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Sample records for hippocampal volume loss

  1. Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment.

    Science.gov (United States)

    Schneider, Christine B; Donix, Markus; Linse, Katharina; Werner, Annett; Fauser, Mareike; Klingelhoefer, Lisa; Löhle, Matthias; von Kummer, Rüdiger; Reichmann, Heinz; Storch, Alexander

    2017-09-01

    Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Irrespective of the study participants' cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

  2. Homotaurine Effects on Hippocampal Volume Loss and Episodic Memory in Amnestic Mild Cognitive Impairment.

    Science.gov (United States)

    Spalletta, Gianfranco; Cravello, Luca; Gianni, Walter; Piras, Federica; Iorio, Mariangela; Cacciari, Claudia; Casini, Anna Rosa; Chiapponi, Chiara; Sancesario, Giuseppe; Fratangeli, Claudia; Orfei, Maria Donata; Caltagirone, Carlo; Piras, Fabrizio

    2016-01-01

    Homotaurine supplementation may have a positive effect on early Alzheimer's disease. Here, we investigated its potential neuroprotective effect on the hippocampus structure and episodic memory performances in amnestic mild cognitive impairment (aMCI). Neuropsychological, clinical, and neuroimaging assessment in 11 treated and 22 untreated patients were performed at baseline and after 1 year. Magnetic resonance data were analyzed using voxel-based morphometry to explore significant differences (Family Wise Error corrected) between the two groups over time. Patients treated with homotaurine showed decreased volume loss in the left and right hippocampal tail, left and right fusiform gyrus, and right inferior temporal cortex which was associated with improved short-term episodic memory performance as measured by the recency effect of the Rey 15-word list learning test immediate recall. Thus, homotaurine supplementation in individuals with aMCI has a positive effect on hippocampus atrophy and episodic memory loss. Future studies should further clarify the mechanisms of its effects on brain morphometry.

  3. Posttraumatic Stress Disorder and Depression Symptom Severities Are Differentially Associated With Hippocampal Subfield Volume Loss in Combat Veterans.

    Science.gov (United States)

    Averill, Christopher L; Satodiya, Ritvij M; Scott, J Cobb; Wrocklage, Kristen M; Schweinsburg, Brian; Averill, Lynnette A; Akiki, Teddy J; Amoroso, Timothy; Southwick, Steven M; Krystal, John H; Abdallah, Chadi G

    2017-01-01

    Two decades of human neuroimaging research have associated volume reductions in the hippocampus with posttraumatic stress disorder. However, little is known about the distribution of volume loss across hippocampal subfields. Recent advances in neuroimaging methods have made it possible to accurately delineate 10 gray matter hippocampal subfields. Here, we apply a volumetric analysis of hippocampal subfields to data from a group of combat-exposed Veterans. Veterans (total, n = 68, posttraumatic stress disorder, n = 36; combat control, n = 32) completed high-resolution structural magnetic resonance imaging. Based on previously validated methods, hippocampal subfield volume measurements were conducted using FreeSurfer 6.0. The Clinician-Administered PTSD Scale assessed posttraumatic stress disorder symptom severity; Beck Depression Inventory assessed depressive symptom severity. Controlling for age and intracranial volume, partial correlation analysis examined the relationship between hippocampal subfields and symptom severity. Correction for multiple comparisons was performed using false discovery rate. Gender, intelligence, combat severity, comorbid anxiety, alcohol/substance use disorder, and medication status were investigated as potential confounds. In the whole sample, total hippocampal volume negatively correlated with Clinician-Administered PTSD Scale and Beck Depression Inventory scores. Of the 10 hippocampal subfields, Clinician-Administered PTSD Scale symptom severity negatively correlated with the hippocampus-amygdala transition area (HATA). Beck Depression Inventory scores negatively correlated with dentate gyrus, cornu ammonis 4 (CA4), HATA, CA2/3, molecular layer, and CA1. Follow-up analysis limited to the posttraumatic stress disorder group showed a negative correlation between Clinician-Administered PTSD Scale symptom severity and each of HATA, CA2/3, molecular layer, and CA4. This study provides the first evidence relating posttraumatic stress

  4. Detection of volume loss in hippocampal layers in Alzheimer's disease using 7 T MRI: A feasibility study

    Directory of Open Access Journals (Sweden)

    Claire Boutet

    2014-01-01

    Full Text Available In Alzheimer's disease (AD, the hippocampus is an early site of tau pathology and neurodegeneration. Histological studies have shown that lesions are not uniformly distributed within the hippocampus. Moreover, alterations of different hippocampal layers may reflect distinct pathological processes. 7 T MRI dramatically improves the visualization of hippocampal subregions and layers. In this study, we aimed to assess whether 7 T MRI can detect volumetric changes in hippocampal layers in vivo in patients with AD. We studied four AD patients and seven control subjects. MR images were acquired using a whole-body 7 T scanner with an eight channel transmit–receive coil. Hippocampal subregions were manually segmented from coronal T2*-weighted gradient echo images with 0.3 × 0.3 × 1.2 mm3 resolution using a protocol that distinguishes between layers richer or poorer in neuronal bodies. Five subregions were segmented in the region of the hippocampal body: alveus, strata radiatum, lacunosum and moleculare (SRLM of the cornu Ammonis (CA, hilum, stratum pyramidale of CA and stratum pyramidale of the subiculum. We found strong bilateral reductions in the SRLM of the cornu Ammonis and in the stratum pyramidale of the subiculum (p < 0.05, with average cross-sectional area reductions ranging from −29% to −49%. These results show that it is possible to detect volume loss in distinct hippocampal layers using segmentation of 7 T MRI. 7 T MRI-based segmentation is a promising tool for AD research.

  5. Changes in Hippocampal Volume are Correlated with Cell Loss but Not with Seizure Frequency in Two Chronic Models of Temporal Lobe Epilepsy

    Science.gov (United States)

    Polli, Roberson S.; Malheiros, Jackeline M.; dos Santos, Renan; Hamani, Clement; Longo, Beatriz M.; Tannús, Alberto; Mello, Luiz E.; Covolan, Luciene

    2014-01-01

    Kainic acid (KA) or pilocarpine (PILO) have been used in rats to model human temporal lobe epilepsy (TLE) but the distribution and severity of structural lesions between these two models may differ. Magnetic resonance imaging (MRI) studies have used quantitative measurements of hippocampal T2 (T2HP) relaxation time and volume, but simultaneous comparative results have not been reported yet. The aim of this study was to compare the MRI T2HP and volume with histological data and frequency of seizures in both models. KA- and PILO-treated rats were imaged with a 2 T MRI scanner. T2HP and volume values were correlated with the number of cells, mossy fiber sprouting, and spontaneous recurrent seizures (SRS) frequency over the 9 months following status epilepticus (SE). Compared to controls, KA-treated rats had unaltered T2HP, pronounced reduction in hippocampal volume and concomitant cell reduction in granule cell layer, CA1 and CA3 at 3 months post SE. In contrast, hippocampal volume was unchanged in PILO-treated animals despite detectable increased T2HP and cell loss in granule cell layer, CA1 and CA3. In the following 6 months, MRI hippocampal volume remained stable with increase of T2HP signal in the KA-treated group. The number of CA1 and CA3 cells was smaller than age-matched CTL group. In contrast, PILO group had MRI volumetric reduction accompanied by reduction in the number of CA1 and CA3 cells. In this group, T2HP signal was unaltered at 6 or 9 months after status. Reductions in the number of cells were not progressive in both models. Notably, the SRS frequency was higher in PILO than in the KA model. The volumetry data correlated well with tissue damage in the epileptic brain, suggesting that MRI may be useful for tracking longitudinal hippocampal changes, allowing the assessment of individual variability and disease progression. Our results indicate that the temporal changes in hippocampal morphology are distinct for both models of TLE and that

  6. Comparison of Hippocampal Volume in Dementia Subtypes

    International Nuclear Information System (INIS)

    Vijayakumar, Avinash; Vijayakumar, Abhishek

    2012-01-01

    Aims. To examine the relationship between different types of dementia and hippocampal volume. Methods. Hippocampal volume was measured using FL3D sequence magnetic resonance imaging in 26 Alzheimer's, vascular dementia, mixed dementia, and normal pressure hydrocephalus patients and 15 healthy controls and also hippocampal ratio, analyzed. Minimental scale was used to stratify patients on cognitive function impairments. Results. Hippocampal volume and ratio was reduced by 25% in Alzheimer's disease, 21% in mixed dementia, 11% in vascular dementia and 5% in normal pressure hydrocephalus in comparison to control. Also an asymmetrical decrease in volume of left hippocampus was noted. The severity of dementia increased in accordance to decreasing hippocampal volume. Conclusion. Measurement in hippocampal volume may facilitate in differentiating different types of dementia and in disease progression. There was a correlation between hippocampal volume and severity of cognitive impairment

  7. Novel genetic loci associated with hippocampal volume

    NARCIS (Netherlands)

    D.P. Hibar (Derrek); H.H.H. Adams (Hieab); N. Jahanshad (Neda); G. Chauhan (Ganesh); J.L. Stein; E. Hofer (Edith); M.E. Rentería (Miguel); J.C. Bis (Joshua); A. Arias-Vásquez (Alejandro); Ikram, M.K. (M. Kamran); S. Desrivières (Sylvane); M.W. Vernooij (Meike); L. Abramovic (Lucija); S. Alhusaini (Saud); N. Amin (Najaf); M. Andersson (Micael); K. Arfanakis (Konstantinos); B. Aribisala (Benjamin); N.J. Armstrong (Nicola J.); L. Athanasiu (Lavinia); T. Axelsson (Tomas); A.H. Beecham (Ashley); A. Beiser (Alexa); M. Bernard (Manon); S.H. Blanton (Susan H.); M.M. Bohlken (Marc M.); M.P.M. Boks (Marco); L.B.C. Bralten (Linda); A.M. Brickman (Adam M.); Carmichael, O. (Owen); M.M. Chakravarty (M. Mallar); Q. Chen (Qiang); C.R.K. Ching (Christopher); V. Chouraki (Vincent); G. Cuellar-Partida (Gabriel); F. Crivello (Fabrice); A. den Braber (Anouk); Doan, N.T. (Nhat Trung); S.M. Ehrlich (Stefan); S. Giddaluru (Sudheer); A.L. Goldman (Aaron L.); R.F. Gottesman (Rebecca); O. Grimm (Oliver); M.D. Griswold (Michael); T. Guadalupe (Tulio); Gutman, B.A. (Boris A.); J. Hass (Johanna); U.K. Haukvik (Unn); D. Hoehn (David); A.J. Holmes (Avram); M. Hoogman (Martine); D. Janowitz (Deborah); T. Jia (Tianye); Jørgensen, K.N. (Kjetil N.); N. Karbalai (Nazanin); D. Kasperaviciute (Dalia); S. Kim (Shinseog); M. Klein (Marieke); B. Kraemer (Bernd); P.H. Lee (Phil); D.C. Liewald (David C.); L.M. Lopez (Lorna); M. Luciano (Michelle); C. MacAre (Christine); Marquand, A.F. (Andre F.); M. Matarin (Mar); R. Mather; M. Mattheisen (Manuel); McKay, D.R. (David R.); Milaneschi, Y. (Yuri); S. Muñoz Maniega (Susana); K. Nho (Kwangsik); A.C. Nugent (Allison); P. Nyquist (Paul); Loohuis, L.M.O. (Loes M. Olde); J. Oosterlaan (Jaap); M. Papmeyer (Martina); Pirpamer, L. (Lukas); B. Pütz (Benno); A. Ramasamy (Adaikalavan); Richards, J.S. (Jennifer S.); S.L. Risacher (Shannon); R. Roiz-Santiañez (Roberto); N. Rommelse (Nanda); S. Ropele (Stefan); E.J. Rose (Emma); N.A. Royle (Natalie); T. Rundek (Tatjana); P.G. Sämann (Philipp); Saremi, A. (Arvin); C.L. Satizabal (Claudia L.); L. Schmaal (Lianne); N.J. Schork (Nicholas); Shen, L. (Li); J. Shin (Jean); Shumskaya, E. (Elena); A.V. Smith (Albert Vernon); R. Sprooten (Roy); L.T. Strike (Lachlan); A. Teumer (Alexander); D. Tordesillas-Gutierrez (Diana); R. Toro (Roberto); D. Trabzuni (Danyah); S. Trompet (Stella); D. Vaidya (Dhananjay); J. van der Grond (Jeroen); S.J. van der Lee (Sven); Van Der Meer, D. (Dennis); M.M.J. Van Donkelaar (Marjolein M. J.); K.R. van Eijk (Kristel); T.G.M. van Erp (Theo G.); Van Rooij, D. (Daan); E. Walton (Esther); L.T. Westlye (Lars); C.D. Whelan (Christopher); B.G. Windham (B Gwen); A.M. Winkler (Anderson); K. Wittfeld (Katharina); G. Woldehawariat (Girma); A. Björnsson (Asgeir); Wolfers, T. (Thomas); L.R. Yanek (Lisa); Yang, J. (Jingyun); A.P. Zijdenbos; M.P. Zwiers (Marcel); I. Agartz (Ingrid); L. Almasy (Laura); D.J. Ames (David); Amouyel, P. (Philippe); O.A. Andreassen (Ole); S. Arepalli (Sampath); A.A. Assareh; S. Barral (Sandra); M.E. Bastin (Mark); Becker, D.M. (Diane M.); J.T. Becker (James); D.A. Bennett (David A.); J. Blangero (John); H. van Bokhoven (Hans); D.I. Boomsma (Dorret); H. Brodaty (Henry); R.M. Brouwer (Rachel); H.G. Brunner; M. Buckner; J.K. Buitelaar (Jan); K. Bulayeva (Kazima); W. Cahn (Wiepke); V.D. Calhoun Vince D. (V.); D.M. Cannon (Dara); G. Cavalleri (Gianpiero); Cheng, C.-Y. (Ching-Yu); S. Cichon (Sven); M.R. Cookson (Mark); A. Corvin (Aiden); B. Crespo-Facorro (Benedicto); J.E. Curran (Joanne); M. Czisch (Michael); A.M. Dale (Anders); G.E. Davies (Gareth); A.J. de Craen (Anton); E.J.C. de Geus (Eco); P.L. de Jager (Philip); G.I. de Zubicaray (Greig); I.J. Deary (Ian J.); S. Debette (Stéphanie); C. DeCarli (Charles); N. Delanty; C. Depondt (Chantal); A.L. DeStefano (Anita); A. Dillman (Allissa); S. Djurovic (Srdjan); D.J. Donohoe (Dennis); D.A. Drevets (Douglas); Duggirala, R. (Ravi); M.D. Dyer (Matthew); C. Enzinger (Christian); S. Erk; T. Espeseth (Thomas); Fedko, I.O. (Iryna O.); Fernández, G. (Guillén); L. Ferrucci (Luigi); S.E. Fisher (Simon); D. Fleischman (Debra); I. Ford (Ian); M. Fornage (Myriam); T. Foroud (Tatiana); P.T. Fox (Peter); C. Francks (Clyde); Fukunaga, M. (Masaki); Gibbs, J.R. (J. Raphael); D.C. Glahn (David); R.L. Gollub (Randy); H.H.H. Göring (Harald H.); R.C. Green (Robert C.); O. Gruber (Oliver); V. Gudnason (Vilmundur); S. Guelfi (Sebastian); Håberg, A.K. (Asta K.); N.K. Hansell (Narelle); J. Hardy (John); C.A. Hartman (C.); Hashimoto, R. (Ryota); K. Hegenscheid (Katrin); J. Heinz (Judith); S. Le Hellard (Stephanie); D.G. Hernandez (Dena); D.J. Heslenfeld (Dirk); Ho, B.-C. (Beng-Choon); P.J. Hoekstra (Pieter); W. Hoffmann (Wolfgang); A. Hofman (Albert); F. Holsboer (Florian); G. Homuth (Georg); N. Hosten (Norbert); J.J. Hottenga (Jouke Jan); M.J. Huentelman (Matthew); H.H. Pol; Ikeda, M. (Masashi); Jack, C.R. (Clifford R.); S. Jenkinson (Sarah); R. Johnson (Robert); Jönsson, E.G. (Erik G.); J.W. Jukema; R. Kahn (René); Kanai, R. (Ryota); I. Kloszewska (Iwona); Knopman, D.S. (David S.); P. Kochunov (Peter); Kwok, J.B. (John B.); S. Lawrie (Stephen); H. Lemaître (Herve); X. Liu (Xinmin); D.L. Longo (Dan L.); O.L. Lopez (Oscar L.); S. Lovestone (Simon); Martinez, O. (Oliver); J.-L. Martinot (Jean-Luc); V.S. Mattay (Venkata S.); McDonald, C. (Colm); A.M. McIntosh (Andrew); McMahon, F.J. (Francis J.); McMahon, K.L. (Katie L.); P. Mecocci (Patrizia); I. Melle (Ingrid); Meyer-Lindenberg, A. (Andreas); S. Mohnke (Sebastian); Montgomery, G.W. (Grant W.); D.W. Morris (Derek W); T.H. Mosley (Thomas H.); T.W. Mühleisen (Thomas); B. Müller-Myhsok (B.); M.A. Nalls (Michael); M. Nauck (Matthias); T.E. Nichols (Thomas); W.J. Niessen (Wiro); M.M. Nöthen (Markus); L. Nyberg (Lars); Ohi, K. (Kazutaka); R.L. Olvera (Rene); R.A. Ophoff (Roel); M. Pandolfo (Massimo); T. Paus (Tomas); Z. Pausova (Zdenka); B.W.J.H. Penninx (Brenda); Pike, G.B. (G. Bruce); S.G. Potkin (Steven); B.M. Psaty (Bruce); S. Reppermund; M. Rietschel (Marcella); J.L. Roffman (Joshua); N. Seiferth (Nina); J.I. Rotter (Jerome I.); M. Ryten (Mina); Sacco, R.L. (Ralph L.); P.S. Sachdev (Perminder); A.J. Saykin (Andrew); R. Schmidt (Reinhold); Schmidt, H. (Helena); C.J. Schofield (Christopher); Sigursson, S. (Sigurdur); Simmons, A. (Andrew); A. Singleton (Andrew); S.M. Sisodiya (Sanjay); Smith, C. (Colin); J.W. Smoller; H. Soininen (H.); V.M. Steen (Vidar); D.J. Stott (David J.); J. Sussmann (Jessika); A. Thalamuthu (Anbupalam); A.W. Toga (Arthur W.); B. Traynor (Bryan); J.C. Troncoso (Juan); M. Tsolaki (Magda); C. Tzourio (Christophe); A.G. Uitterlinden (André); Hernández, M.C.V. (Maria C. Valdés); M.P. van der Brug (Marcel); A. van der Lugt (Aad); N.J. van der Wee (Nic); N.E.M. van Haren (Neeltje E.); D. van 't Ent (Dennis); M.J.D. van Tol (Marie-José); B.N. Vardarajan (Badri); B. Vellas (Bruno); D.J. Veltman (Dick); H. Völzke (Henry); H.J. Walter (Henrik); J. Wardlaw (Joanna); A.M.J. Wassink (Annemarie); M.E. Weale (Michael); Weinberger, D.R. (Daniel R.); Weiner, M.W. (Michael W.); Wen, W. (Wei); E. Westman (Eric); T.J.H. White (Tonya); Wong, T.Y. (Tien Y.); Wright, C.B. (Clinton B.); R.H. Zielke (Ronald H.); A.B. Zonderman; N.G. Martin (Nicholas); C.M. van Duijn (Cornelia); M.J. Wright (Margaret); W.T. Longstreth Jr; G. Schumann (Gunter); H.J. Grabe (Hans Jörgen); B. Franke (Barbara); L.J. Launer (Lenore); S.E. Medland (Sarah Elizabeth); S. Seshadri (Sudha); P.M. Thompson (Paul); M.K. Ikram (Kamran)

