme porphyrin ring, where it forms a hydrogen bond with a heme iron-bound water molecule. Sequence comparisons with other phenol-coupling P450 monooxygenases suggest that Met226 plays a role in determining the substrate regiospecificity of Orf6*. These features provide further insights into the mechanism of the cross-linking mechanisms that occur during glycopeptide antibiotics biosynthesis.

  19. Magnetisation reversal in cylindrical nickel nanobars involving magnetic vortex structure: A micromagnetic study

    Energy Technology Data Exchange (ETDEWEB)

    Barpanda, Prabeer, E-mail: prabeer.barpanda@u-picardie.f [Laboratoire de Reactivite et Chimie des Solides, Universite de Picardie Jules Verne, 33 rue Saint Leu, Amiens Cedex 80039 (France); Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, B3H 3J5 (Canada)

    2011-03-15

    A three-dimensional, Fast-Fourier-Transformed (3D-FFT) micromagnetic simulation was employed to study the magnetization reversal mechanisms in cylindrical nickel nanobars possessing magnetic vortices. Individual Ni nanobars of height 150-250 nm with aspect ratio varying from 2.1 to 2.5 were considered, all of them supporting magnetic vortices domains. Magnetization reversal in these nanobars involves the vortex-creation-annihilation (VCA) mechanism with an inversion symmetry feature observed mid-way during reversal process. The effect of incidence angle of externally applied field on overall magnetization reversal process is examined in detail. The corresponding variations in coercivity, squareness, exchange energy and vortex parameters are described by the micromagnetic study that can shed insights for building practical Ni nanobars magnetic nanostructures/devices.

  20. Involvement of S6K1 in mitochondria function and structure in HeLa cells.

    Science.gov (United States)

    Park, Jisoo; Tran, Quangdon; Mun, Kisun; Masuda, Kouhei; Kwon, So Hee; Kim, Seon-Hwan; Kim, Dong-Hoon; Thomas, George; Park, Jongsun

    2016-12-01

    The major biological function of mitochondria is to generate cellular energy through oxidative phosphorylation. Apart from cellular respiration, mitochondria also play a key role in signaling processes, including aging and cancer metabolism. It has been shown that S6K1-knockout mice are resistant to obesity due to enhanced beta-oxidation, with an increased number of large mitochondria. Therefore, in this report, the possible involvement of S6K1 in regulating mitochondria dynamics and function has been investigated in stable lenti-shS6K1-HeLa cells. Interestingly, S6K1-stably depleted HeLa cells showed phenotypical changes in mitochondria morphology. This observation was further confirmed by detailed image analysis of mitochondria shape. Corresponding molecular changes were also observed in these cells, such as the induction of mitochondrial fission proteins (Drp1 and Fis1). Oxygen consumption is elevated in S6K1-depeleted HeLa cells and FL5.12 cells. In addition, S6K1 depletion leads to enhancement of ATP production in cytoplasm and mitochondria. However, the relative ratio of mitochondrial ATP to cytoplasmic ATP is actually decreased in lenti-shS6K1-HeLa cells compared to control cells. Lastly, induction of mitophagy was found in lenti-shS6K1-HeLa cells with corresponding changes of mitochondria shape on electron microscope analysis. Taken together, our results indicate that S6K1 is involved in the regulation of mitochondria morphology and function in HeLa cells. This study will provide novel insights into S6K1 function in mitochondria-mediated cellular signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. The structural involvement of the cingulate cortex in premanifest and early Huntington's disease.

    Science.gov (United States)

    Hobbs, Nicola Z; Pedrick, Amy V; Say, Miranda J; Frost, Chris; Dar Santos, Rachelle; Coleman, Allison; Sturrock, Aaron; Craufurd, David; Stout, Julie C; Leavitt, Blair R; Barnes, Josephine; Tabrizi, Sarah J; Scahill, Rachael I

    2011-08-01

    The impact of Huntington's disease neuropathology on the structure of the cingulate is uncertain, with evidence of both cortical enlargement and atrophy in this structure in early clinical disease. We sought to determine differences in cingulate volume between premanifest Huntington's disease and early Huntington's disease groups compared with controls using detailed manual measurements. Thirty controls, 30 subjects with premanifest Huntington's disease, and 30 subjects with early Huntington's disease were selected from the Vancouver site of the TRACK-HD study. Subjects underwent 3 Tesla magnetic resonance imaging and motor, cognitive, and neuropsychiatric assessment. The cingulate was manually delineated and subdivided into rostral, caudal, and posterior segments. Group differences in volume and associations with performance on 4 tasks thought to utilize cingulate function were examined, with adjustment for appropriate covariates. Cingulate volumes were, on average, 1.7 mL smaller in early Huntington's disease (P=.001) and 0.9 mL smaller in premanifest Huntington's disease (P=.1) compared with controls. Smaller volumes in subsections of the cingulate were associated with impaired recognition of negative emotions (P=.04), heightened depression (P=.009), and worse visual working memory performance (P=.01). There was no evidence of associations between volume and ability on a performance-monitoring task. This study disputes previous findings of enlargement of the cingulate cortex in Huntington's disease and instead suggests that the cingulate undergoes structural degeneration during early Huntington's disease with directionally consistent, nonsignificant differences seen in premanifest Huntington's disease. Cingulate atrophy may contribute to deficits in mood, emotional processing, and visual working memory in Huntington's disease. Copyright © 2011 Movement Disorder Society.

  2. Competitive adsorption involving phosphate and benzenecarboxylic acids on goethite--effects of molecular structures.

    Science.gov (United States)

    Lindegren, Malin; Persson, Per

    2010-03-01

    The competitive adsorption between phosphate and either one of seven benzenecarboxylates (benzoate, phthalate, trimellitate, trimesoate, hemimellitate, pyromellitate, and mellitate) on the surfaces of fine-particulate goethite (alpha-FeOOH) was investigated as a function of pH. The series of ligands contained molecules with an increasing number of functional groups as well as three structural isomers of the tricarboxylates. Thus, the effects of both the number of carboxylate groups and the relative positions of these groups on the competitive efficiency toward phosphate were probed in this study. Quantitative adsorption experiments in batch mode and infrared spectroscopy were collectively used to evaluate the competitive adsorption reactions. Under the conditions probed, mono- and dicarboxylates had no detectable effect on phosphate adsorption whereas the ligands containing three or more carboxylate groups were able to partially outcompete phosphate. However, the pH dependency and the extent of these competitive effects were strongly dependent on the structure and composition of the benzenecarboxylate. The collective results showed that it was the competition for hydrogen-bonding surface sites rather than inner sphere surface sites that primarily determined the outcome of the competitive adsorption experiments, and it was the ability of the organic ligand to act as hydrogen-bonding acceptor and/or donor in various parts of the pH range that also determined the competitive pH dependency. The importance of H-bonding for the competitive adsorption between phosphate and benzenecarboxylic acids suggested that H-bonding interactions contributed substantially to the stabilities of both the adsorbed benzenecarboxylates and the phosphate ions and that these interactions were structurally specific; i.e., they were sensitive to the locations and the directional properties of the H-acceptor and H-donor surface sites. 2009 Elsevier Inc. All rights reserved.

  3. Structure and Characterization of Proteins and Enzymes Involved in Nucleotide Metabolism and Iron-Sulfur Proteins

    DEFF Research Database (Denmark)

    Løvgreen, Monika Nøhr; Ooi, Bee Lean

    , a program named MyCrystals has been developed to keep track of crystallization trials and results. The program combines pictures with crystallization conditions and is able to sort the pictures based on selected conditions. MyCrystals was used extensively throughout this work and allows for an overview...... extended β-sheet dimers. These dimers were not observed in solution and were likely a result of the high protein concentration in the crystals. WT, A115V and A115G Mt DCD-DUT were successfully purified, and the crystal structure of the A115V variant with dTTP bound was solved. The variants were created...

  4. Structural factors associated with an increased risk of HIV and sexually transmitted infection transmission among street-involved youth

    Directory of Open Access Journals (Sweden)

    Shoveller Jean A

    2009-01-01

    Full Text Available Abstract Background The prevalence of HIV and sexually transmitted infections (STIs among street-involved youth greatly exceed that of the general adolescent population; however, little is known regarding the structural factors that influence disease transmission risk among this population. Methods Between September 2005 and October 2006, 529 street-involved youth were enroled in a prospective cohort known as the At Risk Youth Study (ARYS. We examined structural factors associated with number of sex partners using quasi-Poisson regression and consistent condom use using logistic regression. Results At baseline, 415 (78.4% were sexually active, of whom 253 (61.0% reported multiple sex partners and 288 (69.4% reported inconsistent condom use in the past six months. In multivariate analysis, self-reported barriers to health services were inversely associated with consistent condom use (adjusted odds ratio [aOR] = 0.52, 95%CI: 0.25 – 1.07. Structural factors that were associated with greater numbers of sex partners included homelessness (adjusted incidence rate ratio [aIRR] = 1.54, 95%CI: 1.11 – 2.14 and having an area restriction that affects access to services (aIRR = 2.32, 95%CI: 1.28 – 4.18. Being searched or detained by the police was significant for males (aIRR = 1.36, 95%CI: 1.02 – 1.81. Conclusion Although limited by its cross-sectional design, our study found several structural factors amenable to policy-level interventions independently associated with sexual risk behaviours. These findings imply that the criminalization and displacement of street-involved youth may increase the likelihood that youth will engage in sexual risk behaviours and exacerbate the negative impact of resultant health outcomes. Moreover, our findings indicate that environmental-structural interventions may help to reduce the burden of these diseases among street youth in urban settings.

  5. A cortical-subcortical syntax pathway linking Broca's area and the striatum.

    Science.gov (United States)

    Teichmann, Marc; Rosso, Charlotte; Martini, Jean-Baptiste; Bloch, Isabelle; Brugières, Pierre; Duffau, Hugues; Lehéricy, Stéphane; Bachoud-Lévi, Anne-Catherine

    2015-06-01

    Combinatorial syntax has been shown to be underpinned by cortical key regions such as Broca's area and temporal cortices, and by subcortical structures such as the striatum. The cortical regions are connected via several cortico-to-cortical tracts impacting syntactic processing (e.g., the arcuate) but it remains unclear whether and how the striatum can be integrated into this cortex-centered syntax network. Here, we used a systematic stepwise approach to investigate the existence and syntactic function of an additional deep Broca-striatum pathway. We first asked 15 healthy controls and 12 patients with frontal/striatal lesions to perform three syntax tests. The results obtained were subjected to voxel-based lesion-symptom mapping (VLSM) to provide an anatomo-functional approximation of the pathway. The significant VLSM clusters were then overlapped with the probability maps of four cortico-cortical language tracts generated for 12 healthy participants (arcuate, extreme capsule fiber system, uncinate, aslant), including a probabilistic Broca-striatum tract. Finally, we carried out quantitative analyses of the relationship between the lesion load along the tracts and syntactic processing, by calculating tract-lesion overlap for each patient and analyzing the correlation with syntactic data. Our findings revealed a Broca-striatum tract linking BA45 with the left caudate head and overlapping with VLSM voxel clusters relating to complex syntax. The lesion load values for this tract were correlated with complex syntax scores, whereas no such correlation was observed for the other tracts. These results extend current syntax-network models, by adding a deep "Broca-caudate pathway," and are consistent with functional accounts of frontostriatal circuits. © 2015 Wiley Periodicals, Inc.

  6. Developmentally Sensitive Interaction Effects of Genes and the Social Environment on Total and Subcortical Brain Volumes.

    Directory of Open Access Journals (Sweden)

    Jennifer S Richards

    Full Text Available Smaller total brain and subcortical volumes have been linked to psychopathology including attention-deficit/hyperactivity disorder (ADHD. Identifying mechanisms underlying these alterations, therefore, is of great importance. We investigated the role of gene-environment interactions (GxE in interindividual variability of total gray matter (GM, caudate, and putamen volumes. Brain volumes were derived from structural magnetic resonance imaging scans in participants with (N = 312 and without ADHD (N = 437 from N = 402 families (age M = 17.00, SD = 3.60. GxE effects between DAT1, 5-HTT, and DRD4 and social environments (maternal expressed warmth and criticism; positive and deviant peer affiliation as well as the possible moderating effect of age were examined using linear mixed modeling. We also tested whether findings depended on ADHD severity. Deviant peer affiliation was associated with lower caudate volume. Participants with low deviant peer affiliations had larger total GM volumes with increasing age. Likewise, developmentally sensitive GxE effects were found on total GM and putamen volume. For total GM, differential age effects were found for DAT1 9-repeat and HTTLPR L/L genotypes, depending on the amount of positive peer affiliation. For putamen volume, DRD4 7-repeat carriers and DAT1 10/10 homozygotes showed opposite age relations depending on positive peer affiliation and maternal criticism, respectively. All results were independent of ADHD severity. The presence of differential age-dependent GxE effects might explain the diverse and sometimes opposing results of environmental and genetic effects on brain volumes observed so far.

  7. Subcortical band heterotopia (SBH) in males: clinical, imaging and genetic findings in comparison with females.

    Science.gov (United States)

    D'Agostino, Maria Daniela; Bernasconi, Andrea; Das, Soma; Bastos, Alexandre; Valerio, Rosa M; Palmini, André; Costa da Costa, Jaderson; Scheffer, Ingrid E; Berkovic, Samuel; Guerrini, Renzo; Dravet, Charlotte; Ono, Jiro; Gigli, GianLuigi; Federico, Antonio; Booth, Fran; Bernardi, Bruno; Volpi, Lilia; Tassinari, Carlo Alberto; Guggenheim, Mary Anne; Ledbetter, David H; Gleeson, Joseph G; Lopes-Cendes, Iscia; Vossler, David G; Malaspina, Elisabetta; Franzoni, Emilio; Sartori, Roberto J; Mitchell, Michael H; Mercho, Suha; Dubeau, François; Andermann, Frederick; Dobyns, William B; Andermann, Eva

    2002-11-01

    Subcortical band heterotopia (SBH) or double cortex syndrome is a neuronal migration disorder, which occurs very rarely in males: to date, at least 110 females but only 11 in males have been reported. The syndrome is usually associated with mutations in the doublecortin (DCX) (Xq22.3-q23) gene, and much less frequently in the LIS1 (17p13.3) gene. To determine whether the phenotypic spectrum, the genetic basis and genotype-phenotype correlations of SBH in males are similar to those in females, we compared the clinical, imaging and molecular features in 30 personally evaluated males and 60 previously reported females with SBH. Based on the MRI findings, we defined the following band subtypes: partial, involving one or two cerebral lobes; intermediate, involving two lobes and a portion of a third; diffuse, with substantial involvement of three or more lobes; and pachygyria-SBH, in which posterior SBH merges with anterior pachygyria. Karyo typing and mutation analysis of DCX and/or LIS1 were performed in 23 and 24 patients, respectively. The range of clinical phenotypes in males with SBH greatly overlapped that in females. MRI studies revealed that some anatomical subtypes of SBH, such as partial and intermediate posterior, pachygyria-SBH and diffuse bands with posterior predominance, were more frequently or exclusively present in males. Conversely, classical diffuse SBH and diffuse bands with anterior predominance were more frequent in females. Males had either mild or the most severe band subtypes, and these correlated with the over-representation of normal/borderline intelligence and severe mental retardation, respectively. Conversely, females who had predominantly diffuse bands exhibited mostly mild or moderate mental retardation. Seven patients (29%) had missense mutations in DCX; in four, these were germline mutations, whereas in three there was evidence for somatic mosaicism. A germline missense mutation of LIS1 and a partial trisomy of chromosome 9p were

  8. Subcortical volume and white matter integrity abnormalities in major depressive disorder: findings from UK Biobank imaging data.

    Science.gov (United States)

    Shen, Xueyi; Reus, Lianne M; Cox, Simon R; Adams, Mark J; Liewald, David C; Bastin, Mark E; Smith, Daniel J; Deary, Ian J; Whalley, Heather C; McIntosh, Andrew M

    2017-07-17

    Previous reports of altered grey and white matter structure in Major Depressive Disorder (MDD) have been inconsistent. Recent meta-analyses have, however, reported reduced hippocampal grey matter volume in MDD and reduced white matter integrity in several brain regions. The use of different diagnostic criteria, scanners and imaging sequences may, however, obscure further anatomical differences. In this study, we tested for differences in subcortical grey matter volume (n = 1157) and white matter integrity (n = 1089) between depressed individuals and controls in the subset of 8590 UK Biobank Imaging study participants who had undergone depression assessments. Whilst we found no significant differences in subcortical volumes, significant reductions were found in depressed individuals versus controls in global white matter integrity, as measured by fractional anisotropy (FA) (β = -0.182, p = 0.005). We also found reductions in FA in association/commissural fibres (β = -0.184, pcorrected = 0.010) and thalamic radiations (β = -0.159, pcorrected = 0.020). Tract-specific FA reductions were also found in the left superior longitudinal fasciculus (β = -0.194, pcorrected = 0.025), superior thalamic radiation (β = -0.224, pcorrected = 0.009) and forceps major (β = -0.193, pcorrected = 0.025) in depression (all betas standardised). Our findings provide further evidence for disrupted white matter integrity in MDD.

  9. Temporal Lobe and Frontal-Subcortical Dissociations in Non-Demented Parkinson's Disease with Verbal Memory Impairment.

    Directory of Open Access Journals (Sweden)

    Jared J Tanner

    Full Text Available The current investigation examined verbal memory in idiopathic non-dementia Parkinson's disease and the significance of the left entorhinal cortex and left entorhinal-retrosplenial region connections (via temporal cingulum on memory impairment in Parkinson's disease.Forty non-demented Parkinson's disease patients and forty non-Parkinson's disease controls completed two verbal memory tests--a wordlist measure (Philadelphia repeatable Verbal Memory Test and a story measure (Logical Memory. All participants received T1-weighted and diffusion magnetic resonance imaging (3T; Siemens sequences. Left entorhinal volume and left entorhinal-retrosplenial connectivity (temporal cingulum edge weight were the primary imaging variables of interest with frontal lobe thickness and subcortical structure volumes as dissociating variables.Individuals with Parkinson's disease showed worse verbal memory, smaller entorhinal volumes, but did not differ in entorhinal-retrosplenial connectivity. For Parkinson's disease entorhinal-retrosplenial edge weight had the strongest associations with verbal memory. A subset of Parkinson's disease patients (23% had deficits (z-scores < -1.5 across both memory measures. Relative to non-impaired Parkinson's peers, this memory-impaired group had smaller entorhinal volumes.Although entorhinal cortex volume was significantly reduced in Parkinson's disease patients relative to non-Parkinson's peers, only white matter connections associated with the entorhinal cortex were significantly associated with verbal memory performance in our sample. There was also no suggestion of contribution from frontal-subcortical gray or frontal white matter regions. These findings argue for additional investigation into medial temporal lobe gray and white matter connectivity for understanding memory in Parkinson's disease.

  10. Formulaic Language in Parkinson's Disease and Alzheimer's Disease: Complementary Effects of Subcortical and Cortical Dysfunction

    Science.gov (United States)

    Van Lancker Sidtis, Diana; Choi, JiHee; Alken, Amy; Sidtis, John J.

    2015-01-01

    Purpose: The production of formulaic expressions (conversational speech formulas, pause fillers, idioms, and other fixed expressions) is excessive in the left hemisphere and deficient in the right hemisphere and in subcortical stroke. Speakers with Alzheimer's disease (AD), having functional basal ganglia, reveal abnormally high proportions of…

  11. Aspects of Subcortical Ischaemic Vascular Disease : Early clinical manifestations and associations with Type 2 diabetes mellitus

    NARCIS (Netherlands)

    Harten, van B.

    2006-01-01

    Summary Subcortical ischaemic vascular disease (SIVD) is an important cause of cognitive impairment in elderly patients. Screening and diagnostic tests are needed to identify these patients. The HIV dementia scale (HDS) is a reliable and quantitative scale for identifying HIV dementia1. The

  12. The brain subcortical white matter and aging: A quantitative fractional anisotropy analysis

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

    Full Text Available Abstract To study the integrity of hemispheric subcortical white matter by comparing normal young and elderly subjects using quantitative fractional anisotropy (DTI-FA. Methods: Subjects of two different age groups (young=12, elderly=12 were included. MR - GE Signa Horizon - 1.5T scans were performed. Cases with Fazekas scores £3 were assessed on FLAIR sequence. Standard parameters for DTI-FA were used. ROIs were placed at various sites of the subcortical white matter, and the genu and splenium of the midline corpus callosum. Analysis was performed using Functool. Statistics for anterior and posterior white matter, as well as the genu and splenium were compared between the groups. The study was approved by the Ethics Committee of IPUB-UFRJ and informed consent obtained. Results: DTI-FA showed lower anisotropy values in the anterior region (subcortical white matter and genu, but not in the posterior region (subcortical white matter and splenium, in elderly normal subjects compared to young subjects. Conclusion: The results may represent loss of integrity of anterior (frontal white matter fibers in the elderly subjects. These fibers constitute important intra- and inter-hemispheric tracts, components of neural networks that provide cognitive, behavioral, motor and sensory integration. The loss of integrity of the anterior segments of the studied fiber systems with ageing, represents a disconnection process that may underlie clinical manifestations found in elderly subjects such as executive dysfunction.

  13. A neuropathological, stereo-EEG, and MRI study of subcortical band heterotopia.

    Science.gov (United States)

    Mai, R; Tassi, L; Cossu, M; Francione, S; Lo Russo, G; Garbelli, R; Ferrario, A; Galli, C; Taroni, F; Citterio, A; Spreafico, R

    2003-06-10

    The authors performed an MRI, stereo-EEG, and pathology study on a woman with subcortical band heterotopia and partial epilepsy. Clinical manifestations of seizures always started when ictal discharges were present in outer and heterotopic cortices. Simultaneous activation of both cortices and presence of differentiated neurons in the white matter and the heterotopia strongly suggest that the cortices were anatomically and functionally interconnected.

  14. Subcortical laminar heterotopia in two sisters and their mother : MRI, clinical findings and pathogenesis

    NARCIS (Netherlands)

    van der Valk, PHM; Snoeck, [No Value; Meiners, LC; des Portes, [No Value; Chelly, J; Pinard, JM; Ippel, PF; van Nieuwenhuizen, O

    MR imaging, clinical data and underlying pathogenesis of subcortical laminar heterotopia (SCLH), also known as band heterotopia, in two sisters and their mother are presented. On MR imaging a different degree of SCLH was found in all three affected family-members. The inversion recovery sequence was

  15. Double inversion recovery magnetic resonance imaging of subcortical band heterotopia: a report of 2 cases.

    Science.gov (United States)

    Zhang, Quan; Zhang, Yunting; Zhang, Jing; Li, Qiong

    2011-01-01

    We report 2 cases of subcortical band heterotopia (SBH) with emphasis on double inversion recovery (DIR) magnetic resonance imaging (MRI). The heterotopic gray matter demonstrated homogeneous high signal intensity and the delineation between the SBH and white matter was distinctly depicted on DIR MRI. Double inversion recovery is a useful adjunct to conventional MRI for the diagnosis of SBH.

  16. Identification of DCX gene mutation in lissencephaly spectrum with subcortical band heterotopia using whole exome sequencing.

    Science.gov (United States)

    Jang, Mi-Ae; Woo, Hye In; Kim, Jong-Won; Lee, Jeehun; Ki, Chang-Seok

    2013-05-01

    Malformations of cortical development include a wide range of brain developmental anomalies that commonly lead to developmental delay and epilepsy. Lissencephaly and subcortical band heterotopia are major malformations of cortical development due to abnormal neuronal migration and several genes have been identified including ARX, DCX, LIS1, RELN, TUBA1A, and VLDLR. Traditionally, genetic testing for lissencephaly and subcortical band heterotopia has been done in the order of the probability of detection of mutation according to the radiologic features, but the success rate could be variable with this time-consuming approach. In this study we used whole-exome sequencing to identify mutations in a 5-year-old girl with lissencephaly spectrum with subcortical band heterotopia. After excluding lissencephaly-related genes, one deleterious mutation (NM_178153.2:c.665C > T, p.Thr222Ile) in the DCX gene was identified. Further Sanger sequencing validated the variant in the patient but not in both parents indicating a de novo mutation. The present report demonstrates that whole-exome sequencing may be a useful tool for the identification of mutations in patients with lissencephaly and subcortical band heterotopias as well as malformations of cortical development. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Developmentally Sensitive Interaction Effects of Genes and the Social Environment on Total and Subcortical Brain Volumes

    NARCIS (Netherlands)

    Richards, Jennifer S; Arias Vásquez, Alejandro; Franke, Barbara; Hoekstra, Pieter J; Heslenfeld, Dirk J; Oosterlaan, Jaap; Faraone, Stephen V; Buitelaar, Jan K; Hartman, Catharina A

    2016-01-01

    Smaller total brain and subcortical volumes have been linked to psychopathology including attention-deficit/hyperactivity disorder (ADHD). Identifying mechanisms underlying these alterations, therefore, is of great importance. We investigated the role of gene-environment interactions (GxE) in

  18. Crystal structure of a human membrane protein involved in cysteinyl leukotriene biosynthesis.

    Science.gov (United States)

    Ago, Hideo; Kanaoka, Yoshihide; Irikura, Daisuke; Lam, Bing K; Shimamura, Tatsuro; Austen, K Frank; Miyano, Masashi

    2007-08-02

    The cysteinyl leukotrienes, namely leukotriene (LT)C4 and its metabolites LTD4 and LTE4, the components of slow-reacting substance of anaphylaxis, are lipid mediators of smooth muscle constriction and inflammation, particularly implicated in bronchial asthma. LTC4 synthase (LTC4S), the pivotal enzyme for the biosynthesis of LTC4 (ref. 10), is an 18-kDa integral nuclear membrane protein that belongs to a superfamily of membrane-associated proteins in eicosanoid and glutathione metabolism that includes 5-lipoxygenase-activating protein, microsomal glutathione S-transferases (MGSTs), and microsomal prostaglandin E synthase 1 (ref. 13). LTC4S conjugates glutathione to LTA4, the endogenous substrate derived from arachidonic acid through the 5-lipoxygenase pathway. In contrast with MGST2 and MGST3 (refs 15, 16), LTC4S does not conjugate glutathione to xenobiotics. Here we show the atomic structure of human LTC4S in a complex with glutathione at 3.3 A resolution by X-ray crystallography and provide insights into the high substrate specificity for glutathione and LTA4 that distinguishes LTC4S from other MGSTs. The LTC4S monomer has four transmembrane alpha-helices and forms a threefold symmetric trimer as a unit with functional domains across each interface. Glutathione resides in a U-shaped conformation within an interface between adjacent monomers, and this binding is stabilized by a loop structure at the top of the interface. LTA4 would fit into the interface so that Arg 104 of one monomer activates glutathione to provide the thiolate anion that attacks C6 of LTA4 to form a thioether bond, and Arg 31 in the neighbouring monomer donates a proton to form a hydroxyl group at C5, resulting in 5(S)-hydroxy-6(R)-S-glutathionyl-7,9-trans-11,14-cis-eicosatetraenoic acid (LTC4). These findings provide a structural basis for the development of LTC4S inhibitors for a proinflammatory pathway mediated by three cysteinyl leukotriene ligands whose stability and potency are different

  19. The Relationship between Intelligence and Anxiety: An Association with Subcortical White Matter Metabolism.

    Science.gov (United States)

    Coplan, Jeremy D; Hodulik, Sarah; Mathew, Sanjay J; Mao, Xiangling; Hof, Patrick R; Gorman, Jack M; Shungu, Dikoma C

    2011-01-01

    We have demonstrated in a previous study that a high degree of worry in patients with generalized anxiety disorder (GAD) correlates positively with intelligence and that a low degree of worry in healthy subjects correlates positively with intelligence. We have also shown that both worry and intelligence exhibit an inverse correlation with certain metabolites in the subcortical white matter. Here we re-examine the relationships among generalized anxiety, worry, intelligence, and subcortical white matter metabolism in an extended sample. Results from the original study were combined with results from a second study to create a sample comprised of 26 patients with GAD and 18 healthy volunteers. Subjects were evaluated using the Penn State Worry Questionnaire, the Wechsler Brief intelligence quotient (IQ) assessment, and proton magnetic resonance spectroscopic imaging ((1)H-MRSI) to measure subcortical white matter metabolism of choline and related compounds (CHO). Patients with GAD exhibited higher IQ's and lower metabolite concentrations of CHO in the subcortical white matter in comparison to healthy volunteers. When data from GAD patients and healthy controls were combined, relatively low CHO predicted both relatively higher IQ and worry scores. Relatively high anxiety in patients with GAD predicted high IQ whereas relatively low anxiety in controls also predicted high IQ. That is, the relationship between anxiety and intelligence was positive in GAD patients but inverse in healthy volunteers. The collective data suggest that both worry and intelligence are characterized by depletion of metabolic substrate in the subcortical white matter and that intelligence may have co-evolved with worry in humans.

  20. Are liquid crystalline properties of nucleosomes involved in chromosome structure and dynamics?

    Science.gov (United States)

    Livolant, Françoise; Mangenot, Stéphanie; Leforestier, Amélie; Bertin, Aurélie; Frutos, Marta de; Raspaud, Eric; Durand, Dominique

    2006-10-15

    Nucleosome core particles correspond to the structural units of eukaryotic chromatin. They are charged colloids, 101 Angstrom in diameter and 55 Angstrom in length, formed by the coiling of a 146/147 bp DNA fragment (50 nm) around the histone protein octamer. Solutions of these particles can be concentrated, under osmotic pressure, up to the concentrations found in the nuclei of living cells. In the presence of monovalent cations (Na(+)), nucleosomes self-assemble into crystalline or liquid crystalline phases. A lamello-columnar phase is observed at 'low salt' concentrations, while a two-dimensional hexagonal phase and a three-dimensional quasi-hexagonal phase form at 'high salt' concentrations. We followed the formation of these phases from the dilute isotropic solutions to the ordered phases by combining cryoelectron microscopy and X-ray diffraction analyses. The phase diagram is presented as a function of the monovalent salt concentration and applied osmotic pressure. An alternative method to condense nucleosomes is to induce their aggregation upon addition of divalent or multivalent cations (Mg(2+), spermidine(3+) and spermine(4+)). Ordered phases are also found in the aggregates. We also discuss whether these condensed phases of nucleosomes may be relevant from a biological point of view.

  1. Episodic memory impairment in systemic lupus erythematosus: involvement of thalamic structures.

    Science.gov (United States)

    Zimmermann, Nicolle; Corrêa, Diogo Goulart; Netto, Tania Maria; Kubo, Tadeu; Pereira, Denis Batista; Fonseca, Rochele Paz; Gasparetto, Emerson Leandro

    2015-02-01

    Episodic memory deficits in systemic lupus erythematosus (SLE) have been frequently reported in the literature; however, little is known about the neural correlates of these deficits. We investigated differences in the volumes of different brain structures of SLE patients with and without episodic memory impairments diagnosed by the Rey Auditory Verbal Learning Test (RAVLT). Groups were paired based on age, education, sex, Mini Mental State Examination score, accumulation of disease burden (SLICC), and focused attention dimension score. Patients underwent magnetic resonance imaging (MRI). Cortical volumetric reconstruction and segmentation of the MR images were performed with the FreeSurfer software program. SLE patients with episodic memory deficits presented shorter time of diagnosis than SLE patients without episodic memory deficits. ANOVA revealed that SLE patients with episodic memory deficits had a larger third ventricle volume than SLE patients without episodic memory deficits and controls. Additionally, covariance analysis indicated group effects on the bilateral thalamus and on the third ventricle. Our findings indicate that episodic memory may be impaired in SLE patients with normal hippocampal volume. In addition, the thalamus may undergo volumetric changes associated with episodic memory loss in SLE.

  2. DHX9 helicase is involved in preventing genomic instability induced by alternatively structured DNA in human cells

    Science.gov (United States)

    Jain, Aklank; Bacolla, Albino; del Mundo, Imee M.; Zhao, Junhua; Wang, Guliang; Vasquez, Karen M.

    2013-01-01

    Sequences that have the capacity to adopt alternative (i.e. non-B) DNA structures in the human genome have been implicated in stimulating genomic instability. Previously, we found that a naturally occurring intra-molecular triplex (H-DNA) caused genetic instability in mammals largely in the form of DNA double-strand breaks. Thus, it is of interest to determine the mechanism(s) involved in processing H-DNA. Recently, we demonstrated that human DHX9 helicase preferentially unwinds inter-molecular triplex DNA in vitro. Herein, we used a mutation-reporter system containing H-DNA to examine the relevance of DHX9 activity on naturally occurring H-DNA structures in human cells. We found that H-DNA significantly increased mutagenesis in small-interfering siRNA-treated, DHX9-depleted cells, affecting mostly deletions. Moreover, DHX9 associated with H-DNA in the context of supercoiled plasmids. To further investigate the role of DHX9 in the recognition/processing of H-DNA, we performed binding assays in vitro and chromatin immunoprecipitation assays in U2OS cells. DHX9 recognized H-DNA, as evidenced by its binding to the H-DNA structure and enrichment at the H-DNA region compared with a control region in human cells. These composite data implicate DHX9 in processing H-DNA structures in vivo and support its role in the overall maintenance of genomic stability at sites of alternatively structured DNA. PMID:24049074

  3. Lectin staining shows no evidence of involvement of glycocalyx/mucous layer carbohydrate structures in development of celiac disease

    DEFF Research Database (Denmark)

    Toft-Hansen, Henrik; Nielsen, Christian; Biagini, Matteo

    2013-01-01

    The presence of unique carbohydrate structures in the glycocalyx/mucous layer of the intestine may be involved in a susceptibility to celiac disease (CD) by serving as attachment sites for bacteria. This host-microbiota interaction may influence the development of CD and possibly other diseases...... with autoimmune components. We examined duodenal biopsies from a total of 30 children, of which 10 had both celiac disease (CD) and type 1 diabetes (T1D); 10 had CD alone; and 10 were suspected of having gastrointestinal disease, but had normal duodenal histology (non-CD controls). Patients with both CD and T1D...... showed no significant differences. Based on our material, we found no indication that the presence of Gal-β(1,3)-GalNAc or Fucα1-2Gal-R is involved in the susceptibility to CD, or that the disease process affects the expression of these carbohydrates....

  4. Subcortical White Matter Changes with Normal Aging Detected by Multi-Shot High Resolution Diffusion Tensor Imaging.

    Directory of Open Access Journals (Sweden)

    Sheng Xie

    Full Text Available Subcortical white matter builds neural connections between cortical and subcortical regions and constitutes the basis of neural networks. It plays a very important role in normal brain function. Various studies have shown that white matter deteriorates with aging. However, due to the limited spatial resolution provided by traditional diffusion imaging techniques, microstructural information from subcortical white matter with normal aging has not been comprehensively assessed. This study aims to investigate the deterioration effect with aging in the subcortical white matter and provide a baseline standard for pathological disorder diagnosis. We apply our newly developed multi-shot high resolution diffusion tensor imaging, using self-feeding multiplexed sensitivity-encoding, to measure subcortical white matter changes in regions of interest of healthy persons with a wide age range. Results show significant fractional anisotropy decline and radial diffusivity increasing with age, especially in the anterior part of the brain. We also find that subcortical white matter has more prominent changes than white matter close to the central brain. The observed changes in the subcortical white matter may be indicative of a mild demyelination and a loss of myelinated axons, which may contribute to normal age-related functional decline.

  5. Subcortical White Matter Changes with Normal Aging Detected by Multi-Shot High Resolution Diffusion Tensor Imaging.

    Science.gov (United States)

    Xie, Sheng; Zhang, Zhe; Chang, Feiyan; Wang, Yishi; Zhang, Zhenxia; Zhou, Zhenyu; Guo, Hua

    2016-01-01

    Subcortical white matter builds neural connections between cortical and subcortical regions and constitutes the basis of neural networks. It plays a very important role in normal brain function. Various studies have shown that white matter deteriorates with aging. However, due to the limited spatial resolution provided by traditional diffusion imaging techniques, microstructural information from subcortical white matter with normal aging has not been comprehensively assessed. This study aims to investigate the deterioration effect with aging in the subcortical white matter and provide a baseline standard for pathological disorder diagnosis. We apply our newly developed multi-shot high resolution diffusion tensor imaging, using self-feeding multiplexed sensitivity-encoding, to measure subcortical white matter changes in regions of interest of healthy persons with a wide age range. Results show significant fractional anisotropy decline and radial diffusivity increasing with age, especially in the anterior part of the brain. We also find that subcortical white matter has more prominent changes than white matter close to the central brain. The observed changes in the subcortical white matter may be indicative of a mild demyelination and a loss of myelinated axons, which may contribute to normal age-related functional decline.