    2017-01-01

    textabstractThe hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic

  8. Novel genetic loci associated with hippocampal volume

    NARCIS (Netherlands)

    Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivières, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S.; Armstrong, Nicola J.; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H.; Beiser, Alexa; Bernard, Manon; Blanton, Susan H.; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brickman, Adam M.; Carmichael, Owen; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L.; Gottesman, Rebecca F.; Grimm, Oliver; Griswold, Michael E.; Guadalupe, Tulio; Gutman, Boris A.; Hass, Johanna; Haukvik, Unn K.; Hoehn, David; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N.; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Liewald, David C. M.; Lopez, Lorna M.; Luciano, Michelle; Macare, Christine; Marquand, Andre F.; Matarin, Mar; Mather, Karen A.; Mattheisen, Manuel; McKay, David R.; Milaneschi, Yuri; Muñoz Maniega, Susana; Nho, Kwangsik; Nugent, Allison C.; Nyquist, Paul; Loohuis, Loes M. Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S.; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J.; Royle, Natalie A.; Rundek, Tatjana; Sämann, Philipp G.; Saremi, Arvin; Satizabal, Claudia L.; Schmaal, Lianne; Schork, Andrew J.; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V.; Sprooten, Emma; Strike, Lachlan T.; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; van der Grond, Jeroen; van der Lee, Sven J.; van der Meer, Dennis; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; van Erp, Theo G. M.; van Rooij, Daan; Walton, Esther; Westlye, Lars T.; Whelan, Christopher D.; Windham, Beverly G.; Winkler, Anderson M.; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R.; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P.; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A.; Arepalli, Sampath; Assareh, Amelia A.; Barral, Sandra; Bastin, Mark E.; Becker, Diane M.; Becker, James T.; Bennett, David A.; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I.; Brodaty, Henry; Brouwer, Rachel M.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Bulayeva, Kazima B.; Cahn, Wiepke; Calhoun, Vince D.; Cannon, Dara M.; Cavalleri, Gianpiero L.; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R.; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E.; Czisch, Michael; Dale, Anders M.; Davies, Gareth E.; de Craen, Anton J. M.; de Geus, Eco J. C.; de Jager, Philip L.; de Zubicaray, Greig I.; Deary, Ian J.; Debette, Stéphanie; Decarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C.; Duggirala, Ravi; Dyer, Thomas D.; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O.; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E.; Fleischman, Debra A.; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M.; Fox, Peter T.; Francks, Clyde; Fukunaga, Masaki; Gibbs, J. Raphael; Glahn, David C.; Gollub, Randy L.; Göring, Harald H. H.; Green, Robert C.; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K.; Hansell, Narelle K.; Hardy, John; Hartman, Catharina A.; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G.; Heslenfeld, Dirk J.; Ho, Beng-Choon; Hoekstra, Pieter J.; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Pol, Hilleke E. Hulshoff; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G.; Jukema, J. Wouter; Kahn, René S.; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L.; Lopez, Oscar L.; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S.; McDonald, Colm; McIntosh, Andrew M.; McMahon, Francis J.; McMahon, Katie L.; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W.; Morris, Derek W.; Mosley, Thomas H.; Mühleisen, Thomas W.; Müller-Myhsok, Bertram; Nalls, Michael A.; Nauck, Matthias; Nichols, Thomas E.; Niessen, Wiro J.; Nöthen, Markus M.; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L.; Ophoff, Roel A.; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W. J. H.; Pike, G. Bruce; Potkin, Steven G.; Psaty, Bruce M.; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L.; Romanczuk-Seiferth, Nina; Rotter, Jerome I.; Ryten, Mina; Sacco, Ralph L.; Sachdev, Perminder S.; Saykin, Andrew J.; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R.; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M.; Smith, Colin; Smoller, Jordan W.; Soininen, Hilkka; Steen, Vidar M.; Stott, David J.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G.; Hernández, Maria C. Valdés; van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J. A.; van Haren, Neeltje E. M.; van 't Ent, Dennis; van Tol, Marie-Jose; Vardarajan, Badri N.; Vellas, Bruno; Veltman, Dick J.; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M.; Wassink, Thomas H.; Weale, Michael E.; Weinberger, Daniel R.; Weiner, Michael W.; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y.; Wright, Clinton B.; Zielke, Ronald H.; Zonderman, Alan B.; Martin, Nicholas G.; van Duijn, Cornelia M.; Wright, Margaret J.; Longstreth, W. T.; Schumann, Gunter; Grabe, Hans J.; Franke, Barbara; Launer, Lenore J.; Medland, Sarah E.; Seshadri, Sudha; Thompson, Paul M.; Ikram, M. Arfan

    2017-01-01

    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of

  9. Novel genetic loci associated with hippocampal volume

    OpenAIRE

    Hibar, Derrek P.; Adams, Hieab H. H.; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L.; Hofer, Edith; Renteria, Miguel E.; Bis, Joshua C.; Arias-Vasquez, Alejandro; Ikram, M. Kamran; Desrivieres, Sylvane; Vernooij, Meike W.; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf

    2017-01-01

    International audience; The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal ...

  10. Novel genetic loci associated with hippocampal volume.

    Science.gov (United States)

    Hibar, Derrek P; Adams, Hieab H H; Jahanshad, Neda; Chauhan, Ganesh; Stein, Jason L; Hofer, Edith; Renteria, Miguel E; Bis, Joshua C; Arias-Vasquez, Alejandro; Ikram, M Kamran; Desrivières, Sylvane; Vernooij, Meike W; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beecham, Ashley H; Beiser, Alexa; Bernard, Manon; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Chouraki, Vincent; Cuellar-Partida, Gabriel; Crivello, Fabrice; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Gutman, Boris A; Hass, Johanna; Haukvik, Unn K; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Jørgensen, Kjetil N; Karbalai, Nazanin; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre F; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; McKay, David R; Milaneschi, Yuri; Muñoz Maniega, Susana; Nho, Kwangsik; Nugent, Allison C; Nyquist, Paul; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pirpamer, Lukas; Pütz, Benno; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Ropele, Stefan; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Saremi, Arvin; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Trompet, Stella; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Lee, Sven J; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Craen, Anton J M; De Geus, Eco J C; De Jager, Philip L; De Zubicaray, Greig I; Deary, Ian J; Debette, Stéphanie; DeCarli, Charles; Delanty, Norman; Depondt, Chantal; DeStefano, Anita; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Enzinger, Christian; Erk, Susanne; Espeseth, Thomas; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Fornage, Myriam; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Håberg, Asta K; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Huentelman, Matthew; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Francis J; McMahon, Katie L; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schmidt, Helena; Schofield, Peter R; Sigursson, Sigurdur; Simmons, Andrew; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Tsolaki, Magda; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; van der Lugt, Aad; van der Wee, Nic J A; Van Haren, Neeltje E M; van 't Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Vellas, Bruno; Veltman, Dick J; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, Ronald H; Zonderman, Alan B; Martin, Nicholas G; Van Duijn, Cornelia M; Wright, Margaret J; Longstreth, W T; Schumann, Gunter; Grabe, Hans J; Franke, Barbara; Launer, Lenore J; Medland, Sarah E; Seshadri, Sudha; Thompson, Paul M; Ikram, M Arfan

    2017-01-18

    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r g =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

  11. Hippocampal volume reduction in congenital central hypoventilation syndrome.

    Directory of Open Access Journals (Sweden)

    Paul M Macey

    Full Text Available Children with congenital central hypoventilation syndrome (CCHS, a genetic disorder characterized by diminished drive to breathe during sleep and impaired CO(2 sensitivity, show brain structural and functional changes on magnetic resonance imaging (MRI scans, with impaired responses in specific hippocampal regions, suggesting localized injury.We assessed total volume and regional variation in hippocampal surface morphology to identify areas affected in the syndrome. We studied 18 CCHS (mean age+/-std: 15.1+/-2.2 years; 8 female and 32 healthy control (age 15.2+/-2.4 years; 14 female children, and traced hippocampi on 1 mm(3 resolution T1-weighted scans, collected with a 3.0 Tesla MRI scanner. Regional hippocampal volume variations, adjusted for cranial volume, were compared between groups based on t-tests of surface distances to the structure midline, with correction for multiple comparisons. Significant tissue losses emerged in CCHS patients on the left side, with a trend for loss on the right; however, most areas affected on the left also showed equivalent right-sided volume reductions. Reduced regional volumes appeared in the left rostral hippocampus, bilateral areas in mid and mid-to-caudal regions, and a dorsal-caudal region, adjacent to the fimbria.The volume losses may result from hypoxic exposure following hypoventilation during sleep-disordered breathing, or from developmental or vascular consequences of genetic mutations in the syndrome. The sites of change overlap regions of abnormal functional responses to respiratory and autonomic challenges. Affected hippocampal areas have roles associated with memory, mood, and indirectly, autonomic regulation; impairments in these behavioral and physiological functions appear in CCHS.

  12. Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn H; Skimminge, Arnold; Rasmussen, Hans

    2011-01-01

    . Although patients' ventricles did not change significantly, ventricular increases correlated with less improvement of negative symptoms. Progressive regional volume loss in quetiapine-treated, first-episode schizophrenia patients may be dose-dependent and clinically relevant. The mechanisms underlying...... scarcely been investigated. Here we investigated structural brain changes in antipsychotic-naive, first-episode schizophrenia patients after 6 months treatment with the SGA, quetiapine. We have recently reported on baseline volume reductions in the caudate nucleus and hippocampus. Baseline and follow-up T1......-weighted images (3 T) from 22 patients and 28 matched healthy controls were analysed using tensor-based morphometry. Non-parametric voxel-wise group comparisons were performed. Small volume correction was employed for striatum, hippocampus and ventricles. Dose-dependent medication effects and associations...

  13. Cortisol, Cytokines, and Hippocampal Volume in the Elderly

    Directory of Open Access Journals (Sweden)

    Keith Daniel Sudheimer

    2014-07-01

    Full Text Available Separate bodies of literature report that elevated pro-inflammatory cytokines and cortisol negatively affect hippocampal structure and cognitive functioning, particularly in older adults. Although interactions between cytokines and cortisol occur through a variety of known mechanisms, few studies consider how their interactions affect brain structure. In this preliminary study, we assess the impact of interactions between circulating levels of IL-1Beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha, and waking cortisol on hippocampal volume. Twenty-eight community-dwelling older adults underwent blood draws for quantification of circulating cytokines and saliva collections to quantify the cortisol awakening response. Hippocampal volume measurements were made using structural magnetic resonance imaging. Elevated levels of waking cortisol in conjunction with higher concentrations of IL-6 and TNF-alpha were associated with smaller hippocampal volumes. In addition, independent of cortisol, higher levels of IL-1beta and TNF-alpha were also associated with smaller hippocampal volumes. These data provide preliminary evidence that higher cortisol, in conjunction with higher IL-6 and TNF-alpha, are associated with smaller hippocampal volume in older adults. We suggest that the dynamic balance between the hypothalamic-pituitary adrenal axis and inflammation processes may explain hippocampal volume reductions in older adults better than either set of measures do in isolation.

  14. Hippocampal and Amygdalar Volumes in Dissociative Identity Disorder

    Science.gov (United States)

    Vermetten, Eric; Schmahl, Christian; Lindner, Sanneke; Loewenstein, Richard J.; Bremner, J. Douglas

    2011-01-01

    Objective Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. Method The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. Results Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. Conclusions The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects. PMID:16585437

  15. Hippocampal and amygdalar volumes in dissociative identity disorder.

    Science.gov (United States)

    Vermetten, Eric; Schmahl, Christian; Lindner, Sanneke; Loewenstein, Richard J; Bremner, J Douglas

    2006-04-01

    Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects.

  16. Long-lasting hippocampal synaptic protein loss in a mouse model of posttraumatic stress disorder.

    Directory of Open Access Journals (Sweden)

    Leonie Herrmann

    Full Text Available Despite intensive research efforts, the molecular pathogenesis of posttraumatic stress disorder (PTSD and especially of the hippocampal volume loss found in the majority of patients suffering from this anxiety disease still remains elusive. We demonstrated before that trauma-induced hippocampal shrinkage can also be observed in mice exhibiting a PTSD-like syndrome. Aiming to decipher the molecular correlates of these trans-species posttraumatic hippocampal alterations, we compared the expression levels of a set of neurostructural marker proteins between traumatized and control mice at different time points after their subjection to either an electric footshock or mock treatment which was followed by stressful re-exposure in several experimental groups. To our knowledge, this is the first systematic in vivo study analyzing the long-term neuromolecular sequelae of acute traumatic stress combined with re-exposure. We show here that a PTSD-like syndrome in mice is accompanied by a long-lasting reduction of hippocampal synaptic proteins which interestingly correlates with the strength of the generalized and conditioned fear response but not with the intensity of hyperarousal symptoms. Furthermore, we demonstrate that treatment with the serotonin reuptake inhibitor (SSRI fluoxetine is able to counteract both the PTSD-like syndrome and the posttraumatic synaptic protein loss. Taken together, this study demonstrates for the first time that a loss of hippocampal synaptic proteins is associated with a PTSD-like syndrome in mice. Further studies will have to reveal whether these findings are transferable to PTSD patients.

  17. Longitudinal study of hippocampal volumes in heavy cannabis users.

    Science.gov (United States)

    Koenders, L; Lorenzetti, V; de Haan, L; Suo, C; Vingerhoets, Wam; van den Brink, W; Wiers, R W; Meijer, C J; Machielsen, Mwj; Goudriaan, A E; Veltman, D J; Yücel, M; Cousijn, J

    2017-08-01

    Cannabis exposure, particularly heavy cannabis use, has been associated with neuroanatomical alterations in regions rich with cannabinoid receptors such as the hippocampus in some but not in other (mainly cross-sectional) studies. However, it remains unclear whether continued heavy cannabis use alters hippocampal volume, and whether an earlier age of onset and/or a higher dosage exacerbate these changes. Twenty heavy cannabis users (mean age 21 years, range 18-24 years) and 23 matched non-cannabis using healthy controls were submitted to a comprehensive psychological assessment and magnetic resonance imaging scan at baseline and at follow-up (average of 39 months post-baseline; standard deviation=2.4). Cannabis users started smoking around 16 years and smoked on average five days per week. A novel aspect of the current study is that hippocampal volume estimates were obtained from manual tracing the hippocampus on T1-weighted anatomical magnetic resonance imaging scans, using a previously validated protocol. Compared to controls, cannabis users did not show hippocampal volume alterations at either baseline or follow-up. Hippocampal volumes increased over time in both cannabis users and controls, following similar trajectories of increase. Cannabis dose and age of onset of cannabis use did not affect hippocampal volumes. Continued heavy cannabis use did not affect hippocampal neuroanatomical changes in early adulthood. This contrasts with prior evidence on alterations in this region in samples of older adult cannabis users. In young adults using cannabis at this level, cannabis use may not be heavy enough to affect hippocampal neuroanatomy.

  18. Beyond dizziness: virtual navigation, spatial anxiety and hippocampal volume in bilateral vestibulopathy

    Directory of Open Access Journals (Sweden)

    Olympia eKremmyda

    2016-03-01

    Full Text Available Bilateral vestibulopathy (BVP is defined as the impairment or loss of function of either the labyrinths or the eighth nerves. Patients with total BVP due to bilateral vestibular nerve section exhibit difficulties in spatial memory and navigation and show a loss of hippocampal volume. In clinical practice, most patients do not have a complete loss of function but rather an asymmetrical residual functioning of the vestibular system. The purpose of the current study was to investigate navigational ability and hippocampal atrophy in BVP patients with residual vestibular function. Fifteen patients with BVP and a group of age- and gender- matched healthy controls were examined. Self-reported questionnaires on spatial anxiety and wayfinding were used to assess the applied strategy of wayfinding and quality of life. Spatial memory and navigation were tested directly using a virtual Morris Water Maze Task. The hippocampal volume of these two groups was evaluated by voxel-based morphometry. In the patients, the questionnaire showed a higher spatial anxiety and the Morris Water Maze Task a delayed spatial learning performance. MRI revealed a significant decrease in the gray matter mid-hippocampal volume (Left: p = 0.006, Z = 4.58, Right: p < 0.001, Z = 3.63 and posterior parahippocampal volume (Right: p = 0.005, Z = 4.65, Left: p < 0.001, Z = 3.87 compared to those of healthy controls. In addition, a decrease in hippocampal formation volume correlated with a more dominant route-finding strategy. Our current findings demonstrate that even partial bilateral vestibular loss leads to anatomical and functional

  19. Hippocampal volume and serotonin transporter polymorphism in major depressive disorder

    DEFF Research Database (Denmark)

    Ahdidan, Jamila; Foldager, Leslie; Rosenberg, Raben

    2013-01-01

    Objective: The main aim of the present study was to replicate a previous finding in major depressive disorder (MDD) of association between reduced hippocampal volume and the long variant of the di- and triallelic serotonin transporter polymorphism in SLC6A4 on chromosome 17q11.2. Secondarily, we...... that we aimed to replicate, and no significant associations with the serotonin transporter polymorphism were found. Conclusions: The present quantitative and morphometric MRI study was not able to replicate the previous finding of association between reduced hippocampal volume in depressed patients...... and the serotonin transporter polymorphism....