  6. Subcortical brain segmentation of two dimensional T1-weighted data sets with FMRIB's Integrated Registration and Segmentation Tool (FIRST

    Directory of Open Access Journals (Sweden)

    Michael Amann

    2015-01-01

    Full Text Available Brain atrophy has been identified as an important contributing factor to the development of disability in multiple sclerosis (MS. In this respect, more and more interest is focussing on the role of deep grey matter (DGM areas. Novel data analysis pipelines are available for the automatic segmentation of DGM using three-dimensional (3D MRI data. However, in clinical trials, often no such high-resolution data are acquired and hence no conclusions regarding the impact of new treatments on DGM atrophy were possible so far. In this work, we used FMRIB's Integrated Registration and Segmentation Tool (FIRST to evaluate the possibility of segmenting DGM structures using standard two-dimensional (2D T1-weighted MRI. In a cohort of 70 MS patients, both 2D and 3D T1-weighted data were acquired. The thalamus, putamen, pallidum, nucleus accumbens, and caudate nucleus were bilaterally segmented using FIRST. Volumes were calculated for each structure and for the sum of basal ganglia (BG as well as for the total DGM. The accuracy and reliability of the 2D data segmentation were compared with the respective results of 3D segmentations using volume difference, volume overlap and intra-class correlation coefficients (ICCs. The mean differences for the individual substructures were between 1.3% (putamen and −25.2% (nucleus accumbens. The respective values for the BG were −2.7% and for DGM 1.3%. Mean volume overlap was between 89.1% (thalamus and 61.5% (nucleus accumbens; BG: 84.1%; DGM: 86.3%. Regarding ICC, all structures showed good agreement with the exception of the nucleus accumbens. The results of the segmentation were additionally validated through expert manual delineation of the caudate nucleus and putamen in a subset of the 3D data. In conclusion, we demonstrate that subcortical segmentation of 2D data are feasible using FIRST. The larger subcortical GM structures can be segmented with high consistency. This forms the basis for the application of

  7. Structures of Rhodopsin Kinase in Different Ligand States Reveal Key Elements Involved in G Protein-coupled Receptor Kinase Activation

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Puja; Wang, Benlian; Maeda, Tadao; Palczewski, Krzysztof; Tesmer, John J.G. (Case Western); (Michigan)

    2008-10-08

    G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate activated heptahelical receptors, leading to their uncoupling from G proteins. Here we report six crystal structures of rhodopsin kinase (GRK1), revealing not only three distinct nucleotide-binding states of a GRK but also two key structural elements believed to be involved in the recognition of activated GPCRs. The first is the C-terminal extension of the kinase domain, which was observed in all nucleotide-bound GRK1 structures. The second is residues 5-30 of the N terminus, observed in one of the GRK1{center_dot}(Mg{sup 2+}){sub 2} {center_dot}ATP structures. The N terminus was also clearly phosphorylated, leading to the identification of two novel phosphorylation sites by mass spectral analysis. Co-localization of the N terminus and the C-terminal extension near the hinge of the kinase domain suggests that activated GPCRs stimulate kinase activity by binding to this region to facilitate full closure of the kinase domain.

  8. Memory loss from a subcortical white matter infarct.

    OpenAIRE

    Kooistra, C A; Heilman, K M

    1988-01-01

    Clinical disorders of memory are believed to occur from the dysfunction of either the mesial temporal lobe, the mesial thalamus, or the basal forebrain. Fibre tract damage at the level of the fornix has only inconsistently produced amnesia. A patient is reported who suffered a cerebrovascular accident involving the posterior limb of the left internal capsule that resulted in a persistent and severe disorder of verbal memory. The inferior extent of the lesion effectively disconnected the mesia...

  9. Structural and functional mapping of Rtg2p determinants involved in retrograde signaling and aging of Saccharomyces cerevisiae.

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    Rafaela Maria Rios-Anjos

    Full Text Available In Saccharomyces cerevisiae mitochondrial dysfunction induces retrograde signaling, a pathway of communication from mitochondria to the nucleus that promotes a metabolic remodeling to ensure sufficient biosynthetic precursors for replication. Rtg2p is a positive modulator of this pathway that is also required for cellular longevity. This protein belongs to the ASKHA superfamily, and contains a putative N-terminal ATP-binding domain, but there is no detailed structural and functional map of the residues in this domain that accounts for their contribution to retrograde signaling and aging. Here we use Decomposition of Residue Correlation Networks and site-directed mutagenesis to identify Rtg2p structural determinants of retrograde signaling and longevity. We found that most of the residues involved in retrograde signaling surround the ATP-binding loops, and that Rtg2p N-terminus is divided in three regions whose mutants have different aging phenotypes. We also identified E137, D158 and S163 as possible residues involved in stabilization of ATP at the active site. The mutants shown here may be used to map other Rtg2p activities that crosstalk to other pathways of the cell related to genomic stability and aging.

  10. Structure/function analysis of Na(+)-K(+)-ATPase central isoform-specific region: involvement in PKC regulation.

    Science.gov (United States)

    Pierre, Sandrine V; Duran, Marie-Josée; Carr, Deborah L; Pressley, Thomas A

    2002-11-01

    Specific functions served by the various Na(+)-K(+)-ATPase alpha-isoforms are likely to originate in regions of structural divergence within their primary structures. The isoforms are nearly identical, with the exception of the NH(2) terminus and a 10-residue region near the center of each molecule (isoform-specific region; ISR). Although the NH(2) terminus has been clearly identified as a source of isoform functional diversity, other regions seem to be involved. We investigated whether the central ISR could also contribute to isoform variability. We constructed chimeric molecules in which the central ISRs of rat alpha(1)- and alpha(2)-isoforms were exchanged. After stable transfection into opossum kidney cells, the chimeras were characterized for two properties known to differ dramatically among the isoforms: their K(+) deocclusion pattern and their response to PKC activation. Comparisons with rat full-length alpha(1)- and alpha(2)-isoforms expressed under the same conditions suggest an involvement of the central ISR in the response to PKC but not in K(+) deocclusion.

  11. Genetic influences on schizophrenia and subcortical brain volumes

    DEFF Research Database (Denmark)

    Franke, Barbara; Stein, Jason L; Ripke, Stephan

    2016-01-01

    Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use ge...

  12. Structural and functional study of YER067W, a new protein involved in yeast metabolism control and drug resistance.

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    Tatiana Domitrovic

    2010-06-01

    Full Text Available The genome of Saccharomyces cerevisiae is arguably the best studied eukaryotic genome, and yet, it contains approximately 1000 genes that are still relatively uncharacterized. As the majority of these ORFs have no homologs with characterized sequence or protein structure, traditional sequence-based approaches cannot be applied to deduce their biological function. Here, we characterize YER067W, a conserved gene of unknown function that is strongly induced in response to many stress conditions and repressed in drug resistant yeast strains. Gene expression patterns of YER067W and its paralog YIL057C suggest an involvement in energy metabolism. We show that yeast lacking YER067W display altered levels of reserve carbohydrates and a growth deficiency in media that requires aerobic metabolism. Impaired mitochondrial function and overall reduction of ergosterol content in the YER067W deleted strain explained the observed 2- and 4-fold increase in resistance to the drugs fluconazole and amphotericin B, respectively. Cell fractionation and immunofluorescence microscopy revealed that Yer067w is associated with cellular membranes despite the absence of a transmembrane domain in the protein. Finally, the 1.7 A resolution crystal structure of Yer067w shows an alpha-beta fold with low similarity to known structures and a putative functional site.YER067W's involvement with aerobic energetic metabolism suggests the assignment of the gene name RGI1, standing for respiratory growth induced 1. Altogether, the results shed light on a previously uncharacterized protein family and provide basis for further studies of its apparent role in energy metabolism control and drug resistance.

  13. Functional and Structural Analysis of a β-Glucosidase Involved in β-1,2-Glucan Metabolism in Listeria innocua.

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    Masahiro Nakajima

    Full Text Available Despite the presence of β-1,2-glucan in nature, few β-1,2-glucan degrading enzymes have been reported to date. Recently, the Lin1839 protein from Listeria innocua was identified as a 1,2-β-oligoglucan phosphorylase. Since the adjacent lin1840 gene in the gene cluster encodes a putative glycoside hydrolase family 3 β-glucosidase, we hypothesized that Lin1840 is also involved in β-1,2-glucan dissimilation. Here we report the functional and structural analysis of Lin1840. A recombinant Lin1840 protein (Lin1840r showed the highest hydrolytic activity toward sophorose (Glc-β-1,2-Glc among β-1,2-glucooligosaccharides, suggesting that Lin1840 is a β-glucosidase involved in sophorose degradation. The enzyme also rapidly hydrolyzed laminaribiose (β-1,3, but not cellobiose (β-1,4 or gentiobiose (β-1,6 among β-linked gluco-disaccharides. We determined the crystal structures of Lin1840r in complexes with sophorose and laminaribiose as productive binding forms. In these structures, Arg572 forms many hydrogen bonds with sophorose and laminaribiose at subsite +1, which seems to be a key factor for substrate selectivity. The opposite side of subsite +1 from Arg572 is connected to a large empty space appearing to be subsite +2 for the binding of sophorotriose (Glc-β-1,2-Glc-β-1,2-Glc in spite of the higher Km value for sophorotriose than that for sophorose. The conformations of sophorose and laminaribiose are almost the same on the Arg572 side but differ on the subsite +2 side that provides no interaction with a substrate. Therefore, Lin1840r is unable to distinguish between sophorose and laminaribiose as substrates. These results provide the first mechanistic insights into β-1,2-glucooligosaccharide recognition by β-glucosidase.

  14. Structural insights into the human RyR2 N-terminal region involved in cardiac arrhythmias

    Energy Technology Data Exchange (ETDEWEB)

    Borko, Ľubomír; Bauerová-Hlinková, Vladena, E-mail: vladena.bauerova@savba.sk; Hostinová, Eva; Gašperík, Juraj [Institute of Molecular Biology, Slovak Academy of Sciences, Dúbravská cesta 21, 845 51 Bratislava (Slovakia); Beck, Konrad [Cardiff University School of Dentistry, Heath Park, Cardiff CF14 4XY Wales (United Kingdom); Lai, F. Anthony [Cardiff University School of Medicine, Cardiff CF14 4XN Wales (United Kingdom); Zahradníková, Alexandra, E-mail: vladena.bauerova@savba.sk [Institute of Molecular Biology, Slovak Academy of Sciences, Dúbravská cesta 21, 845 51 Bratislava (Slovakia); Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlárska 5, 833 34 Bratislava (Slovakia); Ševčík, Jozef, E-mail: vladena.bauerova@savba.sk [Institute of Molecular Biology, Slovak Academy of Sciences, Dúbravská cesta 21, 845 51 Bratislava (Slovakia)

    2014-11-01

    X-ray and solution structures of the human RyR2 N-terminal region were obtained under near-physiological conditions. The structure exhibits a unique network of interactions between its three domains, revealing an important stabilizing role of the central helix. Human ryanodine receptor 2 (hRyR2) mediates calcium release from the sarcoplasmic reticulum, enabling cardiomyocyte contraction. The N-terminal region of hRyR2 (amino acids 1–606) is the target of >30 arrhythmogenic mutations and contains a binding site for phosphoprotein phosphatase 1. Here, the solution and crystal structures determined under near-physiological conditions, as well as a homology model of the hRyR2 N-terminal region, are presented. The N-terminus is held together by a unique network of interactions among its three domains, A, B and C, in which the central helix (amino acids 410–437) plays a prominent stabilizing role. Importantly, the anion-binding site reported for the mouse RyR2 N-terminal region is notably absent from the human RyR2. The structure concurs with the differential stability of arrhythmogenic mutations in the central helix (R420W, I419F and I419F/R420W) which are owing to disparities in the propensity of mutated residues to form energetically favourable or unfavourable contacts. In solution, the N-terminus adopts a globular shape with a prominent tail that is likely to involve residues 545–606, which are unresolved in the crystal structure. Docking the N-terminal domains into cryo-electron microscopy maps of the closed and open RyR1 conformations reveals C{sup α} atom movements of up to 8 Å upon channel gating, and predicts the location of the leucine–isoleucine zipper segment and the interaction site for spinophilin and phosphoprotein phosphatase 1 on the RyR surface.

  15. Structure reveals regulatory mechanisms of a MaoC-like hydratase from Phytophthora capsici involved in biosynthesis of polyhydroxyalkanoates (PHAs.

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    Huizheng Wang

    Full Text Available BACKGROUND: Polyhydroxyalkanoates (PHAs have attracted increasing attention as "green plastic" due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC, which belongs to (R-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic. METHODOLOGY/PRINCIPAL FINDINGS: We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC. CONCLUSIONS/SIGNIFICANCE: The data in our study reveal the regulatory mechanism of an (R-hydratase, providing information on enzyme engineering to produce low cost PHAs.

  16. Structural and functional analysis of validoxylamine A 7'-phosphate synthase ValL involved in validamycin A biosynthesis.

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    Lina Zheng

    Full Text Available Validamycin A (Val-A is an effective antifungal agent widely used in Asian countries as crop protectant. Validoxylamine A, the core structure and intermediate of Val-A, consists of two C(7-cyclitol units connected by a rare C-N bond. In the Val-A biosynthetic gene cluster in Streptomyces hygroscopicus 5008, the ORF valL was initially annotated as a validoxylamine A 7'-phosphate(V7P synthase, whose encoded 497-aa protein shows high similarity with trehalose 6-phosphate(T6P synthase. Gene inactivation of valL abolished both validoxylamine A and validamycin A productivity, and complementation with a cloned valL recovered 10% production of the wild-type in the mutant, indicating the involvement of ValL in validoxylamine A biosynthesis. Also we determined the structures of ValL and ValL/trehalose complex. The structural data indicates that ValL adopts the typical fold of GT-B protein family, featuring two Rossmann-fold domains and an active site at domain junction. The residues in the active site are arranged in a manner homologous to that of Escherichia coli (E.coli T6P synthase OtsA. However, a significant discrepancy is found in the active-site loop region. Also noticeable structural variance is found around the active site entrance in the apo ValL structure while the region takes an ordered configuration upon binding of product analog trehalose. Furthermore, the modeling of V7P in the active site of ValL suggests that ValL might have a similar SNi-like mechanism as OtsA.

  17. Gerstmann meets Geschwind: a crossing (or kissing) variant of a subcortical disconnection syndrome?

    Science.gov (United States)

    Kleinschmidt, Andreas; Rusconi, Elena

    2011-12-01

    That disconnection causes clinical symptoms is a very influential concept in behavioral neurology. Criteria for subcortical disconnection usually are symptoms that are distinct from those following cortical lesions and damage to a single, long-range fiber tract. Yet, a recent study combining functional magnetic resonance imaging and fiber tracking concluded that a focal lesion in left parietal white matter provides the only tenable explanation for pure Gerstmann's syndrome, an enigmatic tetrad of acalculia, agraphia, finger agnosia, and left-right disorientation. Such a lesion would affect not only a single fiber tract but crossing or "kissing" of different fiber tracts and hence disconnect separate cortical networks. As fiber crossing is prominent in the cerebral white matter, the authors propose an extension to the subcortical disconnection framework that opens the door to ascribing a more diversified clinical phenomenology to white matter damage and ensuing disconnection than has been the case so far.

  18. Biophysical changes in subcortical nuclei: the impact of diabetes and major depression.

    Science.gov (United States)

    Kumar, A; Yang, S; Ajilore, O; Wu, M; Cohen, J; Lamar, M; Bhaumik, D

    2016-04-01

    Magnetization transfer (MT) is a neuroimaging technique that is frequently used to characterize the biophysical abnormalities in both gray and white matter regions of the brain. In our study, we used MT to examine the integrity of key nodes in frontal-subcortical circuits in four subject groups: patients diagnosed with type 2 diabetes with and without major depression (MDD), a healthy control group, and a group diagnosed with MDD without diabetes. In the MDD group, MT studies demonstrated lower magnetization transfer ratios (MTR), a marker of abnormalities in the macromolecular protein pool, in the thalami when compared with the control groups. The group with diabetes and MDD showed lower MTR in the globus pallidus when compared with the group with MDD. Biophysical measures, in subcortical nuclei, correlated inversely with measures of glycemic control, cerebrovascular burden and depression scores. These findings have broad implications for the underlying neuronal circuitry and neurobiology of mood disorders.

  19. Megalencephalic leukoencephalopathy with subcortical cysts in an adult: quantitative proton MR spectroscopy and diffusion tensor MRI

    Energy Technology Data Exchange (ETDEWEB)

    Brockmann, K.; Hanefeld, F. [Dept. of Paediatrics and Neuropaediatrics, Children' s Hospital, Georg-August-Univ., Goettingen (Germany); Finsterbusch, J.; Frahm, J. [Biomedizinische NMR Forschungs GmbH am Max-Planck-Inst. fuer biophysikalische Chemie, Goettingen (Germany); Terwey, B. [Inst. fuer Magnet-Resonanz-Diagnostik, Zentralkrankenhaus, Bremen (Germany)

    2003-03-01

    A 37-year-old macrocephalic woman was investigated for increasing gait disturbance due to longstanding spasticity and ataxia. MRI showed widespread bilateral increase in signal from cerebral white matter on T2-weighted images. Numerous subcortical cysts were visible in anterior-temporal and parietal regions. These clinical and neuroradiological features are those of megalencephalic leukoencephalopathy with subcortical cysts (MLC), a recently delineated white-matter disease with onset in childhood. Quantitative localised proton MR spectroscopy of white matter revealed marked reduction of N-acetylaspartate, creatine, and choline with normal values for myoinositol, consistent with axonal loss and astrocytic proliferation. Diffusion tensor imaging showed an increased apparent diffusion coefficient and reduced anisotropy in affected white matter pointing to reduced cell density with an increased extracellular space. These findings are in line with histological changes alterations known to occur in MLC. (orig.)

  20. Expanded functional coupling of subcortical nuclei with the motor resting-state network in multiple sclerosis

    DEFF Research Database (Denmark)

    Dogonowski, Anne-Marie; Siebner, Hartwig R; Sørensen, Per Soelberg

    2013-01-01

    BACKGROUND: Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortical connections, affecting functional integration within the motor network. Functional magnetic resonance imaging (fMRI) during motor tasks has revealed altered functional connectivity in MS...... controls underwent a 20-minute resting-state fMRI session at 3 Tesla. Independent component analysis was applied to the fMRI data to identify disease-related changes in motor resting-state connectivity. RESULTS: Patients with MS showed a spatial expansion of motor resting-state connectivity in deep...... subcortical nuclei but not at the cortical level. The anterior and middle parts of the putamen, adjacent globus pallidus, anterior and posterior thalamus and the subthalamic region showed stronger functional connectivity with the motor network in the MS group compared with controls. CONCLUSION: MS...

  1. "Venous congestion" as a cause of subcortical white matter T2 hypointensity on magnetic resonance images

    Directory of Open Access Journals (Sweden)

    Jayaprakash Harsha Kamble

    2016-01-01

    Full Text Available Subcortical T2 hypointensity is an uncommon finding seen in very limited conditions such as multiple sclerosis, Sturge-Weber syndrome, and meningitis. Some of the conditions such as moyamoya disease, severe ischemic-anoxic insults, early cortical ischemia, and infarcts are of "arterial origin." We describe two conditions in which "venous congestion" plays a major role in T2 hypointensity - cerebral venous sinus thrombosis (CVST and dural arteriovenous fistula (dAVF. The third case is a case of meningitis, showing T2 hypointensity as well, and can be explained by the "venous congestion" hypothesis. The same hypothesis can explain few of the other conditions causing subcortical T2 hypointensity.

  2. Cortical and subcortical vascular hypointensity on T2* weighted imaging in moyamoya disease.

    Science.gov (United States)

    Noshiro, Shouhei; Mikami, Takeshi; Komatsu, Katsuya; Miyata, Kei; Akiyama, Yukinori; Wanibuchi, Masahiko; Mikuni, Nobuhiro

    2016-02-01

    Decreased cortical and subcortical vascular signals in gradient echo T2* weighted imaging have been reported in acute stroke due to major artery occlusion. The purpose of this study was to evaluate this cortical and subcortical vascular hypointensity (CSVH) in patients with moyamoya disease. Subjects were 20 consecutive patients with moyamoya disease. The numbers of CSVH in each hemisphere were counted and the numbers were compared between patients with moyamoya disease and controls. The distribution of CSVH, clinical features of cases exhibiting large numbers of CSVH and post-operative changes were analysed. Patients with moyamoya disease had significantly more CSVH in the middle cerebral artery territory (p moyamoya disease. Our small series study shows that revascularization surgery can decrease the number of CSVH.

  3. Association between exercise habits and subcortical gray matter volumes in healthy elderly people: A population-based study in Japan

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    Mikie Yamamoto

    2017-06-01

    Conclusion: Subjects with exercise habits show larger subcortical gray matter volumes than subjects without exercise habits in community-dwelling elderly subjects in Japan. Specifically, the volume of the nucleus accumbens correlates with both exercise habits and cognitive preservation.

  4. Structure of Ca2+-binding protein-6 from Entamoeba histolytica and its involvement in trophozoite proliferation regulation.

    Science.gov (United States)

    Verma, Deepshikha; Murmu, Aruna; Gourinath, Samudrala; Bhattacharya, Alok; Chary, Kandala V R

    2017-05-01

    Cell cycle of Entamoeba histolytica, the etiological agent of amoebiasis, follows a novel pathway, which includes nuclear division without the nuclear membrane disassembly. We report a nuclear localized Ca2+-binding protein from E. histolytica (abbreviated hereafter as EhCaBP6), which is associated with microtubules. We determined the 3D solution NMR structure of EhCaBP6, and identified one unusual, one canonical and two non-canonical cryptic EF-hand motifs. The cryptic EF-II and EF-IV pair with the Ca2+-binding EF-I and EF-III, respectively, to form a two-domain structure similar to Calmodulin and Centrin proteins. Downregulation of EhCaBP6 affects cell proliferation by causing delays in transition from G1 to S phase, and inhibition of DNA synthesis and cytokinesis. We also demonstrate that EhCaBP6 modulates microtubule dynamics by increasing the rate of tubulin polymerization. Our results, including structural inferences, suggest that EhCaBP6 is an unusual CaBP involved in regulating cell proliferation in E. histolytica similar to nuclear Calmodulin.

  5. Cortical and subcortical predictive dynamics and learning during perception, cognition, emotion and action

    Science.gov (United States)

    Grossberg, Stephen

    2009-01-01

    An intimate link exists between the predictive and learning processes in the brain. Perceptual/cognitive and spatial/motor processes use complementary predictive mechanisms to learn, recognize, attend and plan about objects in the world, determine their current value, and act upon them. Recent neural models clarify these mechanisms and how they interact in cortical and subcortical brain regions. The present paper reviews and synthesizes data and models of these processes, and outlines a unified theory of predictive brain processing. PMID:19528003

  6. The Effects of Modified Constraint-Induced Movement Therapy in Acute Subcortical Cerebral Infarction

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    Changshen Yu

    2017-05-01

    Full Text Available Background: Constraint-induced movement therapy (CIMT promotes upper extremity recovery post stroke, however, it is difficult to implement clinically due to its high resource demand and safety of the restraint. Therefore, we propose that modified CIMT (mCIMT be used to treat individuals with acute subcortical infarction.Objective: To evaluate the therapeutic effects of mCIMT in patients with acute subcortical infarction, and investigate the possible mechanisms underlying the effect.Methods: The role of mCIMT was investigated in 26 individuals experiencing subcortical infarction in the preceding 14 days. Patients were randomly assigned to either mCIMT or standard therapy. mCIMT group was treated daily for 3 h over 10 consecutive working days, using a mitt on the unaffected arm for up to 30% of waking hours. The control group was treated with an equal dose of occupational therapy and physical therapy. During the 3-month follow-up, the motor functions of the affected limb were assessed by the Wolf Motor Function Test (WMFT and Motor Activity Log (MAL. Altered cortical excitability was assessed via transcranial magnetic stimulation (TMS.Results: Treatment significantly improved the movement in the mCIMT group compared with the control group. The mean WMF score was significantly higher in the mCIMT group compared with the control group. Further, the appearance of motor-evoked potentials (MEPs were significantly higher in the mCIMT group compared with the baseline data. A significant change in ipsilesional silent period (SP occurred in the mCIMT group compared with the control group. However, we found no difference between two groups in motor function or electrophysiological parameters after 3 months of follow-up.Conclusions: mCIMT resulted in significant functional changes in timed movement immediately following treatment in patients with acute subcortical infarction. Further, early mCIMT improved ipsilesional cortical excitability. However, no long

  7. Hearing it again and again: on-line subcortical plasticity in humans.

    Directory of Open Access Journals (Sweden)

    Erika Skoe

    2010-10-01

    Full Text Available Human brainstem activity is sensitive to local sound statistics, as reflected in an enhanced response in repetitive compared to pseudo-random stimulus conditions [1]. Here we probed the short-term time course of this enhancement using a paradigm that assessed how the local sound statistics (i.e., repetition within a five-note melody interact with more global statistics (i.e., repetition of the melody.To test the hypothesis that subcortical repetition enhancement builds over time, we recorded auditory brainstem responses in young adults to a five-note melody containing a repeated note, and monitored how the response changed over the course of 1.5 hrs. By comparing response amplitudes over time, we found a robust time-dependent enhancement to the locally repeating note that was superimposed on a weaker enhancement of the globally repeating pattern.We provide the first demonstration of on-line subcortical plasticity in humans. This complements previous findings that experience-dependent subcortical plasticity can occur on a number of time scales, including life-long experiences with music and language, and short-term auditory training. Our results suggest that the incoming stimulus stream is constantly being monitored, even when the stimulus is physically invariant and attention is directed elsewhere, to augment the neural response to the most statistically salient features of the ongoing stimulus stream. These real-time transformations, which may subserve humans' strong disposition for grouping auditory objects, likely reflect a mix of local processes and corticofugal modulation arising from statistical regularities and the influences of expectation. Our results contribute to our understanding of the biological basis of statistical learning and initiate a new investigational approach relating to the time-course of subcortical plasticity. Although the reported time-dependent enhancements are believed to reflect universal neurophysiological

  8. The role of frontal-subcortical circuits in the development of obsessive-compulsive disorders

    OpenAIRE

    M. A. Kutlubaev

    2016-01-01

    The paper presents a concise review of investigations into the role of impaired frontal-subcortical circuits in the development of obsessive-compulsive disorder (OCD). It gives data on the frequency of neurosis-like symptoms of the OCD spectrum in neurological diseases.The development of OCD is associated with an imbalance between the activity of the direct (activating) and indirect (inhibitory) pathways of the cortico-striatal-thalamo-cortical feedback loop. These data are confirmed by the r...

  9. Subcortical volumes differ in Parkinson's disease motor subtypes: New insights into the pathophysiology of disparate symptoms

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    Keren Rosenberg-Katz

    2016-07-01

    Full Text Available Objectives: Patients with Parkinson’s disease (PD can be classified, based on their motor symptoms, into the Postural Instability Gait Difficulty (PIGD subtype or the Tremor Dominant (TD subtype. Gray matter changes between the subtypes have been reported using whole brain Voxel-Based Morphometry, however, the evaluation of subcortical gray matter volumetric differences between these subtypes using automated volumetric analysis has only been studied in relatively small sample sizes and needs further study to confirm that the negative findings were not due to the sample size. Therefore, we aim to evaluate volumetric changes in subcortical regions and their association with PD motor subtypes. Methods: Automated volumetric MRI analysis quantified the subcortical gray matter volumes of patients with PD in the PIGD subtype (n=30, in the TD subtype (n=30, and in 28 healthy controls. Results: Significantly lower amygdala and globus pallidus gray matter volume was detected in the PIGD, as compared to the TD subtype, with a trend for an association between globus pallidus degeneration and higher (worse PIGD scores. Furthermore, among all the patients with PD, higher hippocampal volumes were correlated with a higher (better dual tasking gait speed (r=0.30, p<0.002 and with a higher global cognitive score (r=0.36, p<0.0001. Lower putamen volume was correlated (r=-0.28, p<0.004 with higher (worse freezing of gait score, an episodic symptom which is common among the PIGD subtype. As expected, differences detected between healthy controls and patients in the PD subgroups included regions within the amygdala and the dorsal striatum but not the ventral striatum, a brain region that is generally considered to be more preserved in PD.Conclusions: The disparate patterns of subcortical degeneration can explain some of the differences in symptoms between the PD subtypes such as gait disturbances and cognitive functions. These findings may, in the future, help to

  10. Mutation screening in a cohort of patients with lissencephaly and subcortical band heterotopia.

    Science.gov (United States)

    Torres, F R; Montenegro, M A; Marques-De-Faria, A P; Guerreiro, M M; Cendes, F; Lopes-Cendes, I

    2004-03-09

    The authors describe clinical, neuroimaging and molecular findings in a group of 15 patients with classic lissencephaly (LIS) and subcortical band heterotopia (SBH). A 1385A-->C mutation was found in the LIS1 gene in one patient with LIS more severe than expected for individuals with missense mutations in LIS1. The authors believe that the site of the mutation, present in a functionally critical region of the protein, could explain the unusual severe phenotype found in this patient.

  11. Mutation screening in a cohort of patients with lissencephaly and subcortical band heterotopia

    OpenAIRE

    Torres, FR; Montenegro, MA; Marques-de-Faria, AP; Guerreiro, MM; Cendes, F.; Lopes-Cendes, I

    2004-01-01

    The authors describe clinical, neuroimaging and molecular findings in a group of 15 patients with classic lissencephaly ( LIS) and subcortical band heterotopia (SBH). A 1385A-->C mutation was found in the LIS1 gene in one patient with LIS more severe than expected for individuals with missense mutations in LIS1. The authors believe that the site of the mutation, present in a functionally critical region of the protein, could explain the unusual severe phenotype found in this patient.

  12. Disturbances in the positioning, proliferation, and apoptosis of neural progenitors contribute to subcortical band heterotopia formation

    OpenAIRE

    Fitzgerald, MP; Covio, M; Lee, KS

    2010-01-01

    Cortical malformations are commonly associated with intractable epilepsy and other developmental disorders. Our studies utilize the tish rat, a spontaneously occurring genetic model of subcortical band heterotopia (SBH) associated with epilepsy, to evaluate the developmental events underlying SBH formation in the neocortex. Our results demonstrate that Pax6+ and Tbr2+ progenitors are mislocalized in tish+/− and tish−/− neocortex throughout neurogenesis. In addition, mislocalized tish−/− proge...

  13. Males with epilepsy, complete subcortical band heterotopia, and somatic mosaicism for DCX.

    Science.gov (United States)

    Poolos, N P; Das, S; Clark, G D; Lardizabal, D; Noebels, J L; Wyllie, E; Dobyns, W B

    2002-05-28

    Subcortical band heterotopia (SBH) is seen predominantly in females, resulting from mutations in the X-linked doublecortin (DCX) gene, and can present with mild mental retardation and epilepsy. Males carrying DCX mutations usually demonstrate lissencephaly and are clinically much more severely affected. This article reports two cases of males with SBH indistinguishable from the female phenotype, both resulting from somatic mosaicism for DCX mutation.

  14. Evaluation of FDG-PET and ECD-SPECT in patients with subcortical band heterotopia.

    Science.gov (United States)

    Ito, Kimiteru; Nakata, Yasuhiro; Matsuda, Hiroshi; Sugai, Kenji; Watanabe, Masako; Kamiya, Kouhei; Kimura, Yukio; Shigemoto, Yoko; Okazaki, Mitsutoshi; Sasaki, Masayuki; Sato, Noriko

    2014-08-01

    The purpose of this retrospective study was to clarify the cellular activities of ectopic neurons in subcortical bands and to evaluate the imaging features of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and (99m)Tc ethyl cysteinate dimer (ECD) single-photon emission computed tomography (SPECT) in a series of patients with subcortical band heterotopia (SBH). The cases of 12 patients with SBH (3 men and 9 women; age range, 2-51 years) were evaluated on the basis of their MRI findings. Eight (18)F-FDG PET and 12 (99m)Tc-ECD SPECT images were obtained. The uptakes of these images were compared with electroencephalography (EEG) or MRI findings such as band thickness. In all patients, easy Z-score Imaging System (eZIS) software was used to statistically analyze the SPECT images. Of the eight (18)F-FDG PET images, five showed higher uptake in the thick subcortical bands than in the overlying cortex. Of the 12 (99m)Tc-ECD SPECT examinations with eZIS images, nine indicated increased regional cerebral blood flow (rCBF) areas corresponding to the band locations. Of the eight (18)F-FDG PET examination findings, six were congruent with the rCBF distributions on the eZIS images. Eight of the 12 patients showed correspondence to the increased rCBF on the eZIS images, the band locations on MRI, and abnormal discharge sites on EEG. Ectopic neurons in subcortical bands may have higher glucose metabolism and/or increased rCBF compared to the overlying cortex. (18)F-FDG PET and (99m)Tc-ECD SPECT using eZIS can be helpful to clearly detect the cellular activities of ectopic neurons in patients with SBH. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  15. Modeling the Effect of Olivocochlear Efferents on the Subcortical Envelope Following Response in Humans

    Science.gov (United States)

    2016-11-28

    Title: Modeling the Effect of Olivocochlear Efferents on the Subcortical Envelope Following Response in Humans Christopher J. Smalt*, Michael G...added some of the dynamic characteristics of the MOCR with the more recent “ humanized ” version (Zilany, et al., 2014). This effect of the model is to...effectively reduce the outer hair cell gain, depending on the stimulus frequency, level, and timing. Human Envelope Following Responses (EFRs

  16. Focal Cortical and Subcortical Atrophy in Early Parkinson’s Disease

    OpenAIRE

    Tinaz, Sule; Courtney, Maureen G.; Stern, Chantal E.; Phil, D.

    2010-01-01

    Neurodegeneration in clinically manifest Parkinson’s disease affects the substantia nigra pars compacta, and gradually spreads to the limbic cortices and the neocortex. We used MRI imaging coupled with automated surface reconstruction and segmentation methods to examine cortical thickness and subcortical volumes in nondemented, early-stage Parkinson’s disease patients compared to matched healthy control participants. These methods, which have been previously used to document cortical thicknes...

  17. The Association Between Specific Substances of Abuse and Subcortical Intracerebral Hemorrhage versus Ischemic Lacunar Infarction

    Directory of Open Access Journals (Sweden)

    Emma H Kaplan

    2014-09-01

    Full Text Available Background: Hypertension damages small vessels, resulting in both lacunar infarction and subcortical intracerebral hemorrhage (ICH. Substance abuse has also been linked to small vessel pathology. This study explores whether the use of specific substances (eg., cocaine, tobacco is associated with subcortical ICH over ischemia in hypertensive individuals.Methods: Patients with hypertension, admitted with lacunar infarcts (measuring 1 drink per day (women, >2 drinks per day (men. Logistic regression was performed with ICH as the dependent variable comparing those presenting with ICH to those presenting with ischemia.Results: Of the 580 patients included in analysis, 217 (37% presented with ICH. The average age was similar between the two groups (64.7 versus 66.3 years. Illicit/controlled drug use was associated with a significantly increased risk of ICH over stroke in unadjusted models (25% versus 15%, p=0.02, with the largest effect seen in users ≥65 years old (not statistically significant. Smoking was associated with ischemia over ICH in a dose-dependent manner: any history of smoking OR 1.84, CI 1.19-2.84; current use OR 2.23, CI 1.37-3.62; heavy use OR 2.48, CI 1.50-4.13. Alcohol use was not preferentially associated with either outcome (p=0.29.Conclusions: In hypertensive patients, tobacco use is associated with an increased risk of subcortical ischemia compared to ICH; while use of illicit/controlled substances appears to be predictive of hemorrhage.

  18. Intra- and interhemispheric variations of diffusivity in subcortical white matter in normal human brain

    Energy Technology Data Exchange (ETDEWEB)

    Yoshiura, Takashi; Noguchi, Tomoyuki; Hiwatashi, Akio; Togao, Osamu; Yamashita, Koji; Nagao, Eiki; Kamano, Hironori; Honda, Hiroshi [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences, Fukuoka (Japan)

    2010-01-15

    Our purpose was to reveal potential regional variations in water molecular diffusivity within each cerebral hemisphere and across the right and left hemispheres. Diffusion-weighted images of 44 healthy right-handed adult male subjects were obtained using a diffusion tensor imaging sequence. Mean diffusivity (MD) values in subcortical white matter (WM) within 39 regions in each hemisphere were measured using an automated method. Intrahemispheric comparisons of MDs in subcortical WM were performed among six brain regions (frontal, parietal, occipital and temporal lobes and pre- and postcentral gyri). Interhemispheric comparisons of MDs were performed between the right and left counterparts of the 39 regions. In both hemispheres, diffusivity in the precentral gyrus was lower than those in other regions, while diffusivity in the parietal lobe was higher than others. MD asymmetry in which the left was lower than the right was found in the parietal lobe, middle occipital gyrus, and medial and orbital aspects of the frontal lobe. The converse asymmetry was revealed in the frontal operculum, supplementary motor cortex, temporal lobe, limbic cortices, precuneus and cuneus. Our results revealed significant intra- and interhemispheric regional variations in MD in subcortical WM, which may be related to different densities of axons and myelin sheaths. (orig.)

  19. [A clinical study of single subcortical cerebral infarction of middle cerebral artery territory].

    Science.gov (United States)

    Yang, L; Yu, L; Qin, W; Zhang, X Y; Li, Y; Xu, J H; Hu, X Z; Yuan, J L; Gu, H; Hu, W L

    2016-10-01

    Objective: To explore the clinical characteristics of single subcortical cerebral infarction of middle cerebral artery (MCA) territory and the possible pathogenesis. Methods: A total of 344 cases diagnosed as single subcortical cerebral infarction of MCA territory were enrolled in the study and divided into the parent artery disease (PAD) group and the non-PAD group according to whether the MCA stenosis was presented or not. A total of 312 cases diagnosed as single subcortical cerebral infarction of MCA territory were divided into the BAD group and the SVD group according to the relationship between the lesion sites and MCA. Differences in the clinical and imaging feature were compared between different groups. Results: A total of 32 patients were in the PAD group. Compared with the non-PAD group, patients in the PAD group were found with higher prevalence of asymptomatic cerebral arterial atherosclerosis [93.8%(30/32) vs 57.1%(178/312), P territory has different etiology and pathogenesis. Evidence of systemic atherosclerosis should be carefully searched in patients with branch atheromatous disease.

  20. Perineuronal nets in subcortical auditory nuclei of four rodent species with differing hearing ranges.

    Science.gov (United States)

    Beebe, Nichole L; Schofield, Brett R

    2017-12-26

    Perineuronal nets (PNs) are aggregates of extracellular matrix molecules that surround some neurons in the brain. While PNs occur widely across many cortical areas, subcortical PNs are especially associated with motor and auditory systems. The auditory system has recently been suggested as an ideal model system for studying PNs and their functions. However, descriptions of PNs in subcortical auditory areas vary, and it is unclear whether the variation reflects species differences or differences in staining techniques. Here, we used two staining techniques (one lectin stain and one antibody stain) to examine PN distribution in the subcortical auditory system of four different species: guinea pigs (Cavia porcellus), mice (Mus musculus, CBA/CaJ strain), Long-Evans rats (Rattus norvegicus), and naked mole-rats (Heterocephalus glaber). We found that some auditory nuclei exhibit dramatic differences in PN distribution among species while other nuclei have consistent PN distributions. We also found that PNs exhibit molecular heterogeneity, and can stain with either marker individually or with both. PNs within a given nucleus can be heterogeneous or homogenous in their staining patterns. We compared PN staining across the frequency axes of tonotopically organized nuclei and among species with different hearing ranges. PNs were distributed non-uniformly across some nuclei, but only rarely did this appear related to the tonotopic axis. PNs were prominent in all four species; we found no systematic relationship between the hearing range and the number, staining patterns or distribution of PNs in the auditory nuclei. © 2017 Wiley Periodicals, Inc.

  1. Low- and high-frequency subcortical SEP amplitude reduction during pure passive movement.

    Science.gov (United States)

    Insola, Angelo; Padua, Luca; Mazzone, Paolo; Valeriani, Massimiliano

    2015-12-01

    To investigate the effect of pure passive movement on both cortical and subcortical somatosensory evoked potentials (SEPs). Median nerve SEPs were recorded in 8 patients suffering from Parkinson's disease (PD) and two patients with essential tremor. PD patients underwent electrode implantation in the subthalamic (STN) nucleus (3 patients) and pedunculopontine (PPTg) nucleus (5 patients), while 2 patients with essential tremor were implanted in the ventral intermediate nucleus (VIM) of the thalamus. In anesthetized patients, SEPs were recorded at rest and during a passive movement of the thumb of the stimulated wrist from the intracranial electrode contacts and from the scalp. Also the high-frequency oscillations (HFOs) were analyzed. Amplitudes of both deep and scalp components were decreased during passive movement, but the reduction was higher at cortical than subcortical level. Also the HFOs were reduced by movement. The different amount of the movement-related decrease suggests that the cortical SEP gating is not only the result of a subcortical somatosensory volley attenuation, but a further mechanism acting at cortical level should be considered. Our results are important for understanding the physiological mechanism of the sensory-motor interaction during passive movement. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Treatment of seizures in subcortical laminar heterotopia with corpus callosotomy and lamotrigine.

    Science.gov (United States)

    Vossler, D G; Lee, J K; Ko, T S

    1999-05-01

    Focal and generalized cortical dysgeneses are sometimes seen on the magnetic resonance images (MRI) of patients with epilepsy. Subcortical laminar heterotopia are bilateral collections of gray matter in the centrum semiovale that resemble a band or "double cortex" on MRI. We studied one male and two female patients with subcortical laminar heterotopia who had moderate to severe developmental delay, early-onset epilepsy, and medically refractory seizures. Atonic, atypical absence, tonic, myoclonic, complex partial, and generalized tonic-clonic seizures were recorded. Interictal and ictal electroencephalographic patterns were generalized and, less commonly, multifocal. Two years after corpus callosotomy, one patient was free of generalized tonic-clonic and atonic seizures, but the other patient who had undergone callosotomy had no significant reduction in seizure frequency. With lamotrigine treatment, the patient who had not had surgery had complete cessation of monthly episodes of status epilepticus and a dramatic reduction of generalized tonic-clonic seizures, and the other patient who received lamotrigine had a 50% reduction of her atonic seizures. In patients with subcortical laminar heterotopia, atonic and generalized tonic-clonic seizures can be substantially reduced or eliminated by corpus callosotomy or treatment with lamotrigine.

  3. Expanded functional coupling of subcortical nuclei with the motor resting-state network in multiple sclerosis.

    Science.gov (United States)

    Dogonowski, Anne-Marie; Siebner, Hartwig R; Sørensen, Per Soelberg; Wu, Xingchen; Biswal, Bharat; Paulson, Olaf B; Dyrby, Tim B; Skimminge, Arnold; Blinkenberg, Morten; Madsen, Kristoffer H

    2013-04-01

    Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortical connections, affecting functional integration within the motor network. Functional magnetic resonance imaging (fMRI) during motor tasks has revealed altered functional connectivity in MS, but it is unclear how much motor disability contributed to these abnormal functional interaction patterns. To avoid any influence of impaired task performance, we examined disease-related changes in functional motor connectivity in MS at rest. A total of 42 patients with MS and 30 matched controls underwent a 20-minute resting-state fMRI session at 3 Tesla. Independent component analysis was applied to the fMRI data to identify disease-related changes in motor resting-state connectivity. Patients with MS showed a spatial expansion of motor resting-state connectivity in deep subcortical nuclei but not at the cortical level. The anterior and middle parts of the putamen, adjacent globus pallidus, anterior and posterior thalamus and the subthalamic region showed stronger functional connectivity with the motor network in the MS group compared with controls. MS is characterised by more widespread motor connectivity in the basal ganglia while cortical motor resting-state connectivity is preserved. The expansion of subcortical motor resting-state connectivity in MS indicates less efficient funnelling of neural processing in the executive motor cortico-basal ganglia-thalamo-cortical loops.

  4. Characterizing Brain Iron Deposition in Patients with Subcortical Vascular Mild Cognitive Impairment Using Quantitative Susceptibility Mapping: A Potential Biomarker

    OpenAIRE

    Sun, Yawen; Ge, Xin; Han, Xu; Cao, Wenwei; Wang, Yao; Ding, Weina; Cao, Mengqiu; Zhang, Yong; Xu, Qun; Zhou, Yan; Xu, Jianrong

    2017-01-01

    The presence and pattern of iron accumulation in subcortical vascular mild cognitive impairment (svMCI) and their effects on cognition have rarely been investigated. We aimed to examine brain iron deposition in svMCI subjects using quantitative susceptibility mapping (QSM). Moreover, we aimed to investigate the correlation between brain iron deposition and the severity of cognitive impairment as indicated by z-scores. We recruited 20 subcortical ischemic vascular disease (SIVD) patients who f...

  5. HDAC up-regulation in early colon field carcinogenesis is involved in cell tumorigenicity through regulation of chromatin structure.

    Science.gov (United States)

    Stypula-Cyrus, Yolanda; Damania, Dhwanil; Kunte, Dhananjay P; Cruz, Mart Dela; Subramanian, Hariharan; Roy, Hemant K; Backman, Vadim

    2013-01-01

    Normal cell function is dependent on the proper maintenance of chromatin structure. Regulation of chromatin structure is controlled by histone modifications that directly influence chromatin architecture and genome function. Specifically, the histone deacetylase (HDAC) family of proteins modulate chromatin compaction and are commonly dysregulated in many tumors, including colorectal cancer (CRC). However, the role of HDAC proteins in early colorectal carcinogenesis has not been previously reported. We found HDAC1, HDAC2, HDAC3, HDAC5, and HDAC7 all to be up-regulated in the field of human CRC. Furthermore, we observed that HDAC2 up-regulation is one of the earliest events in CRC carcinogenesis and observed this in human field carcinogenesis, the azoxymethane-treated rat model, and in more aggressive colon cancer cell lines. The universality of HDAC2 up-regulation suggests that HDAC2 up-regulation is a novel and important early event in CRC, which may serve as a biomarker. HDAC inhibitors (HDACIs) interfere with tumorigenic HDAC activity; however, the precise mechanisms involved in this process remain to be elucidated. We confirmed that HDAC inhibition by valproic acid (VPA) targeted the more aggressive cell line. Using nuclease digestion assays and transmission electron microscopy imaging, we observed that VPA treatment induced greater changes in chromatin structure in the more aggressive cell line. Furthermore, we used the novel imaging technique partial wave spectroscopy (PWS) to quantify nanoscale alterations in chromatin. We noted that the PWS results are consistent with the biological assays, indicating a greater effect of VPA treatment in the more aggressive cell type. Together, these results demonstrate the importance of HDAC activity in early carcinogenic events and the unique role of higher-order chromatin structure in determining cell tumorigenicity.

  6. HDAC up-regulation in early colon field carcinogenesis is involved in cell tumorigenicity through regulation of chromatin structure.

    Directory of Open Access Journals (Sweden)

    Yolanda Stypula-Cyrus

    Full Text Available Normal cell function is dependent on the proper maintenance of chromatin structure. Regulation of chromatin structure is controlled by histone modifications that directly influence chromatin architecture and genome function. Specifically, the histone deacetylase (HDAC family of proteins modulate chromatin compaction and are commonly dysregulated in many tumors, including colorectal cancer (CRC. However, the role of HDAC proteins in early colorectal carcinogenesis has not been previously reported. We found HDAC1, HDAC2, HDAC3, HDAC5, and HDAC7 all to be up-regulated in the field of human CRC. Furthermore, we observed that HDAC2 up-regulation is one of the earliest events in CRC carcinogenesis and observed this in human field carcinogenesis, the azoxymethane-treated rat model, and in more aggressive colon cancer cell lines. The universality of HDAC2 up-regulation suggests that HDAC2 up-regulation is a novel and important early event in CRC, which may serve as a biomarker. HDAC inhibitors (HDACIs interfere with tumorigenic HDAC activity; however, the precise mechanisms involved in this process remain to be elucidated. We confirmed that HDAC inhibition by valproic acid (VPA targeted the more aggressive cell line. Using nuclease digestion assays and transmission electron microscopy imaging, we observed that VPA treatment induced greater changes in chromatin structure in the more aggressive cell line. Furthermore, we used the novel imaging technique partial wave spectroscopy (PWS to quantify nanoscale alterations in chromatin. We noted that the PWS results are consistent with the biological assays, indicating a greater effect of VPA treatment in the more aggressive cell type. Together, these results demonstrate the importance of HDAC activity in early carcinogenic events and the unique role of higher-order chromatin structure in determining cell tumorigenicity.

  7. Prostaglandin E2 receptor expression in the rat trigeminal-vascular system and other brain structures involved in pain

    DEFF Research Database (Denmark)

    Myren, Maja; Olesen, Jes; Gupta, Saurabh

    2012-01-01

    receptors in both peripheral and central structures involved in pain transmission and perception in migraine: dura mater, cerebral arteries, trigeminal ganglion, trigeminal nucleus caudalis, periaqueductal grey, thalamus, hypothalamus, cortex, pituitary gland, hippocampus and cerebellum. In the trigeminal......Prostaglandin E(2) (PGE(2)) is considered to be a key mediator in migraine pathophysiology. PGE(2) acts via four receptors (EP(1)-EP(4)) but their distribution in the brain districts implicated in migraine has yet to be delineated. We quantified amount of mRNA and protein expression for the EP...... than in dorsal root ganglia (peripheral control), whereas the EP(2) mRNA and protein were highly abundant in the pituitary gland. EP(3) mRNA was mainly found in thalamus and hypothalamus. The most robust mRNA and protein expression for EP(4) receptor was seen in the dorsal root ganglion. In conclusion...

  8. Lectin Staining Shows no Evidence of Involvement of Glycocalyx/Mucous Layer Carbohydrate Structures in Development of Celiac Disease

    Directory of Open Access Journals (Sweden)

    Henrik Toft-Hansen

    2013-11-01

    Full Text Available The presence of unique carbohydrate structures in the glycocalyx/mucous layer of the intestine may be involved in a susceptibility to celiac disease (CD by serving as attachment sites for bacteria. This host-microbiota interaction may influence the development of CD and possibly other diseases with autoimmune components. We examined duodenal biopsies from a total of 30 children, of which 10 had both celiac disease (CD and type 1 diabetes (T1D; 10 had CD alone; and 10 were suspected of having gastrointestinal disease, but had normal duodenal histology (non-CD controls. Patients with both CD and T1D were examined before and after remission following a gluten-free diet. We performed lectin histochemistry using peanut agglutinin (PNA and Ulex europaeus agglutinin (UEA staining for Gal-β(1,3-GalNAc and Fucα1-2Gal-R, respectively, of the glycocalyx/mucous layer. The staining was scored based on dissemination of stained structures on a scale from 0 to 3. Evaluation of the scores revealed no difference between biopsies obtained before and after remission in the group of children with both CD and T1D. A comparison of this pre-remission group with the children who had CD alone or the non-CD controls also showed no significant differences. Based on our material, we found no indication that the presence of Gal-β(1,3-GalNAc or Fucα1-2Gal-R is involved in the susceptibility to CD, or that the disease process affects the expression of these carbohydrates.

  9. Lectin Staining Shows no Evidence of Involvement of Glycocalyx/Mucous Layer Carbohydrate Structures in Development of Celiac Disease

    Science.gov (United States)

    Toft-Hansen, Henrik; Nielsen, Christian; Biagini, Matteo; Husby, Steffen; Lillevang, Søren T.

    2013-01-01

    The presence of unique carbohydrate structures in the glycocalyx/mucous layer of the intestine may be involved in a susceptibility to celiac disease (CD) by serving as attachment sites for bacteria. This host-microbiota interaction may influence the development of CD and possibly other diseases with autoimmune components. We examined duodenal biopsies from a total of 30 children, of which 10 had both celiac disease (CD) and type 1 diabetes (T1D); 10 had CD alone; and 10 were suspected of having gastrointestinal disease, but had normal duodenal histology (non-CD controls). Patients with both CD and T1D were examined before and after remission following a gluten-free diet. We performed lectin histochemistry using peanut agglutinin (PNA) and Ulex europaeus agglutinin (UEA) staining for Gal-β(1,3)-GalNAc and Fucα1-2Gal-R, respectively, of the glycocalyx/mucous layer. The staining was scored based on dissemination of stained structures on a scale from 0 to 3. Evaluation of the scores revealed no difference between biopsies obtained before and after remission in the group of children with both CD and T1D. A comparison of this pre-remission group with the children who had CD alone or the non-CD controls also showed no significant differences. Based on our material, we found no indication that the presence of Gal-β(1,3)-GalNAc or Fucα1-2Gal-R is involved in the susceptibility to CD, or that the disease process affects the expression of these carbohydrates. PMID:24253051

  10. Advocacy coalitions involved in California's menu labeling policy debate: Exploring coalition structure, policy beliefs, resources, and strategies.

    Science.gov (United States)

    Payán, Denise D; Lewis, LaVonna B; Cousineau, Michael R; Nichol, Michael B

    2017-03-01

    Advocacy coalitions often play an important role in the state health policymaking process, yet little is known about their structure, composition, and behavior. In 2008, California became the first state to enact a menu labeling law. Using the advocacy coalition framework, we examine different facets of the coalitions involved in California's menu labeling policy debate. We use a qualitative research approach to identify coalition members and explore their expressed beliefs and policy arguments, resources, and strategies by analyzing legislative documents (n = 87) and newspaper articles (n = 78) produced between 1999 and 2009. Between 2003 and 2008, six menu labeling bills were introduced in the state's legislature. We found the issue received increasing media attention during this period. We identified two advocacy coalitions involved in the debate-a public health (PH) coalition and an industry coalition. State organizations acted as coalition leaders and participated for a longer duration than elected officials. The structure and composition of each coalition varied. PH coalition leadership and membership notably increased compared to the industry coalition. The PH coalition, led by nonprofit PH and health organizations, promoted a clear and consistent message around informed decision making. The industry coalition, led by a state restaurant association, responded with cost and implementation arguments. Each coalition used various resources and strategies to advance desired outcomes. PH coalition leaders were particularly effective at using resources and employing advocacy strategies, which included engaging state legislators as coalition members, using public opinion polls and information, and leveraging media resources to garner support. Policy precedence and a local policy push emerged as important policymaking strategies. Areas for future research on the state health policymaking process are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Matrix architecture dictates three-dimensional migration modes of human macrophages: differential involvement of proteases and podosome-like structures.

    Science.gov (United States)

    Van Goethem, Emeline; Poincloux, Renaud; Gauffre, Fabienne; Maridonneau-Parini, Isabelle; Le Cabec, Véronique

    2010-01-15

    Tissue infiltration of macrophages, although critical for innate immunity, is also involved in pathologies, such as chronic inflammation and cancer. In vivo, macrophages migrate mostly in a constrained three-dimensional (3D) environment. However, in vitro studies, mainly focused on two dimensions, do not provide meaningful clues about the mechanisms involved in 3D macrophage migration. In contrast, tumor cell 3D migration is well documented. It comprises a protease-independent and Rho kinase (ROCK)-dependent amoeboid migration mode and a protease-dependent and ROCK-independent mesenchymal migration mode. In this study, we examined the influence of extracellular matrix (composition, architecture, and stiffness) on 3D migration of human macrophages derived from blood monocytes (MDMs). We show that: 1) MDMs use either the amoeboid migration mode in fibrillar collagen I or the mesenchymal migration mode in Matrigel and gelled collagen I, whereas HT1080 tumor cells only perform mesenchymal migration; 2) when MDMs use the mesenchymal migratory mode, they form 3D collagenolytic structures at the tips of cell protrusions that share several markers with podosomes as described in two dimensions; 3) in contrast to tumor cells, matrix metalloproteinase inhibitors do not impair protease-dependent macrophage 3D migration, suggesting the involvement of other proteolytic systems; and 4) MDMs infiltrating matrices of similar composition but with variable stiffness adapt their migration mode primarily to the matrix architecture. In conclusion, although it is admitted that leukocytes 3D migration is restricted to the amoeboid mode, we show that human macrophages also perform the mesenchymal mode but in a distinct manner than tumor cells, and they naturally adapt their migration mode to the environmental constraints.

  12. Structure of the Response Regulator NsrR from Streptococcus agalactiae, Which Is Involved in Lantibiotic Resistance.

    Directory of Open Access Journals (Sweden)

    Sakshi Khosa

    Full Text Available Lantibiotics are antimicrobial peptides produced by Gram-positive bacteria. Interestingly, several clinically relevant and human pathogenic strains are inherently resistant towards lantibiotics. The expression of the genes responsible for lantibiotic resistance is regulated by a specific two-component system consisting of a histidine kinase and a response regulator. Here, we focused on a response regulator involved in lantibiotic resistance, NsrR from Streptococcus agalactiae, and determined the crystal structures of its N-terminal receiver domain and C-terminal DNA-binding effector domain. The C-terminal domain exhibits a fold that classifies NsrR as a member of the OmpR/PhoB subfamily of regulators. Amino acids involved in phosphorylation, dimerization, and DNA-binding were identified and demonstrated to be conserved in lantibiotic resistance regulators. Finally, a model of the full-length NsrR in the active and inactive state provides insights into protein dimerization and DNA-binding.

  13. The Crystal Structure and Mechanism of an Unusual Oxidoreductase, GilR, Involved in Gilvocarcin V Biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Noinaj, Nicholas; Bosserman, Mary A.; Schickli, M. Alexandra; Piszczek, Grzegorz; Kharel, Madan K.; Pahari, Pallab; Buchanan, Susan K.; Rohr, Jürgen (NIH); (Kentucky)

    2012-11-26

    GilR is a recently identified oxidoreductase that catalyzes the terminal step of gilvocarcin V biosynthesis and is a unique enzyme that establishes the lactone core of the polyketide-derived gilvocarcin chromophore. Gilvocarcin-type compounds form a small distinct family of anticancer agents that are involved in both photo-activated DNA-alkylation and histone H3 cross-linking. High resolution crystal structures of apoGilR and GilR in complex with its substrate pregilvocarcin V reveals that GilR belongs to the small group of a relatively new type of the vanillyl-alcohol oxidase flavoprotein family characterized by bicovalently tethered cofactors. GilR was found as a dimer, with the bicovalently attached FAD cofactor mediated through His-65 and Cys-125. Subsequent mutagenesis and functional assays indicate that Tyr-445 may be involved in reaction catalysis and in mediating the covalent attachment of FAD, whereas Tyr-448 serves as an essential residue initiating the catalysis by swinging away from the active site to accommodate binding of the 6R-configured substrate and consequently abstracting the proton of the hydroxyl residue of the substrate hemiacetal 6-OH group. These studies lay the groundwork for future enzyme engineering to broaden the substrate specificity of this bottleneck enzyme of the gilvocarcin biosynthetic pathway for the development of novel anti-cancer therapeutics.

  14. Transcortical sensory aphasia due to a left frontal subcortical haemorrhage.

    Science.gov (United States)

    Maeshima, S; Kuwata, T; Masuo, O; Yamaga, H; Okita, R; Ozaki, F; Moriwaki, H; Roger, P

    1999-11-01

    A case of transcortical sensory aphasia caused by a cerebral haemorrhage in the left frontal lobe is presented. A 72-year-old right-handed woman was admitted to the hospital, with a history of acute onset of speech disturbance and headache. On initial assessment, her spontaneous speech was fluent. She had no difficulty initiating speech, articulated normally, and did not exhibit logorrhea. Her ability to repeat phonemes and short sentences (5-6 words) was fully preserved, however she had severe difficulty with visual recognition of words, and with aural comprehension at the word level, although she was able to read words aloud. Computed tomography and magnetic resonance imaging showed cerebral haemorrhage in the left frontal lobe, involving the superior and middle frontal gyrus. Single photon emission CT revealed a wider area of low perfusion over the entire left frontal lobe, including the superior, middle and inferior frontal gyrus. The aphasia symptoms, mainly poor comprehension, disappeared quickly several weeks after the event. This may have been due to a reduction in the size of the haematoma and a resolution of the oedema around the haematoma. Clinically, the transcortical sensory aphasia in this case was indistinguishable from that caused by damage to the posterior language areas. Further case reports of transcortical sensory aphasia associated with frontal lobe lesions would help to confirm whether a relatively rapid recovery is characteristic in cases such as this.

  15. Crystal structure of human importin-α1 (Rch1, revealing a potential autoinhibition mode involving homodimerization.

    Directory of Open Access Journals (Sweden)

    Hideyuki Miyatake

    Full Text Available In this study, we determined the crystal structure of N-terminal importin-β-binding domain (IBB-truncated human importin-α1 (ΔIBB-h-importin-α1 at 2.63 Å resolution. The crystal structure of ΔIBB-h-importin-α1 reveals a novel closed homodimer. The homodimer exists in an autoinhibited state in which both the major and minor nuclear localization signal (NLS binding sites are completely buried in the homodimerization interface, an arrangement that restricts NLS binding. Analytical ultracentrifugation studies revealed that ΔIBB-h-importin-α1 is in equilibrium between monomers and dimers and that NLS peptides shifted the equilibrium toward the monomer side. This finding suggests that the NLS binding sites are also involved in the dimer interface in solution. These results show that when the IBB domain dissociates from the internal NLS binding sites, e.g., by binding to importin-β, homodimerization possibly occurs as an autoinhibition state.

  16. Joint assessment of white matter integrity, cortical and subcortical atrophy to distinguish AD from behavioral variant FTD: A two-center study

    Directory of Open Access Journals (Sweden)

    Christiane Möller

    2015-01-01

    Full Text Available We investigated the ability of cortical and subcortical gray matter (GM atrophy in combination with white matter (WM integrity to distinguish behavioral variant frontotemporal dementia (bvFTD from Alzheimer's disease (AD and from controls using voxel-based morphometry, subcortical structure segmentation, and tract-based spatial statistics. To determine which combination of MR markers differentiated the three groups with the highest accuracy, we conducted discriminant function analyses. Adjusted for age, sex and center, both types of dementia had more GM atrophy, lower fractional anisotropy (FA and higher mean (MD, axial (L1 and radial diffusivity (L23 values than controls. BvFTD patients had more GM atrophy in orbitofrontal and inferior frontal areas than AD patients. In addition, caudate nucleus and nucleus accumbens were smaller in bvFTD than in AD. FA values were lower; MD, L1 and L23 values were higher, especially in frontal areas of the brain for bvFTD compared to AD patients. The combination of cortical GM, hippocampal volume and WM integrity measurements, classified 97–100% of controls, 81–100% of AD and 67–75% of bvFTD patients correctly. Our results suggest that WM integrity measures add complementary information to measures of GM atrophy, thereby improving the classification between AD and bvFTD.

  17. Evidence for a role of a cortico-subcortical network for automatic and unconscious motor inhibition of manual responses.

    Directory of Open Access Journals (Sweden)

    Kevin D'Ostilio

    Full Text Available It is now clear that non-consciously perceived stimuli can bias our decisions. Although previous researches highlighted the importance of automatic and unconscious processes involved in voluntary action, the neural correlates of such processes remain unclear. Basal ganglia dysfunctions have long been associated with impairment in automatic motor control. In addition, a key role of the medial frontal cortex has been suggested by administrating a subliminal masked prime task to a patient with a small lesion restricted to the supplementary motor area (SMA. In this task, invisible masked arrows stimuli were followed by visible arrow targets for a left or right hand response at different interstimuli intervals (ISI, producing a traditional facilitation effect for compatible trials at short ISI and a reversal inhibitory effect at longer ISI. Here, by using fast event-related fMRI and a weighted parametric analysis, we showed BOLD related activity changes in a cortico-subcortical network, especially in the SMA and the striatum, directly linked to the individual behavioral pattern. This new imaging result corroborates previous works on subliminal priming using lesional approaches. This finding implies that one of the roles of these regions was to suppress a partially activated movement below the threshold of awareness.

  18. The contribution of brain sub-cortical loops in the expression and acquisition of action understanding abilities☆

    Science.gov (United States)

    Caligiore, Daniele; Pezzulo, Giovanni; Miall, R. Chris; Baldassarre, Gianluca

    2013-01-01

    Research on action understanding in cognitive neuroscience has led to the identification of a wide “action understanding network” mainly encompassing parietal and premotor cortical areas. Within this cortical network mirror neurons are critically involved implementing a neural mechanism according to which, during action understanding, observed actions are reflected in the motor patterns for the same actions of the observer. We suggest that focusing only on cortical areas and processes could be too restrictive to explain important facets of action understanding regarding, for example, the influence of the observer's motor experience, the multiple levels at which an observed action can be understood, and the acquisition of action understanding ability. In this respect, we propose that aside from the cortical action understanding network, sub-cortical processes pivoting on cerebellar and basal ganglia cortical loops could crucially support both the expression and the acquisition of action understanding abilities. Within the paper we will discuss how this extended view can overcome some limitations of the “pure” cortical perspective, supporting new theoretical predictions on the brain mechanisms underlying action understanding that could be tested by future empirical investigations. PMID:23911926

  19. Involvement and structure: a qualitative study of organizational change and sickness absence among women in the public sector in Sweden.

    Science.gov (United States)

    Baltzer, Maria; Westerlund, Hugo; Backhans, Mona; Melinder, Karin

    2011-05-16

    Organizational changes in modern corporate life have become increasingly common and there are indications that they often fail to achieve their ends. An earlier study of 24,036 employees showed that those who had repeatedly been exposed to large increases in staffing during 1991-1996 had an excess risk of both long-term sickness absence and hospital admission during 1997-1999, while moderate expansion appeared to be protective. The former was most salient among female public sector employees. We used qualitative interviews to explore work environment factors underlying the impact of organizational changes (moderate and large expansions in staffing) on sickness absence from an employee perspective. We interviewed 21 strategically selected women from the earlier study using semi-structured telephone interviews focusing on working conditions during the organizational changes. We identified 22 themes which could explain the association between organizational changes and sickness absence. We then used Qualitative Comparative Analysis (QCA) to reduce the number of themes and discover patterns of possible causation. The themes that most readily explained the outcomes were Well Planned Process of Change (a clear structure for involvement of the employees in the changes), Agent of Change (an active role in the implementation of the changes), Unregulated Work (a lack of clear limits and guidelines regarding work tasks from the management and among the employees), and Humiliating Position (feelings of low status or of not being wanted at the workplace), which had been salient throughout the analytic process, in combination with Multiple Contexts (working in several teams in parallel) and Already Ill (having already had a debilitating illness at the beginning of 1991), which may indicate degree of individual exposure and vulnerability. Well Planned Process of Change, Agent of Change and Multiple Contexts are themes that were associated with low sickness absence. Unregulated

  20. Involvement and structure: A qualitative study of organizational change and sickness absence among women in the public sector in Sweden

    Directory of Open Access Journals (Sweden)

    Backhans Mona

    2011-05-01

    Full Text Available Abstract Background Organizational changes in modern corporate life have become increasingly common and there are indications that they often fail to achieve their ends. An earlier study of 24,036 employees showed that those who had repeatedly been exposed to large increases in staffing during 1991-1996 had an excess risk of both long-term sickness absence and hospital admission during 1997-1999, while moderate expansion appeared to be protective. The former was most salient among female public sector employees. We used qualitative interviews to explore work environment factors underlying the impact of organizational changes (moderate and large expansions in staffing on sickness absence from an employee perspective. Method We interviewed 21 strategically selected women from the earlier study using semi-structured telephone interviews focusing on working conditions during the organizational changes. We identified 22 themes which could explain the association between organizational changes and sickness absence. We then used Qualitative Comparative Analysis (QCA to reduce the number of themes and discover patterns of possible causation. Results The themes that most readily explained the outcomes were Well Planned Process of Change (a clear structure for involvement of the employees in the changes, Agent of Change (an active role in the implementation of the changes, Unregulated Work (a lack of clear limits and guidelines regarding work tasks from the management and among the employees, and Humiliating Position (feelings of low status or of not being wanted at the workplace, which had been salient throughout the analytic process, in combination with Multiple Contexts (working in several teams in parallel and Already Ill (having already had a debilitating illness at the beginning of 1991, which may indicate degree of individual exposure and vulnerability. Well Planned Process of Change, Agent of Change and Multiple Contexts are themes that were

  1. Crystal structure of the (R)-specific enoyl-CoA hydratase from Aeromonas caviae involved in polyhydroxyalkanoate biosynthesis.

    Science.gov (United States)

    Hisano, Tamao; Tsuge, Takeharu; Fukui, Toshiaki; Iwata, Tadahisa; Miki, Kunio; Doi, Yoshiharu

    2003-01-03

    The (R)-specific enoyl coenzyme A hydratase ((R)-hydratase) from Aeromonas caviae catalyzes the addition of a water molecule to trans-2-enoyl coenzyme A (CoA), with a chain-length of 4-6 carbons, to produce the corresponding (R)-3-hydroxyacyl-CoA. It forms a dimer of identical subunits with a molecular weight of about 14,000 and is involved in polyhydroxyalkanoate (PHA) biosynthesis. The crystal structure of the enzyme has been determined at 1.5-A resolution. The structure of the monomer consists of a five-stranded antiparallel beta-sheet and a central alpha-helix, folded into a so-called "hot dog" fold, with an overhanging segment. This overhang contains the conserved residues including the hydratase 2 motif residues. In dimeric form, two beta-sheets are associated to form an extended 10-stranded beta-sheet, and the overhangs obscure the putative active sites at the subunit interface. The active site is located deep within the substrate-binding tunnel, where Asp(31) and His(36) form a catalytic dyad. These residues are catalytically important as confirmed by site-directed mutagenesis and are possibly responsible for the activation of a water molecule and the protonation of a substrate molecule, respectively. Residues such as Leu(65) and Val(130) are situated at the bottom of the substrate-binding tunnel, defining the preference of the enzyme for the chain length of the substrate. These results provide target residues for protein engineering, which will enhance the significance of this enzyme in the production of novel PHA polymers. In addition, this study provides the first structural information of the (R)-hydratase family and may facilitate further functional studies for members of the family.

  2. Can micro-imaging based analysis methods quantify structural integrity of rat vertebrae with and without metastatic involvement?

    Science.gov (United States)

    Hojjat, Seyed-Parsa; Beek, Maarten; Akens, Margarete K; Whyne, Cari M

    2012-09-21

    This study compares the ability of μCT image-based registration, 2D structural rigidity analyses and multimodal continuum-level finite element (FE) modeling in evaluating the mechanical stability of healthy, osteolytic, and mixed osteolytic/osteoblastic metastatically involved rat vertebrae. μMR and μCT images (loaded and unloaded) were acquired of lumbar spinal motion segments from 15rnu/rnu rats (five per group). Strains were calculated based on image registration of the loaded and unloaded μCT images and via analysis of FE models created from the μCT and μMR data. Predicted yield load was also calculated through 2D structural rigidity analysis of the axial unloaded μCT slices. Measures from the three techniques were compared to experimental yield loads. The ability of these methods to predict experimental yield loads were evaluated and image registration and FE calculated strains were directly compared. Quantitatively for all samples, only limited weak correlations were found between the image-based measures and experimental yield load. In comparison to the experimental yield load, we observed a trend toward a weak negative correlation with median strain calculated using the image-based strain measurement algorithm (r=-0.405, p=0.067), weak significant correlations (pmodes of failure. Improvements in load characterization, material properties assignments and resolution are necessary to yield a more generalized ability for image-based registration, structural rigidity and FE methods to accurately represent stability in healthy and pathologic scenarios. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Species characterization and responses of subcortical insects to trap-logs and ethanol in a hardwood biomass plantation: Subcortical insects in hardwood plantations

    Energy Technology Data Exchange (ETDEWEB)

    Coyle, David R. [D. B. Warnell School of Forestry and Natural Resources; University of Georgia; 180 E. Green Street Athens GA 30602 U.S.A.; Brissey, Courtney L. [D. B. Warnell School of Forestry and Natural Resources; University of Georgia; 180 E. Green Street Athens GA 30602 U.S.A.; Gandhi, Kamal J. K. [D. B. Warnell School of Forestry and Natural Resources; University of Georgia; 180 E. Green Street Athens GA 30602 U.S.A.

    2015-01-02

    1. We characterized subcortical insect assemblages in economically important eastern cottonwood (Populus deltoides Bartr.), sycamore (Platanus occidentalis L.) and sweetgum (Liquidambar styraciflua L.) plantations in the southeastern U.S.A. Furthermore, we compared insect responses between freshly-cut plant material by placing traps directly over cut hardwood logs (trap-logs), traps baited with ethanol lures and unbaited (control) traps. 2. We captured a total of 15 506 insects representing 127 species in four families in 2011 and 2013. Approximately 9% and 62% of total species and individuals, respectively, and 23% and 79% of total Scolytinae species and individuals, respectively, were non-native to North America. 3. We captured more Scolytinae using cottonwood trap-logs compared with control traps in both years, although this was the case with sycamore and sweetgum only in 2013. More woodborers were captured using cottonwood and sweetgum trap-logs compared with control traps in both years, although only with sycamore in 2013. 4. Ethanol was an effective lure for capturing non-native Scolytinae; however, not all non-native species were captured using ethanol lures. Ambrosiophilus atratus (Eichhoff) and Hypothenemus crudiae (Panzer) were captured with both trap-logs and control traps, whereas Coccotrypes distinctus (Motschulsky) and Xyleborus glabratus Eichhoff were only captured on trap-logs. 5. Indicator species analysis revealed that certain scolytines [e.g. Cnestus mutilates (Blandford) and Xylosandrus crassiusculus (Motschulsky)] showed significant associations with trap-logs or ethanol baits in poplar or sweetgum trap-logs. In general, the species composition of subcortical insects, especially woodboring insects, was distinct among the three tree species and between those associated with trap-logs and control traps.

  4. Genetic influences on individual differences in longitudinal changes in global and subcortical brain volumes: Results of the ENIGMA plasticity working group.

    Science.gov (United States)

    Brouwer, Rachel M; Panizzon, Matthew S; Glahn, David C; Hibar, Derrek P; Hua, Xue; Jahanshad, Neda; Abramovic, Lucija; de Zubicaray, Greig I; Franz, Carol E; Hansell, Narelle K; Hickie, Ian B; Koenis, Marinka M G; Martin, Nicholas G; Mather, Karen A; McMahon, Katie L; Schnack, Hugo G; Strike, Lachlan T; Swagerman, Suzanne C; Thalamuthu, Anbupalam; Wen, Wei; Gilmore, John H; Gogtay, Nitin; Kahn, René S; Sachdev, Perminder S; Wright, Margaret J; Boomsma, Dorret I; Kremen, William S; Thompson, Paul M; Hulshoff Pol, Hilleke E

    2017-09-01

    Structural brain changes that occur during development and ageing are related to mental health and general cognitive functioning. Individuals differ in the extent to which their brain volumes change over time, but whether these differences can be attributed to differences in their genotypes has not been widely studied. Here we estimate heritability (h 2 ) of changes in global and subcortical brain volumes in five longitudinal twin cohorts from across the world and in different stages of the lifespan (N = 861). Heritability estimates of brain changes were significant and ranged from 16% (caudate) to 42% (cerebellar gray matter) for all global and most subcortical volumes (with the exception of thalamus and pallidum). Heritability estimates of change rates were generally higher in adults than in children suggesting an increasing influence of genetic factors explaining individual differences in brain structural changes with age. In children, environmental influences in part explained individual differences in developmental changes in brain structure. Multivariate genetic modeling showed that genetic influences of change rates and baseline volume significantly overlapped for many structures. The genetic influences explaining individual differences in the change rate for cerebellum, cerebellar gray matter and lateral ventricles were independent of the genetic influences explaining differences in their baseline volumes. These results imply the existence of genetic variants that are specific for brain plasticity, rather than brain volume itself. Identifying these genes may increase our understanding of brain development and ageing and possibly have implications for diseases that are characterized by deviant developmental trajectories of brain structure. Hum Brain Mapp 38:4444-4458, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Subcortical atrophy in frontotemporal dementia and Alzheimer's disease: Significance for differential diagnosis and correlation with clinical manifestations

    Directory of Open Access Journals (Sweden)

    Renata Teles Vieira

    Full Text Available Abstract Cerebral subcortical atrophy occurs in both Alzheimer's disease (AD and frontotemporal dementia (FTD but its significance for clinical manifestations and differential diagnosis between these common types of dementia has not been extensively investigated. Objectives: To compare the severity of cerebral subcortical atrophy in FTD and AD and to analyze the correlations between cerebral subcortical atrophy and demographics and clinical characteristics. Methods: Twenty three patients with FTD and 21 with AD formed the sample, which comprised 22 men and 22 women, aged 33 to 89, with mean age (±SD of 68.52±12.08 years, with schooling ranging from 1 to 20 years, with a mean (±SD of 7.35±5.54 years, and disease duration with a mean (±SD of 3.66±3.44 years. The degree of cerebral subcortical atrophy was measured indirectly with a linear measurement of subcortical atrophy, the Bifrontal Index (BFI, using magnetic resonance imaging. We evaluated cognition, activities of daily living and dementia severity with the Mini-Mental State Examination, Functional Activities Questionnaire and the Clinical Dementia Rating, respectively. Results: There was no significant difference (p>0.05 in BFI between FTD and AD. The severity of cognitive deficits (for both FTD and AD groups and level of daily living activities (only for AD group were correlated with BFI. Conclusions: A linear measurement of cerebral subcortical atrophy did not differentiate AD from FTD in this sample. Cognitive function (in both FTD and AD groups and capacity for independent living (only in AD group were inversely correlated with cerebral subcortical atrophy.