  20. BDNF val(66)met affects hippocampal volume and emotion-related hippocampal memory activity

    NARCIS (Netherlands)

    Molendijk, M. L.; van Tol, M-J; Penninx, B. W. J. H.; van der Wee, N. J. A.; Aleman, A.; Veltman, D. J.; Spinhoven, P.; Elzinga, B. M.

    2012-01-01

    The val(66)met polymorphism on the BDNF gene has been reported to explain individual differences in hippocampal volume and memory-related activity. These findings, however, have not been replicated consistently and no studies to date controlled for the potentially confounding impact of early life

  1. Regional hippocampal volumes and development predict learning and memory.

    Science.gov (United States)

    Tamnes, Christian K; Walhovd, Kristine B; Engvig, Andreas; Grydeland, Håkon; Krogsrud, Stine K; Østby, Ylva; Holland, Dominic; Dale, Anders M; Fjell, Anders M

    2014-01-01

    The hippocampus is an anatomically and functionally heterogeneous structure, but longitudinal studies of its regional development are scarce and it is not known whether protracted maturation of the hippocampus in adolescence is related to memory development. First, we investigated hippocampal subfield development using 170 longitudinally acquired brain magnetic resonance imaging scans from 85 participants aged 8-21 years. Hippocampal subfield volumes were estimated by the use of automated segmentation of 7 subfields, including the cornu ammonis (CA) sectors and the dentate gyrus (DG), while longitudinal subfield volumetric change was quantified using a nonlinear registration procedure. Second, associations between subfield volumes and change and verbal learning/memory across multiple retention intervals (5 min, 30 min and 1 week) were tested. It was hypothesized that short and intermediate memory would be more closely related to CA2-3/CA4-DG and extended, remote memory to CA1. Change rates were significantly different across hippocampal subfields, but nearly all subfields showed significant volume decreases over time throughout adolescence. Several subfield volumes were larger in the right hemisphere and in males, while for change rates there were no hemisphere or sex differences. Partly in support of the hypotheses, greater volume of CA1 and CA2-3 was related to recall and retention after an extended delay, while longitudinal reduction of CA2-3 and CA4-DG was related to learning. This suggests continued regional development of the hippocampus across adolescence and that volume and volume change in specific subfields differentially predict verbal learning and memory over different retention intervals, but future high-resolution studies are called for. © 2014 S. Karger AG, Basel.

  2. Serum vitamin D and hippocampal gray matter volume in schizophrenia.

    Science.gov (United States)

    Shivakumar, Venkataram; Kalmady, Sunil V; Amaresha, Anekal C; Jose, Dania; Narayanaswamy, Janardhanan C; Agarwal, Sri Mahavir; Joseph, Boban; Venkatasubramanian, Ganesan; Ravi, Vasanthapuram; Keshavan, Matcheri S; Gangadhar, Bangalore N

    2015-08-30

    Disparate lines of evidence including epidemiological and case-control studies have increasingly implicated vitamin D in the pathogenesis of schizophrenia. Vitamin D deficiency can lead to dysfunction of the hippocampus--a brain region hypothesized to be critically involved in schizophrenia. In this study, we examined for potential association between serum vitamin D level and hippocampal gray matter volume in antipsychotic-naïve or antipsychotic-free schizophrenia patients (n = 35). Serum vitamin D level was estimated using 25-OH vitamin D immunoassay. Optimized voxel-based morphometry was used to analyze 3-Tesla magnetic resonance imaging (MRI) (1-mm slice thickness). Ninety-seven percent of the schizophrenia patients (n = 34) had sub-optimal levels of serum vitamin D (83%, deficiency; 14%, insufficiency). A significant positive correlation was seen between vitamin D and regional gray matter volume in the right hippocampus after controlling for age, years of education and total intracranial volume (Montreal Neurological Institute (MNI) coordinates: x = 35, y = -18, z = -8; t = 4.34 pFWE(Corrected) = 0.018). These observations support a potential role of vitamin D deficiency in mediating hippocampal volume deficits, possibly through neurotrophic, neuroimmunomodulatory and glutamatergic effects. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Hippocampal volume is decreased in adults with hypothyroidism.

    Science.gov (United States)

    Cooke, Gillian E; Mullally, Sinead; Correia, Neuman; O'Mara, Shane M; Gibney, James

    2014-03-01

    Thyroid hormones are important for the adult brain, particularly regions of the hippocampus including the dentate gyrus and CA1 and CA3 regions. The hippocampus is a thyroid hormone receptor-rich region of the brain involved in learning and memory. Consequently, alterations in thyroid hormone levels have been reported to impair hippocampal-associated learning and memory, synaptic plasticity, and neurogenesis. While these effects have been shown primarily in developing rats, as well as in adult rats, little is known about the effects in adult humans. There are currently no data regarding structural changes in the hippocampus as a result of adult-onset hypothyroidism. We aimed to establish whether hippocampal volume was reduced in patients with untreated adult-onset hypothyroidism compared to age-matched healthy controls. High-resolution magnetization-prepared rapid acquisition with gradient echo (MPRAGE) scans were performed on 11 untreated hypothyroid adults and 9 age-matched control subjects. Hypothyroidism was diagnosed based on increased levels of thyrotropin (TSH) and reduced levels of free thyroxine (fT4). Volumetric analysis of the right and left hippocampal regions, using functional magnetic resonance imaging of the brain (FMRIB) integrated registration and segmentation tool (FIRST), demonstrated significant volume reduction in the right hippocampus in the hypothyroid patients relative to the control group. These findings provide preliminary evidence that hypothyroidism results in structural deficits in the adult human brain. Decreases in volume in the right hippocampus were evident in patients with adult-onset overt hypothyroidism, supporting some of the findings in animal models.

  4. Spatial navigation impairment is proportional to right hippocampal volume

    Czech Academy of Sciences Publication Activity Database

    Nedelská, Z.; Andel, R.; Laczó, J.; Vlček, Kamil; Hořínek, D.; Lisý, J.; Sheardová, K.; Bureš, Jan; Hort, J.

    2012-01-01

    Roč. 109, č. 7 (2012), s. 2590-2594 ISSN 0027-8424 R&D Projects: GA ČR(CZ) GA309/09/1053; GA ČR(CZ) GA309/09/0286; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554 Grant - others:GA MZd(CZ) NS10331 Institutional research plan: CEZ:AV0Z50110509 Keywords : spatial navigation * Alzheimer’s Disease * hippocampal volume Subject RIV: FH - Neurology Impact factor: 9.737, year: 2012

  5. Insomnia severity is associated with a decreased volume of the CA3/Dentate Gyrus Hippocampal Subfield

    Science.gov (United States)

    Neylan, Thomas C.; Mueller, Susanne G.; Wang, Zhen; Metzler, Thomas J.; Lenoci, Maryann; Truran, Diana; Marmar, Charles R.; Weiner, Michael W.; Schuff, Norbert

    2010-01-01

    Background Prolonged disruption of sleep in animal studies is associated with decreased neurogenesis in the dentate gyrus. Our objective was to determine if insomnia severity in a sample of PTSD and controls was associated with decreased volume in the CA3/dentate hippocampal subfield. Methods Volumes of hippocampal subfields in seventeen veteran males positive for PTSD (41 ±12 years) and nineteen age-matched male veterans negative for PTSD were measured using 4 Tesla MRI. Subjective sleep quality was measured by the Insomnia Severity Index (ISI) and the Pittsburgh Sleep Quality Index (PSQI). Results Higher scores on the ISI, indicating worse insomnia, were associated with smaller volumes of the CA3/dentate subfields (r= −.48, p < 0.01) in the combined sample. Adding the ISI score as a predictor for CA3/dentate volume to a hierarchical linear regression model after first controlling for age and PTSD symptoms accounted for a 13 % increase in incremental variance (t= −2.47, p= 0.02). Conclusions The findings indicate for the first time in humans that insomnia severity is associated with volume loss of the CA3/dentate subfields. This is consistent with animal studies showing that chronic sleep disruption is associated with decreased neurogenesis and dendritic branching in these structures. PMID:20598672

  6. Delayed recall, hippocampal volume and Alzheimer neuropathology: findings from the Nun Study.

    Science.gov (United States)

    Mortimer, J A; Gosche, K M; Riley, K P; Markesbery, W R; Snowdon, D A

    2004-02-10

    To examine the associations of hippocampal volume and the severity of neurofibrillary lesions determined at autopsy with delayed verbal recall performance evaluated an average of 1 year prior to death. Hippocampal volumes were computed using postmortem brain MRI from the first 56 scanned participants of the Nun Study. Quantitative neuropathologic studies included lesion counts, Braak staging, and determination of whether neuropathologic criteria for Alzheimer disease (AD) were met. Multiple regression was used to assess the association of hippocampal volume and neuropathologic lesions with the number of words (out of 10) recalled on the Consortium to Establish a Registry for Alzheimer's Disease Delayed Word Recall Test administered an average of 1 year prior to death. When entered separately, hippocampal volume, Braak stage, and the mean neurofibrillary tangle counts in the CA-1 region of the hippocampus and the subiculum were strongly associated with the number of words recalled after a delay, adjusting for age and education. When hippocampal volume was entered together with each neuropathologic index, only hippocampal volume retained a significant association with the delayed recall measure. The association between hippocampal volume and the number of words recalled was present in both demented and nondemented individuals as well as in those with and without substantial AD neurofibrillary pathology. The association of neurofibrillary tangles with delayed verbal recall may reflect associated hippocampal atrophy.

  7. Insular and Hippocampal Gray Matter Volume Reductions in Patients with Major Depressive Disorder

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    Kugel, Harald; Krug, Axel; Schöning, Sonja; Ohrmann, Patricia; Uhlmann, Christina; Postert, Christian; Suslow, Thomas; Heindel, Walter; Arolt, Volker; Kircher, Tilo; Dannlowski, Udo

    2014-01-01

    Background Major depressive disorder is a serious psychiatric illness with a highly variable and heterogeneous clinical course. Due to the lack of consistent data from previous studies, the study of morphometric changes in major depressive disorder is still a major point of research requiring additional studies. The aim of the study presented here was to characterize and quantify regional gray matter abnormalities in a large sample of clinically well-characterized patients with major depressive disorder. Methods For this study one-hundred thirty two patients with major depressive disorder and 132 age- and gender-matched healthy control participants were included, 35 with their first episode and 97 with recurrent depression. To analyse gray matter abnormalities, voxel-based morphometry (VBM8) was employed on T1 weighted MRI data. We performed whole-brain analyses as well as a region-of-interest approach on the hippocampal formation, anterior cingulate cortex and amygdala, correlating the number of depressive episodes. Results Compared to healthy control persons, patients showed a strong gray-matter reduction in the right anterior insula. In addition, region-of-interest analyses revealed significant gray-matter reductions in the hippocampal formation. The observed alterations were more severe in patients with recurrent depressive episodes than in patients with a first episode. The number of depressive episodes was negatively correlated with gray-matter volume in the right hippocampus and right amygdala. Conclusions The anterior insula gray matter structure appears to be strongly affected in major depressive disorder and might play an important role in the neurobiology of depression. The hippocampal and amygdala volume loss cumulating with the number of episodes might be explained either by repeated neurotoxic stress or alternatively by higher relapse rates in patients showing hippocampal atrophy. PMID:25051163

  8. Neuropsychology, autobiographical memory and hippocampal volume in younger and older patients with chronic schizophrenia

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    Christina Josefa Herold

    2015-04-01

    Full Text Available Despite a wide range of studies on neuropsychology in schizophrenia, autobiographical memory (AM has been scarcely investigated in these patients. Hence less is known about AM in older patients and hippocampal contribution to autobiographical memories of varying remoteness. Therefore we investigated hippocampal volume and AM along with important neuropsychological domains in patients with chronic schizophrenia and the respective relationships between these parameters. We compared 25 older patients with chronic schizophrenia to 23 younger patients and an older healthy control group (N = 21 with respect to AM, additional neuropsychological parameters and hippocampal volume. Personal episodic and semantic memory was investigated using a semi-structured interview. Additional neuropsychological parameters were assessed by using a battery of standard neuropsychological tests. Structural magnetic resonance imaging data were analysed with an automated region-of-interest procedure. While hippocampal volume reduction and neuropsychological impairment were more pronounced in the older than in the younger patients, both groups showed equivalent reduced AM performance for recent personal episodes. In the patient group significant correlations between left hippocampal volume and recent autobiographical episodes as well as personal semantic memories arose. Verbal memory and working memory were significantly correlated with right hippocampal volume, executive functions, however, were associated with bilateral hippocampal volumes. These findings underline the complexity of AM and its impairments in the course of schizophrenia in comparison to rather progressive neuropsychological deficits and address the importance of hippocampal contribution.

  9. Neuropsychology, autobiographical memory, and hippocampal volume in "younger" and "older" patients with chronic schizophrenia.

    Science.gov (United States)

    Herold, Christina Josefa; Lässer, Marc Montgomery; Schmid, Lena Anna; Seidl, Ulrich; Kong, Li; Fellhauer, Iven; Thomann, Philipp Arthur; Essig, Marco; Schröder, Johannes

    2015-01-01

    Despite a wide range of studies on neuropsychology in schizophrenia, autobiographical memory (AM) has been scarcely investigated in these patients. Hence, less is known about AM in older patients and hippocampal contribution to autobiographical memories of varying remoteness. Therefore, we investigated hippocampal volume and AM along with important neuropsychological domains in patients with chronic schizophrenia and the respective relationships between these parameters. We compared 25 older patients with chronic schizophrenia to 23 younger patients and an older healthy control group (N = 21) with respect to AM, additional neuropsychological parameters, and hippocampal volume. Personal episodic and semantic memory was investigated using a semi-structured interview. Additional neuropsychological parameters were assessed by using a battery of standard neuropsychological tests. Structural magnetic resonance imaging data were analyzed with an automated region-of-interest procedure. While hippocampal volume reduction and neuropsychological impairment were more pronounced in the older than in the younger patients, both groups showed equivalent reduced AM performance for recent personal episodes. In the patient group, significant correlations between left hippocampal volume and recent autobiographical episodes as well as personal semantic memories arose. Verbal memory and working memory were significantly correlated with right hippocampal volume; executive functions, however, were associated with bilateral hippocampal volumes. These findings underline the complexity of AM and its impairments in the course of schizophrenia in comparison to rather progressive neuropsychological deficits and address the importance of hippocampal contribution.

  10. Hippocampal volumes among older Indian adults: Comparison with Alzheimer's disease and mild cognitive impairment

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    Vikas Dhikav

    2016-01-01

    MMSE score and hippocampal volume in the AD group. Conclusion: The volume of the hippocampus in older Indian adults was 2.77 ± 0. 6 cm3 on the right side and 2.73 ± 0.52 cm3 on the left side. There was a significant hippocampal volume loss in MCI/AD compared to cognitively normal subjects.

  11. Hippocampal volume measurement in patients with Meniere's disease : a pilot study

    NARCIS (Netherlands)

    van Cruijsen, Nynke; Hiemstra, Wilma M.; Meiners, Linda C.; Wit, Hero P.; Albers, Frans W. J.

    2007-01-01

    Conclusion. No signs of chronic stress as in hippocampal atrophy were present in patients with Meniere's disease. Objective. To evaluate the effect of chronic stress (allostatic load) by measuring hippocampal volume in patients with Meniere's disease. Subjects and methods. Ten patients with

  12. Reduced hippocampal volume is associated with overgeneralization of negative context in individuals with PTSD.

    Science.gov (United States)

    Levy-Gigi, Einat; Szabo, Csilla; Richter-Levin, Gal; Kéri, Szabolcs

    2015-01-01

    Previous studies demonstrated reduced hippocampal volume in individuals with posttraumatic stress disorder (PTSD). However, the functional role the hippocampus plays in PTSD symptomatology is still unclear. The aim of the present study was to explore generalization learning and its connection to hippocampal volume in individuals with and without PTSD. Animal and human models argue that hippocampal deficit may result in failure to process contextual information. Therefore we predicted associations between reduced hippocampal volume and overgeneralization of context in individuals with PTSD. We conducted MRI scans of bilateral hippocampal and amygdala formations as well as intracranial and total brain volumes. Generalization was measured using a novel-learning paradigm, which separately evaluates generalization of cue and context in conditions of negative and positive outcomes. As expected, MRI scans indicated reduced hippocampal volume in PTSD compared to non-PTSD participants. Behavioral results revealed a selective deficit in context generalization learning in individuals with PTSD, F(1, 43) = 8.27, p < .01, η(p)² = .16. Specifically, as predicted, while generalization of cue was spared in both groups, individuals with PTSD showed overgeneralization of negative context. Hence, they could not learn that a previously negative context is later associated with a positive outcome, F(1, 43) = 7.33, p = .01, η(p)² = .15. Most importantly, overgeneralization of negative context significantly correlated with right and left hippocampal volume (r = .61, p = .000; r = .5, p = .000). Finally, bilateral hippocampal volume provided the strongest prediction of overgeneralization of negative context. Reduced hippocampal volume may account for the difficulty of individuals with PTSD to differentiate negative and novel conditions and hence may facilitate reexperiencing symptoms. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  13. Low-intensity daily walking activity is associated with hippocampal volume in older adults.