  6. Subcortical Shape Changes, Hippocampal Atrophy and Cortical Thinning in Future Alzheimer's Disease Patients.

    Science.gov (United States)

    Kälin, Andrea M; Park, Min T M; Chakravarty, M Mallar; Lerch, Jason P; Michels, Lars; Schroeder, Clemens; Broicher, Sarah D; Kollias, Spyros; Nitsch, Roger M; Gietl, Anton F; Unschuld, Paul G; Hock, Christoph; Leh, Sandra E

    2017-01-01

    Efficacy of future treatments depends on biomarkers identifying patients with mild cognitive impairment at highest risk for transitioning to Alzheimer's disease. Here, we applied recently developed analysis techniques to investigate cross-sectional differences in subcortical shape and volume alterations in patients with stable mild cognitive impairment (MCI) (n = 23, age range 59-82, 47.8% female), future converters at baseline (n = 10, age range 66-84, 90% female) and at time of conversion (age range 68-87) compared to group-wise age and gender matched healthy control subjects (n = 23, age range 61-81, 47.8% female; n = 10, age range 66-82, 80% female; n = 10, age range 68-82, 70% female). Additionally, we studied cortical thinning and global and local measures of hippocampal atrophy as known key imaging markers for Alzheimer's disease. Apart from bilateral striatal volume reductions, no morphometric alterations were found in cognitively stable patients. In contrast, we identified shape alterations in striatal and thalamic regions in future converters at baseline and at time of conversion. These shape alterations were paralleled by Alzheimer's disease like patterns of left hemispheric morphometric changes (cortical thinning in medial temporal regions, hippocampal total and subfield atrophy) in future converters at baseline with progression to similar right hemispheric alterations at time of conversion. Additionally, receiver operating characteristic curve analysis indicated that subcortical shape alterations may outperform hippocampal volume in identifying future converters at baseline. These results further confirm the key role of early cortical thinning and hippocampal atrophy in the early detection of Alzheimer's disease. But first and foremost, and by distinguishing future converters but not patients with stable cognitive abilities from cognitively normal subjects, our results support the value of early subcortical shape alterations and reduced hippocampal

  7. Mosaic mutations of the LIS1 gene cause subcortical band heterotopia.

    Science.gov (United States)

    Sicca, F; Kelemen, A; Genton, P; Das, S; Mei, D; Moro, F; Dobyns, W B; Guerrini, R

    2003-10-28

    Subcortical band heterotopia (SBH) is a neuronal migration disorder. DCX mutations are responsible for almost all familial cases, 80% of sporadic female cases, and 25% of sporadic male cases of SBH, and are associated with more severe gyral and migration abnormality over the anterior brain regions. Somatic mosaicism has previously been hypothesized in a patient with posteriorly predominant SBH and a mutation of the LIS1 gene, which is usually mutated in patients with severe lissencephaly. The authors identified mosaic mutations of LIS1 in two patients (Patients 1 and 2) with predominantly posterior SBH. After ruling out DCX mutations, the authors performed sequencing of the LIS1 gene in lymphocyte DNA. Because sequence peaks in both patients were suggestive of mosaic mutations, they followed up with denaturing high-pressure liquid chromatography analysis on blood and hair root DNA and compared the areas of heteroduplex and homoduplex peaks. A third patient showing the same mutation as Patient 2 but with no evidence of mosaicism was used for comparing the phenotype of mosaic vs full mutation. The two patients with posterior SBH harbored a missense (Arg241Pro) and a nonsense (R8X) mosaic mutation of LIS1. The rate of mosaicism in Patient 1 was 18% in the blood and 21% in the hair roots, whereas in Patient 2 it was 24% and 31% in the same tissues. The patient with a full R8X mutation of LIS1 had severe lissencephaly. Subcortical band heterotopia can occur with mosaic mutations of the LIS1 gene. Mutation analysis of LIS1, using highly sensitive techniques such as denaturing high-pressure liquid chromatography, should be considered for patients with posteriorly predominant subcortical band heterotopia and pachygyria.

  8. Apraxia for differentiating Alzheimer’s disease from subcortical vascular dementia and mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Ozkan S

    2013-07-01

    Full Text Available Serhat Ozkan,1 Demet Ozbabalik Adapinar,1 Nese Tuncer Elmaci,2 Didem Arslantas31Department of Neurology, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey; 2Department of Neurology, Marmara University Medical Faculty, Istanbul, Turkey; 3Department of Public Health, Eskisehir Osmangazi University Medical Faculty, Eskisehir, TurkeyAbstract: Although ideomotor limb apraxia is considered to be a typical sign of cortical pathologies such as Alzheimer’s disease (AD, it has been also reported in subcortical neurodegenerative diseases and vascular lesions. We aimed to investigate the difference between AD, subcortical vascular dementia (SVaD and mild cognitive impairment (MCI patients by means of ideomotor limb apraxia frequency and severity. Ninety-six AD, 72 SVaD, and 84 MCI patients were assessed with the mini-mental status examination (MMSE, clinical dementia rating (CDR and the apraxia screening test of TULIA (AST. Apraxia was significantly more frequent in the AD patients (32.3% than in both of the SVaD (16.7% and MCI (4.8% patients. The frequency of apraxia was also significantly higher in SVaD patients than in MCI patients. AD patients had significantly lower apraxia scores than both SVaD and MCI patients. In addition, a significant difference was found between SVaD and MCI patients in terms of apraxia scores. These results suggest that the widespread belief of the association between apraxia and cortical dementias is not exactly correct. The significant difference between both of the dementia groups and the MCI patients suggests that the absence of apraxia can be an indicator for MCI diagnosis.Keywords: apraxia, Alzheimer’s disease, subcortical vascular dementia, mild cognitive impairment

  9. Longitudinal cognitive decline in subcortical ischemic vascular disease--the LADIS Study

    DEFF Research Database (Denmark)

    Jokinen, Hanna; Kalska, Hely; Ylikoski, Raija

    2009-01-01

    BACKGROUND: Cross-sectional studies have indicated that subcortical ischemic vascular disease (SIVD), as defined according to imaging criteria, is associated with a specific clinical and cognitive profile. Much less is known about the long-term cognitive consequences of SIVD. The aim of the study......, education and medial temporal lobe atrophy. CONCLUSIONS: SIVD, as a manifestation of cerebral small vessel disease, is related to progressive cognitive impairment and a considerable risk of developing dementia. SIVD seems to specifically contribute to the deterioration of psychomotor speed, executive...

  10. Marchiafava-Bignami disease: magnetic resonance imaging findings in corpus callosum and subcortical white matter

    Energy Technology Data Exchange (ETDEWEB)

    Kawarabuki, Kentaro E-mail: bukky@h2.dion.ne.jp; Sakakibara, Takehiko; Hirai, Makoto; Yoshioka, Yuji; Yamamoto, Yasumasa; Yamaki, Tarumi

    2003-11-01

    A case of Marchiafava-Bignami disease (MBD) is presented using magnetic resonance imaging (MRI). A patient with a long history of alcoholism developed a gait disturbance with involuntary movements at the lower extremities. MRI scans taken at the onset showed no particular abnormalities. He progressed to a coma 10 days later. MRI scans taken 20 days after the onset showed a focal lesion at the genu of the corpus callosum and he was diagnosed as having MBD. In addition, multiple lesions were observed in bilateral frontoparietal subcortical white matter. These lesions demonstrated similar intense MRI signals as the corpus callosum.

  11. Protection of Melanized Cryptococcus neoformans from Lethal Dose Gamma Irradiation Involves Changes in Melanin's Chemical Structure and Paramagnetism

    Science.gov (United States)

    Khajo, Abdelahad; Bryan, Ruth A.; Friedman, Matthew; Burger, Richard M.; Levitsky, Yan; Casadevall, Arturo; Magliozzo, Richard S.; Dadachova, Ekaterina

    2011-01-01

    Certain fungi thrive in highly radioactive environments including the defunct Chernobyl nuclear reactor. Cryptococcus neoformans (C. neoformans), which uses L-3,4-dihydroxyphenylalanine (L-DOPA) to produce melanin, was used here to investigate how gamma radiation under aqueous aerobic conditions affects the properties of melanin, with the aim of gaining insight into its radioprotective role. Exposure of melanized fungal cell in aqueous suspensions to doses of γ-radiation capable of killing 50 to 80% of the cells did not lead to a detectable loss of melanin integrity according to EPR spectra of melanin radicals. Moreover, upon UV-visible (Xe-lamp) illumination of melanized cells, the increase in radical population was unchanged after γ-irradiation. Gamma-irradiation of frozen cell suspensions and storage of samples for several days at 77 K however, produced melanin modification noted by a reduced radical population and reduced photoresponse. More direct evidence for structural modification of melanin came from the detection of soluble products with absorbance maxima near 260 nm in supernatants collected after γ-irradiation of cells and cell-free melanin. These products, which include thiobarbituric acid (TBA)-reactive aldehydes, were also generated by Fenton reagent treatment of cells and cell-free melanin. In an assay of melanin integrity based on the metal (Bi+3) binding capacity of cells, no detectable loss in binding was detected after γ-irradiation. Our results show that melanin in C. neoformans cells is susceptible to some damage by hydroxyl radical formed in lethal radioactive aqueous environments and serves a protective role in melanized fungi that involves sacrificial breakdown. PMID:21966422

  12. Protection of melanized Cryptococcus neoformans from lethal dose gamma irradiation involves changes in melanin's chemical structure and paramagnetism.

    Directory of Open Access Journals (Sweden)

    Abdelahad Khajo

    Full Text Available Certain fungi thrive in highly radioactive environments including the defunct Chernobyl nuclear reactor. Cryptococcus neoformans (C. neoformans, which uses L-3,4-dihydroxyphenylalanine (L-DOPA to produce melanin, was used here to investigate how gamma radiation under aqueous aerobic conditions affects the properties of melanin, with the aim of gaining insight into its radioprotective role. Exposure of melanized fungal cell in aqueous suspensions to doses of γ-radiation capable of killing 50 to 80% of the cells did not lead to a detectable loss of melanin integrity according to EPR spectra of melanin radicals. Moreover, upon UV-visible (Xe-lamp illumination of melanized cells, the increase in radical population was unchanged after γ-irradiation. Gamma-irradiation of frozen cell suspensions and storage of samples for several days at 77 K however, produced melanin modification noted by a reduced radical population and reduced photoresponse. More direct evidence for structural modification of melanin came from the detection of soluble products with absorbance maxima near 260 nm in supernatants collected after γ-irradiation of cells and cell-free melanin. These products, which include thiobarbituric acid (TBA-reactive aldehydes, were also generated by Fenton reagent treatment of cells and cell-free melanin. In an assay of melanin integrity based on the metal (Bi(+3 binding capacity of cells, no detectable loss in binding was detected after γ-irradiation. Our results show that melanin in C. neoformans cells is susceptible to some damage by hydroxyl radical formed in lethal radioactive aqueous environments and serves a protective role in melanized fungi that involves sacrificial breakdown.

  13. Subcortical Hypoperfusion following Surgery For Aneurysmal Subarachnoid Haemorrhage: Implications For Cognitive Performance?

    Directory of Open Access Journals (Sweden)

    C. L. Tooth

    2000-01-01

    Full Text Available The incidence and severity of cognitive deficits after surgery for aneurysmal subarachnoid haemorrhage and their relationship to aneurysm site remains controversial. The aim of this study was to investigate the pattern of regional cerebral blood flow which exists in patients one year post-surgery and to identify whether different patterns exist which may be related to the type of cognitive deficit or the location of the aneurysm. 62 patients underwent cognitive assessment and HMPAO SPECT imaging at a mean time of 12 months following surgery. Results were compared to those from healthy control subjects (n = 55 for neuropsychological testing; n = 14 for SPECT imaging. In the patient group, significant stable cognitive deficits occurred in all cognitive domains but no cognitive measure differentiated aneurysm site. On SPECT images, statistical parametric mapping identified a large common area of subcortical hypoperfusion in the patient group as a whole. The findings of this study suggest a possible link between reduced subcortical function and the extent and severity of cognitive deficits.

  14. Minimally Invasive Subcortical Parafascicular Transsulcal Access for Clot Evacuation (Mi SPACE for Intracerebral Hemorrhage

    Directory of Open Access Journals (Sweden)

    Benjamin Ritsma

    2014-01-01

    Full Text Available Background. Spontaneous intracerebral hemorrhage (ICH is common and causes significant mortality and morbidity. To date, optimal medical and surgical intervention remains uncertain. A lack of definitive benefit for operative management may be attributable to adverse surgical effect, collateral tissue injury. This is particularly relevant for ICH in dominant, eloquent cortex. Minimally invasive surgery (MIS offers the potential advantage of reduced collateral damage. MIS utilizing a parafascicular approach has demonstrated such benefit for intracranial tumor resection. Methods. We present a case of dominant hemisphere spontaneous ICH evacuated via the minimally invasive subcortical parafascicular transsulcal access clot evacuation (Mi SPACE model. We use this report to introduce Mi SPACE and to examine the application of this novel MIS paradigm. Case Presentation. The featured patient presented with a left temporal ICH and severe global aphasia. The hematoma was evacuated via the Mi SPACE approach. Postoperative reassessments showed significant improvement. At two months, bedside language testing was normal. MRI tractography confirmed limited collateral injury. Conclusions. This case illustrates successful application of the Mi SPACE model to ICH in dominant, eloquent cortex and subcortical regions. MRI tractography illustrates collateral tissue preservation. Safety and feasibility studies are required to further assess this promising new therapeutic paradigm.

  15. An Italian kindred with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

    Science.gov (United States)

    Ragno, M; Tournier-Lasserve, E; Fiori, M G; Manca, A; Patrosso, M C; Ferlini, A; Sirocchi, G; Trojano, L; Chabriat, H; Salvi, F

    1995-08-01

    Vascular dementia is usually sporadic and associated with definite risk factors. Several cases also occur in a familial fashion, and may affect middle-aged or even younger subjects. Recently, an autosomal dominant inheritance was demonstrated in two unrelated French families, the members of which were affected by stroke-like episodes culminating in progressive dementia. Genetic linkage analysis assigned the disease locus to chromosome 19q12. We report an additional kindred of Italian origin in which at least 16 subjects presented leukoencephalopathic alterations. Recurrent strokes, psychiatric disturbances, dementia, and in 2 members, tetraplegia and pseudobulbar palsy were the hallmarks of this syndrome. Notably, 5 asymptomatic individuals had neuroradiological signs of leukoencephalopathy. Pathological examination of 1 subject revealed a widespread vasculopathy of the perforating arterioles, characterized by deposition of eosinophilic-congophilic material that did not immunostain with antibodies against prion protein, beta-amyloid, cystatin C, transthyretin, or heat-shock protein 70 and was similar to that described in the French families. Based on the maximum lod score, the most likely location for the disease locus was also mapped to chromosome 19q12, and found to coincide with the CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) locus. The present results confirm the existence of a nosologically distinct, autosomal dominant cerebrovascular disease, presenting with recurrent subcortical ischemic strokes independent of vascular risk factors.

  16. A PET study on cortical and subcortical control of pelvic floor musculature in women

    NARCIS (Netherlands)

    Blok, Bertil F.M.; Sturms, Leontien M.; Holstege, Gert

    1997-01-01

    The pelvic floor musculature plays an important role in behaviors such as defecation, micturition, mating behavior, and vomiting. A recent positron emission tomography (PET) study revealed that structures belonging to the emotional motor system are involved in the control of the pelvic floor during

  17. Continuous subcortical motor evoked potential stimulation using the tip of an ultrasonic aspirator for the resection of motor eloquent lesions.

    Science.gov (United States)

    Shiban, Ehab; Krieg, Sandro M; Obermueller, Thomas; Wostrack, Maria; Meyer, Bernhard; Ringel, Florian

    2015-08-01

    Resection of a motor eloquent lesion has become safer because of intraoperative neurophysiological monitoring (IOM). Stimulation of subcortical motor evoked potentials (scMEPs) is increasingly used to optimize patient safety. So far, scMEP stimulation has been performed intermittently during resection of eloquently located lesions. Authors of the present study assessed the possibility of using a resection instrument for continuous stimulation of scMEPs. An ultrasonic surgical aspirator was attached to an IOM stimulator and was used as a monopolar subcortical stimulation probe. The effect of the aspirator's use at different ultrasound power levels (0%, 25%, 50%, 75%, and 100%) on stimulation intensity was examined in a saline bath. Afterward monopolar stimulation with the surgical aspirator was used during the resection of subcortical lesions in the vicinity of the corticospinal tract in 14 patients in comparison with scMEP stimulation via a standard stimulation electrode. During resection, the stimulation current at which an MEP response was still measurable with subcortical stimulation using the surgical aspirator was compared with the corresponding stimulation current needed using a standard monopolar subcortical stimulation probe at the same location. The use of ultrasound at different energy levels did result in a slight but irrelevant increase in stimulation energy via the tip of the surgical aspirator in the saline bath. Stimulation of scMEPs using the surgical aspirator or monopolar probe was successful and almost identical in all patients. One patient developed a new permanent neurological deficit. Transient new postoperative paresis was observed in 28% (4 of 14) of cases. Gross-total resection was achieved in 64% (9 of 14) cases and subtotal resection (> 80% of tumor mass) in 35% (5 of 14). Continuous motor mapping using subcortical stimulation via a surgical aspirator, in comparison with the sequential use of a standard monopolar stimulation probe, is a

  18. FUNCTIONAL AND STRUCTURAL TOPOGRAPHY WITHIN CORTICO- SUBCORTICAL LOOPS IN PARKINSON'S DISEASE USING MAGNETIC RESONANCE IMAGING

    OpenAIRE

    Marquis, Renaud

    2017-01-01

    Parkinson’s disease (PD) is a debilitating neurodegenerative disorder due to loss of dopamine producing cells in the substantia nigra. Given the fact that clinical symptoms emerge after a long preclinical period with gradual decline in dopamine production, there is pressing need to advance our understanding about the progression of motor and non- motor symptoms in symptomatic phase of PD. Recent theoretical work and animal models suggest a link between dopamine-dependent loss of neuronal spec...

  19. Similar cortical but not subcortical gray matter abnormalities in women with posttraumatic stress disorder with versus without dissociative identity disorder.

    Science.gov (United States)

    Chalavi, Sima; Vissia, Eline M; Giesen, Mechteld E; Nijenhuis, Ellert R S; Draijer, Nel; Barker, Gareth J; Veltman, Dick J; Reinders, Antje A T S

    2015-03-30

    Neuroanatomical evidence on the relationship between posttraumatic stress disorder (PTSD) and dissociative disorders is still lacking. We acquired brain structural magnetic resonance imaging (MRI) scans from 17 patients with dissociative identity disorder (DID) and co-morbid PTSD (DID-PTSD) and 16 patients with PTSD but without DID (PTSD-only), and 32 healthy controls (HC), and compared their whole-brain cortical and subcortical gray matter (GM) morphological measurements. Associations between GM measurements and severity of dissociative and depersonalization/derealization symptoms or lifetime traumatizing events were evaluated in the patient groups. DID-PTSD and PTSD-only patients, compared with HC, had similarly smaller cortical GM volumes of the whole brain and of frontal, temporal and insular cortices. DID-PTSD patients additionally showed smaller hippocampal and larger pallidum volumes relative to HC, and larger putamen and pallidum volumes relative to PTSD-only. Severity of lifetime traumatizing events and volume of the hippocampus were negatively correlated. Severity of dissociative and depersonalization/derealization symptoms correlated positively with volume of the putamen and pallidum, and negatively with volume of the inferior parietal cortex. Shared abnormal brain structures in DID-PTSD and PTSD-only, small hippocampal volume in DID-PTSD, more severe lifetime traumatizing events in DID-PTSD compared with PTSD-only, and negative correlations between lifetime traumatizing events and hippocampal volume suggest a trauma-related etiology for DID. Our results provide neurobiological evidence for the side-by-side nosological classification of PTSD and DID in the DSM-5. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Cortical thickness, cortical surface area and subcortical volumes in schizophrenia and bipolar disorder patients with cannabis use.

    Science.gov (United States)

    Hartberg, Cecilie Bhandari; Lange, Elisabeth H; Lagerberg, Trine Vik; Haukvik, Unn K; Andreassen, Ole A; Melle, Ingrid; Agartz, Ingrid

    2018-01-01

    Cannabis is associated with increased risk for severe mental illness and is commonly used among individuals with schizophrenia or bipolar disorder. In this study we investigated associations between cannabis use and brain structures among patients with schizophrenia or bipolar disorders. Magnetic resonance imaging scans were obtained for 77 schizophrenia and 55 bipolar patients with a history of cannabis use (defined as lifetime use >10 times during one month or abuse/dependence), and 97 schizophrenia, 85 bipolar disorder patients and 277 healthy controls without any previous cannabis use. Cortical thickness, cortical surface area and subcortical volumes were compared between groups. Both hypothesis-driven region-of-interest analyses from 11 preselected brain regions in each hemisphere and exploratory point-by-point analyses were performed. We tested for diagnostic interactions and controlled for potential confounders. After controlling for confounders such as tobacco use and alcohol use disorders we found reduced cortical thickness in the caudal middle frontal gyrus compared to non-user patients and healthy controls. The findings were not significant when patients with co-morbid alcohol and illicit drug use were excluded from the analyses, but onset of cannabis use before illness onset was associated with cortical thinning in the caudal middle frontal gyrus. To conclude, we found no structural brain changes associated with cannabis use among patients with severe mental illness, but the findings indicate excess cortical thinning among those who use cannabis before illness onset. The present findings support the understanding that cannabis use is associated with limited brain effects in schizophrenia as well as bipolar disorder. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  1. High thickness histological sections as alternative to study the three-dimensional microscopic human sub-cortical neuroanatomy.

    Science.gov (United States)

    Alho, Eduardo Joaquim Lopes; Alho, Ana Tereza Di Lorenzo; Grinberg, Lea; Amaro, Edson; Dos Santos, Gláucia Aparecida Bento; da Silva, Rafael Emídio; Neves, Ricardo Caires; Alegro, Maryana; Coelho, Daniel Boari; Teixeira, Manoel Jacobsen; Fonoff, Erich Talamoni; Heinsen, Helmut

    2017-11-01

    Stereotaxy is based on the precise image-guided spatial localization of targets within the human brain. Even with the recent advances in MRI technology, histological examination renders different (and complementary) information of the nervous tissue. Although several maps have been selected as a basis for correlating imaging results with the anatomical locations of sub-cortical structures, technical limitations interfere in a point-to-point correlation between imaging and anatomy due to the lack of precise correction for post-mortem tissue deformations caused by tissue fixation and processing. We present an alternative method to parcellate human brain cytoarchitectural regions, minimizing deformations caused by post-mortem and tissue-processing artifacts and enhancing segmentation by means of modified high thickness histological techniques and registration with MRI of the same specimen and into MNI space (ICBM152). A three-dimensional (3D) histological atlas of the human thalamus, basal ganglia, and basal forebrain cholinergic system is displayed. Structure's segmentations were performed in high-resolution dark-field and light-field microscopy. Bidimensional non-linear registration of the histological slices was followed by 3D registration with in situ MRI of the same subject. Manual and automated registration procedures were adopted and compared. To evaluate the quality of the registration procedures, Dice similarity coefficient and normalized weighted spectral distance were calculated and the results indicate good overlap between registered volumes and a small shape difference between them in both manual and automated registration methods. High thickness high-resolution histological slices in combination with registration to in situ MRI of the same subject provide an effective alternative method to study nuclear boundaries in the human brain, enhancing segmentation and demanding less resources and time for tissue processing than traditional methods.

  2. Middle manager involvement in strategy development in not-for profit organizations: the director of nursing perspective--how organizational structure impacts on the role.

    Science.gov (United States)

    Carney, M

    2004-01-01

    An attempt was made to link organizational structure and strategic management and, in the process, to identify how organizational structure impacts on the strategic management role of Directors of Nursing working in acute care hospitals in the Republic of Ireland. Directors of Nursing are recognized as holding a pivotal role in health care delivery. The need for their involvement in strategic management is acknowledged, yet it is not clear if this role is influenced by organizational structure. It is recognized that strategic involvement increases the likelihood that middle managers' initiatives will be in line with top management's concept of corporate strategy. The principal thesis is that organizational members will exercise a higher level of strategic consensus if they have been initially involved in the development of strategy. The study was undertaken in not-for-profit health service organizations, through a series of 25 semi-structured interviews with Directors of Nursing. The review of the literature was undertaken simultaneously with grounded theory analysis of the interviews. This research suggests that structure does impact on the role, conferring both positive benefits and negative consequences. Structure is identified in this study, in terms of organizational hierarchy, and the locus of control pertaining in each organization. Two predominating structure models are discussed and analysed.

  3. Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: involvement of adenosine and dopamine receptors.

    Science.gov (United States)

    Feduccia, Allison A; Wang, Yuanyuan; Simms, Jeffrey A; Yi, Henry Y; Li, Rui; Bjeldanes, Leonard; Ye, Chuangxing; Bartlett, Selena E

    2012-08-01

    Purine compounds, such as caffeine, have many health-promoting properties and have proven to be beneficial in treating a number of different conditions. Theacrine, a purine alkaloid structurally similar to caffeine and abundantly present in Camellia kucha, has recently become of interest as a potential therapeutic compound. In the present study, theacrine was tested using a rodent behavioral model to investigate the effects of the drug on locomotor activity. Long Evans rats were injected with theacrine (24 or 48 mg/kg, i.p.) and activity levels were measured. Results showed that the highest dose of theacrine (48 mg/kg, i.p.) significantly increased locomotor activity compared to control animals and activity remained elevated throughout the duration of the session. To test for the involvement of adenosine receptors underlying theacrine's motor-activating properties, rats were administered a cocktail of the adenosine A₁ agonist, N⁶-cyclopentyladenosine (CPA; 0.1 mg/kg, i.p.) and A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680; 0.2 mg/kg, i.p.). Pre-treatment with theacrine significantly attenuated the motor depression induced by the adenosine receptor agonists, indicating that theacrine is likely acting as an adenosine receptor antagonist. Next, we examined the role of DA D₁ and D₂ receptor antagonism on theacrine-induced hyperlocomotion. Both antagonists, D₁R SCH23390 (0.1 or 0.05 mg/kg, i.p.) and D₂R eticlopride (0.1 mg/kg, i.p.), significantly reduced theacrine-stimulated activity indicating that this behavioral response, at least in part, is mediated by DA receptors. In order to investigate the brain region where theacrine may be acting, the drug (10 or 20 μg) was infused bilaterally into nucleus accumbens (NAc). Theacrine enhanced activity levels in a dose-dependent manner, implicating a role of the NAc in modulating theacrine's effects on locomotion. In addition, theacrine did not induce locomotor

  4. The influence of sensation-seeking and parental and peer influences in early adolescence on risk involvement through middle adolescence: A structural equation modeling analysis.

    Science.gov (United States)

    Wang, Bo; Deveaux, Lynette; Lunn, Sonja; Dinaj-Koci, Veronica; Li, Xiaoming; Stanton, Bonita

    2016-03-01

    This study examined the relationships between youth and parental sensation-seeking, peer influence, parental monitoring and youth risk involvement in adolescence using structural equation modeling. Beginning in grade-six, longitudinal data were collected from 543 students over three years. Youth sensation-seeking in grade six contributed to risk involvement in early adolescence (grades six and seven) indirectly through increased peer risk influence and decreased parental monitoring but did not have a direct contribution. It contributed directly and indirectly to risk involvement in middle adolescence (grades eight and nine). Parent sensation-seeking at baseline was positively associated with peer risk influence and negatively associated with parental monitoring; it had no direct effect on adolescent risk involvement. Parental monitoring buffers negative peer influence on adolescent risk involvement. Results highlight the need for intervention efforts to provide normative feedback about adolescent risky behaviors and to vary among families in which parents and/or youth have high sensation-seeking propensities.

  5. Structural and functional characterization of CSDA protein complexes involved in the modulation of fetal globin gene expression

    OpenAIRE

    Gaudino, Sara

    2009-01-01

    Impaired switching from fetal hemoglobin (HbF) to adult globin gene expression leads to hereditary persistence of fetal hemoglobin (HPFH) in adult life. This is of prime interest because elevated HbF levels ameliorate beta-thalassemia and sickle cell anemia. Fetal hemoglobin levels are regulated by complex mechanisms involving factors linked or not to the beta-globin gene locus. To search for factors putatively involved in gamma-globin gene expression, we examined the reticulocyte transcripto...

  6. [Preoperative direct cortical and sub-cortical electric stimulation during cerebral surgery in functional areas].

    Science.gov (United States)

    Duffau, H; Capelle, L; Sichez, J P; Bitar, A; Faillot, T; Arthuis, F; Van Effenterre, R; Fohanno, D

    1999-09-01

    Indications of surgical treatment for lesions in functional cerebral areas depend on the ratio between the definitive neurological deficit and the beneficial effect of resection. Detection of eloquent cortex is difficult because of important individual variability. Peroperative direct cortical and subcortical electrical stimulations (DCS) provide the most precise and reliable method currently available allowing identification and preservation of neurons essential for motricity, sensitivity++ and language. We report our preliminary experience with DCS in surgery of intracerebral infiltrative tumors with a consecutive series of 15 patients operated from November 96 through September 97 in our institution. Presenting symptoms in the 15 patients (8 males, 7 females, mean age 43 years) were seizures in 11 cases (73%) and neurological deficit in 4 cases (27%). Clinical examination was normal in 11 patients and revealed hemiparesia in 4. Magnetic resonance imaging (MRI) with three-dimensional reconstruction showed a precentral tumor in 10 cases, central lesion in one patient, postcentral lesion in two cases, right insular tumor (non-dominant hemisphere) in one case. All patients underwent surgical resection using DCS with detection in 13 cases of motor cortex and subcortical pathways under genera anesthesia, in one case of somatosensory area under local anesthesia, and in one case of language areas also under local anesthesia. The tumor was recurrent in two patients had been operated earlier but without DCS. Resection, verified by postoperative MRI, was total in 12 cases (80%) and estimated at 80% in 3 patients. Histological examination revealed an infiltrative glioma in 12 cases (8 low grade astrocytomas, 3 low grade oligodendrogliomas, and one anaplastic oligodendroglioma), and metastases in 3 cases. Eight patients had no postoperative deficit, while the other 7 patients were impaired, with, in all cases except one, complete recovery in 15 days to 2 months. Direct

  7. Impact of Vortioxetine on Synaptic Integration in Prefrontal-Subcortical Circuits: Comparisons with Escitalopram

    Science.gov (United States)

    Chakroborty, Shreaya; Geisbush, Thomas R.; Dale, Elena; Pehrson, Alan L.; Sánchez, Connie; West, Anthony R.

    2017-01-01

    Prefrontal-subcortical circuits support executive functions which often become dysfunctional in psychiatric disorders. Vortioxetine is a multimodal antidepressant that is currently used in the clinic to treat major depressive disorder. Mechanisms of action of vortioxetine include serotonin (5-HT) transporter blockade, 5-HT1A receptor agonism, 5-HT1B receptor partial agonism, and 5-HT1D, 5-HT3, and 5-HT7 receptor antagonism. Vortioxetine facilitates 5-HT transmission in the medial prefrontal cortex (mPFC), however, the impact of this compound on related prefrontal-subcortical circuits is less clear. Thus, the current study examined the impact of systemic vortioxetine administration (0.8 mg/kg, i.v.) on spontaneous spiking and spikes evoked by electrical stimulation of the mPFC in the anterior cingulate cortex (ACC), medial shell of the nucleus accumbens (msNAc), and lateral septal nucleus (LSN) in urethane-anesthetized rats. We also examined whether vortioxetine modulated afferent drive in the msNAc from hippocampal fimbria (HF) inputs. Similar studies were performed using the selective 5-HT reuptake inhibitor [selective serotonin reuptake inhibitors (SSRI)] escitalopram (1.6 mg/kg, i.v.) to enable comparisons between the multimodal actions of vortioxetine and SSRI-mediated effects. No significant differences in spontaneous activity were observed in the ACC, msNAc, and LSN across treatment groups. No significant impact of treatment on mPFC-evoked responses was observed in the ACC. In contrast, vortioxetine decreased mPFC-evoked activity recorded in the msNAc as compared to parallel studies in control and escitalopram treated groups. Thus, vortioxetine may reduce mPFC-msNAc afferent drive via a mechanism that, in addition to an SSRI-like effect, requires 5-HT receptor modulation. Recordings in the LSN revealed a significant increase in mPFC-evoked activity following escitalopram administration as compared to control and vortioxetine treated groups, indicating that

  8. Impact of Vortioxetine on Synaptic Integration in Prefrontal-Subcortical Circuits: Comparisons with Escitalopram

    Directory of Open Access Journals (Sweden)

    Shreaya Chakroborty

    2017-10-01

    Full Text Available Prefrontal-subcortical circuits support executive functions which often become dysfunctional in psychiatric disorders. Vortioxetine is a multimodal antidepressant that is currently used in the clinic to treat major depressive disorder. Mechanisms of action of vortioxetine include serotonin (5-HT transporter blockade, 5-HT1A receptor agonism, 5-HT1B receptor partial agonism, and 5-HT1D, 5-HT3, and 5-HT7 receptor antagonism. Vortioxetine facilitates 5-HT transmission in the medial prefrontal cortex (mPFC, however, the impact of this compound on related prefrontal-subcortical circuits is less clear. Thus, the current study examined the impact of systemic vortioxetine administration (0.8 mg/kg, i.v. on spontaneous spiking and spikes evoked by electrical stimulation of the mPFC in the anterior cingulate cortex (ACC, medial shell of the nucleus accumbens (msNAc, and lateral septal nucleus (LSN in urethane-anesthetized rats. We also examined whether vortioxetine modulated afferent drive in the msNAc from hippocampal fimbria (HF inputs. Similar studies were performed using the selective 5-HT reuptake inhibitor [selective serotonin reuptake inhibitors (SSRI] escitalopram (1.6 mg/kg, i.v. to enable comparisons between the multimodal actions of vortioxetine and SSRI-mediated effects. No significant differences in spontaneous activity were observed in the ACC, msNAc, and LSN across treatment groups. No significant impact of treatment on mPFC-evoked responses was observed in the ACC. In contrast, vortioxetine decreased mPFC-evoked activity recorded in the msNAc as compared to parallel studies in control and escitalopram treated groups. Thus, vortioxetine may reduce mPFC-msNAc afferent drive via a mechanism that, in addition to an SSRI-like effect, requires 5-HT receptor modulation. Recordings in the LSN revealed a significant increase in mPFC-evoked activity following escitalopram administration as compared to control and vortioxetine treated groups

  9. Impact of Vortioxetine on Synaptic Integration in Prefrontal-Subcortical Circuits: Comparisons with Escitalopram.

    Science.gov (United States)

    Chakroborty, Shreaya; Geisbush, Thomas R; Dale, Elena; Pehrson, Alan L; Sánchez, Connie; West, Anthony R

    2017-01-01

    Prefrontal-subcortical circuits support executive functions which often become dysfunctional in psychiatric disorders. Vortioxetine is a multimodal antidepressant that is currently used in the clinic to treat major depressive disorder. Mechanisms of action of vortioxetine include serotonin (5-HT) transporter blockade, 5-HT1A receptor agonism, 5-HT1B receptor partial agonism, and 5-HT1D, 5-HT3, and 5-HT7 receptor antagonism. Vortioxetine facilitates 5-HT transmission in the medial prefrontal cortex (mPFC), however, the impact of this compound on related prefrontal-subcortical circuits is less clear. Thus, the current study examined the impact of systemic vortioxetine administration (0.8 mg/kg, i.v.) on spontaneous spiking and spikes evoked by electrical stimulation of the mPFC in the anterior cingulate cortex (ACC), medial shell of the nucleus accumbens (msNAc), and lateral septal nucleus (LSN) in urethane-anesthetized rats. We also examined whether vortioxetine modulated afferent drive in the msNAc from hippocampal fimbria (HF) inputs. Similar studies were performed using the selective 5-HT reuptake inhibitor [selective serotonin reuptake inhibitors (SSRI)] escitalopram (1.6 mg/kg, i.v.) to enable comparisons between the multimodal actions of vortioxetine and SSRI-mediated effects. No significant differences in spontaneous activity were observed in the ACC, msNAc, and LSN across treatment groups. No significant impact of treatment on mPFC-evoked responses was observed in the ACC. In contrast, vortioxetine decreased mPFC-evoked activity recorded in the msNAc as compared to parallel studies in control and escitalopram treated groups. Thus, vortioxetine may reduce mPFC-msNAc afferent drive via a mechanism that, in addition to an SSRI-like effect, requires 5-HT receptor modulation. Recordings in the LSN revealed a significant increase in mPFC-evoked activity following escitalopram administration as compared to control and vortioxetine treated groups, indicating that

  10. Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex

    Science.gov (United States)

    Goldstein, Rita Z.; Volkow, Nora D.

    2005-01-01

    Objective Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. Method An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. Results The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to track, update, and modulate the salience of a reinforcer as a function of context and expectation and the ability to control and inhibit prepotent responses. Conclusions These results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervaluing of alternative reinforcers, and deficits in inhibitory control for drug responses. These changes in addiction, which the authors call I-RISA (impaired response inhibition and salience attribution), expand the traditional concepts of drug dependence that emphasize limbic-regulated responses to pleasure and reward. PMID:12359667

  11. BRAIN PLASTICITY: MUSICAL TRAINING INVOLVEMENT

    Directory of Open Access Journals (Sweden)

    Verónika Diaz Abrahan

    2012-12-01

    Full Text Available The main research about the effect of musical training in adult and childhood brain was revised in this work. The music realizes unique demands to our ner-vous system. This call the attention of several researchers causing, in the past years, an enhancement of the exploration about this topic; this increment was benefit for the emergence of new neuroimaging techniques, the music positioned as an investigation tool of human cognition and superior brain mechanisms. The musical perception and production are specific functions of the human brain that depend of a wide cortical-subcortical neural net distributed across both hemi-spheres and cerebellum. The main findings in this area indicated structural and functional differences in the adult and child brain due to musical training, and this is more relevant that innate properties of the subject. There is brain plasticity due to adaptive processes product of the environmental stimulation.

  12. The Effects of Perceptions of Organizational Structure on Job Involvement, Job Satisfaction, and Organizational Commitment Among Indian Police Officers.

    Science.gov (United States)

    Lambert, Eric G; Qureshi, Hanif; Klahm, Charles; Smith, Brad; Frank, James

    2017-12-01

    Successful police organizations rely on involved, satisfied, and committed workers. The concepts of job involvement (i.e., connection with the job), job satisfaction (i.e., affective feeling toward the job), and organizational commitment (i.e., bond with the employing organization) have been shown to significantly affect intentions and behaviors of employees. The current study used multivariate ordinary least squares (OLS) regression analysis on survey results from a sample of 827 Indian police officers to explore how perceptions of work environment factors affect officers' job involvement, job satisfaction, and organizational commitment. Organizational support, formalization (i.e., level of codified written rules and guidelines), promotional opportunities, institutional communication (i.e., salient work information is transmitted), and input into decision-making (i.e., having a voice in the process) significantly influenced the job involvement, job satisfaction, and organizational commitment of Indian police officers. Specifically, in the multivariate analysis, perceptions of formalization and instrumental communication had a positive relationship with job involvement; perceptions of organizational support, promotional opportunities, instrumental communication, and input into decision-making had positive associations with job satisfaction; and perceptions of organizational support, formalization, promotional opportunities, instrumental communication, and input into decision-making had positive relationships with organizational commitment.

  13. Structure and Mechanism of Staphylococcus aureus TarS, the Wall Teichoic Acid β-glycosyltransferase Involved in Methicillin Resistance.

    Directory of Open Access Journals (Sweden)

    Solmaz Sobhanifar

    2016-12-01

    Full Text Available In recent years, there has been a growing interest in teichoic acids as targets for antibiotic drug design against major clinical pathogens such as Staphylococcus aureus, reflecting the disquieting increase in antibiotic resistance and the historical success of bacterial cell wall components as drug targets. It is now becoming clear that β-O-GlcNAcylation of S. aureus wall teichoic acids plays a major role in both pathogenicity and antibiotic resistance. Here we present the first structure of S. aureus TarS, the enzyme responsible for polyribitol phosphate β-O-GlcNAcylation. Using a divide and conquer strategy, we obtained crystal structures of various TarS constructs, mapping high resolution overlapping N-terminal and C-terminal structures onto a lower resolution full-length structure that resulted in a high resolution view of the entire enzyme. Using the N-terminal structure that encapsulates the catalytic domain, we furthermore captured several snapshots of TarS, including the native structure, the UDP-GlcNAc donor complex, and the UDP product complex. These structures along with structure-guided mutants allowed us to elucidate various catalytic features and identify key active site residues and catalytic loop rearrangements that provide a valuable platform for anti-MRSA drug design. We furthermore observed for the first time the presence of a trimerization domain composed of stacked carbohydrate binding modules, commonly observed in starch active enzymes, but adapted here for a poly sugar-phosphate glycosyltransferase.

  14. Fathers' Involvement with Their Preschool-Age Children: How Fathers Spend Time with Their Children in Different Family Structures

    Science.gov (United States)

    Halme, Nina; Astedt-Kurki, Paivi; Tarkka, Marja-Terttu

    2009-01-01

    The purpose of this study was to describe how fathers (n = 263) spent time with their preschool-age children and to compare it in different family structures. Data were gathered by structured questionnaires. The instrument included five categories of variables for the time spent: the quantity of time, physical activities, fathers' attitude towards…

  15. Mutant GlialCAM Causes Megalencephalic Leukoencephalopathy with Subcortical Cysts, Benign Familial Macrocephaly, and Macrocephaly with Retardation and Autism

    NARCIS (Netherlands)

    López-Hernández, T.; Ridder, M.C.; Montolio, M.; Capdevila-Nortes, X.; Polder, E.; Sirisi, S.; Duarri, A.; Schulte, U.; Fakler, B.; Nunes, V.; Scheper, G.C.; Martinez, A; Estevez, R.; van der Knaap, M.S.

    2011-01-01

    Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a leukodystrophy characterized by early-onset macrocephaly and delayed-onset neurological deterioration. Recessive MLC1 mutations are observed in 75% of patients with MLC. Genetic-linkage studies failed to identify another gene. We

  16. Efficacy of two insecticides for protecting loblolly pines (Pinus taeda L.) from subcortical beetles (Coleoptera: Curculionidae and Cerambycidae)

    Science.gov (United States)

    Jordon L. Burke; James L. Hanula; Scott Horn; Jackson P. Audley; Kamal JK. Gandhi

    2012-01-01

    Tests were conducted on two insecticides (carbaryl and bifenthrin) for excluding subcortical beetles (Coleoptera: Curculionidae and Cerambycidae) from loblolly pine trees (Pinus taeda L.). Two trap designs (single- and double-pane windows) and two trapping heights (1.5 and 4m) were also evaluated for maximizing beetle catches.

  17. A Computational Approach From Gene to Structure Analysis of the Human ABCA4 Transporter Involved in Genetic Retinal Diseases.

    Science.gov (United States)

    Trezza, Alfonso; Bernini, Andrea; Langella, Andrea; Ascher, David B; Pires, Douglas E V; Sodi, Andrea; Passerini, Ilaria; Pelo, Elisabetta; Rizzo, Stanislao; Niccolai, Neri; Spiga, Ottavia

    2017-10-01

    The aim of this article is to report the investigation of the structural features of ABCA4, a protein associated with a genetic retinal disease. A new database collecting knowledge of ABCA4 structure may facilitate predictions about the possible functional consequences of gene mutations observed in clinical practice. In order to correlate structural and functional effects of the observed mutations, the structure of mouse P-glycoprotein was used as a template for homology modeling. The obtained structural information and genetic data are the basis of our relational database (ABCA4Database). Sequence variability among all ABCA4-deposited entries was calculated and reported as Shannon entropy score at the residue level. The three-dimensional model of ABCA4 structure was used to locate the spatial distribution of the observed variable regions. Our predictions from structural in silico tools were able to accurately link the functional effects of mutations to phenotype. The development of the ABCA4Database gathers all the available genetic and structural information, yielding a global view of the molecular basis of some retinal diseases. ABCA4 modeled structure provides a molecular basis on which to analyze protein sequence mutations related to genetic retinal disease in order to predict the risk of retinal disease across all possible ABCA4 mutations. Additionally, our ABCA4 predicted structure is a good starting point for the creation of a new data analysis model, appropriate for precision medicine, in order to develop a deeper knowledge network of the disease and to improve the management of patients.

  18. Brainstem Evoked Potential Indices of Subcortical Auditory Processing After Mild Traumatic Brain Injury.

    Science.gov (United States)

    Vander Werff, Kathy R; Rieger, Brian

    The primary aim of this study was to assess subcortical auditory processing in individuals with chronic symptoms after mild traumatic brain injury (mTBI) by measuring auditory brainstem responses (ABRs) to standard click and complex speech stimuli. Consistent with reports in the literature of auditory problems after mTBI (despite normal-hearing thresholds), it was hypothesized that individuals with mTBI would have evidence of impaired neural encoding in the auditory brainstem compared to noninjured controls, as evidenced by delayed latencies and reduced amplitudes of ABR components. We further hypothesized that the speech-evoked ABR would be more sensitive than the click-evoked ABR to group differences because of its complex nature, particularly when recorded in a background noise condition. Click- and speech-ABRs were collected in 32 individuals diagnosed with mTBI in the past 3 to 18 months. All mTBI participants were experiencing ongoing injury symptoms for which they were seeking rehabilitation through a brain injury rehabilitation management program. The same data were collected in a group of 32 age- and gender-matched controls with no history of head injury. ABRs were recorded in both left and right ears for all participants in all conditions. Speech-ABRs were collected in both quiet and in a background of continuous 20-talker babble ipsilateral noise. Peak latencies and amplitudes were compared between groups and across subgroups of mTBI participants categorized by their behavioral auditory test performance. Click-ABR results were not significantly different between the mTBI and control groups. However, when comparing the control group to only those mTBI subjects with measurably decreased performance on auditory behavioral tests, small differences emerged, including delayed latencies for waves I, III, and V. Similarly, few significant group differences were observed for peak amplitudes and latencies of the speech-ABR when comparing at the whole group level

  19. Neuropsychological profile of a 9-year-old child with subcortical band heterotopia or 'double cortex'.

    Science.gov (United States)

    Jacobs, R; Anderson, V; Harvey, A S

    2001-09-01

    Subcortical band heterotopia (SBH) or 'double cortex', is a congenital brain abnormality that results from aberrant migration of neurons during development of the cortex. MRI shows a continuous band of heterotopic grey matter located between the cortex and ventricular walls, separated from them by a thin layer of white matter. The condition is quite rare, found predominantly in females, and is occasionally familial with an X-linked dominant inheritance. Current research has focused on genetic and neurological correlates, with cognitive assessment restricted to a global measure of general intellectual functioning. This paper describes in detail the results of a neuropsychological assessment of a 9-year-old female recently diagnosed with SBH. Predominant features were a significantly reduced speed of processing for visuomotor and oral output and reduced immediate registration of information. This difficulty has functional implications affecting skill acquisition, learning in the classroom, and social interaction.

  20. [A male case of subcortical band heterotopia with somatic mosaicism of DCX mutation].

    Science.gov (United States)

    Igarashi, Aiko; Kawatani, Masao; Ohta, Genrei; Kometani, Hiroshi; Ohshima, Yusei; Kato, Mitsuhiro

    2013-09-01

    This report describes a male case of subcortical band heterotopia (SBH) with somatic mosaicism of doublecortin (DCX) mutation. His brain MRI revealed bilateral SBH with anterior dominant pachygyria. Although he had infantile spasms from 5-months old and showed mild developmental delay, he responded well to vitamin B6 and ACTH therapy. We conducted DCX mutation analysis using peripheral blood lymphocytes of the proband and his parents. Only the present case showed the mixture pattern of missense mutation (c. 167 G>C) and normal sequence of DCX gene indicating that the present case resulted from somatic mosaicism of de novo DCX mutation. Male patients with DCX mutations generally present with the classical type of lissencephaly, severe developmental delay, and intractable epilepsy. However, somatic mosaic mutation of DCX can lead to SBH in males.

  1. Subcortical laminar heterotopia in two sisters and their mother: MRI, clinical findings and pathogenesis.

    Science.gov (United States)

    van der Valk, P H; Snoeck, I; Meiners, L C; des Portes, V; Chelly, J; Pinard, J M; Ippel, P F; van Nieuwenhuizen, O; Peters, A C

    1999-06-01

    MR imaging, clinical data and underlying pathogenesis of subcortical laminar heterotopia (SCLH), also known as band heterotopia, in two sisters and their mother are presented. On MR imaging a different degree of SCLH was found in all three affected family-members. The inversion recovery sequence was considered most useful in the demonstration of the heterotopic band of gray matter and the assessment of cortical thickness. The younger sister presented with epileptic seizures at the age of five months and a delayed achievement of developmental milestones. The older sister of seven years had epileptic seizures since the age of one year, and developmental delay. Their mother has only had one seizure-like episode at the age of 39. Her psychomotor development had been normal. Investigation of DNA samples of the three female family-members revealed a mutation in the X-linked doublecortin gene. Within families with band heterotopia, this gene has also been related to male family members with lissencephaly.

  2. Elderly listeners with low intelligibility scores under reverberation show degraded subcortical representation of reverberant speech.

    Science.gov (United States)

    Fujihira, H; Shiraishi, K; Remijn, G B

    2017-01-10

    In order to elucidate why many elderly listeners have difficulty understanding speech under reverberation, we investigated the relationship between word intelligibility and auditory brainstem responses (ABRs) in 28 elderly listeners. We hypothesized that the elderly listeners with low word intelligibility scores under reverberation would show degraded subcortical encoding information of reverberant speech as expressed in their ABRs towards a reverberant /da/ syllable. The participants were divided into two groups (top and bottom performance groups) according to their word intelligibility scores for anechoic and reverberant words, and ABR characteristics between groups were compared. We found that correlation coefficients between responses to anechoic and reverberant /da/ were lower in the bottom performance group than in the top performance group. This result suggests that degraded neural representation toward information of reverberant speech may account for lower intelligibility of reverberant speech in elderly listeners. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  3. Neuropsychiatric characteristics of PiB-negative subcortical vascular dementia versus behavioral variant frontotemporal dementia.

    Science.gov (United States)

    Jung, Na-Yeon; Kim, Hee Jin; Kim, Yeo Jin; Kim, Seonwoo; Seo, Sang Won; Kim, Eun-Joo; Na, Duk L

    2016-01-01

    Neuropsychiatric symptoms of subcortical vascular dementia (SVaD) are mainly associated with damage to frontal-subcortical circuits and may be similar to symptoms of behavioral variant frontotemporal dementia (bvFTD). The aim of this study was to determine whether the neuropsychiatric manifestations of the Pittsburgh compound B (PiB)-negative SVaD and bvFTD groups differ. We compared the Caregiver-Administered Neuropsychiatry Inventory (CGA-NPI) between 48 patients with PiB(-) SVaD and 31 patients with bvFTD. A stepwise logistic regression was applied to determine the best model to predict SVaD. The SVaD group showed a higher frequency of depression, whereas the bvFTD group had a higher frequency of elation, aberrant motor behavior and appetite/eating disorders. Regarding NPI subscores, the bvFTD group had greater severity of elation, apathy, disinhibition, aberrant motor behavior and appetite/eating disorders, whereas SVaD did not have significantly higher subscores in any domains. The most predictive models that tend to find suggestions of SVaD, as opposed to bvFTD, are as follows: (1) the presence of depression and the absence of appetite/eating disorders, (2) higher NPI subscores of depression and lower NPI subscores of irritability and aberrant motor behavior. Apart from apathy, SVaD differed from bvFTD in that negative symptoms were more common in SVaD than bvFTD, whereas positive symptoms were predominant in bvFTD compared to SVaD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Acute phencyclidine administration induces c-Fos-immunoreactivity in interneurons in cortical and subcortical regions.

    Science.gov (United States)

    Hervig, Mona E; Thomsen, Morten S; Kalló, Imre; Mikkelsen, Jens D

    2016-10-15

    Dysfunction of N-Methyl-d-aspartate receptors (NMDARs) is believed to underlie some of the symptoms in schizophrenia, and non-competitive NMDAR antagonists (including phencyclidine (PCP)) are widely used as pharmacological schizophrenia models. Furthermore, mounting evidence suggests that impaired γ-aminobutyric acid (GABA) neurotransmission contributes to the cognitive deficits in schizophrenia. Thus alterations in GABAergic interneurons have been observed in schizophrenia patients and animal models. Acute systemic administration of PCP increases levels of c-Fos in several cortical and subcortical areas, but whether such induction occurs in specific populations of GABAergic interneuron subtypes still remains to be established. We performed an immunohistochemical analysis of the PCP-induced c-Fos-immunoreactivity (IR) in parvalbumin (PV) and calbindin (CB) interneuron subtypes in the cortex and thalamus of rats. A single dose of PCP (10mg/kg, s.c.) significantly increased total number of c-Fos-IR in: (1) the prelimbic, infralimbic, anterior cingulate, ventrolateral orbital, motor, somatosensory and retrosplenial cortices as well as the nucleus accumbens (NAc), field CA1 of the hippocampus (CA1) field of hippocampus and mediodorsal thalamus (MD); (2) PV-IR cells in the ventrolateral orbitofrontal and retrosplenial cortices and CA1 field of hippocampus; and (3) CB-IR cells in the motor cortex. Overall, our data indicate that PCP activates a wide range of cortical and subcortical brain regions and that a substantial part of this activation is present in GABAergic interneurons in certain regions. This suggests that the psychotomimetic effect of PCP may be mediated via GABAergic interneurons. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Subcortical encoding of speech cues in children with congenital blindness.

    Science.gov (United States)

    Jafari, Zahra; Malayeri, Saeed

    2016-09-21

    Congenital visual deprivation underlies neural plasticity in different brain areas, and provides an outstanding opportunity to study the neuroplastic capabilities of the brain. The present study aimed to investigate the effect of congenital blindness on subcortical auditory processing using electrophysiological and behavioral assessments in children. A total of 47 children aged 8-12 years, including 22 congenitally blind (CB) children and 25 normal-sighted (NS) control, were studied. All children were tested using an auditory brainstem response (ABR) test with both click and speech stimuli. Speech recognition and musical abilities were tested using standard tools. Significant differences were observed between the two groups in speech ABR wave latencies A, F and O (p≤0.043), wave amplitude F (p = 0.039), V-A slope (p = 0.026), and three spectral magnitudes F0, F1 and HF (p≤0.002). CB children showed a superior performance compared to NS peers in all the subtests and the total score of musical abilities (p≤0.003). Moreover, they had significantly higher scores during the nonsense syllable test in noise than the NS children (p = 0.034). Significant negative correlations were found only in CB children between the total music score and both wave A (p = 0.039) and wave F (p = 0.029) latencies, as well as nonsense-syllable test in noise and the wave A latency (p = 0.041). Our results suggest that neuroplasticity resulting from congenital blindness can be measured subcortically and has a heightened effect on temporal, musical and speech processing abilities. The findings have been discussed based on models of plasticity and the influence of corticofugal modulation in synthesizing complex auditory stimuli.

  6. Quantitative characterization of new supramolecular synthons involving fluorine atoms in the crystal structures of di- and tetrafluorinated benzamides.

    Science.gov (United States)

    Mondal, Pradip Kumar; Yadav, Hare Ram; Choudhury, Angshuman Roy; Chopra, Deepak

    2017-10-01

    Strong hydrogen bonds play a significant role in crystal packing. In particular, the involvement of interactions involving fluorine in controlling the crystal packing requires appropriate attention, especially in the presence of other strong hydrogen bonds. In the present study, a detailed quantitative assessment has been performed of the nature, energetics and topological properties derived from the electron density in model compounds based on fluorinated benzamides (a total of 46 fluorine-substituted benzamides containing multiple fluorine atoms) in the solid state. The primary motivation in the design of such molecules is to enhance the acidity of the interacting H atoms in the presence of an increasing number of F atoms on the molecular scaffold, resulting in increased propensity towards the formation of intermolecular interactions involving organic fluorine. This exercise has resulted in the identification of new and frequently occurring supramolecular synthons involving F atoms in the packing of molecules in the solid state. The energetics associated with short and directional intermolecular Csp 2 -H...F-Csp 2 interactions with significantly high electrostatic contributions is noteworthy, and the topological analysis reveals the bonding character of these ubiquitous interactions in crystal packing in addition to the presence of Csp 2 -F...F-Csp 2 contacts.

  7. Xtal-xplore-R: a graphical tool for exploring the residual function involved in crystal structure determination.

    Science.gov (United States)

    Simons, Jan Marten; Roth, Georg

    2015-08-01

    This work presents Xtal-xplore-R, a tool dedicated to the visualization of two-dimensional cuts through the multidimensional crystallographic residual function. It imports arbitrary crystal structures, generates artificial diffraction data, and calculates and investigates the residual function in parameter space. The program serves two major purposes. Firstly, it is part of a more general project dealing with structure determination via global optimization techniques. In this context, the tool is being used to systematically analyse characteristic universal features of the target function (residual function) which can be used to develop appropriate problem-specific heuristic optimization algorithms. Secondly, Xtal-xplore-R is intended as a didactic tool to visualize how changes in atom parameters affect the residual function and can be used to demonstrate manual structure optimization for simple crystal structures.

  8. Assessing genetic structure with multiple classes of molecular markers: a case study involving the introduced fire ant Solenopsis invicta

    OpenAIRE

    Ross, K. G.; Shoemaker, D. D.; Krieger, M. J.; DeHeer, C. J.; Keller, L.

    1999-01-01

    We used 30 genetic markers of 6 different classes to describe hierarchical genetic structure in introduced populations of the fire ant Solenopsis invicta. These included four classes of presumably neutral nuclear loci (allozymes, codominant random amplified polymorphic DNAs (RAPDs), microsatellites, and dominant RAPDs), a class comprising two linked protein-coding nuclear loci under selection, and a marker of the mitochondrial DNA (mtDNA). Patterns of structure revealed by F statistics and ex...

  9. Functional and Structural Characterization of a Receptor-Like Kinase Involved in Germination and Cell Expansion in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Zhen Wu

    2017-11-01

    Full Text Available Leucine-rich repeat receptor-like kinases (LRR-RLKs are widespread in different plant species and play important roles in growth and development. Germination inhibition is vital for the completion of seed maturation and cell expansion is a fundamental cellular process driving plant growth. Here, we report genetic and structural characterizations of a functionally uncharacterized LRR-RLK, named GRACE (Germination Repression and Cell Expansion receptor-like kinase. Overexpression of GRACE in Arabidopsis exhibited delayed germination, enlarged cotyledons, rosette leaves and stubbier petioles. Conversely, these phenotypes were reversed in the T-DNA insertion knock-down mutant grace-1 plants. A crystal structure of the extracellular domain of GRACE (GRACE-LRR determined at the resolution of 3.0 Å revealed that GRACE-LRR assumed a right-handed super-helical structure with an island domain (ID. Structural comparison showed that structure of the ID in GRACE-LRR is strikingly different from those observed in other LRR-RLKs. This structural observation implies that GRACE might perceive a new ligand for signaling. Collectively, our data support roles of GRACE in repressing seed germination and promoting cell expansion of Arabidopsis, presumably by perception of unknown ligand(s.

  10. Au@SiO2 core-shell structure involved with methotrexate: Fabrication, biodegradation process and bioassay explore.

    Science.gov (United States)

    Huo, Xiaolei; Dai, Chaofan; Tian, Deying; Li, Shuping; Li, Xiaodong

    2015-12-30

    A new strategy is proposed to synthesize a kind of Au@SiO2 core-shell structure with methotrexate (MTX) loaded within it. Firstly, MTX molecules are attracted to the surface and vicinity of Au nanoparticles (NPs). Then the enriched MTX molecules on the surface of Au NPs have a good chance to be wrapped into the core-shell structure when SiO2 is uniformly deposited on the Au core. Secondly, the effect of Au amount and MTX content on the drug-loading capacity is emphatically studied and the result shows that core-shell structure plays a vital role in drug loading. In addition, the biodegradation process is also examined in phosphate buffer solution (PBS) at 37°C. The results show that the biodegradation of Au-MTX@SiO2 core-shell structure can be divided into two stages: the release of drug together with the fragmentation of core-shell structure and the subsequent dissolution of SiO2 layers. Lastly, in vitro bioassay tests give the evidence that obvious tumor inhibition can be achieved in presence of Au-MTX@SiO2 NPs even at low concentration and the efficacy can be greatly enhanced by the photothermal therapy on Au cores. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Structural biology of disease-associated repetitive DNA sequences and protein-DNA complexes involved in DNA damage and repair

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, G.; Santhana Mariappan, S.V.; Chen, X.; Catasti, P.; Silks, L.A. III; Moyzis, R.K.; Bradbury, E.M.; Garcia, A.E.

    1997-07-01

    This project is aimed at formulating the sequence-structure-function correlations of various microsatellites in the human (and other eukaryotic) genomes. Here the authors have been able to develop and apply structure biology tools to understand the following: the molecular mechanism of length polymorphism microsatellites; the molecular mechanism by which the microsatellites in the noncoding regions alter the regulation of the associated gene; and finally, the molecular mechanism by which the expansion of these microsatellites impairs gene expression and causes the disease. Their multidisciplinary structural biology approach is quantitative and can be applied to all coding and noncoding DNA sequences associated with any gene. Both NIH and DOE are interested in developing quantitative tools for understanding the function of various human genes for prevention against diseases caused by genetic and environmental effects.

  12. Limbic justice--amygdala involvement in immediate rejection in the Ultimatum Game.

    Directory of Open Access Journals (Sweden)

    Katarina Gospic

    2011-05-01

    Full Text Available Imaging studies have revealed a putative neural account of emotional bias in decision making. However, it has been difficult in previous studies to identify the causal role of the different sub-regions involved in decision making. The Ultimatum Game (UG is a game to study the punishment of norm-violating behavior. In a previous influential paper on UG it was suggested that frontal insular cortex has a pivotal role in the rejection response. This view has not been reconciled with a vast literature that attributes a crucial role in emotional decision making to a subcortical structure (i.e., amygdala. In this study we propose an anatomy-informed model that may join these views. We also present a design that detects the functional anatomical response to unfair proposals in a subcortical network that mediates rapid reactive responses. We used a functional MRI paradigm to study the early components of decision making and challenged our paradigm with the introduction of a pharmacological intervention to perturb the elicited behavioral and neural response. Benzodiazepine treatment decreased the rejection rate (from 37.6% to 19.0% concomitantly with a diminished amygdala response to unfair proposals, and this in spite of an unchanged feeling of unfairness and unchanged insular response. In the control group, rejection was directly linked to an increase in amygdala activity. These results allow a functional anatomical detection of the early neural components of rejection associated with the initial reactive emotional response. Thus, the act of immediate rejection seems to be mediated by the limbic system and is not solely driven by cortical processes, as previously suggested. Our results also prompt an ethical discussion as we demonstrated that a commonly used drug influences core functions in the human brain that underlie individual autonomy and economic decision making.

  13. The Structural Basis of Substrate Recognition in an exo-beta-d-Glucosaminidase Involved in Chitosan Hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Lammerts van Bueren, A.; Ghinet, M; Gregg, K; Fleury, A; Brzezinski, R; Boraston, A

    2009-01-01

    Family 2 of the glycoside hydrolase classification is one of the largest families. Structurally characterized members of this family include enzymes with beta-galactosidase activity (Escherichia coli LacZ), beta-glucuronidase activity (Homo sapiens GusB), and beta-mannosidase activity (Bacteroides thetaiotaomicron BtMan2A). Here, we describe the structure of a family 2 glycoside hydrolase, CsxA, from Amycolatopsis orientalis that has exo-beta-D-glucosaminidase (exo-chitosanase) activity. Analysis of a product complex (1.85 A resolution) reveals a unique negatively charged pocket that specifically accommodates the nitrogen of nonreducing end glucosamine residues, allowing this enzyme to discriminate between glucose and glucosamine. This also provides structural evidence for the role of E541 as the catalytic nucleophile and D469 as the catalytic acid/base. The structures of an E541A mutant in complex with a natural beta-1,4-D-glucosamine tetrasaccharide substrate and both E541A and D469A mutants in complex with a pNP-beta-D-glucosaminide synthetic substrate provide insight into interactions in the +1 subsite of this enzyme. Overall, a comparison with the active sites of other GH2 enzymes highlights the unique architecture of the CsxA active site, which imparts specificity for its cationic substrate.

  14. The Structural Basis of Substrate Recognition in an exo-b-d-glucosaminidase Involved in Chitosan Hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Van Bueren, A.; Ghinet, M; Gregg, K; Fleury, A; Brzezinski, R; Boraston, A

    2009-01-01

    Family 2 of the glycoside hydrolase classification is one of the largest families. Structurally characterized members of this family include enzymes with ?-galactosidase activity (Escherichia coli LacZ), ?-glucuronidase activity (Homo sapiens GusB), and ?-mannosidase activity (Bacteroides thetaiotaomicron BtMan2A). Here, we describe the structure of a family 2 glycoside hydrolase, CsxA, from Amycolatopsis orientalis that has exo-?-d-glucosaminidase (exo-chitosanase) activity. Analysis of a product complex (1.85 A resolution) reveals a unique negatively charged pocket that specifically accommodates the nitrogen of nonreducing end glucosamine residues, allowing this enzyme to discriminate between glucose and glucosamine. This also provides structural evidence for the role of E541 as the catalytic nucleophile and D469 as the catalytic acid/base. The structures of an E541A mutant in complex with a natural ?-1,4-d-glucosamine tetrasaccharide substrate and both E541A and D469A mutants in complex with a pNP-?-d-glucosaminide synthetic substrate provide insight into interactions in the + 1 subsite of this enzyme. Overall, a comparison with the active sites of other GH2 enzymes highlights the unique architecture of the CsxA active site, which imparts specificity for its cationic substrate.

  15. The composition of ectopic lymphoid structures suggests involvement of a local immune response in cardiac allograft vasculopathy

    NARCIS (Netherlands)

    Huibers, Manon M. H.; Gareau, Alison J.; Vink, Aryan; Kruit, Rianne; Feringa, Hannah; Beerthuijzen, Johanna M. T.; Siera-de Koning, Erica; Peeters, Ton; de Jonge, Nicolaas; de Weger, Roel A.; Lee, Timothy D. G.

    BACKGROUND: Cardiac allograft vasculopathy (CAV) is a multifactorial pathology limiting the survival of cardiac transplants. The etiology of CAV is unclear, but antibody-mediated and cellular-mediated responses have been implicated. We, and others, have observed ectopic lymphoid structures (ELS)

  16. Sequence and Structural Analysis of the Chitinase Insertion Domain Reveals Two Conserved Motifs Involved in Chitin-Binding

    Science.gov (United States)

    Li, Hai; Greene, Lesley H.

    2010-01-01

    Background Chitinases are prevalent in life and are found in species including archaea, bacteria, fungi, plants, and animals. They break down chitin, which is the second most abundant carbohydrate in nature after cellulose. Hence, they are important for maintaining a balance between carbon and nitrogen trapped as insoluble chitin in biomass. Chitinases are classified into two families, 18 and 19 glycoside hydrolases. In addition to a catalytic domain, which is a triosephosphate isomerase barrel, many family 18 chitinases contain another module, i.e., chitinase insertion domain. While numerous studies focus on the biological role of the catalytic domain in chitinase activity, the function of the chitinase insertion domain is not completely understood. Bioinformatics offers an important avenue in which to facilitate understanding the role of residues within the chitinase insertion domain in chitinase function. Results Twenty-seven chitinase insertion domain sequences, which include four experimentally determined structures and span five kingdoms, were aligned and analyzed using a modified sequence entropy parameter. Thirty-two positions with conserved residues were identified. The role of these conserved residues was explored by conducting a structural analysis of a number of holo-enzymes. Hydrogen bonding and van der Waals calculations revealed a distinct subset of four conserved residues constituting two sequence motifs that interact with oligosaccharides. The other conserved residues may be key to the structure, folding, and stability of this domain. Conclusions Sequence and structural studies of the chitinase insertion domains conducted within the framework of evolution identified four conserved residues which clearly interact with the substrates. Furthermore, evolutionary studies propose a link between the appearance of the chitinase insertion domain and the function of family 18 chitinases in the subfamily A. PMID:20084296

  17. Ferritin structure from Mycobacterium tuberculosis: comparative study with homologues identifies extended C-terminus involved in ferroxidase activity.

    Directory of Open Access Journals (Sweden)

    Garima Khare

    Full Text Available Ferritins are recognized as key players in the iron storage and detoxification processes. Iron acquisition in the case of pathogenic bacteria has long been established as an important virulence mechanism. Here, we report a 3.0 Å crystal structure of a ferritin, annotated as Bacterioferritin B (BfrB, from Mycobacterium tuberculosis (Mtb, the causative agent of tuberculosis that continues to be one of the world's deadliest diseases. Similar to the other members of ferritin family, the Mtb BfrB subunit exhibits the characteristic fold of a four-helical bundle that possesses the ferroxidase catalytic centre. We compare the structure of Mtb BfrB with representatives of the ferritin family belonging to the archaea, eubacteria and eukarya. Unlike most other ferritins, Mtb BfrB has an extended C-terminus. To dissect the role of this extended C-terminus, truncated Mtb BfrB was purified and biochemical studies implicate this region in ferroxidase activity and iron release in addition to providing stability to the protein. Functionally important regions in a protein of known 3D-structure can be determined by estimating the degree of conservation of the amino-acid sites with its close homologues. Based on the comparative studies, we identify the slowly evolving conserved sites as well as the rapidly evolving variable sites and analyze their role in relation to structure and function of Mtb BfrB. Further, electrostatic computations demonstrate that although the electrostatic environment of catalytic residues is preserved within the family, extensive variability is exhibited by residues defining the channels and pores, in all likelihood keeping up with the diverse functions executed by these ferritins in varied environments.

  18. Structural-dynamical investigation of the ZnuA histidine-rich loop: involvement in zinc management and transport.

    Science.gov (United States)

    Falconi, Mattia; Oteri, Francesco; Di Palma, Francesco; Pandey, Saurabh; Battistoni, Andrea; Desideri, Alessandro

    2011-02-01

    Comparative homology modelling techniques have been used to model the protein ZnuA from Salmonella enterica serovar Typhimurium using the 3D structure of the homologous protein from Escherichia coli. These two-domain proteins bind one Zn(2+) atom, with high affinity, in the inter-domain cleft and possess a histidine-rich loop in the N-terminal domain. Alternative structures of the ZnuA histidine-rich loop, never resolved by the X-ray diffraction method, have been modelled. A model of the apo form, one with the histidine-rich loop deleted and two alternative structures with a second zinc ion bound to the histidine-rich loop, have been generated. In all the modelled proteins, investigated through molecular dynamics simulation, the histidine-rich loop is highly mobile and its fluctuations are correlated to the ligand stability observed in the zinc sites. Based on the plasticity of the histidine-rich loop and its significant effects on protein mobility a possible role in the capture and/or transfer of the zinc ions has been suggested.

  19. Grey matter density changes of structures involved in Posttraumatic Stress Disorder (PTSD) after recovery following Eye Movement Desensitization and Reprocessing (EMDR) therapy.

    Science.gov (United States)

    Boukezzi, Sarah; El Khoury-Malhame, Myriam; Auzias, Guillaume; Reynaud, Emmanuelle; Rousseau, Pierre-François; Richard, Emmanuel; Zendjidjian, Xavier; Roques, Jacques; Castelli, Nathalie; Correard, Nadia; Guyon, Valérie; Gellato, Caroline; Samuelian, Jean-Claude; Cancel, Aida; Comte, Magali; Latinus, Marianne; Guedj, Eric; Khalfa, Stéphanie

    2017-08-30

    Recovery of stress-induced structural alterations in Posttraumatic Stress Disorder (PTSD) remains largely unexplored. This study aimed to determine whether symptoms improvement is associated with grey matter (GM) density changes of brain structures involved in PTSD. Two groups of PTSD patients were involved in this study. The first group was treated with Eye Movement Desensitization and Reprocessing (EMDR) therapy and recovered from their symptoms (recovery group) (n = 11); Patients were scanned prior to therapy (T1), one week (T2) and five months after the end of therapy (T3). The second group included patients which followed a supportive therapy and remained symptomatic (wait-list group) (n = 7). They were scanned at three time-steps mimicking the same inter-scan intervals. Voxel-based morphometry (VBM) was used to characterize GM density evolution. GM density values showed a significant group-by-time interaction effect between T1 and T3 in prefrontal cortex areas. These interaction effects were driven by a GM density increase in the recovery group with respect to the wait-list group. Symptoms removal goes hand-in-hand with GM density enhancement of structures involved in emotional regulation. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  20. Structures of trehalose synthase from Deinococcus radiodurans reveal that a closed conformation is involved in catalysis of the intramolecular isomerization.