    Science.gov (United States)

    Varma, Vijay R; Chuang, Yi-Fang; Harris, Gregory C; Tan, Erwin J; Carlson, Michelle C

    2015-05-01

    Hippocampal atrophy is associated with memory impairment and dementia and serves as a key biomarker in the preclinical stages of Alzheimer's disease. Physical activity, one of the most promising behavioral interventions to prevent or delay cognitive decline, has been shown to be associated with hippocampal volume; specifically increased aerobic activity and fitness may have a positive effect on the size of the hippocampus. The majority of older adults, however, are sedentary and have difficulty initiating and maintaining exercise programs. A modestly more active lifestyle may nonetheless be beneficial. This study explored whether greater objectively measured daily walking activity was associated with larger hippocampal volume. We additionally explored whether greater low-intensity walking activity, which may be related to leisure-time physical, functional, and social activities, was associated with larger hippocampal volume independent of exercise and higher-intensity walking activity. Segmentation of hippocampal volumes was performed using Functional Magnetic Resonance Imaging of the Brain's Software Library (FSL), and daily walking activity was assessed using a step activity monitor on 92, nondemented, older adult participants. After controlling for age, education, body mass index, cardiovascular disease risk factors, and the Mini Mental State Exam, we found that a greater amount, duration, and frequency of total daily walking activity were each associated with larger hippocampal volume among older women, but not among men. These relationships were specific to hippocampal volume, compared with the thalamus, used as a control brain region, and remained significant for low-intensity walking activity, independent of moderate- to vigorous-intensity activity and self-reported exercise. This is the first study, to our knowledge, to explore the relationship between objectively measured daily walking activity and hippocampal volume in an older adult population. Findings

  14. Reading, writing, and reserve: Literacy activities are linked to hippocampal volume and memory in multiple sclerosis.

    Science.gov (United States)

    Sumowski, James F; Rocca, Maria A; Leavitt, Victoria M; Riccitelli, Gianna; Meani, Alessandro; Comi, Giancarlo; Filippi, Massimo

    2016-10-01

    Engagement in cognitive leisure activities during early adulthood has been linked to preserved memory and larger hippocampal volume in persons with multiple sclerosis (MS). To investigate which specific types of cognitive leisure activities contribute to hippocampal volume and memory. We investigated links between three types of cognitive activities (Reading-Writing, Art-Music, Games-Hobbies) and (a) hippocampal volume within independent samples of Italian (n=187) and American (n=55) MS patients and (b) memory in subsamples of Italian (n=97) and American (n=53) patients. Reading-Writing was the only predictor of hippocampal volume (rp=.204, p=.002), and the best predictor of memory (rp=.288, p=.001). Findings inform the development of targeted evidence-based enrichment programs aiming to bolster reserve against memory decline. © The Author(s), 2016.

  15. Correlation between hippocampal volumes and medial temporal lobe atrophy in patients with Alzheimer's disease

    OpenAIRE

    Dhikav, Vikas; Duraiswamy, Sharmila; Anand, Kuljeet Singh

    2017-01-01

    Introduction: Hippocampus undergoes atrophy in patients with Alzheimer's disease (AD). Calculation of hippocampal volumes can be done by a variety of methods using T1-weighted images of magnetic resonance imaging (MRI) of the brain. Medial temporal lobes atrophy (MTL) can be rated visually using T1-weighted MRI brain images. The present study was done to see if any correlation existed between hippocampal volumes and visual rating scores of the MTL using Scheltens Visual Rating Method. Materia...

  16. Hippocampal volume in relation to clinical and cognitive outcome after electroconvulsive therapy in depression.

    Science.gov (United States)

    Nordanskog, P; Larsson, M R; Larsson, E-M; Johanson, A

    2014-04-01

    In a previous magnetic resonance imaging (MRI) study, we found a significant increase in hippocampal volume immediately after electroconvulsive therapy (ECT) in patients with depression. The aim of this study was to evaluate hippocampal volume up to 1 year after ECT and investigate its possible relation to clinical and cognitive outcome. Clinical and cognitive outcome in 12 in-patients with depression receiving antidepressive pharmacological treatment referred for ECT were investigated with the Montgomery-Asberg Depression Rating Scale (MADRS) and a broad neuropsychological test battery within 1 week before and after ECT. The assessments were repeated 6 and 12 months after baseline in 10 and seven of these patients, respectively. Hippocampal volumes were measured on all four occasions with 3 Tesla MRI. Hippocampal volume returned to baseline during the follow-up period of 6 months. Neither the significant antidepressant effect nor the significant transient decrease in executive and verbal episodic memory tests after ECT could be related to changes in hippocampal volume. No persistent cognitive side effects were observed 1 year after ECT. The immediate increase in hippocampal volume after ECT is reversible and is not related to clinical or cognitive outcome. © 2013 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.

  17. The association of visual memory with hippocampal volume.

    Science.gov (United States)

    Zammit, Andrea R; Ezzati, Ali; Katz, Mindy J; Zimmerman, Molly E; Lipton, Michael L; Sliwinski, Martin J; Lipton, Richard B

    2017-01-01

    In this study we investigated the role of hippocampal volume (HV) in visual memory. Participants were a subsample of older adults (> = 70 years) from the Einstein Aging Study. Visual performance was measured using the Complex Figure (CF) copy and delayed recall tasks from the Repeatable Battery for the Assessment of Neuropsychological Status. Linear regressions were fitted to study associations between HV and visual tasks. Participants' (n = 113, mean age = 78.9 years) average scores on the CF copy and delayed recall were 17.4 and 11.6, respectively. CF delayed recall was associated with total (β = .031, p = 0.001) and left (β = 0.031, p = 0.001) and right HVs (β = 0.24, p = 0.012). CF delayed recall remained significantly associated with left HV even after we also included right HV (β = 0.27, p = 0.025) and the CF copy task (β = 0.30, p = 0.009) in the model. CF copy did not show any significant associations with HV. Our results suggest that left HV contributes in retrieval of visual memory in older adults.

  18. The association of visual memory with hippocampal volume.

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    Andrea R Zammit

    Full Text Available In this study we investigated the role of hippocampal volume (HV in visual memory.Participants were a subsample of older adults (> = 70 years from the Einstein Aging Study. Visual performance was measured using the Complex Figure (CF copy and delayed recall tasks from the Repeatable Battery for the Assessment of Neuropsychological Status. Linear regressions were fitted to study associations between HV and visual tasks.Participants' (n = 113, mean age = 78.9 years average scores on the CF copy and delayed recall were 17.4 and 11.6, respectively. CF delayed recall was associated with total (β = .031, p = 0.001 and left (β = 0.031, p = 0.001 and right HVs (β = 0.24, p = 0.012. CF delayed recall remained significantly associated with left HV even after we also included right HV (β = 0.27, p = 0.025 and the CF copy task (β = 0.30, p = 0.009 in the model. CF copy did not show any significant associations with HV.Our results suggest that left HV contributes in retrieval of visual memory in older adults.

  19. COMT Val158Met polymorphism moderates the association between PTSD symptom severity and hippocampal volume.

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    Hayes, Jasmeet P; Logue, Mark W; Reagan, Andrew; Salat, David; Wolf, Erika J; Sadeh, Naomi; Spielberg, Jeffrey M; Sperbeck, Emily; Hayes, Scott M; McGlinchey, Regina E; Milberg, William P; Verfaellie, Mieke; Stone, Annjanette; Schichman, Steven A; Miller, Mark W

    2017-03-01

    Memory-based alterations are among the hallmark symptoms of posttraumatic stress disorder (PTSD) and may be associated with the integrity of the hippocampus. However, neuroimaging studies of hippocampal volume in individuals with PTSD have yielded inconsistent results, raising the possibility that various moderators, such as genetic factors, may influence this association. We examined whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism, which has previously been shown to be associated with hippocampal volume in healthy individuals, moderates the association between PTSD and hippocampal volume. Recent war veterans underwent structural MRI on a 3 T scanner. We extracted volumes of the right and left hippocampus using FreeSurfer and adjusted them for individual differences in intracranial volume. We assessed PTSD severity using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to model the genotype (Val158Met polymorphism) × PTSD severity interaction and its association with hippocampal volume. We included 146 white, non-Hispanic recent war veterans (90% male, 53% with diagnosed PTSD) in our analyses. A significant genotype × PTSD symptom severity interaction emerged such that individuals with greater current PTSD symptom severity who were homozygous for the Val allele showed significant reductions in left hippocampal volume. The direction of proposed effects is unknown, thus precluding definitive assessment of whether differences in hippocampal volume reflect a consequence of PTSD, a pre-existing characteristic, or both. Our findings suggest that the COMT polymorphism moderates the association between PTSD and hippocampal volume. These results highlight the role that the dopaminergic system has in brain structure and suggest a possible mechanism for memory disturbance in individuals with PTSD.

  20. The impact of sleep loss on hippocampal function

    Science.gov (United States)

    Prince, Toni-Moi; Abel, Ted

    2013-01-01

    Hippocampal cellular and molecular processes critical for memory consolidation are affected by the amount and quality of sleep attained. Questions remain with regard to how sleep enhances memory, what parameters of sleep after learning are optimal for memory consolidation, and what underlying hippocampal molecular players are targeted by sleep deprivation to impair memory consolidation and plasticity. In this review, we address these topics with a focus on the detrimental effects of post-learning sleep deprivation on memory consolidation. Obtaining adequate sleep is challenging in a society that values “work around the clock.” Therefore, the development of interventions to combat the negative cognitive effects of sleep deprivation is key. However, there are a limited number of therapeutics that are able to enhance cognition in the face of insufficient sleep. The identification of molecular pathways implicated in the deleterious effects of sleep deprivation on memory could potentially yield new targets for the development of more effective drugs. PMID:24045505

  1. Memory Dysfunction in Type 2 Diabetes Mellitus Correlates with Reduced Hippocampal CA1 and Subiculum Volumes

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    Yan-Wei Zhang

    2015-01-01

    Full Text Available Background: Little attention has been paid to the role of subcortical deep gray matter (SDGM structures in type 2 diabetes mellitus (T2DM-induced cognitive impairment, especially hippocampal subfields. Our aims were to assess the in vivo volumes of SDGM structures and hippocampal subfields using magnetic resonance imaging (MRI and to test their associations with cognitive performance in T2DM. Methods: A total of 80 T2DM patients and 80 neurologically unimpaired healthy controls matched by age, sex and education level was enrolled in this study. We assessed the volumes of the SDGM structures and seven hippocampal subfields on MRI using a novel technique that enabled automated volumetry. We used Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA scores as measures of cognitive performance. The association of glycosylated hemoglobin (HbA1c with SDGM structures and neuropsychological tests and correlations between hippocampal subfields and neuropsychological tests were assessed by partial correlation analysis in T2DM. Results: Bilaterally, the hippocampal volumes were smaller in T2DM patients, mainly in the CA1 and subiculum subfields. Partial correlation analysis showed that the MoCA scores, particularly those regarding delayed memory, were significantly positively correlated with reduced hippocampal CA1 and subiculum volumes in T2DM patients. Additionally, higher HbA1c levels were significantly associated with poor memory performance and hippocampal atrophy among T2DM patients. Conclusions: These data indicate that the hippocampus might be the main affected region among the SDGM structures in T2DM. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction, suggesting that degeneration in these regions could be responsible for memory impairments in T2DM patients.

  2. Temporal lobe epilepsy with mesial temporal sclerosis: hippocampal neuronal loss as a predictor of surgical outcome

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    Anaclara Prada Jardim

    2012-05-01

    Full Text Available OBJECTIVE: To analyze retrospectively a series of patients with temporal lobe epilepsy (TLE and mesial temporal sclerosis (MTS, and the association of patterns of hippocampal sclerosis with clinical data and surgical prognosis. METHOD: Sixty-six patients with medically refractory TLE with unilateral MTS after anterior temporal lobectomy were included. Quantitative neuropathological evaluation was performed on NeuN-stained hippocampal sections. Patient's clinical data and surgical outcome were reviewed. RESULTS: Occurrence of initial precipitating insult (IPI, as well as better postoperative seizure control (i.e. Engel class 1, were associated with classical and severe patterns of hippocampal sclerosis (MTS type 1a and 1b, respectively. CONCLUSION: Quantitative evaluation of hippocampal neuronal loss patterns predicts surgical outcome in patients with TLE-MTS.

  3. Temporal lobe epilepsy with mesial temporal sclerosis: hippocampal neuronal loss as a predictor of surgical outcome.

    Science.gov (United States)

    Jardim, Anaclara Prada; Neves, Rafael Scarpa da Costa; Caboclo, Luís Otávio Sales Ferreira; Lancellotti, Carmen Lucia Penteado; Marinho, Murilo Martinez; Centeno, Ricardo Silva; Cavalheiro, Esper Abrão; Scorza, Carla Alessandra; Yacubian, Elza Márcia Targas

    2012-05-01

    To analyze retrospectively a series of patients with temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS), and the association of patterns of hippocampal sclerosis with clinical data and surgical prognosis. Sixty-six patients with medically refractory TLE with unilateral MTS after anterior temporal lobectomy were included. Quantitative neuropathological evaluation was performed on NeuN-stained hippocampal sections. Patient's clinical data and surgical outcome were reviewed. Occurrence of initial precipitating insult (IPI), as well as better postoperative seizure control (i.e. Engel class 1), were associated with classical and severe patterns of hippocampal sclerosis (MTS type 1a and 1b, respectively). Quantitative evaluation of hippocampal neuronal loss patterns predicts surgical outcome in patients with TLE-MTS.

  4. Perceived Stress Is Differentially Related to Hippocampal Subfield Volumes among Older Adults.

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    Molly E Zimmerman

    Full Text Available Chronic exposure to stress has been shown to impact a wide range of health-related outcomes in older adults. Despite extensive animal literature revealing deleterious effects of biological markers of stress on the dentate gyrus subfield of the hippocampus, links between hippocampal subfields and psychological stress have not been studied in humans. This study examined the relationship between perceived stress and hippocampal subfield volumes among racially/ethnically diverse older adults.Between July 2011 and March 2014, 116 nondemented participants were consecutively drawn from the Einstein Aging Study, an ongoing community-based sample of individuals over the age of 70 residing in Bronx, New York. All participants completed the Perceived Stress Scale, Geriatric Depression Scale, and underwent 3.0 T MRI. FreeSurfer was used to derive total hippocampal volume, hippocampal subfield volumes (CA1, CA2/CA3, CA4/Dentate Gyrus (CA4/DG, and subiculum, entorhinal cortex volume, whole brain volume, and total intracranial volume.Linear regression analyses revealed that higher levels of perceived stress were associated with smaller total hippocampal volume (β = -0.20, t = -2.40, p = 0.02, smaller CA2/CA3 volumes (β = -0.18, t = -2.24, p = 0.03 and smaller CA4/DG volumes (β = -0.19, t = -2.28, p = 0.03 after controlling for total intracranial volume, age, gender, and race. These findings remained unchanged after removal of individuals with clinically significant symptoms of depression.Our findings provide evidence of a relationship between a direct indicator of psychological stress and specific hippocampal subfield volumes in elderly individuals. These results highlight the importance of clinical screening for chronic stress in otherwise healthy older adults.

  5. Hippocampal adaptive response following extensive neuronal loss in an inducible transgenic mouse model.

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    Kristoffer Myczek

    Full Text Available Neuronal loss is a common component of a variety of neurodegenerative disorders (including Alzheimer's, Parkinson's, and Huntington's disease and brain traumas (stroke, epilepsy, and traumatic brain injury. One brain region that commonly exhibits neuronal loss in several neurodegenerative disorders is the hippocampus, an area of the brain critical for the formation and retrieval of memories. Long-lasting and sometimes unrecoverable deficits caused by neuronal loss present a unique challenge for clinicians and for researchers who attempt to model these traumas in animals. Can these deficits be recovered, and if so, is the brain capable of regeneration following neuronal loss? To address this significant question, we utilized the innovative CaM/Tet-DT(A mouse model that selectively induces neuronal ablation. We found that we are able to inflict a consistent and significant lesion to the hippocampus, resulting in hippocampally-dependent behavioral deficits and a long-lasting upregulation in neurogenesis, suggesting that this process might be a critical part of hippocampal recovery. In addition, we provide novel evidence of angiogenic and vasculature changes following hippocampal neuronal loss in CaM/Tet-DTA mice. We posit that angiogenesis may be an important factor that promotes neurogenic upregulation following hippocampal neuronal loss, and both factors, angiogenesis and neurogenesis, can contribute to the adaptive response of the brain for behavioral recovery.

  6. Smaller hippocampal volume as a vulnerability factor for the persistence of post-traumatic stress disorder.

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    van Rooij, S J H; Kennis, M; Sjouwerman, R; van den Heuvel, M P; Kahn, R S; Geuze, E

    2015-10-01

    Smaller hippocampal volume has often been observed in patients with post-traumatic stress disorder (PTSD). However, there is no consensus whether this is a result of stress/trauma exposure, or constitutes a vulnerability factor for the development of PTSD. Second, it is unclear whether hippocampal volume normalizes with successful treatment of PTSD, or whether a smaller hippocampus is a risk factor for the persistence of PTSD. Magnetic resonance imaging (MRI) scans and clinical interviews were collected from 47 war veterans with PTSD, 25 healthy war veterans (combat controls) and 25 healthy non-military controls. All veterans were scanned a second time with a 6- to 8-month interval, during which PTSD patients received trauma-focused therapy. Based on post-treatment PTSD symptoms, patients were divided into a PTSD group who was in remission (n = 22) and a group in whom PTSD symptoms persisted (n = 22). MRI data were analysed with Freesurfer. Smaller left hippocampal volume was observed in PTSD patients compared with both control groups. Hippocampal volume of the combat controls did not differ from healthy controls. Second, pre- and post-treatment analyses of the PTSD patients and combat controls revealed reduced (left) hippocampal volume only in the persistent patients at both time points. Importantly, hippocampal volume did not change with treatment. Our findings suggest that a smaller (left) hippocampus is not the result of stress/trauma exposure. Furthermore, hippocampal volume does not increase with successful treatment. Instead, we demonstrate for the first time that a smaller (left) hippocampus constitutes a risk factor for the persistence of PTSD.

  7. Relationship between hippocampal subfield volumes and memory deficits in patients with thalamus infarction.

    Science.gov (United States)

    Chen, Li; Luo, Tianyou; Lv, Fajin; Shi, Dandan; Qiu, Jiang; Li, Qi; Fang, Weidong; Peng, Juan; Li, Yongmei; Zhang, Zhiwei; Li, Yang

    2016-09-01

    Clinical studies have shown that thalamus infarction (TI) affects memory function. The thalamic nucleus is directly or indirectly connected to the hippocampal system in animal models. However, this connection has not been investigated using structural magnetic resonance imaging (MRI) in humans. From the pathological perspective, TI patients may serve as valid models for revealing the interaction between the thalamus and hippocampus in memory function. In this study, we aim to assess different hippocampal subfield volumes in TI patients and control subjects using MRI and test their associations with memory function. A total of 37 TI patients (TI group), 38 matched healthy control subjects (HC group), and 22 control patients with other stroke location (SC group) underwent 3.0-T MRI scans and clinical memory examinations. Hippocampal subfield volumes were measured and compared by using FreeSurfer software. We examined the correlation between hippocampal subfield volumes and memory scores. Smaller ipsilesional presubiculum and subiculum volumes were observed, and former was related to graphics recall in both left and right TI patients. The left subiculum volume was correlated with short-delayed recall in left TI patients. The right presubiculum volume was correlated with short- and long-delayed recall in right TI patients. TI was found to result in hippocampal abnormality and memory deficits, and its neural mechanisms might be related with and interaction between the thalamus and hippocampus.

  8. Neuropsychology, Autobiographical Memory, and Hippocampal Volume in ?Younger? and ?Older? Patients with Chronic Schizophrenia

    OpenAIRE

    Herold, Christina Josefa; L?sser, Marc Montgomery; Schmid, Lena Anna; Seidl, Ulrich; Kong, Li; Fellhauer, Iven; Thomann, Philipp Arthur; Essig, Marco; Schr?der, Johannes

    2015-01-01

    Despite a wide range of studies on neuropsychology in schizophrenia, autobiographical memory (AM) has been scarcely investigated in these patients. Hence, less is known about AM in older patients and hippocampal contribution to autobiographical memories of varying remoteness. Therefore, we investigated hippocampal volume and AM along with important neuropsychological domains in patients with chronic schizophrenia and the respective relationships between these parameters. We compared 25 older ...

  9. Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: preliminary findings.

    Science.gov (United States)

    Leavitt, V M; Cirnigliaro, C; Cohen, A; Farag, A; Brooks, M; Wecht, J M; Wylie, G R; Chiaravalloti, N D; DeLuca, J; Sumowski, J F

    2014-01-01

    Multiple sclerosis leads to prominent hippocampal atrophy, which is linked to memory deficits. Indeed, 50% of multiple sclerosis patients suffer memory impairment, with negative consequences for quality of life. There are currently no effective memory treatments for multiple sclerosis either pharmacological or behavioral. Aerobic exercise improves memory and promotes hippocampal neurogenesis in nonhuman animals. Here, we investigate the benefits of aerobic exercise in memory-impaired multiple sclerosis patients. Pilot data were collected from two ambulatory, memory-impaired multiple sclerosis participants randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. The following baseline/follow-up measurements were taken: high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Intervention was 30-minute sessions 3 times per week for 3 months. Aerobic exercise resulted in 16.5% increase in hippocampal volume and 53.7% increase in memory, as well as increased hippocampal resting-state functional connectivity. Improvements were specific, with no comparable changes in overall cerebral gray matter (+2.4%), non-hippocampal deep gray matter structures (thalamus, caudate: -4.0%), or in non-memory cognitive functioning (executive functions, processing speed, working memory: changes ranged from -11% to +4%). Non-aerobic exercise resulted in relatively no change in hippocampal volume (2.8%) or memory (0.0%), and no changes in hippocampal functional connectivity. This is the first evidence for aerobic exercise to increase hippocampal volume and connectivity and improve memory in multiple sclerosis. Aerobic exercise represents a cost-effective, widely available, natural, and self-administered treatment with no adverse side effects that may be the first effective memory treatment for multiple sclerosis patients.

  10. Combined effects of marijuana and nicotine on memory performance and hippocampal volume.

    Science.gov (United States)

    Filbey, Francesca M; McQueeny, Tim; Kadamangudi, Shrinath; Bice, Collette; Ketcherside, Ariel

    2015-10-15

    Combined use of marijuana (MJ) and tobacco is highly prevalent in today's population. Individual use of either substance is linked to structural brain changes and altered cognitive function, especially with consistent reports of hippocampal volume deficits and poorer memory performance. However, the combined effects of MJ and tobacco on hippocampal structure and on learning and memory processes remain unknown. In this study, we examined both the individual and combined effects of MJ and tobacco on hippocampal volumes and memory performance in four groups of adults taken from two larger studies: MJ-only users (n=36), nicotine-only (Nic-only, n=19), combined marijuana and nicotine users (MJ+Nic, n=19) and non-using healthy controls (n=16). Total bilateral hippocampal volumes and memory performance (WMS-III logical memory) were compared across groups controlling for total brain size and recent alcohol use. Results found MJ and MJ+Nic groups had smaller total hippocampal volumes compared to Nic-only and controls. No significant difference between groups was found between immediate and delayed story recall. However, the controls showed a trend for larger hippocampal volumes being associated with better memory scores, while MJ+Nic users showed a unique inversion, whereby smaller hippocampal volume was associated with better memory. Overall, results suggest abnormalities in the brain-behavior relationships underlying memory processes with combined use of marijuana and nicotine use. Further research will need to address these complex interactions between MJ and nicotine. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Hippocampal volumes are important predictors for memory function in elderly women

    Directory of Open Access Journals (Sweden)

    Adolfsdottir Steinunn

    2009-08-01

    Full Text Available Abstract Background Normal aging involves a decline in cognitive function that has been shown to correlate with volumetric change in the hippocampus, and with genetic variability in the APOE-gene. In the present study we utilize 3D MR imaging, genetic analysis and assessment of verbal memory function to investigate relationships between these factors in a sample of 170 healthy volunteers (age range 46–77 years. Methods Brain morphometric analysis was performed with the automated segmentation work-flow implemented in FreeSurfer. Genetic analysis of the APOE genotype was determined with polymerase chain reaction (PCR on DNA from whole-blood. All individuals were subjected to extensive neuropsychological testing, including the California Verbal Learning Test-II (CVLT. To obtain robust and easily interpretable relationships between explanatory variables and verbal memory function we applied the recent method of conditional inference trees in addition to scatterplot matrices and simple pairwise linear least-squares regression analysis. Results APOE genotype had no significant impact on the CVLT results (scores on long delay free recall, CVLT-LD or the ICV-normalized hippocampal volumes. Hippocampal volumes were found to decrease with age and a right-larger-than-left hippocampal asymmetry was also found. These findings are in accordance with previous studies. CVLT-LD score was shown to correlate with hippocampal volume. Multivariate conditional inference analysis showed that gender and left hippocampal volume largely dominated predictive values for CVLT-LD scores in our sample. Left hippocampal volume dominated predictive values for females but not for males. APOE genotype did not alter the model significantly, and age was only partly influencing the results. Conclusion Gender and left hippocampal volumes are main predictors for verbal memory function in normal aging. APOE genotype did not affect the results in any part of our analysis.

  12. Preservation of hippocampal neuron numbers and hippocampal subfield volumes in behaviorally characterized aged tree shrews

    NARCIS (Netherlands)

    Keuker, J.I.H.; de Biurrun, G.; Luiten, P.G.M.; Fuchs, E.

    2004-01-01

    Aging is associated with a decreased ability to store and retrieve information. The hippocampal formation plays a critical role in such memory processes, and its integrity is affected during normal aging. We used tree shrews (Tupaia belangeri) as an animal model of aging, because in many

  13. Bigger is better! Hippocampal volume and declarative memory performance in healthy young men.

    Science.gov (United States)

    Pohlack, Sebastian T; Meyer, Patric; Cacciaglia, Raffaele; Liebscher, Claudia; Ridder, Stephanie; Flor, Herta

    2014-01-01

    The importance of the hippocampus for declarative memory processes is firmly established. Nevertheless, the issue of a correlation between declarative memory performance and hippocampal volume in healthy subjects still remains controversial. The aim of the present study was to investigate this relationship in more detail. For this purpose, 50 healthy young male participants performed the California Verbal Learning Test. Hippocampal volume was assessed by manual segmentation of high-resolution 3D magnetic resonance images. We found a significant positive correlation between putatively hippocampus-dependent memory measures like short-delay retention, long-delay retention and discriminability and percent hippocampal volume. No significant correlation with measures related to executive processes was found. In addition, percent amygdala volume was not related to any of these measures. Our data advance previous findings reported in studies of brain-damaged individuals in a large and homogeneous young healthy sample and are important for theories on the neural basis of episodic memory.

  14. A prospective evaluation of hippocampal radiation dose volume effects and memory deficits following cranial irradiation.

    Science.gov (United States)

    Ma, Ting Martin; Grimm, Jimm; McIntyre, Riley; Anderson-Keightly, Heather; Kleinberg, Lawrence R; Hales, Russell K; Moore, Joseph; Vannorsdall, Tracy; Redmond, Kristin J

    2017-11-01

    To prospectively evaluate hippocampal radiation dose volume effects and memory decline following cranial irradiation. Effects of hippocampal radiation over a wide range of doses were investigated by combining data from three prospective studies. In one, adults with small cell lung cancer received hippocampal-avoidance prophylactic cranial irradiation. In the other two, adults with glioblastoma multiforme received neural progenitor cell sparing radiation or no sparing with extra dose delivered to subventricular zone. Memory was measured by the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 6 months after radiation. Dose-volume histograms were generated and dose-response data were fitted to a nonlinear model. Of 60 patients enrolled, 30 were analyzable based on HVLT-R DR testing completion status, baseline HVLT-R DR and intracranial metastasis/recurrence or prior hippocampal resection status. We observed a dose-response of radiation to the hippocampus with regard to decline in HVLT-R DR. D50% of the bilateral hippocampi of 22.1 Gy is associated with 20% risk of decline. This prospective study demonstrates an association between hippocampal dose volume effects and memory decline measured by HVLT-R DR over a wide dose range. These data support a potential benefit of hippocampal sparing and encourage continued trial enrollment. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Hyperexcitability and cell loss in kainate-treated hippocampal slice cultures

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Casaccia-Bonnefil, P; Stelzer, A

    1993-01-01

    Loss of hippocampal interneurons has been reported in patients with severe temporal lobe epilepsy and in animals treated with kainate. We investigated the relationship between KA induced epileptiform discharge and loss of interneurons in hippocampal slice cultures. Application of KA (1 micro......M) produced reversible epileptiform discharge without neurotoxicity. KA (5 microM), in contrast, produced irreversible epileptiform discharge and neurotoxicity, suggesting that the irreversible epileptiform discharge was required for the neuronal loss. Loss of CA3 pyramidal cells and parvalbumin......-like immunoreactive (PV-I) interneurons preceded loss of somatostatin-like immunoreactive (SS-I) interneurons suggesting a different time course of KA neurotoxicity in these subpopulations of interneurons....

  16. An association between human hippocampal volume and topographical memory in healthy young adults.

    Directory of Open Access Journals (Sweden)

    Tom eHartley

    2012-12-01

    Full Text Available The association between human hippocampal structure and topographical memory was investigated in healthy adults (N=30. Structural MR images were acquired, and voxel-based morphometry (VBM was used to estimate local gray matter volume throughout the brain. A complementary automated mesh-based segmentation approach was used to independently isolate and measure specified structures including the hippocampus. Topographical memory was assessed using a version of the Four Mountains Task, a short test designed to target hippocampal spatial function. Each item requires subjects to briefly study a landscape scene before recognizing the depicted place from a novel viewpoint and under altered non-spatial conditions when presented amongst similar alternative scenes. Positive correlations between topographical memory performance and hippocampal volume were observed in both VBM and segmentation-based analyses. Score on the topographical memory task was also correlated with the volume of some subcortical structures, extra-hippocampal gray matter and total brain volume, with the most robust and extensive covariation seen in circumscribed neocortical regions in the insula and anterior temporal lobes. Taken together with earlier findings, the results suggest that global variations in brain morphology affect the volume of the hippocampus and its specific contribution to topographical memory. We speculate that behavioral variation might arise directly through the impact of resource constraints on spatial representations in the hippocampal formation and its inputs, and perhaps indirectly through an increased reliance on non-allocentric strategies.

  17. Religiosity is associated with hippocampal but not amygdala volumes in patients with refractory epilepsy

    OpenAIRE

    Wuerfel, J; Krishnamoorthy, E; Brown, R; Lemieux, L; Koepp, M; v Tebartz,; Trimble, M

    2004-01-01

    Method: Magnetic resonance images were obtained from 33 patients with refractory epilepsy and mesial temporal structure volumes assessed. Amygdala and hippocampal volumes were then compared in high and low scorers on the religiosity, writing, and sexuality sub-scales of the Neurobehavioural Inventory.

  18. Reduced interference in working memory following mindfulness training is associated with increases in hippocampal volume.

    Science.gov (United States)

    Greenberg, Jonathan; Romero, Victoria L; Elkin-Frankston, Seth; Bezdek, Matthew A; Schumacher, Eric H; Lazar, Sara W

    2018-03-17

    Proactive interference occurs when previously relevant information interferes with retaining newer material. Overcoming proactive interference has been linked to the hippocampus and deemed critical for cognitive functioning. However, little is known about whether and how this ability can be improved or about the neural correlates of such improvement. Mindfulness training emphasizes focusing on the present moment and minimizing distraction from competing thoughts and memories. It improves working memory and increases hippocampal density. The current study examined whether mindfulness training reduces proactive interference in working memory and whether such improvements are associated with changes in hippocampal volume. 79 participants were randomized to a 4-week web-based mindfulness training program or a similarly structured creative writing active control program. The mindfulness group exhibited lower proactive interference error rates compared to the active control group following training. No group differences were found in hippocampal volume, yet proactive interference improvements following mindfulness training were significantly associated with volume increases in the left hippocampus. These results provide the first evidence to suggest that (1) mindfulness training can protect against proactive interference, and (2) that these benefits are related to hippocampal volumetric increases. Clinical implications regarding the application of mindfulness training in conditions characterized by impairments to working memory and reduced hippocampal volume such as aging, depression, PTSD, and childhood adversity are discussed.

  19. Hippocampal volume and CDR-SB can predict conversion to dementia in MCI patients

    Directory of Open Access Journals (Sweden)

    João Guilherme Fiorani Borgio

    2012-11-01

    Full Text Available OBJECTIVE: To evaluate the combination of two factors: clinical dementia rating sum of boxes scores (CDR-SB and hippocampal volume (HV as predictors of conversion from mild cognitive impairment (MCI to dementia. METHODS: Twenty-eight individuals (9 normal and 19 with MCI were classified according to their CDR sum of boxes scores into 3 groups. RESULTS: The hippocampal volume was significantly lower in the high-risk group and in those who developed dementia after two years. The rate of conversion was crescent among the three groups. CONCLUSION: We were proposed an additional measurement of the hippocampal volume which may be helpful in the prognosis. However, we noted that the CDR-SB is a method as efficient as neuroimaging to predict dementia with the advantage of being a procedure for low cost and easy implementation, more consistent with public policy.

  20. Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation.

    Science.gov (United States)

    Guderian, Sebastian; Dzieciol, Anna M; Gadian, David G; Jentschke, Sebastian; Doeller, Christian F; Burgess, Neil; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2015-10-21

    The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with "moderate" hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on hippocampal integrity in humans is

  1. MRI-Based Measurement of Hippocampal Volume in Patients With Combat-Related Posttraumatic Stress Disorder

    Science.gov (United States)

    Bremner, J. Douglas; Randall, Penny; Scott, Tammy M.; Bronen, Richard A.; Seibyl, John P.; Southwick, Steven M.; Delaney, Richard C.; McCarthy, Gregory; Charney, Dennis S.; Innis, Robert B.

    2011-01-01

    Objective Studies in nonhuman primates suggest that high levels of cortisol associated with stress have neurotoxic effects on the hippocampus, a brain structure involved in memory. The authors previously showed that patients with combat-related posttraumatic stress disorder (PTSD) had deficits in short-term memory. The purpose of this study was to compare the hippocampal volume of patients with PTSD to that of subjects without psychiatric disorder. Method Magnetic resonance imaging was used to measure the volume of the hippocampus in 26 Vietnam combat veterans with PTSD and 22 comparison subjects selected to be similar to the patients in age, sex, race, years of education, socioeconomic status, body size, and years of alcohol abuse. Results The PTSD patients had a statistically significant 8% smaller right hippocampal volume relative to that of the comparison subjects, but there was no difference in the volume of other brain regions (caudate and temporal lobe). Deficits in short-term verbal memory as measured with the Wechsler Memory Scale were associated with smaller right hippocampal volume in the PTSD patients only. Conclusions These findings are consistent with a smaller right hippocampal volume in PTSD that is associated with functional deficits in verbal memory. PMID:7793467

  2. Factors affecting graded and ungraded memory loss following hippocampal lesions.

    Science.gov (United States)

    Winocur, Gordon; Moscovitch, Morris; Sekeres, Melanie J

    2013-11-01

    This review evaluates three current theories--Standard Consolidation (Squire & Wixted, 2011), Overshadowing (Sutherland, Sparks, & Lehmann, 2010), and Multiple Trace-Transformation (Winocur, Moscovitch, & Bontempi, 2010)--in terms of their ability to account for the role of the hippocampus in recent and remote memory in animals. Evidence, based on consistent findings from tests of spatial memory and memory for acquired food preferences, favours the transformation account, but this conclusion is undermined by inconsistent results from studies that measured contextual fear memory, probably the most commonly used test of hippocampal involvement in anterograde and retrograde memory. Resolution of this issue may depend on exercising greater control over critical factors (e.g., contextual environment, amount of pre-exposure to the conditioning chamber, the number and distribution of foot-shocks) that can affect the representation of the memory shortly after learning and over the long-term. Research strategies aimed at characterizing the neural basis of long-term consolidation/transformation, as well as other outstanding issues are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Chronic Loss of CA2 Transmission Leads to Hippocampal Hyperexcitability.

    Science.gov (United States)

    Boehringer, Roman; Polygalov, Denis; Huang, Arthur J Y; Middleton, Steven J; Robert, Vincent; Wintzer, Marie E; Piskorowski, Rebecca A; Chevaleyre, Vivien; McHugh, Thomas J

    2017-05-03

    Hippocampal CA2 pyramidal cells project into both the neighboring CA1 and CA3 subfields, leaving them well positioned to influence network physiology and information processing for memory and space. While recent work has suggested unique roles for CA2, including encoding position during immobility and generating ripple oscillations, an interventional examination of the integrative functions of these connections has yet to be reported. Here we demonstrate that CA2 recruits feedforward inhibition in CA3 and that chronic genetically engineered shutdown of CA2-pyramidal-cell synaptic transmission consequently results in increased excitability of the recurrent CA3 network. In behaving mice, this led to spatially triggered episodes of network-wide hyperexcitability during exploration accompanied by the emergence of high-frequency discharges during rest. These findings reveal CA2 as a regulator of network processing in hippocampus and suggest that CA2-mediated inhibition in CA3 plays a key role in establishing the dynamic excitatory and inhibitory balance required for proper network function. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Memory function and hippocampal volumes in preterm born very-low-birth-weight (VLBW) young adults.