    Science.gov (United States)

    Wang, Yung Lin; Chow, Sih Yao; Lin, Yi Ting; Hsieh, Yu Chiao; Lee, Guan Chiun; Liaw, Shwu Huey

    2014-12-01

    Trehalose synthase catalyzes the simple conversion of the inexpensive maltose into trehalose with a side reaction of hydrolysis. Here, the crystal structures of the wild type and the N253A mutant of Deinococcus radiodurans trehalose synthase (DrTS) in complex with the inhibitor Tris are reported. DrTS consists of a catalytic (β/α)8 barrel, subdomain B, a C-terminal β domain and two TS-unique subdomains (S7 and S8). The C-terminal domain and S8 contribute the majority of the dimeric interface. DrTS shares high structural homology with sucrose hydrolase, amylosucrase and sucrose isomerase in complex with sucrose, in particular a virtually identical active-site architecture and a similar substrate-induced rotation of subdomain B. The inhibitor Tris was bound and mimics a sugar at the -1 subsite. A maltose was modelled into the active site, and subsequent mutational analysis suggested that Tyr213, Glu320 and Glu324 are essential within the +1 subsite for the TS activity. In addition, the interaction networks between subdomains B and S7 seal the active-site entrance. Disruption of such networks through the replacement of Arg148 and Asn253 with alanine resulted in a decrease in isomerase activity by 8-9-fold and an increased hydrolase activity by 1.5-1.8-fold. The N253A structure showed a small pore created for water entry. Therefore, our DrTS-Tris may represent a substrate-induced closed conformation that will facilitate intramolecular isomerization and minimize disaccharide hydrolysis.

  1. Structural and dynamic characterization of a freestanding acyl carrier protein involved in the biosynthesis of cyclic lipopeptide antibiotics.

    Science.gov (United States)

    Paul, Subrata; Ishida, Hiroaki; Nguyen, Leonard T; Liu, Zhihong; Vogel, Hans J

    2017-05-01

    Friulimicin is a cyclic lipodecapeptide antibiotic that is produced by Actinoplanes friuliensis. Similar to the related lipopeptide drug daptomycin, the peptide skeleton of friulimicin is synthesized by a large multienzyme nonribosomal peptide synthetase (NRPS) system. The LipD protein plays a major role in the acylation reaction of friulimicin. The attachment of the fatty acid group promotes its antibiotic activity. Phylogenetic analysis reveals that LipD is most closely related to other freestanding acyl carrier proteins (ACPs), for which the genes are located near to NRPS gene clusters. Here, we report that the solution NMR structure of apo-LipD is very similar to other four-helix bundle forming ACPs from fatty acid synthase (FAS), polyketide synthase, and NRPS systems. By recording NMR dynamics data, we found that the backbone motions in holo-LipD are more restricted than in apo-LipD due to the attachment of phosphopantetheine moiety. This enhanced stability of holo-LipD was also observed in differential scanning calorimetry experiments. Furthermore, we demonstrate that, unlike several other ACPs, the folding of LipD does not depend on the presence of divalent cations, although the presence of Mg 2+ or Ca 2+ can increase the protein stability. We propose that small structural rearrangements in the tertiary structure of holo-LipD which lead to the enhanced stability are important for the cognate enzyme recognition for the acylation reaction. Our results also highlight the different surface charges of LipD and FAS-ACP from A. friuliensis that would allow the acyl-CoA ligase to interact preferentially with the LipD instead of binding to the FAS-ACP. © 2017 The Protein Society.

  2. Structural Analysis of Streptococcus pyogenes NADH Oxidase: Conformational Dynamics Involved in Formation of the C(4a)-Peroxyflavin Intermediate.

    Science.gov (United States)

    Wallen, Jamie R; Mallett, T Conn; Okuno, Takashi; Parsonage, Derek; Sakai, Hiroaki; Tsukihara, Tomitake; Claiborne, Al

    2015-11-17

    In probing the oxygen reactivity of an Enterococcus faecalis NADH oxidase (Nox; O2 → 2H2O) C42S mutant lacking the Cys42-sulfenic acid (Cys42-SOH) redox center, we provided direct evidence of a C(4a)-peroxyflavin intermediate in the oxidative half-reaction and also described a conformational or chemical change that is rate-limiting for full reoxidation of the homodimer. In this work, the Nox from Streptococcus pyogenes (SpyNox) has been expressed and crystallized, and the overoxidized wild-type [Cys44-SOH → Cys44-sulfinic acid (Cys44-SO2H)] and C44S mutant enzyme structures have been refined at 2.0 and 2.15 Å, respectively. We show that azide binds to the two-electron reduced wild-type (EH2) enzyme and to the mutant enzyme in solution, but with a significantly higher affinity for the mutant protein. The spectral course of the titration with the SpyNox EH2 form clearly indicates progressive displacement of the Cys44-S(-) → FAD charge-transfer interaction. An azide soak with C44S Nox crystals led to the structure of the complex, as refined at 2.10 Å. The active-site N3(-) ligand is proximal to the Ser44 and His11 side chains, and a significant shift in the Ser44 side chain also appears. This provides an attractive explanation for the azide-induced loss of charge-transfer absorbance seen with the wild-type EH2 form and also permits accommodation of a C(4a)-peroxyflavin structural model. The conformation of Ser44 and the associated helical element, and the resulting steric accommodation, appear to be linked to the conformational change described in the E. faecalis C42S Nox oxidative half-reaction.

  3. Enzymatic properties of a GH19 chitinase isolated from rice lacking a major loop structure involved in chitin binding.

    Science.gov (United States)

    Tanaka, Jun; Fukamizo, Tamo; Ohnuma, Takayuki

    2017-05-01

    The catalytic domains of family GH19 chitinases have been found to consist of a conserved, α-helical core-region and different numbers (1-6) of loop structures, located at both ends of the substrate-binding groove and which extend over the glycon- and aglycon-binding sites. We expressed, purified and enzymatically characterized a GH19 chitinase from rice, Oryza sativa L. cv. Nipponbare (OsChia2a), lacking a major loop structure (loop III) connected to the functionally important β-stranded region. The new enzyme thus contained the five remaining loop structures (loops I, II, IV, V and C-term). The OsChia2a recombinant protein catalyzed hydrolysis of chitin oligosaccharides, (GlcNAc)n (n = 3-6), with inversion of anomeric configuration, indicating that OsChia2a correctly folded without loop III. From thermal unfolding experiments and calorimetric titrations using the inactive OsChia2a mutant (OsChia2a-E68Q), in which the catalytic residue Glu68 was mutated to glutamine, we found that the binding affinities towards (GlcNAc)n (n = 2-6) were almost proportional to the degree of polymerization of (GlcNAc)n, but were much lower than those obtained for a moss GH19 chitinase having only loop III [Ohnuma T, Sørlie M, Fukuda T, Kawamoto N, Taira T, Fukamizo T. 2011. Chitin oligosaccharide binding to a family GH19 chitinase from the moss, Bryum coronatum. FEBS J. 278:3991-4001]. Nevertheless, OsChia2a exhibited significant antifungal activity. It appears that loop III connected to the β-stranded region is important for (GlcNAc)n binding, but is not essential for antifungal activity. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Structural analysis of PseH, the Campylobacter jejuni N-acetyltransferase involved in bacterial O-linked glycosylation

    Energy Technology Data Exchange (ETDEWEB)

    Song, Wan Seok; Nam, Mi Sun; Namgung, Byeol [Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Yoon, Sung-il, E-mail: sungil@kangwon.ac.kr [Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701 (Korea, Republic of)

    2015-03-20

    Campylobacter jejuni is a bacterium that uses flagella for motility and causes worldwide acute gastroenteritis in humans. The C. jejuni N-acetyltransferase PseH (cjPseH) is responsible for the third step in flagellin O-linked glycosylation and plays a key role in flagellar formation and motility. cjPseH transfers an acetyl group from an acetyl donor, acetyl coenzyme A (AcCoA), to the amino group of UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine to produce UDP-2,4-diacetamido-2,4,6-trideoxy-β-L-altropyranose. To elucidate the catalytic mechanism of cjPseH, crystal structures of cjPseH alone and in complex with AcCoA were determined at 1.95 Å resolution. cjPseH folds into a single-domain structure of a central β-sheet decorated by four α-helices with two continuously connected grooves. A deep groove (groove-A) accommodates the AcCoA molecule. Interestingly, the acetyl end of AcCoA points toward an open space in a neighboring shallow groove (groove-S), which is occupied by extra electron density that potentially serves as a pseudosubstrate, suggesting that the groove-S may provide a substrate-binding site. Structure-based comparative analysis suggests that cjPseH utilizes a unique catalytic mechanism of acetylation that has not been observed in other glycosylation-associated acetyltransferases. Thus, our studies on cjPseH will provide valuable information for the design of new antibiotics to treat C. jejuni-induced gastroenteritis. - Highlights: • cjPseH adopts a single-domain structure of a central β-sheet decorated by α-helices. • cjPseH features two continuously connected grooves on the protein surface. • Acetyl coenzyme A (AcCoA) binds into a deep groove of cjPseH in an ‘L’ shape. • The acetyl end of AcCoA points to a wide groove, a potential substrate-binding site.

  5. Structural basis of the substrate preference towards CMP for a thymidylate synthase MilA involved in mildiomycin biosynthesis.

    Science.gov (United States)

    Zhao, Gong; Chen, Cheng; Xiong, Wei; Gao, Tuling; Deng, Zixin; Wu, Geng; He, Xinyi

    2016-12-21

    Modified pyrimidine monophosphates such as methyl dCMP (mdCMP), hydroxymethyl dUMP (hmdUMP) and hmdCMP in some phages are synthesized by a large group of enzymes termed as thymidylate synthases (TS). Thymidylate is a nucleotide required for DNA synthesis and thus TS is an important drug target. In the biosynthetic pathway of the nucleoside fungicide mildiomycin isolated from Streptomyces rimofaciens ZJU5119, a cytidylate (CMP) hydroxymethylase, MilA, catalyzes the conversion of CMP into 5'-hydroxymethyl CMP (hmCMP) with an efficiency (kcat/KM) of 5-fold faster than for deoxycytidylate (dCMP). MilA is thus the first enzyme of the TS superfamily preferring CMP to dCMP. Here, we determined the crystal structures of MilA and its complexes with various substrates including CMP, dCMP and hmCMP. Comparing these structures to those of dCMP hydroxymethylase (CH) from T4 phage and TS from Escherichia coli revealed that two residues in the active site of CH and TS, a serine and an arginine, are respectively replaced by an alanine and a lysine, Ala176 and Lys133, in MilA. Mutation of A176S/K133R of MilA resulted in a reversal of substrate preference from CMP to dCMP. This is the first study reporting the evolution of the conserved TS in substrate selection from DNA metabolism to secondary nucleoside biosynthesis.

  6. Blocking systemic nitric oxide production alters neuronal activation in brain structures involved in cardiovascular regulation during polymicrobial sepsis.

    Science.gov (United States)

    Bruhn, Fernando Henrique Pascoti; Corrêa, Pollyanna Barbosa Farias; Oliveira-Pelegrin, Gabriela Ravanelli; Rocha, Maria José Alves

    2009-04-10

    In a previous study, we concluded that overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) in the late phase of sepsis prevents hypothalamic activation, blunts vasopressin secretion and contributes to hypotension, irreversible shock and death. The aim of this follow-up study was to evaluate if the same neuronal activation pattern happens in brain structures related to cardiovascular functions. Male Wistar rats received intraperitoneal injections of aminoguanidine, an iNOS inhibitor, or saline 30 min before cecal ligation and puncture (CLP) or sham surgeries. The animals were perfused 6 or 24h after the surgeries and the brains were removed and processed for Fos immunocytochemistry. We observed an increase (Pafter CLP in the area postrema (AP), nucleus of the tractus solitarius (NTS), ventral lateral medulla (VLM), locus coeruleus (LC) and parabrachial nucleus (PB). At 24h after CLP, however, c-fos expression was strongly decreased in all these nuclei (Pafter CLP, but showed an opposite effect at 24h, with an increase in the AP, NTS, and also in the VLM. No such effect was observed in the LC and PB at 6 or 24h. In all control animals, c-fos expression was minimal or absent. We conclude that in the early phase of sepsis iNOS-derived NO may be partially responsible for the activation of brain structures related to cardiovascular regulation. During the late phase, however, this activation is reduced or abolished.

  7. Structural Studies of RNA Helicases Involved in Eukaryotic Pre-mRNA Splicing, Ribosome Biogenesis, and Translation Initiation

    DEFF Research Database (Denmark)

    He, Yangzi

    Ribonucleic acids (RNAs) take centre stage in gene expression. In eukaryotes, most RNAs are transcribed as precursors, and these precursors are co- or post-transcriptionally processed and assemble with particular proteins to form ribonucleoproteins (RNPs). Mature RNPs participate in various gene...... and ligates the neighbouring exons to generate mature mRNAs. Prp43 is an RNA helicase of the DEAH/RHA family. In yeast, once mRNAs are released, Prp43 catalyzes the disassembly of spliceosomes. The 18S, 5.8S and 25S rRNAs are transcribed as a single polycistronic transcript—the 35S pre-rRNA....... It is nucleolytically cleaved and chemically modified to generate mature rRNAs, which assemble with ribosomal proteins to form the ribosome. Prp43 is required for the processing of the 18S rRNA. Using X-ray crystallography, I determined a high resolution structure of Prp43 bound to ADP, the first structure of a DEAH...

  8. Structure-function analysis of STRUBBELIG, an Arabidopsis atypical receptor-like kinase involved in tissue morphogenesis.

    Directory of Open Access Journals (Sweden)

    Prasad Vaddepalli

    Full Text Available Tissue morphogenesis in plants requires the coordination of cellular behavior across clonally distinct histogenic layers. The underlying signaling mechanisms are presently being unraveled and are known to include the cell surface leucine-rich repeat receptor-like kinase STRUBBELIG in Arabidopsis. To understand better its mode of action an extensive structure-function analysis of STRUBBELIG was performed. The phenotypes of 20 EMS and T-DNA-induced strubbelig alleles were assessed and homology modeling was applied to rationalize their possible effects on STRUBBELIG protein structure. The analysis was complemented by phenotypic, cell biological, and pharmacological investigations of a strubbelig null allele carrying genomic rescue constructs encoding fusions between various mutated STRUBBELIG proteins and GFP. The results indicate that STRUBBELIG accepts quite some sequence variation, reveal the biological importance for the STRUBBELIG N-capping domain, and reinforce the notion that kinase activity is not essential for its function in vivo. Furthermore, individual protein domains of STRUBBELIG cannot be related to specific STRUBBELIG-dependent biological processes suggesting that process specificity is mediated by factors acting together with or downstream of STRUBBELIG. In addition, the evidence indicates that biogenesis of a functional STRUBBELIG receptor is subject to endoplasmic reticulum-mediated quality control, and that an MG132-sensitive process regulates its stability. Finally, STRUBBELIG and the receptor-like kinase gene ERECTA interact synergistically in the control of internode length. The data provide genetic and molecular insight into how STRUBBELIG regulates intercellular communication in tissue morphogenesis.

  9. Structural characterization of CYP165D3, a cytochrome P450 involved in phenolic coupling in teicoplanin biosynthesis.

    Science.gov (United States)

    Cryle, Max J; Staaden, Jessica; Schlichting, Ilme

    2011-03-01

    Teicoplanin is a glycopeptide antibiotic with activity against Gram-positive bacteria and remains one of the last lines of clinical defense against certain bacterial infections. We have cloned, expressed, and purified the cytochrome P450 OxyE (CYP165D3) from the teicoplanin biosynthetic gene cluster of Actinoplanes teichomyceticus, which is responsible for the phenolic coupling of the aromatic side chains of the first and third peptide residues in the teicoplanin peptide. The crystal structure of OxyE has been determined to 2.5Å resolution, revealing the probable binding surface for the carrier protein substrate and an extension of the active site into a pocket located above the β-1 sheet. The binding of potential substrates to OxyE shows that peptidyl carrier protein-bound linear peptides bind to OxyE, albeit with low affinity in the absence of a phenolic cross-link that should normally be installed by another Oxy protein in the teicoplanin biosynthetic pathway. This result indicates that the carrier protein alone is not sufficient for tight substrate binding to OxyE and that the Oxy proteins sense the structure of the bound peptide in addition to the presence of the carrier protein, a feature distinct from other carrier protein/P450 systems. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. A clinical case of a patient with probable cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL from Chuvashia

    Directory of Open Access Journals (Sweden)

    Tatiana Vladimirovna Mokina

    2015-01-01

    Full Text Available Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL syndrome is a congenital small-vessel disease running with recurrent lacunar infarcts and leading to gradually progressive subcortical, pseudobulbar, and cerebellar syndromes and dementia. Neuroimaging reveal multiple lacunar infarcts in the basal ganglia, thalamus, pons Varolii, and cerebral hemispheric white matter, as well as cerebral atrophy. The specific feature of the disease is white matter lesion adjacent to the temporal horns of the lateral ventricles and to the external capsules. The paper describes a patient with CADASIL syndrome. The latter runs a progressive course and includes the following neurological disorders: cognitive, pyramidal, extrapyramidal, and axial ones. This clinical case was differentially diagnosed with multiple sclerosis, including with consideration for neuroimaging findings. The CADASIL syndrome is a rare potentially menacing neurological condition that is observed in young patients and requires a detailed examination using current diagnostic techniques.

  11. Transcripts involved in hemostasis: Exploring salivary complexes from Haementeria vizottoi leeches through transcriptomics, phylogenetic studies and structural features.

    Science.gov (United States)

    Amorim, Adriane Michele Xavier Prado; de Oliveira, Ursula Castro; Faria, Fernanda; Pasqualoto, Kerly Fernanda Mesquita; Junqueira-de-Azevedo, Inácio de L M; Chudzinski-Tavassi, Ana Marisa

    2015-11-01

    Throughout evolution, parasites have adapted in order to successfully intervene in the host defense, producing specific peptides and proteins. Interestingly, these peptides and proteins have been exploited as potential drug candidates against several diseases. Furthermore, biotechnology studies and cDNA libraries have remarkably contributed to identify potentially bioactive molecules. In this regard, herein, a cDNA library of salivary complexes from Haementeria vizottoi leeches was constructed, the transcriptome was characterized and a phylogenetic analysis was performed considering antistasin-like and antiplatelet-like proteins. Hundred twenty three transcripts were identified coding for putative proteins involved in animal feeding (representing about 10% of the expression level). These sequences showed similarities with myohemerythrins, carbonic anhydrases, anticoagulants, antimicrobials, proteases and protease inhibitors. The phylogenetic analysis, regarding antistasin-like and antiplatetlet-like proteins, revealed two main clades in the Rhynchobdellida leeches. As expected, the sequences from H. vizottoi have presented high similarities with those types of proteins. Thus, our findings could be helpful not only to identify new coagulation inhibitors, but also to better understand the biological composition of the salivary complexes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Large-Scale Deletions and SMADIP1 Truncating Mutations in Syndromic Hirschsprung Disease with Involvement of Midline Structures

    Science.gov (United States)

    Amiel, Jeanne; Espinosa-Parrilla, Yolanda; Steffann, Julie; Gosset, Philippe; Pelet, Anna; Prieur, Marguerite; Boute, Odile; Choiset, Agnès; Lacombe, Didier; Philip, Nicole; Le Merrer, Martine; Tanaka, Hajime; Till, Marianne; Touraine, Renaud; Toutain, Annick; Vekemans, Michel; Munnich, Arnold; Lyonnet, Stanislas

    2001-01-01

    Hirschsprung disease (HSCR) is a common malformation of neural-crest–derived enteric neurons that is frequently associated with other congenital abnormalities. The SMADIP1 gene recently has been recognized as disease causing in some patients with 2q22 chromosomal rearrangement, resulting in syndromic HSCR with mental retardation, with microcephaly, and with facial dysmorphism. We screened 19 patients with HSCR and mental retardation and eventually identified large-scale SMADIP1 deletions or truncating mutations in 8 of 19 patients. These results allow further delineation of the spectrum of malformations ascribed to SMADIP1 haploinsufficiency, which includes frequent features such as hypospadias and agenesis of the corpus callosum. Thus, SMADIP1, which encodes a transcriptional corepressor of Smad target genes, may play a role not only in the patterning of neural-crest–derived cells and of CNS but also in the development of midline structures in humans. PMID:11595972

  13. Rotavirus stimulates release of serotonin (5-HT) from human enterochromaffin cells and activates brain structures involved in nausea and vomiting.

    Science.gov (United States)

    Hagbom, Marie; Istrate, Claudia; Engblom, David; Karlsson, Thommie; Rodriguez-Diaz, Jesus; Buesa, Javier; Taylor, John A; Loitto, Vesa-Matti; Magnusson, Karl-Eric; Ahlman, Håkan; Lundgren, Ove; Svensson, Lennart

    2011-07-01

    Rotavirus (RV) is the major cause of severe gastroenteritis in young children. A virus-encoded enterotoxin, NSP4 is proposed to play a major role in causing RV diarrhoea but how RV can induce emesis, a hallmark of the illness, remains unresolved. In this study we have addressed the hypothesis that RV-induced secretion of serotonin (5-hydroxytryptamine, 5-HT) by enterochromaffin (EC) cells plays a key role in the emetic reflex during RV infection resulting in activation of vagal afferent nerves connected to nucleus of the solitary tract (NTS) and area postrema in the brain stem, structures associated with nausea and vomiting. Our experiments revealed that RV can infect and replicate in human EC tumor cells ex vivo and in vitro and are localized to both EC cells and infected enterocytes in the close vicinity of EC cells in the jejunum of infected mice. Purified NSP4, but not purified virus particles, evoked release of 5-HT within 60 minutes and increased the intracellular Ca²⁺ concentration in a human midgut carcinoid EC cell line (GOT1) and ex vivo in human primary carcinoid EC cells concomitant with the release of 5-HT. Furthermore, NSP4 stimulated a modest production of inositol 1,4,5-triphosphate (IP₃), but not of cAMP. RV infection in mice induced Fos expression in the NTS, as seen in animals which vomit after administration of chemotherapeutic drugs. The demonstration that RV can stimulate EC cells leads us to propose that RV disease includes participation of 5-HT, EC cells, the enteric nervous system and activation of vagal afferent nerves to brain structures associated with nausea and vomiting. This hypothesis is supported by treating vomiting in children with acute gastroenteritis with 5-HT₃ receptor antagonists.

  14. Rotavirus stimulates release of serotonin (5-HT from human enterochromaffin cells and activates brain structures involved in nausea and vomiting.

    Directory of Open Access Journals (Sweden)

    Marie Hagbom

    2011-07-01

    Full Text Available Rotavirus (RV is the major cause of severe gastroenteritis in young children. A virus-encoded enterotoxin, NSP4 is proposed to play a major role in causing RV diarrhoea but how RV can induce emesis, a hallmark of the illness, remains unresolved. In this study we have addressed the hypothesis that RV-induced secretion of serotonin (5-hydroxytryptamine, 5-HT by enterochromaffin (EC cells plays a key role in the emetic reflex during RV infection resulting in activation of vagal afferent nerves connected to nucleus of the solitary tract (NTS and area postrema in the brain stem, structures associated with nausea and vomiting. Our experiments revealed that RV can infect and replicate in human EC tumor cells ex vivo and in vitro and are localized to both EC cells and infected enterocytes in the close vicinity of EC cells in the jejunum of infected mice. Purified NSP4, but not purified virus particles, evoked release of 5-HT within 60 minutes and increased the intracellular Ca²⁺ concentration in a human midgut carcinoid EC cell line (GOT1 and ex vivo in human primary carcinoid EC cells concomitant with the release of 5-HT. Furthermore, NSP4 stimulated a modest production of inositol 1,4,5-triphosphate (IP₃, but not of cAMP. RV infection in mice induced Fos expression in the NTS, as seen in animals which vomit after administration of chemotherapeutic drugs. The demonstration that RV can stimulate EC cells leads us to propose that RV disease includes participation of 5-HT, EC cells, the enteric nervous system and activation of vagal afferent nerves to brain structures associated with nausea and vomiting. This hypothesis is supported by treating vomiting in children with acute gastroenteritis with 5-HT₃ receptor antagonists.

  15. [Posterior tibial tendon dysfunction: what other structures are involved in the development of acquired adult flat foot?].

    Science.gov (United States)

    Herráiz Hidalgo, L; Carrascoso Arranz, J; Recio Rodríguez, M; Jiménez de la Peña, M; Cano Alonso, R; Álvarez Moreno, E; Martínez de Vega Fernández, V

    2014-01-01

    To evaluate the association of posterior tibial tendon dysfunction and lesions of diverse ankle structures diagnosed at MRI with radiologic signs of flat foot. We retrospectively compared 29 patients that had posterior tibial tendon dysfunction (all 29 studied with MRI and 21 also studied with weight-bearing plain-film X-rays) with a control group of 28 patients randomly selected from among all patients who underwent MRI and weight-bearing plain-film X-rays for other ankle problems. In the MRI studies, we analyzed whether a calcaneal spur, talar beak, plantar fasciitis, calcaneal bone edema, Achilles' tendinopathy, spring ligament injury, tarsal sinus disease, and tarsal coalition were present. In the weight-bearing plain-film X-rays, we analyzed the angle of Costa-Bertani and radiologic signs of flat foot. To analyze the differences between groups, we used Fisher's exact test for the MRI findings and for the presence of flat foot and analysis of variance for the angle of Costa-Bertani. Calcaneal spurs, talar beaks, tarsal sinus disease, and spring ligament injury were significantly more common in the group with posterior tibial tendon dysfunction (P<.05). Radiologic signs of flat foot and anomalous values for the angle of Costa-Bertani were also significantly more common in the group with posterior tibial tendon dysfunction (P<.001). We corroborate the association between posterior tibial tendon dysfunction and lesions to the structures analyzed and radiologic signs of flat foot. Knowledge of this association can be useful in reaching an accurate diagnosis. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

  16. Collagen-Like Glycoprotein BclS Is Involved in the Formation of Filamentous Structures of the Lysinibacillus sphaericus Exosporium

    Science.gov (United States)

    Zhao, Ni; Ge, Yong; Shi, Tingyu; Hu, Xiaomin

    2014-01-01

    Lysinibacillus sphaericus produces mosquitocidal binary toxins (Bin toxins) deposited within a balloon-like exosporium during sporulation. Unlike Bacillus cereus group strains, the exosporium of L. sphaericus is usually devoid of the hair-like nap, an external filamentous structure formed by a collagen-like protein, BclA. In this study, a new collagen-like exosporium protein encoded by Bsph_0411 (BclS) from L. sphaericus C3-41 was characterized. Thin-section electron microscopy revealed that deletion of bclS resulted in the loss of the filamentous structures that attach to the exosporium basal layer and spread through the interspace of spores. In vivo visualization of BclS-green fluorescent protein (GFP)/mCherry fusion proteins revealed a dynamic pattern of fluorescence that encased the spore from the mother cell-distal (MCD) pole of the forespore, and the BclS-GFP fusions were found to be located in the interspace of the spore, as confirmed by three-dimensional (3D) superresolution fluorescence microscopy. Further studies demonstrated that the bclS mutant spores were more sensitive to wet-heat treatment and germinated at a lower rate than wild-type spores and that these phenotypes were significantly restored in the bclS-complemented strain. These results suggested novel roles of collagen-like protein in exosporium assembly and spore germination, providing a hint for a further understanding of the genetic basis of the high level of persistence of Bin toxins in nature. PMID:25149519

  17. Subcortical connections of normotopic and heterotopic neurons in sensory and motor cortices of the tish mutant rat.

    Science.gov (United States)

    Schottler, F; Couture, D; Rao, A; Kahn, H; Lee, K S

    1998-05-25

    Orthograde and retrograde tracers were used to examine subcortical connections of neurons in the neurological mutant tish rat. This animal exhibits bilateral heterotopia similar to those observed in epileptic humans with subcortical band heterotopia. Terminal varicosities were labeled in the striatum, thalamus, brainstem, and spinal cord following injections of the anterograde tracer biotinylated dextran amine (BDA) into the heterotopic cortex. The general topography of corticothalamic projections was evaluated by injecting the retrograde tracer Fluoro-Gold (FG) into ventral thalamic nuclei. Retrograde labeling of small-to-medium sized neurons was observed in layer VI of topographically restricted portions of the normotopic cortex. Similar appearing cells were labeled in the neighboring portions of the underlying heterotopia; however, these neurons did not display characteristic lamination or radial orientation. Thalamocortical terminals labeled by injecting BDA into the ventroposterolateral nucleus (VPL) were observed primarily in layer IV of the medial aspect of the normotopic somatosensory cortex. In contrast, a radial column of terminals was present in the underlying heterotopia. Typical barrel labeling was found in the lateral aspect of the normotopic somatosensory cortex after injecting the ventroposteromedial nucleus (VPM), whereas more diffuse patches of labeling were observed in the underlying heterotopia. Heterotopic neurons in the tish cortex, thus, exhibit characteristic features of subcortical connectivity. Both normotopic and heterotopic neurons in the tish brain project to appropriate subcortical sites and establish bidirectional topographic connections with the thalamus. These results suggest that primary sensory-motor information is represented in a parallel manner in the normotopic and heterotopic cortices of the tish rat.

  18. Brain-wide Maps Reveal Stereotyped Cell-Type-Based Cortical Architecture and Subcortical Sexual Dimorphism.

    Science.gov (United States)

    Kim, Yongsoo; Yang, Guangyu Robert; Pradhan, Kith; Venkataraju, Kannan Umadevi; Bota, Mihail; García Del Molino, Luis Carlos; Fitzgerald, Greg; Ram, Keerthi; He, Miao; Levine, Jesse Maurica; Mitra, Partha; Huang, Z Josh; Wang, Xiao-Jing; Osten, Pavel

    2017-10-05

    The stereotyped features of neuronal circuits are those most likely to explain the remarkable capacity of the brain to process information and govern behaviors, yet it has not been possible to comprehensively quantify neuronal distributions across animals or genders due to the size and complexity of the mammalian brain. Here we apply our quantitative brain-wide (qBrain) mapping platform to document the stereotyped distributions of mainly inhibitory cell types. We discover an unexpected cortical organizing principle: sensory-motor areas are dominated by output-modulating parvalbumin-positive interneurons, whereas association, including frontal, areas are dominated by input-modulating somatostatin-positive interneurons. Furthermore, we identify local cell type distributions with more cells in the female brain in 10 out of 11 sexually dimorphic subcortical areas, in contrast to the overall larger brains in males. The qBrain resource can be further mined to link stereotyped aspects of neuronal distributions to known and unknown functions of diverse brain regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Circulating Biomarkers in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Patients.

    Science.gov (United States)

    Pescini, Francesca; Donnini, Ida; Cesari, Francesca; Nannucci, Serena; Valenti, Raffaella; Rinnoci, Valentina; Poggesi, Anna; Gori, Anna Maria; Giusti, Betti; Rogolino, Angela; Carluccio, Alessandra; Bianchi, Silvia; Dotti, Maria Teresa; Federico, Antonio; Balestrino, Maurizio; Adriano, Enrico; Abbate, Rosanna; Inzitari, Domenico; Pantoni, Leonardo

    2017-04-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microangiopathy presenting with variable features, including migraine, psychiatric disorders, stroke, and cognitive decline and variable disability. On neuroimaging, CADASIL is characterized by leukoencephalopathy, multiple lacunar infarcts, and microbleeds. Previous studies suggest a possible role of endothelial impairment in the pathogenesis of the disease. We assessed plasma levels of von Willebrand factor (vWF) and thrombomodulin (TM) and the blood levels of endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs) in 49 CADASIL patients and 49 age-matched controls and their association with clinical/functional and neuroimaging features. In multivariate analysis, CADASIL patients had significantly higher vWF and lower EPC levels. TM levels were similar in the 2 groups. CADASIL patients with a more severe clinical phenotype (history of stroke or dementia) presented lower CPC levels in comparison with patients with a milder phenotype. On correlation analysis, lower CPC levels were associated with worse performances on neuropsychological, motor and functional tests, and with higher lesion load on brain magnetic resonance imaging (degree of leukoencephalopathy and number of lacunar infarcts). This is the first CADASIL series in which multiple circulating biomarkers have been studied. Our findings support previous studies on the presence and the possible modulating effect of endothelial impairment in the disease. Furthermore, our research data suggest that blood CPCs may be markers of disease severity. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  20. NEUROPSI battery subtest profile in subcortical vascular dementia and Alzheimer's disease

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    Maria Niures P.S. Matioli

    Full Text Available ABSTRACT Objective: To investigate the diagnostic value of subtests of the NEUROPSI battery for differentiating subcortical vascular dementia (SVaD from Alzheimer's disease (AD. Methods: Thirteen patients with mild SVaD, 15 patients with mild probable AD, and 30 healthy controls, matched for age, education and dementia severity (in the case of patients, were submitted to the Mini-Mental State Examination (MMSE and NEUROPSI battery. The performance of AD and SVaD groups on NEUROPSI subtests was compared. The statistical analyses were performed using Kruskal-Wallis, Chi-square and Mann-Whitney tests. The results were interpreted at the 5% significance level (p<0.05. Bonferroni's correction was applied to multiple comparisons (a=0.02. Results: SVaD and AD patients showed no statistical difference in MMSE scores (SVaD=20.8 and AD=21.0; p=1.0 or in NEUROPSI total score (SVaD=65.0 and AD=64.3; p=0.56, suggesting a similar severity of dementia. The AD group performed worse on memory recall (<0.01 and SVaD group was worse in verbal fluency subtests (p=0.02. Conclusion: NEUROPSI's memory and language subtests can be an auxiliary tool for differentiating SVaD from AD.

  1. Microstructural abnormalities in subcortical reward circuitry of subjects with major depressive disorder.

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    Anne J Blood

    2010-11-01

    Full Text Available Previous studies of major depressive disorder (MDD have focused on abnormalities in the prefrontal cortex and medial temporal regions. There has been little investigation in MDD of midbrain and subcortical regions central to reward/aversion function, such as the ventral tegmental area/substantia nigra (VTA/SN, and medial forebrain bundle (MFB.We investigated the microstructural integrity of this circuitry using diffusion tensor imaging (DTI in 22 MDD subjects and compared them with 22 matched healthy control subjects. Fractional anisotropy (FA values were increased in the right VT and reduced in dorsolateral prefrontal white matter in MDD subjects. Follow-up analysis suggested two distinct subgroups of MDD patients, which exhibited non-overlapping abnormalities in reward/aversion circuitry. The MDD subgroup with abnormal FA values in VT exhibited significantly greater trait anxiety than the subgroup with normal FA values in VT, but the subgroups did not differ in levels of anhedonia, sadness, or overall depression severity.These findings suggest that MDD may be associated with abnormal microstructure in brain reward/aversion regions, and that there may be at least two subtypes of microstructural abnormalities which each impact core symptoms of depression.

  2. The Chinese (Cantonese Montreal Cognitive Assessment in Patients with Subcortical Ischemic Vascular Dementia

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    Jin-song You

    2011-09-01

    Full Text Available Background: Subcortical ischemic vascular dementia (SIVD has been proposed as the most frequent subtype of vascular cognitive impairment. The aim of this study was to evaluate the psychometric properties of the Chinese (Cantonese Montreal Cognitive Assessment (CC- MoCA in patients with SIVD in the Guangdong Province of China. Methods: 71 SIVD patients and 60 matched controls were recruited for the CC-MoCA, Mini Mental State Examination and executive clock drawing tasks. Receiver-operating characteristic curve analyses were performed to determine optimal sensitivity and specificity of the CC-MoCA total score in differentiating mild vascular dementia (VaD patients from moderate VaD patients and controls. Results: The mean CC-MoCA scores of the controls, and mild and moderate VaD patients were 25.2 ± 3.8, 16.4 ± 3.7, and 10.0 ± 5.1, respectively. In our study, the optimal cutoff value for the CC-MoCA to be able to differentiate patients with mild VaD from controls is 21/22, and 13/14 to differentiate mild VaD from moderate VaD. Conclusion: The CC-MoCA is a useful cognitive screening instrument in SIVD patients.

  3. The role of frontal-subcortical circuits in the development of obsessive-compulsive disorders

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    M. A. Kutlubaev

    2016-01-01

    Full Text Available The paper presents a concise review of investigations into the role of impaired frontal-subcortical circuits in the development of obsessive-compulsive disorder (OCD. It gives data on the frequency of neurosis-like symptoms of the OCD spectrum in neurological diseases.The development of OCD is associated with an imbalance between the activity of the direct (activating and indirect (inhibitory pathways of the cortico-striatal-thalamo-cortical feedback loop. These data are confirmed by the results of neuroimaging and neuropsychological studies in patients with OCD. The frequency of OCD symptoms is high in organic brain lesions. OCP may be a manifestation of neurological diseases so their timely detection is an important aspect of a neurologist's work. The treatment of patients with neurosis-like disorders of the OCD spectrum within neurological diseases requires a multidisciplinary approach with the participation of a neurologist, a psychiatrist/psychotherapist, and a psychologist. It is necessary to combine pathogenetic treatment of the underlying disease and its neurosis-like manifestations. 

  4. Subcortical cerebral blood flow and metabolic changes elicited by cortical spreading depression in rat

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    Mraovitch, S.; Calando, Y.; Goadsby, P.J.; Seylaz, J. (Laboratoire de Recherches Cerebrovasculaire, Paris (France))

    1992-06-01

    Changes in cerebral cortical perfusion (CBF{sub LDF}), local cerebral blood flow (lCBF) and local cerebral glucose utilization (lCGU) elicited by unilateral cortical spreading depression (SD) were monitored and measured in separate groups of rats anesthetized with {alpha}-chloralose. CBF{sub LDF} was recorded with laser Doppler flowmetry, while lCBF and lCGU were measured by the quantitative autoradiographic ({sup 14}C)iodoantipyrine and ({sup 14}C)-2-deoxyglucose methods, respectively. SD elicited a wave of hyperemia after a latency of 2 to 3 min followed by an oligemic phase. Ninety minutes following the onset of SD cortical lCBF and lCGU were essentially the same as on the contralateral side and in sham-treated rats. However, alteration in the lCBF and lCGU in upper and lower brainstem persisted. The present results demonstrate that long-lasting cerebrovascular and metabolic alterations take place within the subcortical regions following SD. These regions provide an attractive site to integrate observations in man concerning spreading depression and the aura of migraine with the other features of the syndrome. 19 refs., 2 figs., 1 tab.

  5. Mutation analysis of the DCX gene and genotype/phenotype correlation in subcortical band heterotopia.

    Science.gov (United States)

    Matsumoto, N; Leventer, R J; Kuc, J A; Mewborn, S K; Dudlicek, L L; Ramocki, M B; Pilz, D T; Mills, P L; Das, S; Ross, M E; Ledbetter, D H; Dobyns, W B

    2001-01-01

    Subcortical band heterotopia (SBH) comprises part of a spectrum of phenotypes associated with classical lissencephaly (LIS). LIS and SBH are caused by alterations in at least two genes: LIS1 (PAFAH1B1) at 17p13.3 and DCX (doublecortin) at Xq22.3-q23. DCX mutations predominantly cause LIS in hemizygous males and SBH in heterozygous females, and we have evaluated several families with LIS male and SBH female siblings. In this study, we performed detailed DCX mutation analysis and genotype-phenotype correlation in a large cohort with typical SBH. We screened 26 sporadic SBH females and 11 LIS/SBH families for DCX mutations by direct sequencing. We found 29 mutations in 22 sporadic patients and 11 pedigrees, including five deletions, four nonsense mutations, 19 missense mutations and one splice donor site mutation. The DCX mutation prevalence was 84.6% (22 of 26) in sporadic SBH patients and 100% (11 of 11) in SBH pedigrees. Maternal germline mosaicism was found in one family. Significant differences in genotype were found in relation to band thickness and familial vs sporadic status.

  6. A novel missense mutation of doublecortin: mutation analysis of Korean patients with subcortical band heterotopia.

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    Kim, Myeong-Kyu; Park, Man-Seok; Kim, Byeong-Chae; Cho, Ki-Hyun; Kim, Young-Seon; Kim, Jin-Hee; Lee, Min-Cheol; Heo, Tag; Kim, Eun-Young

    2005-08-01

    The neuronal migration disorders, X-linked lissencephaly syndrome (XLIS) and subcortical band heterotopia (SBH), also called "double cortex", have been linked to missense, nonsense, aberrant splicing, deletion, and insertion mutations in doublecortin (DCX) in families and sporadic cases. Most DCX mutations identified to date are located in two evolutionarily conserved domains. We performed mutation analysis of DCX in two Korean patients with SBH. The SBH patients had mild to moderate developmental delays, drug-resistant generalized seizures, and diffuse thick SBH upon brain MRI. Sequence analysis of the DCX coding region in Patient 1 revealed a c.386 C>T change in exon 3. The sequence variation results in a serine to leucine amino acid change at position 129 (S129L), which has not been found in other family members of Patient 1 or in a large panel of 120 control X-chromosomes. We report here a novel c.386 C>T mutation of DCX that is responsible for SBH.

  7. Disturbances in the positioning, proliferation and apoptosis of neural progenitors contribute to subcortical band heterotopia formation.

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    Fitzgerald, M P; Covio, M; Lee, K S

    2011-03-10

    Cortical malformations are commonly associated with intractable epilepsy and other developmental disorders. Our studies utilize the tish rat, a spontaneously occurring genetic model of subcortical band heterotopia (SBH) associated with epilepsy, to evaluate the developmental events underlying SBH formation in the neocortex. Our results demonstrate that Pax6(+) and Tbr2(+) progenitors are mislocalized in tish(+/-) and tish(-/-)- neocortex throughout neurogenesis. In addition, mislocalized tish(-/-) progenitors possess a longer cell cycle than wild type or normally-positioned tish(-/-) progenitors, owing to a lengthened G(2)+M+G(1) time. This mislocalization is not associated with adherens junction breakdown or loss of radial glial polarity in the ventricular zone (VZ), as assessed by immunohistochemistry against phalloidin (to identify F-actin), aPKC-λ and Par3. However, vimentin immunohistochemistry indicates that the radial glial scaffold is disrupted in the region of the tish(-/-) heterotopia. Moreover, lineage tracing experiments using in utero electroporation in tish(-/-) neocortex demonstrate that mislocalized progenitors do not retain contact with the ventricular surface and that ventricular/subventricular zone (SVZ) progenitors produce neurons that migrate into both the heterotopia and cortical plate (CP). Taken together, these findings define a series of developmental errors contributing to SBH formation that differs fundamentally from a primary error in neuronal migration. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Functional MRI study of verbal fluency in a patient with subcortical laminar heterotopia.

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    Keene, Daniel L; Olds, Janet; Logan, William J

    2004-05-01

    Double cortex syndrome is a malformation in which there is a band of subcortical heterotopic grey matter separated from the cortex by white matter. The functional activity of the heterotopic neurons is unclear. A 13-year-old female was evaluated for seizures. The EEG showed bifrontal spike wave disturbance. Band heterotopia, in association with mild reduction of sulcation of the cerebral hemispheres, was found on MRI. Psychological assessment indicated the presence of variable cognitive abilities, with verbal IQ [82] generally better than nonverbal IQ [59], and specific difficulties in language comprehension and mathematics. Functional MRI was used to localize the areas of language and motor activation. The language activation paradigm was a visual verb generation task with a visual fixation baseline. The motor paradigm consisted of alternating blocks of sequential finger tapping and rest. Coronal functional and anatomical images were obtained. The motor paradigm produced activation of the primary motor cortex, the band heterotopia and the supplementary motor cortex. The language paradigm produced activation of the left inferior frontal gyrus and left supplementary motor area, but not of the band heterotopia. The activation of heterotopic grey matter during a motor task demonstrates a hemodynamic association with motor activity and suggests that this tissue may be functional. Such association was not seen with the language task. We speculate that later maturing functions such as language are restricted in their development to the normal situated superficial cortex in our patient.

  9. Training conquers multitasking costs by dividing task representations in the frontoparietal-subcortical system

    Science.gov (United States)

    Garner, K. G.; Dux, Paul E.

    2015-01-01

    Negotiating the information-rich sensory world often requires the concurrent management of multiple tasks. Despite this requirement, humans are thought to be poor at multitasking because of the processing limitations of frontoparietal and subcortical (FP-SC) brain regions. Although training is known to improve multitasking performance, it is unknown how the FP-SC system functionally changes to support improved multitasking. To address this question, we characterized the FP-SC changes that predict training outcomes using an individual differences approach. Participants (n = 100) performed single and multiple tasks in pre- and posttraining magnetic resonance imaging (fMRI) sessions interspersed by either a multitasking or an active-control training regimen. Multivoxel pattern analyses (MVPA) revealed that training induced multitasking improvements were predicted by divergence in the FP-SC blood oxygen level-dependent (BOLD) response patterns to the trained tasks. Importantly, this finding was only observed for participants who completed training on the component (single) tasks and their combination (multitask) and not for the control group. Therefore, the FP-SC system supports multitasking behavior by segregating constituent task representations. PMID:26460014

  10. Subcortical cerebral blood flow and metabolic changes elicited by cortical spreading depression in rat.

    Science.gov (United States)

    Mraovitch, S; Calando, Y; Goadsby, P J; Seylaz, J

    1992-06-01

    Changes in cerebral cortical perfusion (CBFLDF), local cerebral blood flow (lCBF) and local cerebral glucose utilization (lCGU) elicited by unilateral cortical spreading depression (SD) were monitored and measured in separate groups of rats anesthetized with alpha-chloralose. CBFLDF was recorded with laser Doppler flowmetry, while lCBF and lCGU were measured by the quantitative autoradiographic [14C]iodoantipyrine and [14C]-2-deoxyglucose methods, respectively. SD elicited a wave of hyperemia after a latency of 2 to 3 min followed by an oligemic phase. Ninety minutes following the onset of SD cortical (frontal, parietal and occipital) lCBF and lCGU were essentially the same as on the contralateral side and in sham-treated rats. However, alteration in the lCBF and lCGU in upper and lower brainstem persisted. The present results demonstrate, for the first time, that long-lasting cerebrovascular and metabolic alterations take place within the subcortical regions following SD. These regions provide an attractive site to integrate observations in man concerning spreading depression and the aura of migraine with the other features of the syndrome.

  11. Lack of Association between Apolipoprotein E Polymorphism with Age at Onset of Subcortical Vascular Dementia

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    Hye Guk Ryu

    2012-01-01

    Full Text Available Background and Purpose: The relationship between apolipoprotein E (ApoE and onset of vascular dementia remains controversial. The aim of this study was to evaluate the relationship between ApoE polymorphism and the onset of subcortical vascular dementia (SVaD compared to Alzheimer’s disease (AD and normal controls. Methods: The study was comprised of 61 patients with SVaD (42 Binswanger type, 19 lacunar type and 112 patients with AD (16 early-onset AD, 96 late-onset AD as well as 284 age-, gender- and education-matched normal controls. The diagnosis of SVaD was based on modified NINDS-AIREN criteria, and the diagnosis of AD was based on NINCDS-ADRDA criteria. ApoE polymorphism was genotyped in all participants. Results: None of the three ApoE alleles was more prevalent in SVaD patients compared to normal controls, which was the case when both Binswanger and lacunar types were analyzed separately. ApoE Ε4 did not accelerate the onset of SVaD (OR 1.66, 95% CI: 0.8–3.4, in contrast to a significant relation with late-onset AD (OR 3.78, 95% CI: 2.2–6.5. Conclusion: Our results suggest that ApoE polymorphism is not associated with the onset of SVaD and that the two subtypes of SVaD may share similar pathophysiologies.

  12. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL: Three case reports from Serbia

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    Zidverc-Trajković Jasna

    2008-01-01

    Full Text Available Introduction Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL is a hereditary microangiopathy leading to recurrent strokes and vascular dementia in young and middleaged patients. The diagnosis of CADASIL is based on typical clinical presentation and characteristic magnetic resonance imaging (MRI changes, and has to be confirmed by biopsy of the sural nerve, muscle and skin, as well as by genetic analysis. Mutations within the Notch3 gene were identified as the underlying genetic defect in CADASIL. Case Outline The clinical manifestations of the first presented patient with migraine from the age of thirteen, stroke without vascular risk factors and stepwise progression of vascular dementia comprising the typical clinical picture of CADASIL, were confirmed after seven years with pathological verification. The second presented case did not satisfy the clinical criteria for CADASIL. His stroke was considered to be related with vascular risk factors - diabetes mellitus and hypertension. The aetiological diagnosis was established only when his brother without vascular risk factors presented with similar clinical manifestations. Conclusion Until the development of the new neuroimaging techniques like MRI, pathologic and genetic analysis, CADASIL was considered as a rare disorder. However, the increasing number of CADASIL families has been identified throughout the world showing that this entity is usually underdiagnosed. This article presents three patients from two Serbian families with clinical suspicion of CADASIL verified by pathologic examination. .

  13. Training conquers multitasking costs by dividing task representations in the frontoparietal-subcortical system.

    Science.gov (United States)

    Garner, K G; Dux, Paul E

    2015-11-17

    Negotiating the information-rich sensory world often requires the concurrent management of multiple tasks. Despite this requirement, humans are thought to be poor at multitasking because of the processing limitations of frontoparietal and subcortical (FP-SC) brain regions. Although training is known to improve multitasking performance, it is unknown how the FP-SC system functionally changes to support improved multitasking. To address this question, we characterized the FP-SC changes that predict training outcomes using an individual differences approach. Participants (n = 100) performed single and multiple tasks in pre- and posttraining magnetic resonance imaging (fMRI) sessions interspersed by either a multitasking or an active-control training regimen. Multivoxel pattern analyses (MVPA) revealed that training induced multitasking improvements were predicted by divergence in the FP-SC blood oxygen level-dependent (BOLD) response patterns to the trained tasks. Importantly, this finding was only observed for participants who completed training on the component (single) tasks and their combination (multitask) and not for the control group. Therefore, the FP-SC system supports multitasking behavior by segregating constituent task representations.

  14. Screening for New Biomarkers for Subcortical Vascular Dementia and Alzheimer’s Disease

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    Annika Öhrfelt

    2011-01-01

    Full Text Available Background: Novel biomarkers are important for identifying as well as differentiating subcortical vascular dementia (SVD and Alzheimer’s disease (AD at an early stage in the disease process. Methods: In two independent cohorts, a multiplex immunoassay was utilized to analyze 90 proteins in cerebrospinal fluid (CSF samples from dementia patients and patients at risk of developing dementia (mild cognitive impairment. Results: The levels of several CSF proteins were increased in SVD and its incipient state, and in moderate-to-severe AD compared with the control group. In contrast, some CSF proteins were altered in AD, but not in SVD. The levels of heart-type fatty acid binding protein (H-FABP were consistently increased in all groups with dementia but only in some of their incipient states. Conclusions: In summary, these results support the notion that SVD and AD are driven by different pathophysiological mechanisms reflected in the CSF protein profile and that H-FABP in CSF is a general marker of neurodegeneration.

  15. Vitamin D, Homocysteine, and Folate in Subcortical Vascular Dementia and Alzheimer Dementia

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    Rita Moretti

    2017-05-01

    Full Text Available Dementia is a worldwide health problem which affects millions of patients; Alzheimer's disease (AD and subcortical vascular dementia (sVAD are the two most frequent forms of its presentation. As no definite therapeutic options have been discovered, different risk factors for cognitive impairment have been searched for potential therapies. This report focuses on the possible evidence that vitamin D deficiency and hyper-homocysteinemia can be considered as two important factors for the development or the progression of neurodegenerative or vascular pathologies. To this end, we assessed: the difference in vascular risk factors and vitamin D-OH25 levels among groups of sVAD, AD, and healthy age-matched controls; the association of folate, B12, homocysteine, and vitamin D with sVAD/AD and whether a deficiency of vitamin D and an increment in homocysteine levels may be related to neurodegenerative or vessel damages. The commonly-considered vascular risk factors were collected in 543 patients and compared with those obtained from a healthy old volunteer population. ANOVA group comparison showed that vitamin D deficiency was present in demented cases, as well as low levels of folate and high levels of homocysteine, more pronounced in sVAD cases. The statistical models we employed, with regression models built, and adjustments for biochemical, demographic and neuropsychiatric scores, confirmed the association between the three measures (folate decrease, hyperhomocysteinemia and vitamin D decrease and dementia, more pronounced in sVAD than in AD.

  16. Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

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    Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

    2017-02-01

    Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas

  17. Gymnosperm B-sister genes may be involved in ovule/seed development and, in some species, in the growth of fleshy fruit-like structures.

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    Lovisetto, Alessandro; Guzzo, Flavia; Busatto, Nicola; Casadoro, Giorgio

    2013-08-01

    The evolution of seeds together with the mechanisms related to their dispersal into the environment represented a turning point in the evolution of plants. Seeds are produced by gymnosperms and angiosperms but only the latter have an ovary to be transformed into a fruit. Yet some gymnosperms produce fleshy structures attractive to animals, thus behaving like fruits from a functional point of view. The aim of this work is to increase our knowledge of possible mechanisms common to the development of both gymnosperm and angiosperm fruits. B-sister genes from two gymnosperms (Ginkgo biloba and Taxus baccata) were isolated and studied. The Ginkgo gene was also functionally characterized by ectopically expressing it in tobacco. In Ginkgo the fleshy structure derives from the outer seed integument and the B-sister gene is involved in its growth. In Taxus the fleshy structure is formed de novo as an outgrowth of the ovule peduncle, and the B-sister gene is not involved in this growth. In transgenic tobacco the Ginkgo gene has a positive role in tissue growth and confirms its importance in ovule/seed development. This study suggests that B-sister genes have a main function in ovule/seed development and a subsidiary role in the formation of fleshy fruit-like structures when the latter have an ovular origin, as occurs in Ginkgo. Thus, the 'fruit function' of B-sister genes is quite old, already being present in Gymnosperms as ancient as Ginkgoales, and is also present in Angiosperms where a B-sister gene has been shown to be involved in the formation of the Arabidopsis fruit.

  18. Cortical-subcortical interactions in hypersomnia disorders: mechanisms underlying cognitive and behavioral aspects of the sleep-wake cycle

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    Linda J Larson-Prior

    2014-09-01

    Full Text Available Subcortical circuits mediating sleep-wake functions have been well characterized in animal models, and corroborated by more recent human studies. Disruptions in these circuits have been identified in hypersomnia disorders such as narcolepsy and Klein-Levin Syndrome, as well as in neurodegenerative disorders expressing excessive daytime sleepiness. However, the behavioral expression of sleep-wake functions is not a simple on-or-off state determined by subcortical circuits, but encompasses a complex range of behaviors determined by the interaction between cortical networks and subcortical circuits. While conceived as disorders of sleep, hypersomnia disorders are equally disorders of wake, representing a fundamental instability in neural state characterized by lapses of alertness during wake. These episodic lapses in alertness and wakefulness are also frequently seen in neurodegenerative disorders where EEG demonstrates abnormal function in cortical regions associated with cognitive fluctuations. Moreover, functional connectivity MRI shows instability of cortical networks in individuals with cognitive fluctuations. We propose that the inability to stabilize neural state due to disruptions in the sleep-wake control networks is common to the sleep and cognitive dysfunctions seen in hypersomnia and neurodegenerative disorders.

  19. Focal neuronal loss, reversible subcortical focal T2 hypointensity in seizures with a nonketotic hyperglycemic hyperosmolar state

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    Raghavendra, S.; Ashalatha, R.; Thomas, Sanjeev V. [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Neurology, Trivandrum, Kerala (India); Kesavadas, C. [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Imaging Sciences and Interventional Radiology, Trivandrum (India)

    2007-04-15

    Neuroimaging in seizures associated with nonketotic hyperglycemia (NKH) is considered normal. We report magnetic resonance imaging (MRI) abnormalities in four patients with NKH and seizures. We prospectively evaluated clinical and radiological abnormalities in four patients with NKH during the period March 2004 to December 2005. All patients presented with seizures, either simple or complex partial seizures or epilepsia partialis continua. Two of them had transient hemianopia. MRI showed subcortical T2 hypointensity in the occipital white matter and in or around the central sulcus (two patients each), T2 hyperintensity of the overlying cortex (two patients), focal overlying cortical enhancement (three patients) and bilateral striatal hyperintensity (one patient). Diffusion-weighted imaging (DWI) performed in three patients showed restricted diffusion. The ictal semiology and electroencephalographic (EEG) findings correlated with the MRI abnormalities. On clinical recovery, the subcortical T2 hypointensity and striatal hyperintensity reversed in all patients. The initial cortical change evolved to FLAIR hyperintensity suggestive of focal cortical gliosis. The radiological differential diagnosis considered initially included encephalitis, malignancy and hemorrhagic infarct rendering a diagnostic dilemma. We identified subcortical T2 hypointensity rather than hyperintensity as a characteristic feature of seizures associated with NKH. Only very few similar reports exist in literature. Reversible bilateral striatal T2 hyperintensity in NKH has not been reported to the best of our knowledge. (orig.)

  20. Speech and language disorders secondary to diffuse subcortical vascular lesions: Neurolinguistic and acoustic analysis. A case report.

    Science.gov (United States)

    Tomić, Gordana; Stojanović, Milena; Pavlović, Aleksandra; Stanković, Predrag; Zidverc-Trajković, Jasna; Pavlović, Dragan; Marković-Jovanović, Zagorka; Covicković-Sternić, Nadezda

    2009-08-15

    Subcortical white matter (WM) plays an important role in speech production and language processing. Most frequently, cerebral WM lesions are secondary to small vessel disease in patients with vascular risk factors. We report the case of a 53-year-old man with history of hypertension and ischemic subcortical lesions, who presented with speech difficulties and mild cognitive impairment. Language and cognitive assessment included Boston Diagnostic Aphasia Examination, Boston Naming Test, Rey Auditory-Verbal Learning Test, Rey-Osterrieth Complex Figure Test, Trail Making Test A and B, Wisconsin Card Sorting Test, Scale for Evaluation of Perceptive Characteristics of Voice and Speech, and Multidimensional Evaluation of Speech and Voice. Brain MRI showed ischemic WM lesions and lacunar infarcts in the brainstem and right cerebellum. Cognitive testing revealed mild cognitive impairment, predominantly affecting attention and executive functions. Speech and language analysis demonstrated dysarthria, dysphonia with hypophonia, and imprecise articulation, as well as short rushes of speech, palilalia and mild subcortical dysphasia. Neurolinguistic and acoustic analysis in patients with ischemic WM lesions can provide additional information in the understanding of language and speech disturbances, and can assist in patient management.

  1. Impact of left versus right hemisphere subcortical stroke on the neural processing of action observation and imagery.

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    Dettmers, Christian; Nedelko, Violetta; Schoenfeld, Mircea Ariel

    2015-01-01

    Mental training appears to be an attractive tool in stroke rehabilitation. The objective of this study was to investigate whether any differences in the processing of action observation and imagery might exist between patients with left and right hemisphere subcortical strokes. Eighteen patients with strictly subcortical stroke (nine right-hemispheric) underwent a functional magnetic resonance imaging (fMRI) study with an experimental paradigm in which motor acts had to be observed and/or imagined from a first person perspective. Changes in hemodynamic activity were measured using fMRI. The activity level was found to be higher in the non-lesioned compared to the lesioned hemisphere. Patients with lesions in the left hemisphere had a higher activation level in visual (fusiform and lingual gyri), superior temporal areas and dorsal premotor regions across all performed comparisons than those with right hemisphere lesions. Furthermore they had more vivid imagery experiences and lower scores on the Stroke Impact Scale. Patients with left hemisphere subcortical lesions recruit more cortical regions in the processing of action pictures and videos. This recruitment was further enhanced during imagery. This is most likely related to the fact that the lesion touched the dominant hemisphere.

  2. Periventricular nodular and subcortical neuronal heterotopia in adult epileptic patients Heterotopía neuronal nodular y subcortical en pacientes adultos con epilepsia

    Directory of Open Access Journals (Sweden)

    Damián E. Consalvo

    2006-04-01

    Full Text Available Developmental malformations are brain abnormalities that occur during embryogenesis. Neuronal migration disorders, including heterotopic lesions, constitute one type of such abnormalities. The aim of the study was to compare the epileptic clinical patterns of patients with periventricular nodular heterotopia (PNH (G1 with those affected by subcortical heterotopia (SCH (G2 looking for differences between both groups which, eventually, might suggest the type of the underlying malformation. The variables studied in both groups were: type of the heterotopia depicted on MRI studies, sex, age, age at seizure onset, annual seizure frequency, localization of the ictal symptomatogenic zone, characteristics of the EEG, other associated anomalies on the magnetic resonance images (MRI besides the heterotopia, and response to treatment. The only difference found between both groups was the type of heterotopia as shown by MRI studies. The other assessed variables did not significantly (p>0.05 differ between groups. No differences in the clinical features characterizing epilepsy could be found in patients with PNH or SCH, being the images the only tool able to differentiate them.Las malformaciones de la corteza cerebral son un grupo de entidades que se producen durante las etapas del desarrollo embrionario y cuya manifestación clínica puede ser la epilepsia. Estas malformaciones pueden ser diagnosticadas in vivo a través de las imágenes por resonancia magnética (IRM. Un subtipo particular de éstas lo constituyen los trastornos en la migración neuronal, dentro de los cuales se ubican las heterotopías (HT. El objetivo del estudio fue comparar enfermos portadores de HT periventriculares (G1 con aquellos portadores de HT subcorticales (G2. Se analizaron las variables sexo, edad y edad de inicio de la epilepsia (EI en años, antecedentes familiares (AF o prenatales (AP, frecuencia anual de crisis (FAC y características semiológicas de las crisis

  3. Structural and mutational analysis of amino acid residues involved in ATP specificity of Escherichia coli acetate kinase.

    Science.gov (United States)

    Yoshioka, Aya; Murata, Kousaku; Kawai, Shigeyuki

    2014-11-01

    Acetate kinase (AK) generally utilizes ATP as a phosphoryl donor, but AK from Entamoeba histolytica (PPi-ehiAK) uses pyrophosphate (PPi), not ATP, and is PPi-specific. The determinants of the phosphoryl donor specificity are unknown. Here, we inferred 5 candidate amino acid residues associated with this specificity, based on structural information. Each candidate residue in Escherichia coli ATP-specific AK (ATP-ecoAK), which is unable to use PPi, was substituted with the respective PPi-ehiAK amino acid residue. Each variant ATP-ecoAK had an increased Km for ATP, indicating that the 5 residues are the determinants for the specificity to ATP in ATP-ecoAK. Moreover, Asn-337 of ATP-ecoAK was shown to be particularly significant for the specificity to ATP. The 5 residues are highly conserved in 2625 PPi-ehiAK homologs, implying that almost all organisms have ATP-dependent, rather than PPi-dependent, AK. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  4. Structural Injury after Lithium Treatment in Human and Rat Kidney involves Glycogen Synthase Kinase-3β Positive Epithelium

    DEFF Research Database (Denmark)

    Kjærsgaard, Gitte; Madsen, Kirsten; Marcussen, Niels

    2011-01-01

    Lithium is reabsorbed by distal nephron segments in sodium depleted states. It was hypothesized that lithium causes permanent injury to the developing kidney particularly in the sodium-retaining phase around weaning through entry into epithelial cells of the distal nephron and inhibition of glyco......Lithium is reabsorbed by distal nephron segments in sodium depleted states. It was hypothesized that lithium causes permanent injury to the developing kidney particularly in the sodium-retaining phase around weaning through entry into epithelial cells of the distal nephron and inhibition...... of glycogen synthase kinase-3β (GSK-3β). GSK-3β and pGSK-3β was investigated in a developing series of rat kidney cortex and medulla. Li+ was given to female wistar rats with litters through food pellets at postnatal (P) days 7-28. In human fetal and adult kidney the expression of GSK-3β was examined and also....... Lithium causes proliferation, structural injury and increases inactive pGSK-3β abundance in these segments. The data are compatible with epithelial entry of lithium and a causal role for GSK-3β in postnatal developing cortical collecting duct epithelium....

  5. Balance deficit with opened or closed eyes reveals involvement of different structures of the central nervous system in multiple sclerosis.

    Science.gov (United States)

    Prosperini, Luca; Petsas, Nikolaos; Raz, Eytan; Sbardella, Emilia; Tona, Francesca; Mancinelli, Chiara Rosa; Pozzilli, Carlo; Pantano, Patrizia

    2014-01-01

    To evaluate whether balance deficit in patients with multiple sclerosis (MS), as assessed with eyes opened (EO) and closed (EC), is associated with damage of different structures of the central nervous system (CNS). Fifty patients with MS and 20 healthy controls (HCs) underwent static posturography to calculate the body's center of pressure displacement (COP path) with EO and EC. They were scanned using a 3.0T magnet to obtain PD/T2 and 3D-T1-weighted images of the brain and spinal cord. We determined the mid-sagittal cerebellum area (MSCA) and upper cervical cord cross-sectional area (UCCA). We also measured the patients' lesion volumes (T2-LVs) on the whole brain and at different infratentorial levels. MS patients had wider COP paths with both EO and EC (p Balance deficit in MS was related to atrophy of both the cerebellum and spinal cord, but the extent of COP path under the two different conditions (EO or EC) implied different patterns of damage in the CNS.

  6. Psychopathology of addiction: May a SCL-90-based five dimensions structure be applied irrespectively of the involved drug?

    Science.gov (United States)

    Pani, Pier Paolo; Maremmani, Angelo G I; Trogu, Emanuela; Vigna-Taglianti, Federica; Mathis, Federica; Diecidue, Roberto; Kirchmayer, Ursula; Amato, Laura; Ghibaudi, Joli; Camposeragna, Antonella; Saponaro, Alessio; Davoli, Marina; Faggiano, Fabrizio; Maremmani, Icro

    2016-01-01

    We previously found a five cluster of psychological symptoms in heroin use disorder (HUD) patients: 'worthlessness-being trapped', 'somatic-symptoms', 'sensitivity-psychoticism', 'panic-anxiety', and 'violence-suicide'. We demonstrated that this aggregation is independent of the chosen treatment, of intoxication status and of the presence of psychiatric problems. 2314 Subjects, with alcohol, heroin or cocaine dependence were assigned to one of the five clusters. Differences between patients dependent on alcohol, heroin and cocaine in the frequency of the five clusters and in their severity were analysed. The association between the secondary abuse of alcohol and cocaine and the five clusters was also considered in the subsample of HUD patients. We confirmed a positive association of the 'somatic symptoms' dimension with the condition of heroin versus cocaine dependence and of the 'sensitivity-psychoticism' dimension with the condition of alcohol versus heroin dependence. 'Somatic symptoms' and 'panic anxiety' successfully discriminated between patients as being alcohol, heroin or cocaine dependents. Looking at the subsample of heroin dependents, no significant differences were observed. The available evidence coming from our results, taken as a whole, seems to support the extension of the psychopathological structure previously observed in opioid addicts to the population of alcohol and cocaine dependents.

  7. BCL-3 attenuation of TNFA expression involves an incoherent feed-forward loop regulated by chromatin structure.

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    Thomas Walker

    Full Text Available Induction of genes is rarely an isolated event; more typically occurring as part of a web of parallel interactions, or motifs, which act to refine and control gene expression. Here, we define an Incoherent Feed-forward Loop motif in which TNFα-induced NF-κB signalling activates expression of the TNFA gene itself and also controls synthesis of the negative regulator BCL-3. While sharing a common inductive signal, the two genes have distinct temporal expression profiles. Notably, while the TNFA gene promoter is primed to respond immediately to activated NF-κB in the nucleus, induction of BCL3 expression only occurs after a time delay of about 1h. We show that this time delay is defined by remodelling of the BCL3 gene promoter, which is required to activate gene expression, and characterise the chromatin delayed induction of BCL3 expression using mathematical models. The models show how a delay in inhibitor production effectively uncouples the rate of response to inflammatory cues from the final magnitude of inhibition. Hence, within this regulatory motif, a delayed (incoherent feed-forward loop together with differential rates of TNFA (fast and BCL3 (slow mRNA turnover provide robust, pulsatile expression of TNFα . We propose that the structure of the BCL-3-dependent regulatory motif has a beneficial role in modulating expression dynamics and the inflammatory response while minimising the risk of pathological hyper-inflammation.

  8. BCL-3 attenuation of TNFA expression involves an incoherent feed-forward loop regulated by chromatin structure.

    Science.gov (United States)

    Walker, Thomas; Adamson, Antony; Jackson, Dean A

    2013-01-01

    Induction of genes is rarely an isolated event; more typically occurring as part of a web of parallel interactions, or motifs, which act to refine and control gene expression. Here, we define an Incoherent Feed-forward Loop motif in which TNFα-induced NF-κB signalling activates expression of the TNFA gene itself and also controls synthesis of the negative regulator BCL-3. While sharing a common inductive signal, the two genes have distinct temporal expression profiles. Notably, while the TNFA gene promoter is primed to respond immediately to activated NF-κB in the nucleus, induction of BCL3 expression only occurs after a time delay of about 1h. We show that this time delay is defined by remodelling of the BCL3 gene promoter, which is required to activate gene expression, and characterise the chromatin delayed induction of BCL3 expression using mathematical models. The models show how a delay in inhibitor production effectively uncouples the rate of response to inflammatory cues from the final magnitude of inhibition. Hence, within this regulatory motif, a delayed (incoherent) feed-forward loop together with differential rates of TNFA (fast) and BCL3 (slow) mRNA turnover provide robust, pulsatile expression of TNFα . We propose that the structure of the BCL-3-dependent regulatory motif has a beneficial role in modulating expression dynamics and the inflammatory response while minimising the risk of pathological hyper-inflammation.

  9. Structure, Mechanism, and Specificity of a Eukaryal tRNA Restriction Enzyme Involved in Self-Nonself Discrimination

    Directory of Open Access Journals (Sweden)

    Anupam K. Chakravarty

    2014-04-01

    Full Text Available tRNA restriction by anticodon nucleases underlies cellular stress responses and self-nonself discrimination in a wide range of taxa. Anticodon breakage inhibits protein synthesis, which, in turn, results in growth arrest or cell death. The eukaryal ribotoxin PaT secreted by Pichia acaciae inhibits growth of Saccharomyces cerevisiae via cleavage of tRNAGln(UUG. We find that recombinant PaT incises a synthetic tRNAGln(UUG stem-loop RNA by transesterification at a single site 3′ of the wobble uridine, yielding 2′,3′-cyclic phosphate and 5′-OH ends. Incision is suppressed by replacement of the wobble nucleobase with adenine or guanine. The crystal structure of PaT reveals a distinctive fold and active site, essential components of which are demonstrated by mutagenesis. Pichia acaciae evades self-toxicity via a distinctive intracellular immunity protein, ImmPaT, which binds PaT and blocks nuclease activity. Our results highlight the evolutionary diversity of tRNA restriction and immunity systems.

  10. Lipolytic enzymes involving lipolysis in Teleost: Synteny, structure, tissue distribution, and expression in grass carp (Ctenopharyngodon idella).

    Science.gov (United States)

    Sun, Jian; Ji, Hong; Li, Xue-Xian; Shi, Xiao-Chen; Du, Zhen-Yu; Chen, Li-Qiao

    2016-08-01

    Lipolysis is the biochemical pathway responsible for the sequential hydrolysis of triacylglycerols (TAGs) stored in cellular lipid droplets. Three enzymes are known to participate in TAGs hydrolysis, including adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase (MGL), and each is present in mammals as only one isoform. Here we show that the genome of grass carp (Ctenopharyngodon idella) and other teleosts codes for one ATGL, two HSLs, and one MGL isoforms. Two isoforms of HSL gene, HSLa and HSLb, derived from paralogous genes that could be originated from teleost-specific genome duplication (TSGD) event. The genes encoding for fish ATGL and MGL were conserved and contained nine and seven coding exons, respectively. However, two isoforms of HSL gene had a remarkable variation in gene structure, such as HSLa gene contained ten and HSLb contained thirteen exons. All three enzymes, including two isoforms of HSL, were expressed in a wide range of tissues, but the abundance of each gene mRNA showed the tissue-dependent expression patterns. During fasting, only ATGL and HSLa showed a significant increase in adipose tissue and adipocyte, indicating that ATGL and HSLa may be the main rate-limiting enzymes controlling the hydrolysis of TAGs in fasting-induced lipolysis. Different expression of HSLa and HSLb suggests that they might serve different roles in fasting-induced lipolysis. These results provide evidence about the conservation and divergence of genes of fish lipolytic enzymes. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Enhancing action of LSD on neuronal responsiveness to serotonin in a brain structure involved in obsessive-compulsive disorder.

    Science.gov (United States)

    Zghoul, Tarek; Blier, Pierre

    2003-03-01

    Potent serotonin (5-HT) reuptake inhibitors are the only drugs that consistently exert a therapeutic action in obsessive-compulsive disorder (OCD). Given that some hallucinogens were reported to exert an anti-OCD effect outlasting their psychotomimetic action, possible modifications of neuronal responsiveness to 5-HT by LSD were examined in two rat brain structures: one associated with OCD, the orbitofrontal cortex (OFC), and another linked to depression, the hippocampus. The effects of concurrent microiontophoretic application of LSD and 5-HT were examined on neuronal firing rate in the rat OFC and hippocampus under chloral hydrate anaesthesia. In order to determine whether LSD could also exert a modification of 5-HT neuronal responsiveness upon systemic administration, after a delay when hallucinosis is presumably no longer present, it was given once daily (100 microg/kg i.p.) for 4 d and the experiments were carried out 24 h after the last dose. LSD attenuated the firing activity of OFC neurons, and enhanced the inhibitory effect of 5-HT when concomitantly ejected on the same neurons. In the hippocampus, LSD also decreased firing rate by itself but decreased the inhibitory action of 5-HT. The inhibitory action of 5-HT was significantly greater in the OFC, but smaller in the hippocampus, when examined after subacute systemic administration of LSD. It is postulated that some hallucinogens could have a beneficial action in OCD by enhancing the responsiveness to 5-HT in the OFC, and not necessarily in direct relation to hallucinosis. The latter observation may have theoretical implications for the pharmacotherapy of OCD.

  12. Determination of ghrelin structure in the barfin flounder (Verasper moseri and involvement of ingested fatty acids in ghrelin acylation

    Directory of Open Access Journals (Sweden)

    Hiroyuki eKaiya

    2013-09-01

    Full Text Available Ghrelin is a peptide hormone that is acylated with a fatty acid, usually n-octanoic acid, at the third amino acid residue (usually a serine or threonine, and this acylation is known to be essential for ghrelin activity not only in mammals but also in non-mammals, such as fish. However, the modification mechanisms of ghrelin modification in fish are not known. In this study, we elucidated the structure of ghrelin in a teleost, the barfin flounder (Verasper moseri, and determined whether ingested free fatty acids of various chain lengths participated in ghrelin acylation. Complementary DNA cloning revealed the barfin flounder prepro-ghrelin to be a 106-amino acid (aa peptide and the mature ghrelin to be a 20-aa peptide (GSSFLSPSHKPPNKGKPPRA. However, purification of ghrelin peptides from stomach extracts demonstrated that the major form of the hormone was a 19-aa decanoylated peptide (GSS[C10:0]FLSPSHKPPNKGKPPR missing the last alanine of the 20-aa peptide. Ingestion of feed enriched with n-heptanoic acid (C7, n-octanoic acid (C8, or n-nonanoic acid (C9 changed the modification status of the peptide: ingestion of C8 or C9 increased the amount of C8:0 or C9:0 19-aa ghrelin, respectively, but no C7:0 ghrelin was isolated after ingestion of C7. These results indicate that ingested free fatty acids are substrates for ghrelin acylation in the barfin flounder, but the types of free fatty acids utilized as substrates may be limited.