    Science.gov (United States)

    Aanes, Synne; Bjuland, Knut Jørgen; Skranes, Jon; Løhaugen, Gro C C

    2015-01-15

    The hippocampi are regarded as core structures for learning and memory functions, which is important for daily functioning and educational achievements. Previous studies have linked reduction in hippocampal volume to working memory problems in very low birth weight (VLBW; ≤ 1500 g) children and reduced general cognitive ability in VLBW adolescents. However, the relationship between memory function and hippocampal volume has not been described in VLBW subjects reaching adulthood. The aim of the study was to investigate memory function and hippocampal volume in VLBW young adults, both in relation to perinatal risk factors and compared to term born controls, and to look for structure-function relationships. Using Wechsler Memory Scale-III and MRI, we included 42 non-disabled VLBW and 61 control individuals at age 19-20 years, and related our findings to perinatal risk factors in the VLBW-group. The VLBW young adults achieved lower scores on several subtests of the Wechsler Memory Scale-III, resulting in lower results in the immediate memory indices (visual and auditory), the working memory index, and in the visual delayed and general memory delayed indices, but not in the auditory delayed and auditory recognition delayed indices. The VLBW group had smaller absolute and relative hippocampal volumes than the controls. In the VLBW group inferior memory function, especially for the working memory index, was related to smaller hippocampal volume, and both correlated with lower birth weight and more days in the neonatal intensive care unit (NICU). Our results may indicate a structural-functional relationship in the VLBW group due to aberrant hippocampal development and functioning after preterm birth. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Childhood trauma and hippocampal and amygdalar volumes in first-episode psychosis.

    Science.gov (United States)

    Hoy, Katrina; Barrett, Suzanne; Shannon, Ciaran; Campbell, Clodagh; Watson, David; Rushe, Teresa; Shevlin, Mark; Bai, Feng; Cooper, Stephen; Mulholland, Ciaran

    2012-11-01

    A history of childhood trauma is common in individuals who later develop psychosis. Similar neuroanatomical abnormalities are observed in people who have been exposed to childhood trauma and people with psychosis. However, the relationship between childhood trauma and such abnormalities in psychosis has not been investigated. This study aimed to explore the association between the experience of childhood trauma and hippocampal and amygdalar volumes in a first-episode psychosis (FEP) population. The study employed an observational retrospective design. Twenty-one individuals, who had previously undergone magnetic resonance imaging procedures as part of the longitudinal Northern Ireland First-Episode Psychosis Study, completed measures assessing traumatic experiences and were included in the analysis. Data were subject to correlation analyses (r and r (pb)). Potential confounding variables (age at FEP and delay to scan from recruitment) were selected a priori for inclusion in multiple regression analyses. There was a high prevalence of lifetime (95%) and childhood (76%) trauma in the sample. The experience of childhood trauma was a significant predictor of left hippocampal volume, although age at FEP also significantly contributed to this model. There was no significant association between predictor variables and right hippocampal volume. The experience of childhood trauma was a significant predictor of right and total amygdalar volumes and the hippocampal/amygdalar complex volume as a whole. The findings indicate that childhood trauma is associated with neuroanatomical measures in FEP. Future research controlling for childhood traumatic experiences may contribute to explaining brain morphology in people with psychosis.

  6. SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS INDUCED BY OKADAIC ACID (EXPERIMENTAL STUDY).

    Science.gov (United States)

    Chighladze, M; Dashniani, M; Beselia, G; Kruashvili, L; Naneishvili, T

    2016-01-01

    In the present study, we evaluated and compared effect of intracerebroventricular (ICV) and intrahippocampal bilateral microinjection of okadaic acid (OA) on spatial memory function assessed in one day water maze paradigm and hippocampal structure in rats. Rats were divided in following groups: Control(icv) - rats injected with ICV and aCSF; Control(hipp) - rats injected intrahippocampally with aCSF; OAicv - rats injected with ICV and OA; OAhipp - rats injected intrahippocampally with OA. Nissl staining of hippocampal sections showed that the pyramidal cell loss in OAhipp group is significantly higher than that in the OAicv. The results of behavioral experiments showed that ICV or intrahippocampal bilateral microinjection of OA did not affect learning process and short-term spatial memory but induced impairment in spatial long-term memory assessed in probe test performance 24 h after training. OA-induced spatial memory impairment may be attributed to the hippocampal cell death. Based on these results OA induced memory deficit and hippocampal cell loss in rat may be considered as a potential animal model for preclinical evaluation of antidementic drug activity.

  7. Increase in hippocampal water diffusion and volume during experimental pneumococcal meningitis is aggravated by bacteremia

    DEFF Research Database (Denmark)

    Holler, Jon G; Brandt, Christian T; Leib, Stephen L

    2014-01-01

    BACKGROUND: The hippocampus undergoes apoptosis in experimental pneumococcal meningitis leading to neurofunctional deficits in learning and memory function. The aim of the present study was 1) to investigate hippocampal apparent diffusion coefficient (ADC) and volume with MRI during the course...... and the volume and size of brain ventricles were positively correlated (Spearman Rank, p volume and the extent of apoptosis (p > 0.05). CONCLUSIONS: In experimental meningitis increase in volume and water diffusion of the hippocampus are significantly...... of experimental pneumococcal meningitis, 2) to explore the influence of accompanying bacteremia on hippocampal water distribution and volume, 3) and to correlate these findings to the extent of apoptosis in the hippocampus. METHODS: Experimental meningitis in rats was induced by intracisternal injection of live...

  8. Behavioral inhibition in childhood predicts smaller hippocampal volume in adolescent offspring of parents with panic disorder

    Science.gov (United States)

    Schwartz, C E; Kunwar, P S; Hirshfeld-Becker, D R; Henin, A; Vangel, M G; Rauch, S L; Biederman, J; Rosenbaum, J F

    2015-01-01

    Behavioral inhibition (BI) is a genetically influenced behavioral profile seen in 15–20% of 2-year-old children. Children with BI are timid with people, objects and situations that are novel or unfamiliar, and are more reactive physiologically to these challenges as evidenced by higher heart rate, pupillary dilation, vocal cord tension and higher levels of cortisol. BI predisposes to the later development of anxiety, depression and substance abuse. Reduced hippocampal volumes have been observed in anxiety disorders, depression and posttraumatic stress disorder. Animal models have demonstrated that chronic stress can damage the hippocampal formation and implicated cortisol in these effects. We, therefore, hypothesized that the hippocampi of late adolescents who had been behaviorally inhibited as children would be smaller compared with those who had not been inhibited. Hippocampal volume was measured with high-resolution structural magnetic resonance imaging in 43 females and 40 males at 17 years of age who were determined to be BI+ or BI− based on behaviors observed in the laboratory as young children. BI in childhood predicted reduced hippocampal volumes in the adolescents who were offspring of parents with panic disorder, or panic disorder with comorbid major depression. We discuss genetic and environmental factors emanating from both child and parent that may explain these findings. To the best of our knowledge, this is the first study to demonstrate a relationship between the most extensively studied form of temperamentally based human trait anxiety, BI, and hippocampal structure. The reduction in hippocampal volume, as reported by us, suggests a role for the hippocampus in human trait anxiety and anxiety disorder that warrants further investigation. PMID:26196438

  9. Neuropsychology, Autobiographical Memory, and Hippocampal Volume in “Younger” and “Older” Patients with Chronic Schizophrenia

    Science.gov (United States)

    Herold, Christina Josefa; Lässer, Marc Montgomery; Schmid, Lena Anna; Seidl, Ulrich; Kong, Li; Fellhauer, Iven; Thomann, Philipp Arthur; Essig, Marco; Schröder, Johannes

    2015-01-01

    Despite a wide range of studies on neuropsychology in schizophrenia, autobiographical memory (AM) has been scarcely investigated in these patients. Hence, less is known about AM in older patients and hippocampal contribution to autobiographical memories of varying remoteness. Therefore, we investigated hippocampal volume and AM along with important neuropsychological domains in patients with chronic schizophrenia and the respective relationships between these parameters. We compared 25 older patients with chronic schizophrenia to 23 younger patients and an older healthy control group (N = 21) with respect to AM, additional neuropsychological parameters, and hippocampal volume. Personal episodic and semantic memory was investigated using a semi-structured interview. Additional neuropsychological parameters were assessed by using a battery of standard neuropsychological tests. Structural magnetic resonance imaging data were analyzed with an automated region-of-interest procedure. While hippocampal volume reduction and neuropsychological impairment were more pronounced in the older than in the younger patients, both groups showed equivalent reduced AM performance for recent personal episodes. In the patient group, significant correlations between left hippocampal volume and recent autobiographical episodes as well as personal semantic memories arose. Verbal memory and working memory were significantly correlated with right hippocampal volume; executive functions, however, were associated with bilateral hippocampal volumes. These findings underline the complexity of AM and its impairments in the course of schizophrenia in comparison to rather progressive neuropsychological deficits and address the importance of hippocampal contribution. PMID:25954208

  10. Comparison between visual assessment of MTA and hippocampal volumes in an elderly, non-demented population

    International Nuclear Information System (INIS)

    Cavallin, Lena; Axelsson, Rimma; Bronge, Lena; Zhang, Yi; Oeksengaard, Anne-Rita; Wahlund, Lars-Olof; Fratiglioni, Laura

    2012-01-01

    Background: It is important to have a replicable easy method for monitoring atrophy progression in Alzheimer's disease. Volumetric methods for calculating hippocampal volume are time-consuming and commonly used in research. Visual assessments of medial temporal lobe atrophy (vaMTA) is a rapid method for clinical use. This method has not been tested in a large non-demented population in comparison with volumetry measurements. Since hippocampal volume decreases with time even in normal aging there is also a need to study the normal age differences of medial temporal lobe atrophy. Purpose: To compare visual assessment of medial temporal lobe atrophy (vaMTA) with hippocampal volume in a healthy, non-demented elderly population. To describe normal ageing using vaMTA. Material and Methods: Non-demented individuals aged 60, 66, 72, 78, 81, 84, and ≥87 years old were recruited from the Swedish National study on Ageing and Care in Kungsholmen (SNAC-K), Sweden. Standard magnetic resonance imaging (MRI) scans, vaMTA, and calculations of hippocampal volumes were performed in 544 subjects. Results: Significant correlation (rs = -0.32, P 80-year-old individuals

  11. Amygdala to hippocampal volume ratio is associated with negative memory bias in healthy subjects

    NARCIS (Netherlands)

    Gerritsen, L.; Rijpkema, M.J.P.; Oostrom, I.I.H. van; Buitelaar, J.K.; Franke, B.; Fernandez, G.S.E.; Tendolkar, I.

    2012-01-01

    Background. Negative memory bias is thought to be one of the main cognitive risk and maintenance factors for depression, but its neural substrates are largely unknown. Here, we studied whether memory bias is related to amygdala and hippocampal volume, two structures that are critical for emotional

  12. Hippocampal volume as an index of Alzheimer neuropathology: findings from the Nun Study.

    Science.gov (United States)

    Gosche, K M; Mortimer, J A; Smith, C D; Markesbery, W R; Snowdon, D A

    2002-05-28

    To determine whether hippocampal volume is a sensitive and specific indicator of Alzheimer neuropathology, regardless of the presence or absence of cognitive and memory impairment. Postmortem MRI scans were obtained for the first 56 participants of the Nun Study who were scanned. The area under receiver operating characteristic curves, sensitivity, specificity, and positive and negative predictive values were used to assess the diagnostic accuracy of hippocampal volume in predicting fulfillment of Alzheimer neuropathologic criteria and differences in Braak staging. Hippocampal volume predicted fulfillment of neuropathologic criteria for AD for all 56 participants (p < 0.001): 24 sisters who were demented (p = 0.036); 32 sisters who remained nondemented (p < 0.001), 8 sisters who remained nondemented but had memory impairment (p < 0.001), and 24 sisters who were intact with regard to memory and cognition at the final examination prior to death (p = 0.003). In individuals who remained nondemented, hippocampal volume was a better indicator of AD neuropathology than a delayed memory measure. Among nondemented sisters, Braak stages III and VI were distinguishable from Braak stages II or lower (p = 0.001). Among cognitively intact individuals, those in Braak stage II could be distinguished from those in stage I or less (p = 0.025). Volumetric measures of the hippocampus may be useful in identifying nondemented individuals who satisfy neuropathologic criteria for AD as well as pathologic stages of AD that may be present decades before initial clinical expression.

  13. Decreased hippocampal volume, indirectly measured, is associated with depressive symptoms and consolidation deficits in multiple sclerosis

    NARCIS (Netherlands)

    Kiy, G.; Lehmann, P.; Hahn, H.K.; Eling, P.A.T.M.; Kastrup, A.; Hildebrandt, H.

    2011-01-01

    Background: The human hippocampus plays a role in episodic memory and depression. Recently, it has been shown, using manual tracings, that the hippocampus is smaller in volume in MS patients compared with healthy controls, and that, at least for depression, hippocampal atrophy correlates with

  14. Common variants at 12q14 and 12q24 are associated with hippocampal volume

    NARCIS (Netherlands)

    Bis, J.C.; DeCarli, C.S.; Vernon Smith, A.; van der Lijn, F.; Crivello, F.; Fornage, M.; Debette, S.; Shulman, J.M.; Schmidt, H.; Srikanth, V.; Schuur, M.; Yu, L.; Choi, S.; Sigurdsson, S.; Verhaaren, B.F.J.; DeStefano, A.L.; Lambert, J.C.; Jack, C.R., Jr.; Struchalin, M.; Stankovich, J.; Ibrahim-Verbaas, C.A.; Fleischman, D.; Zijdenbos, A.; den Heijer, T.; Mazoyer, B.; Coker, L.H.; Enzinger, C.; Danoy, P.; Amin, N.; Arfanakis, K.; van Buchem, M.A.; de Bruijn, R.F.A.G.; Beiser, A.; Dufouil, C.; Huang, J.; Cavalieri, M.; Thomson, R.; Niessen, W.J.; Chibnik, L.B.; Gislason, G.K.; Hofman, A.; Pikula, A.; Amouyel, P.; Freeman, K.B.; Phan, T.G.; Oostra, B.A.; Stein, J.L.; Medland, S.E.; Vasquez, A.A.; Hibar, D.P.; Wright, M.J.; Franke, B.; Martin, N.G.; Thompson, P.M.; Hottenga, J.J.; Boomsma, D.I.; Nalls, M.A.; Uitterlinden, A.G.; Au, R.; Elbaz, A.; Beare, R.J.; van Swieten, J.C.; Lopez, O.L.; Harris, T.B.; Chouraki, V.; Breteler, M.M.B.; de Jager, P.L.; Becker, J.T.; Vernooij, M.W.; Knopman, D.; Fazekas, F.; Wolf, P.A.; van der Lugt, A.; Gudnason, V.; Longstreth, Jr. W.T.; Brown, M.A.; Bennett, D.A.; van Duijn, C.M.; Mosley, T.H.; Schmidt, R.; Tzourio, C.; Launer, L.J.; Arfan Ikram, M.; Seshadri, S.

    2012-01-01

    Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10

  15. What causes the hippocampal volume decrease in depression? : Are neurogenesis, glial changes and apoptosis implicated?

    NARCIS (Netherlands)

    Czeh, B.; Lucassen, P.J.

    2007-01-01

    Even though in vivo imaging studies document significant reductions of hippocampal volume in depressed patients, the exact underlying cellular mechanisms are unclear. Since stressful life events are associated with an increased risk of developing depression, preclinical studies in which animals are

  16. Recurrent major depression and right hippocampal volume: A bivariate linkage and association study.

    Science.gov (United States)

    Mathias, Samuel R; Knowles, Emma E M; Kent, Jack W; McKay, D Reese; Curran, Joanne E; de Almeida, Marcio A A; Dyer, Thomas D; Göring, Harald H H; Olvera, Rene L; Duggirala, Ravi; Fox, Peter T; Almasy, Laura; Blangero, John; Glahn, David C

    2016-01-01

    Previous work has shown that the hippocampus is smaller in the brains of individuals suffering from major depressive disorder (MDD) than those of healthy controls. Moreover, right hippocampal volume specifically has been found to predict the probability of subsequent depressive episodes. This study explored the utility of right hippocampal volume as an endophenotype of recurrent MDD (rMDD). We observed a significant genetic correlation between the two traits in a large sample of Mexican American individuals from extended pedigrees (ρg = -0.34, p = 0.013). A bivariate linkage scan revealed a significant pleiotropic quantitative trait locus on chromosome 18p11.31-32 (LOD = 3.61). Bivariate association analysis conducted under the linkage peak revealed a variant (rs574972) within an intron of the gene SMCHD1 meeting the corrected significance level (χ(2) = 19.0, p = 7.4 × 10(-5)). Univariate association analyses of each phenotype separately revealed that the same variant was significant for right hippocampal volume alone, and also revealed a suggestively significant variant (rs12455524) within the gene DLGAP1 for rMDD alone. The results implicate right-hemisphere hippocampal volume as a possible endophenotype of rMDD, and in so doing highlight a potential gene of interest for rMDD risk. © 2015 Wiley Periodicals, Inc.