  13. Structure-based analysis of A19D, a variant of transthyretin involved in familial amyloid cardiomyopathy.

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    Priscila Ferreira

    Full Text Available Transthyretin (TTR is a tetrameric beta-sheet-rich protein. Its deposits have been implicated in four different amyloid diseases. Although aggregation of the wild-type sequence is responsible for the senile form of the disease, more than one hundred variants have been described thus far, most of which confer a more amyloidogenic character to TTR, mainly because they compromise the stability of the protein in relation to monomer formation, which upon misfolding is intrinsically aggregation-prone. We report the case of a Brazilian patient suffering from a severe cardiomyopathy who carries a rare mutation in exon 2 of the TTR gene that results in an Ala to Asp substitution at position 19 (A19D. The putative pathogenic mechanisms of this variant were analyzed in silico. We constructed a structural model for the A19D tetramer from which its thermodynamic stability was compared to that displayed by the V30M (more amyloidogenic than WT-TTR and T119M (non-amyloidogenic variants. The FoldX force field predicted that A19D and V30M are 10.88 and 8.07 kCal/mol less stable than the WT-TTR, while T119M is 5.15 kCal/mol more stable, which is consistent with the aggregation propensities exhibited by these variants. We analyzed the step in which the tetramer-dimer-monomer-unfolded monomer equilibrium might contribute the most to the increased or decreased amyloidogenicity in each variant. Our results suggest that the concentration of four non-native negative charges occur inside thyroxine-binding channels, and the loss of contacts at both the tetrameric and dimeric interfaces would account for an overall decreased stability of the tetramer and the consequent enhanced amyloidogenicity of the A19D variant. As far as we know, this is the first description of a non-V30M mutation in Brazil.

  14. Structural and Molecular Mechanism of CdpR Involved in Quorum-Sensing and Bacterial Virulence in Pseudomonas aeruginosa.

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    Jingru Zhao

    2016-04-01

    Full Text Available Although quorum-sensing (QS systems are important regulators of virulence gene expression in the opportunistic human pathogen Pseudomonas aeruginosa, their detailed regulatory mechanisms have not been fully characterized. Here, we show that deletion of PA2588 resulted in increased production of pyocyanin and biofilm, as well as enhanced pathogenicity in a mouse model. To gain insights into the function of PA2588, we performed a ChIP-seq assay and identified 28 targets of PA2588, including the intergenic region between PA2588 and pqsH, which encodes the key synthase of Pseudomonas quinolone signal (PQS. Though the C-terminal domain was similar to DNA-binding regions of other AraC family members, structural studies revealed that PA2588 has a novel fold at the N-terminal region (NTR, and its C-terminal HTH (helix-turn-helix domain is also unique in DNA recognition. We also demonstrated that the adaptor protein ClpS, an essential regulator of ATP-dependent protease ClpAP, directly interacted with PA2588 before delivering CdpR to ClpAP for degradation. We named PA2588 as CdpR (ClpAP-degradation and pathogenicity Regulator. Moreover, deletion of clpP or clpS/clpA promotes bacterial survival in a mouse model of acute pneumonia infection. Taken together, this study uncovered that CdpR is an important QS regulator, which can interact with the ClpAS-P system to regulate the expression of virulence factors and pathogenicity.

  15. Homogenization-based interval analysis for structural-acoustic problem involving periodical composites and multi-scale uncertain-but-bounded parameters.

    Science.gov (United States)

    Chen, Ning; Yu, Dejie; Xia, Baizhan; Liu, Jian; Ma, Zhengdong

    2017-04-01

    This paper presents a homogenization-based interval analysis method for the prediction of coupled structural-acoustic systems involving periodical composites and multi-scale uncertain-but-bounded parameters. In the structural-acoustic system, the macro plate structure is assumed to be composed of a periodically uniform microstructure. The equivalent macro material properties of the microstructure are computed using the homogenization method. By integrating the first-order Taylor expansion interval analysis method with the homogenization-based finite element method, a homogenization-based interval finite element method (HIFEM) is developed to solve a periodical composite structural-acoustic system with multi-scale uncertain-but-bounded parameters. The corresponding formulations of the HIFEM are deduced. A subinterval technique is also introduced into the HIFEM for higher accuracy. Numerical examples of a hexahedral box and an automobile passenger compartment are given to demonstrate the efficiency of the presented method for a periodical composite structural-acoustic system with multi-scale uncertain-but-bounded parameters.

  16. Parental involvement

    OpenAIRE

    Ezra S Simon

    2005-01-01

    This study was conducted in Ghana to investigate, (1) factors that predict parental involvement, (2) the relationship between parental home and school involvement and the educational achievement of adolescents, (3) the relationship between parental authoritativeness and the educational achievement of adolescent students, (4) parental involvement serving as a mediator between their authoritativeness and the educational achievement of the students, and (5) whether parental involvement decreases...

  17. Study of diffusion tensor imaging in subcortical ischemic vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    Hui-ying GUO

    2014-04-01

    Full Text Available Objective Using diffusion tensor imaging (DTI to explore the microstructure changes of white matter in subcortical ischemic vascular cognitive impairment (SIVCI and its correlation with cognitive function.  Methods Forty-nine patients with subcortical ischemic cerebrovascular diseases were collected. By using Clinical Dementia Rating Scale (CDR, they were classified into 10 cases of vascular dementia (VaD group, 20 cases of vascular cognitive impairment-no dementia (VCIND group and 19 cases of normal cognitive function (control group. Conventional MRI and DTI were performed in all cases. Based on the DTI data, voxel-based analysis was used to assess the whole brain region. Correlation analysis was applied to illustrate the relationship between DTI parameters and cognitive scale in VaD patients.  Results Compared with the control group, fractional anisotropy (FA values of patients in VaD group decreased in medial prefrontal cortex, anterior cingulate cortex, corpus callosum stem, bilateral parietal lobes, right temporal lobe and bilateral orbitofrontal lobes (P = 0.000, for all, and FA values of patients in VCIND group decreased in right inferior frontal gyrus, right hippocampus and bilateral precuneus (P = 0.000, for all. Compared with VCIND group, FA values of patients in VaD group decreased in medial prefrontal cortex, anterior cingulate, corpus callosum, bilateral parietal lobes and right temporal lobe (P = 0.000, for all. Compared with the control group, mean diffusivity (MD values in VaD group increased in medial prefrontal cortex, corpus callosum, bilateral parietal lobes, bilateral temporal lobes and anterior cingulate (P = 0.000, for all, while in VCIND group increased in bilateral precuneus and right hippocampus (P = 0.000, for all. Compared with VCIND group, MD values in VaD group increased in right medial prefrontal cortex, anterior cingulate cortex, corpus callosum stem, bilateral parietal lobes and bilateral temporal lobes (P = 0

  18. Voxel-based 3D MRI analysis helps to detect subtle forms of subcortical band heterotopia.

    Science.gov (United States)

    Huppertz, Hans-Jürgen; Wellmer, Jörg; Staack, Anke Maren; Altenmüller, Dirk-Matthias; Urbach, Horst; Kröll, Judith

    2008-05-01

    To evaluate the potential diagnostic value of a novel magnetic resonance image (MRI) postprocessing technique in subtle forms of subcortical band heterotopia (SBH). The method was introduced to improve the visualization of blurred gray-white matter junctions associated with focal cortical dysplasia but was found to be applicable also to SBH. In the voxel-based MRI analysis presented here, T1-weighted MRI volume data sets are normalized and segmented using standard algorithms of SPM5. The distribution of gray and white matter is analyzed on a voxelwise basis and compared with a normal database of 150 controls. Based on this analysis, a three-dimensional feature map is created that highlights brain areas if their signal intensities fall within the range between normal gray and white matter and differ from the normal database in this respect. The method was applied to the MRI data of 378 patients with focal epilepsy in three different epilepsy centers. SBH was diagnosed in seven patients with five of them showing subtle forms of SBH that had gone unrecognized in conventional visual analysis of MRI and were only detected by MRI postprocessing. In contrast to distinct double cortex syndrome, these patients had partial double cortex with SBH mostly confined to posterior brain regions. The results of this study suggest that a considerable part of cases with SBH might remain unrecognized by conventional MRI. Voxel-based MRI analysis may help to identify subtle forms and appears to be a valuable additional diagnostic tool in the evaluation of patients with cryptogenic epilepsy.

  19. Effects of cannabis and familial loading on subcortical brain volumes in first-episode schizophrenia.

    Science.gov (United States)

    Malchow, Berend; Hasan, Alkomiet; Schneider-Axmann, Thomas; Jatzko, Alexander; Gruber, Oliver; Schmitt, Andrea; Falkai, Peter; Wobrock, Thomas

    2013-11-01

    Schizophrenia is a severe neuropsychiatric disorder with familial loading as heritable risk factor and cannabis abuse as the most relevant environmental risk factor up to date. Cannabis abuse has been related to an earlier onset of the disease and persisting cannabis consumption is associated with reduced symptom improvement. However, the underlying morphological and biochemical brain alterations due to these risk factors as well as the effects of gene-environmental interaction are still unclear. In this magnetic resonance imaging (MRI) study in 47 first-episode schizophrenia patients and 30 healthy control subjects, we investigated effects of previous cannabis abuse and increased familial risk on subcortical brain regions such as hippocampus, amygdala, caudate nucleus, putamen, thalamus and subsegments of the corpus callosum (CC). In a subsequent single-volume (1)H-magnetic resonance spectroscopy study, we investigated spectra in the left hippocampus and putamen to detect metabolic alterations. Compared to healthy controls, schizophrenia patients displayed decreased volumes of the left hippocampus, bilateral amygdala and caudate nucleus as well as an increased area of the midsagittal CC1 segment of the corpus callosum. Patients fulfilling the criteria for cannabis abuse at admission showed an increased area of the CC2 segment compared to those who did not fulfill the criteria. Patients with a family history of schizophrenia combined with previous cannabis abuse showed lower volumes of the bilateral caudate nucleus compared to all other patients, implicating an interaction between the genetic background and cannabis abuse as environmental factor. Patients with cannabis abuse also had higher ratios of N-acetyl aspartate/choline in the left putamen, suggesting a possible neuroprotective effect in this area. However, antipsychotic medication prior to MRI acquisition and gender effects may have influenced our results. Future longitudinal studies in first

  20. Increased Pittsburgh Compound-B Accumulation in the Subcortical White Matter of Alzheimer's Disease Brain.

    Science.gov (United States)

    Wakabayashi, Yuichi; Ishii, Kazunari; Hosokawa, Chisa; Hyodo, Tomoko; Kaida, Hayato; Yamada, Minoru; Yagyu, Yukinobu; Tsurusaki, Masakatsu; Kozuka, Takenori; Sugimura, Kazuro; Murakami, Takamichi

    2017-03-13

    Using 11C-Pittsburgh compound B (PiB)-PET and MRI volume data, we investigated whether white matter (WM) PiB uptake in Alzheimer's disease (AD) brain is larger than that of cortical PiB uptake-negative (PiB-negative) brain. Forty-five subjects who underwent both PiB-PET and MRI were included in the study (32 AD patients with cortical PiB-positive and 13 cortical amyloid -negative patients). Individual areas of gray matter (GM) and WM were segmented, then regional GM and WM standard uptake value ratio (SUVR) normalized to cerebellar GM with partial volume effects correction was calculated. Three regional SUVRs except WM in the centrum semiovale in the AD group were significantly larger than those in the PiB-negative groups. Frontal WM SUVR in the AD group vs frontal WM SUVR in the PiB-negative group was 2.57 ± 0.55 vs 1.64 ± 0.22; parietal, 2.50 ± 0.52 vs 1.74 ± 0.22; posterior cingulate, 2.84 ± 0.59 vs 1.73 ± 0.22; and WM in the centrum semiovale, 2.21 ± 0.53 vs 2.42 ± 0.36, respectively. We found that PiB uptake in AD brain is significantly larger than that in PiB-negative brain in the frontal, parietal and posterior cingulate subcortical WM, except in the centrum semiovale.

  1. Distinctive Resting State Network Disruptions Among Alzheimer's Disease, Subcortical Vascular Dementia, and Mixed Dementia Patients.

    Science.gov (United States)

    Kim, Hee Jin; Cha, Jungho; Lee, Jong-Min; Shin, Ji Soo; Jung, Na-Yeon; Kim, Yeo Jin; Choe, Yearn Seong; Lee, Kyung Han; Kim, Sung Tae; Kim, Jae Seung; Lee, Jae Hong; Na, Duk L; Seo, Sang Won

    2016-01-01

    Recent advances in resting-state functional MRI have revealed altered functional networks in Alzheimer's disease (AD), especially those of the default mode network (DMN) and central executive network (CEN). However, few studies have evaluated whether small vessel disease (SVD) or combined amyloid and SVD burdens affect the DMN or CEN. The aim of this study was to evaluate whether SVD or combined amyloid and SVD burdens affect the DMN or CEN. In this cross-sectional study, we investigated the resting-state functional connectivity within DMN and CEN in 37 Pittsburgh compound-B (PiB)(+) AD, 37 PiB(-) subcortical vascular dementia (SVaD), 13 mixed dementia patients, and 65 normal controls. When the resting-state DMN of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(+) AD patients displayed lower functional connectivity in the inferior parietal lobule while the PiB(-) SVaD patients displayed lower functional connectivity in the medial frontal and superior frontal gyri. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the DMN in the posterior cingulate gyrus. When the resting-state CEN connectivity of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(-) SVaD patients displayed lower functional connectivity in the anterior insular region. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the CEN in the inferior frontal gyrus. Our findings suggest that in PiB(+) AD and PiB(-) SVaD, there is divergent disruptions in resting-state DMN and CEN. Furthermore, patients with combined amyloid and SVD burdens exhibited more disrupted resting-state DMN and CEN than patients with only amyloid or SVD burden.

  2. Seoul criteria for PiB(-) subcortical vascular dementia based on clinical and MRI variables.

    Science.gov (United States)

    Kim, Geon Ha; Lee, Jae Hong; Seo, Sang Won; Ye, Byoung Seok; Cho, Hanna; Kim, Hee Jin; Noh, Young; Yoon, Cindy W; Chin, Ju Hee; Oh, Seung Jun; Kim, Jae Seung; Choe, Yearn Seong; Lee, Kyung Han; Kim, Sung Tae; Jeong, Jee Hyang; Na, Duk L

    2014-04-29

    The purpose of this study was to propose new criteria for differentiating Pittsburgh compound B (PiB)-negative from PiB-positive subcortical vascular dementia (SVaD) using clinical and MRI variables. We measured brain amyloid deposition using PiB-PET in 77 patients with SVaD. All patients met DSM-IV criteria for vascular dementia and had severe white matter hyperintensities on MRI, defined as a cap or band ≥ 10 mm as well as a deep white matter lesion ≥ 25 mm. Eleven models were considered to differentiate PiB(-) from PiB(+) SVaD using 4 variables, including age, number of lacunes, medial temporal atrophy (MTA), and APOE ε4. The ideal cutoff values in each of the 11 models were selected using the highest Youden index. A total of 49 of 77 patients (63.6%) tested negative for PiB retention, while 28 (36.4%) tested positive for PiB retention. The ideal model for differentiating PiB(-) from PiB(+) SVaD was as follows: age ≤ 75 years, ≥ 5 lacunes, and MTA ≤ 3, which together yielded an accuracy of 67.5%. When patients meet the DSM-IV criteria for vascular dementia and also have severe white matter hyperintensities, younger age, greater number of lacunes, and lesser MTA, these are predictive of a PiB(-) scan in patients with SVaD. This study provides Class II evidence that the combination of younger age, greater number of lacunes, and lesser MTA identifies patients with SVaD at lower risk of Alzheimer disease pathology.

  3. Towards accurate models for amorphous GeTe: Crucial effect of dispersive van der Waals corrections on the structural properties involved in the phase-change mechanism

    Science.gov (United States)

    Micoulaut, M.; Piarristeguy, A.; Flores-Ruiz, H.; Pradel, A.

    2017-11-01

    The effect of van der Waals dispersion correction in combination with density functional theory is investigated on a canonical amorphous phase-change material. Density functional theory (DFT), using the generalized gradient approximation, usually fails to reproduce the structure of amorphous tellurides, which manifests by an overestimation of the interatomic bond distances, and particularly the Ge-Te one involved in local geometries (tetrahedral or defect octahedral). Here, we take into account dispersion forces in a semiempirical way and apply such DFT simulations to amorphous GeTe. We obtain a substantial improvement of the simulated structure factor and pair-correlation function, which now reproduce the experimental counterparts with an unprecedented accuracy, including on a recent partial contribution from anomalous x-ray scattering and from x-ray absorption. A detailed analysis of the corresponding structures indicates that the dispersion correction reduces the Ge-Te bond length, increases the fraction of tetrahedral germanium, and reduces the presence of heteropolar so-called fourfold ABAB rings. Given that these structural features have been stressed to be central for the understanding of the phase-change mechanism, the present results challenge our current understanding of the crystal to amorphous transformation at play.

  4. Suggestive Evidence for the Involvement of the Second Calcium and Surface Loop in Interfacial Binding: Monoclinci and Trigonal Crystal Structures of a Quadruple Mutant of Phospholipase A2

    Energy Technology Data Exchange (ETDEWEB)

    Sekar,K.; Yogavel, M.; Kanaujia, S.; Sharma, A.; Velmurugan, D.; Poi, M.; Dauter, Z.; Tsai, M.

    2006-01-01

    The crystal structures of the monoclinic and trigonal forms of the quadruple mutant K53,56,120,121M of recombinant bovine pancreatic phospholipase A{sub 2} (PLA{sub 2}) have been solved and refined at 1.9 and 1.1 Angstroms resolution, respectively. Interestingly, the monoclinic form reveals the presence of the second calcium ion. Furthermore, the surface-loop residues are ordered and the conformation of residues 62-66 is similar to that observed in other structures containing the second calcium ion. On the other hand, in the trigonal form the surface loop is disordered and the second calcium is absent. Docking studies suggest that the second calcium and residues Lys62 and Asp66 from the surface loop could be involved in the interaction with the polar head group of the membrane phospholipid. It is hypothesized that the two structures of the quadruple mutant, monoclinic and trigonal, represent the conformations of PLA2 at the lipid interface and in solution, respectively. A docked structure with a phospholipid molecule and with a transition-state analogue bound, one at the active site coordinating to the catalytic calcium and the other at the second calcium site, but both at the i-face, is presented.

  5. Cortical Structural Abnormalities in Deficit Versus Nondeficit Schizophrenia

    Science.gov (United States)

    Fischer, Bernard A.; Keller, William R.; Arango, Celso; Pearlson, Godfrey; McMahon, Robert P.; Meyer, Walter A.; Francis, Alan; Kirkpatrick, Brian; Carpenter, William T.; Buchanan, Robert W.

    2012-01-01

    Objective To examine the structural integrity of the dorsolateral prefrontal-basal ganglia-thalamocortical circuit in people with the deficit form of schizophrenia. Method A three-dimensional structural MRI sequence was used to conduct morphometric assessments of cortical and subcortical regions in deficit and nondeficit outpatients with schizophrenia and healthy controls. Results The superior prefrontal and superior and middle temporal gyral gray matter volumes were significantly smaller in the deficit versus the nondeficit group and normal control groups. There were no significant group differences in examined subcortical structures. Conclusion People with deficit schizophrenia are characterized by selective reductions in the prefrontal and temporal cortex. PMID:22336954

  6. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL): Assessment of the involved white matter tracts by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kassem, Hassan [Department of Radiology, Benha University (Egypt); Wafaie, Ahmed, E-mail: a_wafaie@yahoo.com [Department of Radiology, Cairo University (Egypt); Abdelfattah, Sherif [Department of Radiology, Cairo University (Egypt); Farid, Tarek [Pediatric Department, Egyptian National Research Center (Egypt)

    2014-01-15

    Background and purpose: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a recently identified autosomal recessive disorder with early onset of symptoms and slowly progressive pyramidal, cerebellar and dorsal column dysfunction. LBSL is characterized by distinct white matter abnormalities and selective involvement of brainstem and spinal cord tracts. The purpose of this study is to assess the imaging features of the involved white matter tracts in cases of LBSL by MRI. Patients and methods: We retrospectively reviewed the imaging features of the selectively involved white matter tracts in sixteen genetically proven cases of leukoencephalopathy with brainstem and spinal cord involvement and elevated brain lactate (LBSL). All patients presented with slowly progressive cerebellar sensory ataxia with spasticity and dorsal column dysfunction. MRI of the brain and spine using 1.5 T machine and proton magnetic resonance spectroscopy ({sup 1}H MRS) on the abnormal white matter were done to all patients. The MRI and MRS data sets were analyzed according to lesion location, extent, distribution and signal pattern as well as metabolite values and ratios in MRS. Laboratory examinations ruled out classic leukodystrophies. Results: In all cases, MRI showed high signal intensity in T2-weighted and FLAIR images within the cerebral subcortical, periventricular and deep white matter, posterior limbs of internal capsules, centrum semiovale, medulla oblongata, intraparenchymal trajectory of trigeminal nerves and deep cerebellar white matter. In the spine, the signal intensity of the dorsal column and lateral cortico-spinal tracts were altered in all patients. The subcortical U fibers, globi pallidi, thalami, midbrain and transverse pontine fibers were spared in all cases. In 11 cases (68.8%), the signal changes were inhomogeneous and confluent whereas in 5 patients (31.2%), the signal abnormalities were spotty. MRI also showed variable

  7. Ictal/interictal EEG patterns and functional neuroimaging findings in subcortical band heterotopia: report of three cases and review of the literature.

    Science.gov (United States)

    Dericioglu, Nese; Oguz, Kader Karli; Ergun, Eser Lay; Tezer, Fadime Irsel; Saygi, Serap

    2008-01-01

    Subcortical band heterotopia (SBH) is a rare, genetic disorder of neuronal migration, which is seen almost exclusively in females. Little is known about the functionality of the band heterotopia, in terms of both physiology and pathology, in this malformation. Patients are reported to have several different types of seizures, which are usually drug resistant. Interictal EEG findings are known to correlate with the type of seizures, however less is known about the ictal EEG patterns. We present 3 female patients who were investigated at our center with video-scalp EEG monitoring, interictal single photon emission computed tomography (SPECT), functional magnetic resonance (MR) imaging (fMRI) and MR spectroscopy (MRS) besides routine MR imaging. They had several different types of seizures, and one of them reported also having circling seizures that have not been reported previously in patients with SBH. Ictal EEG recordings were remarkable for their unusual patterns of propagation. The findings in structural and functional neuroradiological investigations are discussed in light of the literature.

  8. Brain networks involved in early versus late response anticipation and their relation to conflict processing.

    Science.gov (United States)

    Lütcke, Henry; Gevensleben, Holger; Albrecht, Björn; Frahm, Jens

    2009-11-01

    Previous electrophysiological studies have clearly identified separable neural events underlying early and late components of response anticipation. Functional neuroimaging studies, however, have so far failed to account for this separation. Here, we performed functional magnetic resonance imaging (fMRI) of an anticipation paradigm in 12 healthy adult subjects that reliably produced early and late expectancy waves in the electroencephalogram. We furthermore compared fMRI activations elicited during early and late anticipation to those associated with response conflict. Our results demonstrate the existence of distinct cortical and subcortical brain regions underlying early and late anticipation. Although late anticipatory behavior was associated with activations in dorsal ACC, frontal cortex, and thalamus, brain responses linked to the early expectancy wave were localized mainly in motor and premotor cortical areas as well as the caudate nucleus. Additionally, late anticipation was associated with increased activity in midbrain dopaminergic nuclei, very likely corresponding to the substantia nigra. Furthermore, whereas regions involved in late anticipation proved to be very similar to activations elicited by response conflict, this was not the case for early anticipation. The current study supports a distinction between early and late anticipatory processes, in line with a plethora of neurophysiological work, and for the first time describes the brain structures differentially involved in these processes.

  9. Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder

    Science.gov (United States)

    Myung, W; Han, C E; Fava, M; Mischoulon, D; Papakostas, G I; Heo, J-Y; Kim, K W; Kim, S T; Kim, D J H; Kim, D K; Seo, S W; Seong, J-K; Jeon, H J

    2016-01-01

    Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal

  10. The impact of ADHD persistence, recent cannabis use, and age of regular cannabis use onset on subcortical volume and cortical thickness in young adults.

    Science.gov (United States)

    Lisdahl, Krista M; Tamm, Leanne; Epstein, Jeffery N; Jernigan, Terry; Molina, Brooke S G; Hinshaw, Stephen P; Swanson, James M; Newman, Erik; Kelly, Clare; Bjork, James M

    2016-04-01

    Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Stacked base-pair structures of adenine nucleosides stabilized by the formation of hydrogen-bonding network involving the two sugar groups

    Energy Technology Data Exchange (ETDEWEB)

    Asami, Hiroya [Graduate School of Bio- and Nanosystem Sciences, Yokohama City University, Yokohama 236-0027 (Japan); Yagi, Kiyoshi [Department of Chemistry, School of Chemical Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States); Ohba, Masashi [Yokohama College of Pharmacy, Yokohama 245-0066 (Japan); Urashima, Shu-hei [Graduate School of Bio- and Nanosystem Sciences, Yokohama City University, Yokohama 236-0027 (Japan); Saigusa, Hiroyuki, E-mail: saigusa@yokohama-cu.ac.jp [Graduate School of Bio- and Nanosystem Sciences, Yokohama City University, Yokohama 236-0027 (Japan)

    2013-06-20

    Highlights: ► A combination of laser desorption and supersonic jet-cooling is used to produce base pairs of adenine nucleosides. ► Stacked base-pair structure of N6,N6-dimethyladnosine is identified by IR vibrational spectroscopy. ► Anharmonic vibrational calculation is employed to analyze the vibrational mode coupling in the stacked base pair. - Abstract: We have employed a laser desorption technique combined with supersonic-jet cooling for producing base pairs of adenine nucleosides, adenosine (Ado) and N6,N6-dimethyladenosine (DMAdo) under low-temperature conditions. The resulting base pairs are then ionized through resonant two-photon ionization (R2PI) and analyzed by time-of-flight mass spectrometry. It is found that dimers of these adenine nucleosides are stable, especially in the case of DMAdo, with respect to those of the corresponding bases, i.e., adenine and N6,N6-dimethyladenine. Structural analysis of the DMAdo dimer is performed based on the IR–UV double resonance measurements and theoretical calculations. The result demonstrates that the dimer possesses a stacked structure being stabilized by the formation of hydrogen-bonding network involving the two sugar groups. The occurrence of the frequency shift and broadening is explained satisfactorily based on the anharmonic coupling of the OH stretching modes with specific bending modes and low-frequency modes of base and sugar moieties.

  12. Non-structural proteins P17 and P33 are involved in the assembly of the internal membrane-containing virus PRD1

    Energy Technology Data Exchange (ETDEWEB)

    Karttunen, Jenni; Mäntynen, Sari [Centre of Excellence in Biological Interactions, Department of Biological and Environmental Science and Nanoscience Center, University of Jyväskylä, P.O. Box 35, 40014 Jyväskylä (Finland); Ihalainen, Teemu O. [Stem Cells in Neurological Applications Group, BioMediTech, University of Tampere, Tampere (Finland); Bamford, Jaana K.H. [Centre of Excellence in Biological Interactions, Department of Biological and Environmental Science and Nanoscience Center, University of Jyväskylä, P.O. Box 35, 40014 Jyväskylä (Finland); Oksanen, Hanna M., E-mail: hanna.oksanen@helsinki.fi [Institute of Biotechnology and Department of Biosciences, University of Helsinki, Biocenter 2, P.O. Box 56 (Viikinkaari 5), FIN-00014 Helsinki (Finland)

    2015-08-15

    Bacteriophage PRD1, which has been studied intensively at the structural and functional levels, still has some gene products with unknown functions and certain aspects of the PRD1 assembly process have remained unsolved. In this study, we demonstrate that the phage-encoded non-structural proteins P17 and P33, either individually or together, complement the defect in a temperature-sensitive GroES mutant of Escherichia coli for host growth and PRD1 propagation. Confocal microscopy of fluorescent fusion proteins revealed co-localisation between P33 and P17 as well as between P33 and the host chaperonin GroEL. A fluorescence recovery after photobleaching assay demonstrated that the diffusion of the P33 fluorescent fusion protein was substantially slower in E. coli than theoretically calculated, presumably resulting from intermolecular interactions. Our results indicate that P33 and P17 function in procapsid assembly, possibly in association with the host chaperonin complex GroEL/GroES. - Highlights: • Two non-structural proteins of PRD1 are involved in the virus assembly. • P17 and P33 complement the defect in GroES of Escherichia coli. • P33 co-localises with GroEL and P17 in the bacterium. • Slow motion of P33 in the bacterium suggests association with cellular components.

  13. Lesion Explorer: a comprehensive segmentation and parcellation package to obtain regional volumetrics for subcortical hyperintensities and intracranial tissue.

    Science.gov (United States)

    Ramirez, J; Gibson, E; Quddus, A; Lobaugh, N J; Feinstein, A; Levine, B; Scott, C J M; Levy-Cooperman, N; Gao, F Q; Black, S E

    2011-01-15

    Subcortical hyperintensities (SH) are a commonly observed phenomenon on MRI of the aging brain (Kertesz et al., 1988). Conflicting behavioral, cognitive and pathological associations reported in the literature underline the need to develop an intracranial volumetric analysis technique to elucidate pathophysiological origins of SH in Alzheimer's disease (AD), vascular cognitive impairment (VCI) and normal aging (De Leeuw et al., 2001; Mayer and Kier, 1991; Pantoni and Garcia, 1997; Sachdev et al., 2008). The challenge is to develop processing tools that effectively and reliably quantify subcortical small vessel disease in the context of brain tissue compartments. Segmentation and brain region parcellation should account for SH subtypes which are often classified as: periventricular (pvSH) and deep white (dwSH), incidental white matter disease or lacunar infarcts and Virchow-Robin spaces. Lesion Explorer (LE) was developed as the final component of a comprehensive volumetric segmentation and parcellation image processing stream built upon previously published methods (Dade et al., 2004; Kovacevic et al., 2002). Inter-rater and inter-method reliability was accomplished both globally and regionally. Volumetric analysis showed high inter-rater reliability both globally (ICC=.99) and regionally (ICC=.98). Pixel-wise spatial congruence was also high (SI=.97). Whole brain pvSH volumes yielded high inter-rater reliability (ICC=.99). Volumetric analysis against an alternative kNN segmentation revealed high inter-method reliability (ICC=.97). Comparison with visual rating scales showed high significant correlations (ARWMC: r=.86; CHIPS: r=.87). The pipeline yields a comprehensive and reliable individualized volumetric profile for subcortical vasculopathy that includes regionalized (26 brain regions) measures for: GM, WM, sCSF, vCSF, lacunar and non-lacunar pvSH and dwSH. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Impairment of visuospatial/visuoconstructional skills in multiple sclerosis patients: the correlation with regional lesion load and subcortical atrophy.

    Science.gov (United States)

    Marasescu, R; Cerezo Garcia, M; Aladro Benito, Y

    2016-04-01

    About 20% to 26% of patients with multiple sclerosis (MS) show alterations in visuospatial/visuoconstructive (VS-VC) skills even though temporo-parieto-occipital impairment is a frequent finding in magnetic resonance imaging. No studies have specifically analysed the relationship between these functions and lesion volume (LV) in these specific brain areas. To evaluate the relationship between VS-VC impairment and magnetic resonance imaging temporo-parieto-occipital LV with subcortical atrophy in patients with MS. Of 100 MS patients undergoing a routine neuropsychological evaluation, 21 were selected because they displayed VS-VC impairments in the following tests: Incomplete picture, Block design (WAIS-III), and Rey-Osterrieth complex figure test. We also selected 13 MS patients without cognitive impairment (control group). Regional LV was measured in FLAIR and T1-weighted images using a semiautomated method; subcortical atrophy was measured by bicaudate ratio and third ventricle width. Partial correlations (controlling for age and years of school) and linear regression analysis were employed to analyse correlations between magnetic resonance imaging parameters and cognitive performance. All measures of LV and brain atrophy were significantly higher in patients with cognitive impairment. Regional LV, bicaudate ratio, and third ventricle width are significantly and inversely correlated with cognitive performance; the strongest correlation was between third ventricle width and VC performance (Block design: P=.001; Rey-Osterrieth complex figure: P<.000). In the multivariate analysis, third ventricle width only had a significant effect on performance of VC tasks (Block design: P=.000; Rey-Osterrieth complex figure: P=.000), and regional FLAIR VL was linked to the VS task (Incomplete picture; P=.002). Measures of subcortical atrophy explain the variations in performance on visuocostructive tasks, and regional FLAIR VL measures are linked to VS tasks. Copyright © 2015

  15. Assessment of cerebral hemodynamics to acetazolamide using brain perfusion SPECT in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

    Science.gov (United States)

    Park, Soon-Ah; Yang, Chung-Yong; Choi, See-Sung; Kim, Woo Hyoung

    2011-02-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy caused by mutations in the Notch3 gene located on chromosome 19, leading to 4 cardinal features with aura, cerebrovascular ischemic events, mood disturbances, and dementia. Acetazolamide (ACZ) has been promoted as a drug to determine cerebral hemodynamics, including cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) in patients with cerebrovascular disease. In CADASIL patients with small-vessel disease, ACZ may be possible to increase CBF. We present that reduced CBF was dramatically improved after administration of ACZ on Tc-99m ECD brain perfusion SPECT in a CADASIL patient.

  16. Subcortical elevation of metabolism in Parkinson's disease--a critical reappraisal in the context of global mean normalization

    DEFF Research Database (Denmark)

    Borghammer, Per; Cumming, Paul; Aanerud, Joel

    2009-01-01

    article, Ma and colleagues presented a study seeking to establish that a pattern of widespread hypermetabolism, known as the Parkinson's disease related pattern (PDRP) is a genuine metabolic feature of PD. In the present paper, we respond to the arguments presented by Ma et al., and we provide a critical...... reappraisal of the evidence for the existence of the PDRP. To this end, we present new analyses of PET data sets, which demonstrate that very similar patterns of relative subcortical increases are seen in PD, Alzheimer's disease, hepatic encephalopathy, healthy aging, and simulation data. Furthermore...

  17. Neuropsychological performance in patients with subcortical stroke Perfil neuropsicológico em pacientes com lesões vasculares subcorticais

    Directory of Open Access Journals (Sweden)

    Silviane Pinheiro Campos de Andrade

    2012-05-01

    Full Text Available Vascular cognitive impairment (VCI is characterized by cognitive compromise predominantly of executive dysfunction. OBJECTIVES: To assess cognitive functions in VCI, focusing on executive functions, to observe functional losses in relation to activities of daily living (ADLs and to detect early symptoms prior to the onset of dementia. METHODS: We evaluated healthy subjects matched for gender, education and age to patients with diagnosis of subcortical vascular disease who had a stroke classified into three groups: 1 vascular lesions and no impairment; 2 vascular cognitive impairment with no dementia (VCIND; 3 vascular dementia (VaD. RESULTS AND DISCUSSION: The performance on neuropsychological tests differed among groups, worsening with increased impairment level. The probable VaD group demonstrated impaired performance in memory, processing speed and verbal production, while the VCIND group showed attention deficits. CONCLUSION: Impairment in executive functions and difficulties in ADLs allow us to differentiate levels of impairment in groups of subcortical vascular disease.O comprometimento cognitivo vascular (CCV é caracterizado por comprometimento cognitivo predominantemente sob a forma de disfunção executiva. OBJETIVOS: Avaliar as funções cognitivas no CCV, enfocando as funções executivas, observar as perdas funcionais em relação às atividades cotidianas (AVDs e detectar os primeiros sintomas antes do início da demência. MÉTODOS: Foram avaliados indivíduos controles saudáveis pareados por sexo, escolaridade e idade com pacientes com diagnóstico de doença vascular subcortical que sofreram derrame classificados em três grupos: 1 lesões vasculares sem déficit; 2 comprometimento cognitivo vascular sem demência (CCVSD; 3 demência vascular (DV. RESULTADOS E DISCUSSÃO: O desempenho em testes neuropsicológicos diferiu entre os grupos, sendo o desempenho tanto pior quanto maior o comprometimento. O grupo DV prov

  18. Subcortical connections of an 'oculomotor' region in the ventral bank of the anterior ectosylvian sulcus in the cat.

    Science.gov (United States)

    Tamai, Y; Miyashita, E

    1989-12-01

    Subcortical connections of an 'oculomotor' region in the ventral bank of the anterior ectosylvian sulcus (AESo), where eye movements were evoked by intracortical microstimulation, were studied in cats using a wheatgerm agglutinin horseradish peroxidase (WGA-HRP) tracing method. Following injection of WGA-HRP into the AESo, both anterogradely-labeled terminals and retrogradely-labeled cells were found with the highest conce