  17. Smaller hippocampal volume as a vulnerability factor for the persistence of post-traumatic stress disorder

    NARCIS (Netherlands)

    van Rooij, S J H; Kennis, M; Sjouwerman, R; van den Heuvel, M P; Kahn, R S; Geuze, E

    2015-01-01

    BACKGROUND: Smaller hippocampal volume has often been observed in patients with post-traumatic stress disorder (PTSD). However, there is no consensus whether this is a result of stress/trauma exposure, or constitutes a vulnerability factor for the development of PTSD. Second, it is unclear whether

  18. Comparison between visual assessment of MTA and hippocampal volumes in an elderly, non-demented population

    Energy Technology Data Exchange (ETDEWEB)

    Cavallin, Lena; Axelsson, Rimma [CLINTEC, Div. of Medical Imaging and Technology, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Dept. of Radiology, Karolinska Univ. Hospital, Stockholm (Sweden)], e-mail: lena.cavallin@karolinska.se; Bronge, Lena [CLINTEC, Div. of Medical Imaging and Technology, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Aleris Diagnostics, Stockholm (Sweden); Zhang, Yi [NVS, Novum, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Oeksengaard, Anne-Rita [NVS, Novum, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Ulleval Univ. Hospital and Asker and Baerum Hospital, Oslo (Norway); Wahlund, Lars-Olof [NVS, Novum, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden); Swedish Brain Power, Karolinska Univ. Hospital, Stockholm (Sweden); Fratiglioni, Laura [ARC Karolinska Inst. Stockholm (Sweden)

    2012-06-15

    Background: It is important to have a replicable easy method for monitoring atrophy progression in Alzheimer's disease. Volumetric methods for calculating hippocampal volume are time-consuming and commonly used in research. Visual assessments of medial temporal lobe atrophy (vaMTA) is a rapid method for clinical use. This method has not been tested in a large non-demented population in comparison with volumetry measurements. Since hippocampal volume decreases with time even in normal aging there is also a need to study the normal age differences of medial temporal lobe atrophy. Purpose: To compare visual assessment of medial temporal lobe atrophy (vaMTA) with hippocampal volume in a healthy, non-demented elderly population. To describe normal ageing using vaMTA. Material and Methods: Non-demented individuals aged 60, 66, 72, 78, 81, 84, and {>=}87 years old were recruited from the Swedish National study on Ageing and Care in Kungsholmen (SNAC-K), Sweden. Standard magnetic resonance imaging (MRI) scans, vaMTA, and calculations of hippocampal volumes were performed in 544 subjects. Results: Significant correlation (rs = -0.32, P < 0.001, sin; and rs = -0.26, P < 0.001, dx) was found between hippocampal volume measurements and vaMTA. In normal ageing, almost 95% of {<=}66-year-olds had a medial temporal lobe atrophy (MTA) score {<=}1, with possible scores ranging from 0 to 4. Subjects aged 72, 78, and 81 years scored {<=}2, while the two oldest age groups had scores {<=}3. Conclusion: There was a highly significant correlation between volumetric measurements of the hippocampus and MTA scoring. In normal ageing, there is increasing MTA score. For non-demented elderly individuals {<=}70 years, an MTA score of 0-1 may be considered normal, compared with MTA {<=}2 for 70-80-years and MTA 3 for >80-year-old individuals.

  19. Long-Term Treatment with Paroxetine Increases Verbal Declarative Memory and Hippocampal Volume in Posttraumatic Stress Disorder

    Science.gov (United States)

    Vermetten, Eric; Vythilingam, Meena; Southwick, Steven M.; Charney, Dennis S.; Bremner, J. Douglas

    2011-01-01

    Background Animal studies have shown that stress is associated with damage to the hippocampus, inhibition of neurogenesis, and deficits in hippocampal-based memory dysfunction. Studies in patients with posttraumatic stress disorder (PTSD) found deficits in hippocampal-based declarative verbal memory and smaller hippocampal volume, as measured with magnetic resonance imaging (MRI). Recent preclinical evidence has shown that selective serotonin reuptake inhibitors promote neurogenesis and reverse the effects of stress on hippocampal atrophy. This study assessed the effects of long-term treatment with paroxetine on hippocampal volume and declarative memory performance in PTSD. Methods Declarative memory was assessed with the Wechsler Memory Scale–Revised and Selective Reminding Test before and after 9–12 months of treatment with paroxetine in PTSD. Hippocampal volume was measured with MRI. Of the 28 patients who started the protocol, 23 completed the full course of treatment and neuropsychological testing. Twenty patients were able to complete MRI imaging. Results Patients with PTSD showed a significant improvement in PTSD symptoms with treatment. Treatment resulted in significant improvements in verbal declarative memory and a 4.6% increase in mean hippocampal volume. Conclusions These findings suggest that long-term treatment with paroxetine is associated with improvement of verbal declarative memory deficits and an increase in hippocampal volume in PTSD. PMID:14512209

  20. Volume of hippocampal subfields and episodic memory in childhood and adolescence.

    Science.gov (United States)

    Lee, Joshua K; Ekstrom, Arne D; Ghetti, Simona

    2014-07-01

    Episodic memory critically depends on the hippocampus to bind the features of an experience into memory. Episodic memory develops in childhood and adolescence, and hippocampal changes during this period may contribute to this development. Little is known, however, about how the hippocampus contributes to episodic memory development. The hippocampus is comprised of several cytoarchitectural subfields with functional significance for episodic memory. However, hippocampal subfields have not been assessed in vivo during child development, nor has their relation with episodic memory been assessed during this period. In the present study, high-resolution T2-weighted images of the hippocampus were acquired in 39 children and adolescents aged 8 to 14 years (M=11.30, SD=2.38), and hippocampal subfields were segmented using a protocol previously validated in adult populations. We first validated the method in children and adolescents and examined age-related differences in hippocampal subfields and correlations between subfield volumes and episodic memory. Significant age-related increases in the subfield volume were observed into early adolescence in the right CA3/DG and CA1. The right CA3/DG subfield volumes were positively correlated with accurate episodic memory for item-color relations, and the right CA3/DG and subiculum were negatively correlated with item false alarm rates. Subfield development appears to follow a protracted developmental trajectory, and likely plays a pivotal role in episodic memory development. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Correlation between volume and morphological changes in the hippocampal formation in Alzheimer's disease: rounding of the outline of the hippocampal body on coronal MR images

    International Nuclear Information System (INIS)

    Adachi, Michito; Sato, Takamichi; Kawakatsu, Shinobu; Ohshima, Fumi

    2012-01-01

    The aim of this study was to investigate whether the outline of the hippocampal body becomes rounded on coronal magnetic resonance imaging (MRI) as the volume of the hippocampal formation decreases in Alzheimer's disease (AD). Institutional review board approval of the study protocol was obtained, and all subjects provided informed consent for the mini-mental state examination (MMSE) and MRI. The MRI and MMSE were prospectively performed in all 103 subjects (27 men and 76 women; mean age ± standard deviation, 77.7 ± 7.8 years) who had AD or were concerned about having of dementia and who consulted our institute over 1 year. The subjects included 14 non-dementia cases (MMSE score ≥ 28) and 89 AD cases (MMSE score ≤ 27). The total volume of the bilateral hippocampal formation (VHF) was assessed with a tracing method, and the ratio of the VHF to the intracranial volume (RVHF) and the rounding ratio (RR) of the hippocampal body (mean ratio of its short dimension to the long dimension in the bilateral hippocampal body) were calculated. Using Spearman's correlation coefficient, the correlations between RR and VHF and between RR and RVHF were assessed. Correlation coefficients between RR and VHF and between RR and RVHF were -0.419 (p < 0.01) and -0.418 (p < 0.01), respectively. There was a significant negative correlation between RR and the volume of the hippocampal formation. The outline of the body of the hippocampal formation becomes rounded on coronal images as its volume decreases in AD. (orig.)

  2. Synaptic vesicle exocytosis in hippocampal synaptosomes correlates directly with total mitochondrial volume

    Science.gov (United States)

    Ivannikov, Maxim V.; Sugimori, Mutsuyuki; Llinás, Rodolfo R.

    2012-01-01

    Synaptic plasticity in many regions of the central nervous system leads to the continuous adjustment of synaptic strength, which is essential for learning and memory. In this study, we show by visualizing synaptic vesicle release in mouse hippocampal synaptosomes that presynaptic mitochondria and specifically, their capacities for ATP production are essential determinants of synaptic vesicle exocytosis and its magnitude. Total internal reflection microscopy of FM1-43 loaded hippocampal synaptosomes showed that inhibition of mitochondrial oxidative phosphorylation reduces evoked synaptic release. This reduction was accompanied by a substantial drop in synaptosomal ATP levels. However, cytosolic calcium influx was not affected. Structural characterization of stimulated hippocampal synaptosomes revealed that higher total presynaptic mitochondrial volumes were consistently associated with higher levels of exocytosis. Thus, synaptic vesicle release is linked to the presynaptic ability to regenerate ATP, which itself is a utility of mitochondrial density and activity. PMID:22772899

  3. Subfield-specific loss of hippocampal N-acetyl aspartate in temporal lobe epilepsy.

    Science.gov (United States)

    Vielhaber, Stefan; Niessen, Heiko G; Debska-Vielhaber, Grazyna; Kudin, Alexei P; Wellmer, Jörg; Kaufmann, Jörn; Schönfeld, Mircea Ariel; Fendrich, Robert; Willker, Wieland; Leibfritz, Dieter; Schramm, Johannes; Elger, Christian E; Heinze, Hans-Jochen; Kunz, Wolfram S

    2008-01-01

    In patients with mesial temporal lobe epilepsy (MTLE) it remains an unresolved issue whether the interictal decrease in N-acetyl aspartate (NAA) detected by proton magnetic resonance spectroscopy ((1)H-MRS) reflects the epilepsy-associated loss of hippocampal pyramidal neurons or metabolic dysfunction. To address this problem, we applied high-resolution (1)H-MRS at 14.1 Tesla to measure metabolite concentrations in ex vivo tissue slices from three hippocampal subfields (CA1, CA3, dentate gyrus) as well as from the parahippocampal region of 12 patients with MTLE. In contrast to four patients with lesion-caused MTLE, we found a large variance of NAA concentrations in the individual hippocampal regions of patients with Ammon's horn sclerosis (AHS). Specifically, in subfield CA3 of AHS patients despite of a moderate preservation of neuronal cell densities the concentration of NAA was significantly lowered, while the concentrations of lactate, glucose, and succinate were elevated. We suggest that these subfield-specific alterations of metabolite concentrations in AHS are very likely caused by impairment of mitochondrial function and not related to neuronal cell loss. A subfield-specific impairment of energy metabolism is the probable cause for lowered NAA concentrations in sclerotic hippocampi of MTLE patients.

  4. Relationship of collegiate football experience and concussion with hippocampal volume and cognitive outcomes.

    Science.gov (United States)

    Singh, Rashmi; Meier, Timothy B; Kuplicki, Rayus; Savitz, Jonathan; Mukai, Ikuko; Cavanagh, LaMont; Allen, Thomas; Teague, T Kent; Nerio, Christopher; Polanski, David; Bellgowan, Patrick S F

    2014-05-14

    Concussion and subconcussive impacts have been associated with short-term disrupted cognitive performance in collegiate athletes, but there are limited data on their long-term neuroanatomic and cognitive consequences. To assess the relationships of concussion history and years of football experience with hippocampal volume and cognitive performance in collegiate football athletes. Cross-sectional study conducted between June 2011 and August 2013 at a US psychiatric research institute specializing in neuroimaging among collegiate football players with a history of clinician-diagnosed concussion (n = 25), collegiate football players without a history of concussion (n = 25), and non-football-playing, age-, sex-, and education-matched healthy controls (n = 25). History of clinician-diagnosed concussion and years of football experience. High-resolution anatomical magnetic resonance imaging was used to quantify brain volumes. Baseline scores on a computerized concussion-related cognitive battery were used for cognitive assessment in athletes. Players with and without a history of concussion had smaller hippocampal volumes relative to healthy control participants (with concussion: t48 = 7.58; P history of concussion had smaller hippocampal volumes than players without concussion (t48 = 3.15; P football played (t46 = -3.62; P history on 5 cognitive measures but did show an inverse correlation between years of playing football and reaction time (ρ42 = -0.43; 95% CI, -0.46 to -0.40; P = .005). Among a group of collegiate football athletes, there was a significant inverse relationship of concussion and years of football played with hippocampal volume. Years of football experience also correlated with slower reaction time. Further research is needed to determine the temporal relationships of these findings.

  5. he effect of exercise on hippocampal volume and neurotrophines in patients with major depression–A randomized clinical trial

    DEFF Research Database (Denmark)

    Krogh, Jesper; Rostrup, Egill; Thomsen, Carsten

    2014-01-01

    BACKGROUND: The hippocampal volume is reduced in patients with major depression. Exercise leads to an increased hippocampal volume in schizophrenia and in healthy old adults. The effect of exercise on hippocampal volume is potentially mediated by brain derived neurotrophic factor (BDNF), vascular...... endothelial growth factor (VEGF), and insulin like growth factor 1 (IGF-1). The aim of this trial was to assess the effect of an aerobic exercise intervention on hippocampal volume and serum BDNF, VEGF, and IGF-1 in patients with major depression. METHODS: Patients were randomized to an aerobic exercise...... intervention (n=41) or a control condition (n=38). Both interventions consisted of three supervised sessions per week during a three months period. RESULTS: Post-intervention the increase in maximal oxygen uptake was 3.90 ml/kg/min (SD 5.1) in the aerobic exercise group and 0.95 ml/kg/min (SD 6...

  6. Influence of parental care on offspring hippocampal volume in young adults varies as a function of overprotection

    OpenAIRE

    Wang, Yinan; Song, Yiying; Li, Xueting; Zhang, Lin; Liu, Jia

    2017-01-01

    Parental care results in increased hippocampal volumes through adaptive stress responses in developing animals. However, human studies have not yet provided consistent findings analogous to the animal literature, possibly because parental care in humans is likely intermingled with parental overprotection, as suggested by the optimal parenting theory. Here, we tested the hypothesis that the effect of parental care on offspring hippocampal volume varies as a function of parental overprotection ...

  7. Polygenic Risk Score for Alzheimer's Disease: Implications for Memory Performance and Hippocampal Volumes in Early Life.

    Science.gov (United States)

    Axelrud, Luiza K; Santoro, Marcos L; Pine, Daniel S; Talarico, Fernanda; Gadelha, Ary; Manfro, Gisele G; Pan, Pedro M; Jackowski, Andrea; Picon, Felipe; Brietzke, Elisa; Grassi-Oliveira, Rodrigo; Bressan, Rodrigo A; Miguel, Eurípedes C; Rohde, Luis A; Hakonarson, Hakon; Pausova, Zdenka; Belangero, Sintia; Paus, Tomas; Salum, Giovanni A

    2018-06-01

    Alzheimer's disease is a heritable neurodegenerative disorder in which early-life precursors may manifest in cognition and brain structure. The authors evaluate this possibility by examining, in youths, associations among polygenic risk score for Alzheimer's disease, cognitive abilities, and hippocampal volume. Participants were children 6-14 years of age in two Brazilian cities, constituting the discovery (N=364) and replication samples (N=352). As an additional replication, data from a Canadian sample (N=1,029), with distinct tasks, MRI protocol, and genetic risk, were included. Cognitive tests quantified memory and executive function. Reading and writing abilities were assessed by standardized tests. Hippocampal volumes were derived from the Multiple Automatically Generated Templates (MAGeT) multi-atlas segmentation brain algorithm. Genetic risk for Alzheimer's disease was quantified using summary statistics from the International Genomics of Alzheimer's Project. Analyses showed that for the Brazilian discovery sample, each one-unit increase in z-score for Alzheimer's polygenic risk score significantly predicted a 0.185 decrement in z-score for immediate recall and a 0.282 decrement for delayed recall. Findings were similar for the Brazilian replication sample (immediate and delayed recall, β=-0.259 and β=-0.232, both significant). Quantile regressions showed lower hippocampal volumes bilaterally for individuals with high polygenic risk scores. Associations fell short of significance for the Canadian sample. Genetic risk for Alzheimer's disease may affect early-life cognition and hippocampal volumes, as shown in two independent samples. These data support previous evidence that some forms of late-life dementia may represent developmental conditions with roots in childhood. This result may vary depending on a sample's genetic risk and may be specific to some types of memory tasks.

  8. Lack of an association of BDNF Val66Met polymorphism and plasma BDNF with hippocampal volume and memory

    Science.gov (United States)

    Kim, Ana; Fagan, Anne M; Goate, Alison M; Benzinger, Tammie LS; Morris, John C; Head, Denise

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) has been shown to be important for neuronal survival and synaptic plasticity in the hippocampus in non-human animals. The Val66Met polymorphism in the BDNF gene, involving a valine (Val) to methionine (Met) substitution at codon 66, has been associated with lower BDNF secretion in vitro. However, there have been mixed results regarding associations between either circulating BDNF or the BDNF Val66Met polymorphism with hippocampal volume and memory in humans. The current study examined the association of BDNF genotype and plasma BDNF with hippocampal volume and memory in two large independent cohorts of middle-aged and older adults (both cognitively normal and early-stage dementia). Sample sizes ranged from 123 to 649. Measures of the BDNF genotype, plasma BDNF, MRI-based hippocampal volume and memory performance were obtained from the Knight Alzheimer Disease Research Center (ADRC) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). There were no significant differences between BDNF Met+ and Met- groups on either hippocampal volume or memory in either cohort. In addition, plasma BDNF was not significantly associated with either hippocampal volume or memory in either cohort. Neither age, cognitive status nor gender moderated any of the relationships. Overall, current findings suggest that BDNF genotype and plasma BDNF may not be robust predictors for variance in hippocampal volume and memory in middle age and older adult cohorts. PMID:25784293

  9. Failure of hippocampal deactivation during loss events in treatment-resistant depression.

    Science.gov (United States)

    Johnston, Blair A; Tolomeo, Serenella; Gradin, Victoria; Christmas, David; Matthews, Keith; Steele, J Douglas

    2015-09-01

    Major depressive disorder is characterized by anhedonia, cognitive biases, ruminations, hopelessness and increased anxiety. Blunted responses to rewards have been reported in a number of recent neuroimaging and behavioural studies of major depressive disorder. In contrast, neural responses to aversive events remain an under-studied area. While selective serotonergic reuptake inhibitors are often effective in treating major depressive disorder, their mechanism of action remains unclear. Following a series of animal model investigations of depressive illness and serotonergic function, Deakin and Graeff predicted that brain activity in patients with major depressive disorder is associated with an overactive dorsal raphe nucleus with overactive projections to the amygdala, periaqueductal grey and striatum, and an underactive median raphe nucleus with underactive projections to the hippocampus. Here we describe an instrumental loss-avoidance and win-gain reinforcement learning functional magnetic resonance imaging study with 40 patients with highly treatment-resistant major depressive disorder and never-depressed controls. The dorsal raphe nucleus/ periaqueductal grey region of the midbrain and hippocampus were found to be overactive in major depressive disorder during unsuccessful loss-avoidance although the median raphe nucleus was not found to be underactive. Hippocampal overactivity was due to a failure to deactivate during loss events in comparison to controls, and hippocampal over-activity correlated with depression severity, self-report 'hopelessness' and anxiety. Deakin and Graeff argued that the median raphe nucleus normally acts to inhibit consolidation of aversive memories via the hippocampus and this system is underactive in major depressive disorder, facilitating the development of ruminations, while the dorsal raphe nucleus system is engaged by distal cues predictive of threats and is overactive in major depressive disorder. During win events the striatum

  10. Influence of parental care on offspring hippocampal volume in young adults varies as a function of overprotection.

    Science.gov (United States)

    Wang, Yinan; Song, Yiying; Li, Xueting; Zhang, Lin; Liu, Jia

    2017-04-12

    Parental care results in increased hippocampal volumes through adaptive stress responses in developing animals. However, human studies have not yet provided consistent findings analogous to the animal literature, possibly because parental care in humans is likely intermingled with parental overprotection, as suggested by the optimal parenting theory. Here, we tested the hypothesis that the effect of parental care on offspring hippocampal volume varies as a function of parental overprotection with a large cohort of young adult participants (N = 257). Consistent with some previous human studies, we found that parental care in childhood alone had little association with the hippocampal volume in adulthood. However, when parental overprotection was low, parental care was positively correlated with offspring hippocampal volume, whereas there was no association between parental care and offspring hippocampal volume when parental overprotection was high. Thus, an interaction exists between parental care and overprotection in human's hippocampal development, which contributes to the elucidation of the complex relationship between brain structure and environmental factors.

  11. Hippocampal CA3-dentate gyrus volume uniquely linked to improvement in associative memory from childhood to adulthood.

    Science.gov (United States)

    Daugherty, Ana M; Flinn, Robert; Ofen, Noa

    2017-06-01

    Associative memory develops into adulthood and critically depends on the hippocampus. The hippocampus is a complex structure composed of subfields that are functionally-distinct, and anterior-posterior divisions along the length of the hippocampal horizontal axis that may also differ by cognitive correlates. Although each of these aspects has been considered independently, here we evaluate their relative contributions as correlates of age-related improvement in memory. Volumes of hippocampal subfields (subiculum, CA1-2, CA3-dentate gyrus) and anterior-posterior divisions (hippocampal head, body, tail) were manually segmented from high-resolution images in a sample of healthy participants (age 8-25 years). Adults had smaller CA3-dentate gyrus volume as compared to children, which accounted for 67% of the indirect effect of age predicting better associative memory via hippocampal volumes. Whereas hippocampal body volume demonstrated non-linear age differences, larger hippocampal body volume was weakly related to better associative memory only when accounting for the mutual correlation with subfields measured within that region. Thus, typical development of associative memory was largely explained by age-related differences in CA3-dentate gyrus. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Hippocampal CA3-dentate gyrus volume uniquely linked to improvement in associative memory from childhood to adulthood

    Science.gov (United States)

    Daugherty, Ana M.; Flinn, Robert; Ofen, Noa

    2017-01-01

    Associative memory develops into adulthood and critically depends on the hippocampus. The hippocampus is a complex structure composed of subfields that are functionally-distinct, and anterior-posterior divisions along the length of the hippocampal horizontal axis that may also differ by cognitive correlates. Although each of these aspects has been considered independently, here we evaluate their relative contributions as correlates of age-related improvement in memory. Volumes of hippocampal subfields (subiculum, CA1-2, CA3-dentate gyrus) and anterior-posterior divisions (hippocampal head, body, tail) were manually segmented from high-resolution proton density-weighted images in a sample of healthy participants (age 8–25 years). Adults had smaller CA3-dentate gyrus volume as compared to children, which accounted for 67% of the indirect effect of age predicting better associative memory via hippocampal volumes. Whereas hippocampal body volume demonstrated non-linear age differences, larger hippocampal body volume was weakly related to better associative memory only when accounting for the mutual correlation with subfields measured within that region. Thus, typical development of associative memory was largely explained by age-related differences in CA3-dentate gyrus. PMID:28342999

  13. Aerobic fitness relates to learning on a virtual morris water task and hippocampal volume in adolescents

    Science.gov (United States)

    Herting, Megan M.; Nagel, Bonnie J.

    2012-01-01

    In rodents, exercise increases hippocampal neurogenesis and allows for better learning and memory performance on water maze tasks. While exercise has also been shown to be beneficial for the brain and behavior in humans, no study has examined how exercise impacts spatial learning using a directly translational water maze task, or if these relationships exist during adolescence – a developmental period which the animal literature has shown to be especially vulnerable to exercise effects. In this study, we investigated the influence of aerobic fitness on hippocampal size and subsequent learning and memory, including visuospatial memory using a human analogue of the Morris Water Task, in 34 adolescents. Results showed that higher aerobic fitness predicted better learning on the virtual Morris Water Task and larger hippocampal volumes. No relationship between virtual Morris Water Task memory recall and aerobic fitness was detected. Aerobic fitness, however, did not relate to global brain volume, or verbal learning, which might suggest some specificity of the influence of aerobic fitness on the adolescent brain. This study provides a direct translational approach to the existing animal literature on exercise, as well as adds to the sparse research that exists on how aerobic exercise impacts the developing human brain and memory. PMID:22610054

  14. Aerobic fitness relates to learning on a virtual Morris Water Task and hippocampal volume in adolescents.

    Science.gov (United States)

    Herting, Megan M; Nagel, Bonnie J

    2012-08-01

    In rodents, exercise increases hippocampal neurogenesis and allows for better learning and memory performance on water maze tasks. While exercise has also been shown to be beneficial for the brain and behavior in humans, no study has examined how exercise impacts spatial learning using a directly translational water maze task, or if these relationships exist during adolescence--a developmental period which the animal literature has shown to be especially vulnerable to exercise effects. In this study, we investigated the influence of aerobic fitness on hippocampal size and subsequent learning and memory, including visuospatial memory using a human analogue of the Morris Water Task, in 34 adolescents. Results showed that higher aerobic fitness predicted better learning on the virtual Morris Water Task and larger hippocampal volumes. No relationship between virtual Morris Water Task memory recall and aerobic fitness was detected. Aerobic fitness, however, did not relate to global brain volume or verbal learning, which might suggest some specificity of the influence of aerobic fitness on the adolescent brain. This study provides a direct translational approach to the existing animal literature on exercise, as well as adds to the sparse research that exists on how aerobic exercise impacts the developing human brain and memory. Published by Elsevier B.V.

  15. Identification of common variants associated with human hippocampal and intracranial volumes

    Science.gov (United States)

    Stein, Jason L; Medland, Sarah E; Vasquez, Alejandro Arias; Hibar, Derrek P; Senstad, Rudy E; Winkler, Anderson M; Toro, Roberto; Appel, Katja; Bartecek, Richard; Bergmann, Ørjan; Bernard, Manon; Brown, Andrew A; Cannon, Dara M; Chakravarty, M Mallar; Christoforou, Andrea; Domin, Martin; Grimm, Oliver; Hollinshead, Marisa; Holmes, Avram J; Homuth, Georg; Hottenga, Jouke-Jan; Langan, Camilla; Lopez, Lorna M; Hansell, Narelle K; Hwang, Kristy S; Kim, Sungeun; Laje, Gonzalo; Lee, Phil H; Liu, Xinmin; Loth, Eva; Lourdusamy, Anbarasu; Mattingsdal, Morten; Mohnke, Sebastian; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; O’Brien, Carol; Papmeyer, Martina; Pütz, Benno; Ramasamy, Adaikalavan; Rasmussen, Jerod; Rijpkema, Mark; Risacher, Shannon L; Roddey, J Cooper; Rose, Emma J; Ryten, Mina; Shen, Li; Sprooten, Emma; Strengman, Eric; Teumer, Alexander; Trabzuni, Daniah; Turner, Jessica; van Eijk, Kristel; van Erp, Theo G M; van Tol, Marie-Jose; Wittfeld, Katharina; Wolf, Christiane; Woudstra, Saskia; Aleman, Andre; Alhusaini, Saud; Almasy, Laura; Binder, Elisabeth B; Brohawn, David G; Cantor, Rita M; Carless, Melanie A; Corvin, Aiden; Czisch, Michael; Curran, Joanne E; Davies, Gail; de Almeida, Marcio A A; Delanty, Norman; Depondt, Chantal; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fagerness, Jesen; Fox, Peter T; Freimer, Nelson B; Gill, Michael; Göring, Harald H H; Hagler, Donald J; Hoehn, David; Holsboer, Florian; Hoogman, Martine; Hosten, Norbert; Jahanshad, Neda; Johnson, Matthew P; Kasperaviciute, Dalia; Kent, Jack W; Kochunov, Peter; Lancaster, Jack L; Lawrie, Stephen M; Liewald, David C; Mandl, René; Matarin, Mar; Mattheisen, Manuel; Meisenzahl, Eva; Melle, Ingrid; Moses, Eric K; Mühleisen, Thomas W; Nauck, Matthias; Nöthen, Markus M; Olvera, Rene L; Pandolfo, Massimo; Pike, G Bruce; Puls, Ralf; Reinvang, Ivar; Rentería, Miguel E; Rietschel, Marcella; Roffman, Joshua L; Royle, Natalie A; Rujescu, Dan; Savitz, Jonathan; Schnack, Hugo G; Schnell, Knut; Seiferth, Nina; Smith, Colin; Steen, Vidar M; Valdés Hernández, Maria C; Van den Heuvel, Martijn; van der Wee, Nic J; Van Haren, Neeltje E M; Veltman, Joris A; Völzke, Henry; Walker, Robert; Westlye, Lars T; Whelan, Christopher D; Agartz, Ingrid; Boomsma, Dorret I; Cavalleri, Gianpiero L; Dale, Anders M; Djurovic, Srdjan; Drevets, Wayne C; Hagoort, Peter; Hall, Jeremy; Heinz, Andreas; Jack, Clifford R; Foroud, Tatiana M; Le Hellard, Stephanie; Macciardi, Fabio; Montgomery, Grant W; Poline, Jean Baptiste; Porteous, David J; Sisodiya, Sanjay M; Starr, John M; Sussmann, Jessika; Toga, Arthur W; Veltman, Dick J; Walter, Henrik; Weiner, Michael W; Bis, Joshua C; Ikram, M Arfan; Smith, Albert V; Gudnason, Vilmundur; Tzourio, Christophe; Vernooij, Meike W; Launer, Lenore J; DeCarli, Charles; Seshadri, Sudha; Andreassen, Ole A; Apostolova, Liana G; Bastin, Mark E; Blangero, John; Brunner, Han G; Buckner, Randy L; Cichon, Sven; Coppola, Giovanni; de Zubicaray, Greig I; Deary, Ian J; Donohoe, Gary; de Geus, Eco J C; Espeseth, Thomas; Fernández, Guillén; Glahn, David C; Grabe, Hans J; Hardy, John; Hulshoff Pol, Hilleke E; Jenkinson, Mark; Kahn, René S; McDonald, Colm; McIntosh, Andrew M; McMahon, Francis J; McMahon, Katie L; Meyer-Lindenberg, Andreas; Morris, Derek W; Müller-Myhsok, Bertram; Nichols, Thomas E; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W; Potkin, Steven G; Sämann, Philipp G; Saykin, Andrew J; Schumann, Gunter; Smoller, Jordan W; Wardlaw, Joanna M; Weale, Michael E; Martin, Nicholas G; Franke, Barbara; Wright, Margaret J; Thompson, Paul M

    2013-01-01

    Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer’s disease1,2 and is reduced in schizophrenia3, major depression4 and mesial temporal lobe epilepsy5. Whereas many brain imaging phenotypes are highly heritable6,7, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10−16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10−12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10−7). PMID:22504417

  16. Less Daily Computer Use is Related to Smaller Hippocampal Volumes in Cognitively Intact Elderly.

    Science.gov (United States)

    Silbert, Lisa C; Dodge, Hiroko H; Lahna, David; Promjunyakul, Nutta-On; Austin, Daniel; Mattek, Nora; Erten-Lyons, Deniz; Kaye, Jeffrey A

    2016-01-01

    Computer use is becoming a common activity in the daily life of older individuals and declines over time in those with mild cognitive impairment (MCI). The relationship between daily computer use (DCU) and imaging markers of neurodegeneration is unknown. The objective of this study was to examine the relationship between average DCU and volumetric markers of neurodegeneration on brain MRI. Cognitively intact volunteers enrolled in the Intelligent Systems for Assessing Aging Change study underwent MRI. Total in-home computer use per day was calculated using mouse movement detection and averaged over a one-month period surrounding the MRI. Spearman's rank order correlation (univariate analysis) and linear regression models (multivariate analysis) examined hippocampal, gray matter (GM), white matter hyperintensity (WMH), and ventricular cerebral spinal fluid (vCSF) volumes in relation to DCU. A voxel-based morphometry analysis identified relationships between regional GM density and DCU. Twenty-seven cognitively intact participants used their computer for 51.3 minutes per day on average. Less DCU was associated with smaller hippocampal volumes (r = 0.48, p = 0.01), but not total GM, WMH, or vCSF volumes. After adjusting for age, education, and gender, less DCU remained associated with smaller hippocampal volume (p = 0.01). Voxel-wise analysis demonstrated that less daily computer use was associated with decreased GM density in the bilateral hippocampi and temporal lobes. Less daily computer use is associated with smaller brain volume in regions that are integral to memory function and known to be involved early with Alzheimer's pathology and conversion to dementia. Continuous monitoring of daily computer use may detect signs of preclinical neurodegeneration in older individuals at risk for dementia.

  17. The influence of negative life events on hippocampal and amygdala volumes in old age: a life-course perspective.

    Science.gov (United States)

    Gerritsen, L; Kalpouzos, G; Westman, E; Simmons, A; Wahlund, L O; Bäckman, L; Fratiglioni, L; Wang, H X

    2015-04-01

    Psychosocial stress has been related to changes in the nervous system, with both adaptive and maladaptive consequences. The aim of this study was to examine the relationship of negative events experienced throughout the entire lifespan and hippocampal and amygdala volumes in older adults. In 466 non-demented old adults (age range 60-96 years, 58% female), hippocampal and amygdala volumes were segmented using Freesurfer. Negative life events and the age at which these events occurred were assessed by means of a structured questionnaire. Using generalized linear models, hippocampal and amygdala volumes were estimated with life events as independent variables. The statistical analyses were adjusted for age, gender, intracranial volume, lifestyle factors, cardiovascular risk factors, depressive symptoms, and cognitive functioning. Total number of negative life events and of late-life events, but not of early-life, early-adulthood, or middle-adulthood events, was related to larger amygdala volume. There were interactions of early-life events with age and gender. Participants who reported two or more early-life events had significantly smaller amygdala and hippocampal volumes with increasing age. Furthermore, smaller hippocampal volume was found in men who reported two or more early-life events, but not in women. These results suggest that the effect of negative life events on the brain depends on the time when the events occurred, with the strongest effects observed during the critical time periods of early and late life.

  18. Diffusion-weighted MRI and quantitative biophysical modeling of hippocampal neurite loss in chronic stress.

    Directory of Open Access Journals (Sweden)

    Peter Vestergaard-Poulsen

    Full Text Available Chronic stress has detrimental effects on physiology, learning and memory and is involved in the development of anxiety and depressive disorders. Besides changes in synaptic formation and neurogenesis, chronic stress also induces dendritic remodeling in the hippocampus, amygdala and the prefrontal cortex. Investigations of dendritic remodeling during development and treatment of stress are currently limited by the invasive nature of histological and stereological methods. Here we show that high field diffusion-weighted MRI combined with quantitative biophysical modeling of the hippocampal dendritic loss in 21 day restraint stressed rats highly correlates with former histological findings. Our study strongly indicates that diffusion-weighted MRI is sensitive to regional dendritic loss and thus a promising candidate for non-invasive studies of dendritic plasticity in chronic stress and stress-related disorders.

  19. Hippocampal dose volume histogram predicts Hopkins Verbal Learning Test scores after brain irradiation

    Directory of Open Access Journals (Sweden)

    Catherine Okoukoni, PhD

    2017-10-01

    Full Text Available Purpose: Radiation-induced cognitive decline is relatively common after treatment for primary and metastatic brain tumors; however, identifying dosimetric parameters that are predictive of radiation-induced cognitive decline is difficult due to the heterogeneity of patient characteristics. The memory function is especially susceptible to radiation effects after treatment. The objective of this study is to correlate volumetric radiation doses received by critical neuroanatomic structures to post–radiation therapy (RT memory impairment. Methods and materials: Between 2008 and 2011, 53 patients with primary brain malignancies were treated with conventionally fractionated RT in prospectively accrued clinical trials performed at our institution. Dose-volume histogram analysis was performed for the hippocampus, parahippocampus, amygdala, and fusiform gyrus. Hopkins Verbal Learning Test-Revised scores were obtained at least 6 months after RT. Impairment was defined as an immediate recall score ≤15. For each anatomic region, serial regression was performed to correlate volume receiving a given dose (VD(Gy with memory impairment. Results: Hippocampal V53.4Gy to V60.9Gy significantly predicted post-RT memory impairment (P < .05. Within this range, the hippocampal V55Gy was the most significant predictor (P = .004. Hippocampal V55Gy of 0%, 25%, and 50% was associated with tumor-induced impairment rates of 14.9% (95% confidence interval [CI], 7.2%-28.7%, 45.9% (95% CI, 24.7%-68.6%, and 80.6% (95% CI, 39.2%-96.4%, respectively. Conclusions: The hippocampal V55Gy is a significant predictor for impairment, and a limiting dose below 55 Gy may minimize radiation-induced cognitive impairment.

  20. Reduced hippocampal and parahippocampal volumes in murderers with schizophrenia.

    Science.gov (United States)

    Yang, Yaling; Raine, Adrian; Han, Chen-Bo; Schug, Robert A; Toga, Arthur W; Narr, Katherine L

    2010-04-30

    Evidence has accumulated to suggest that individuals with schizophrenia are at increased risk for violent offending. Furthermore, converging evidence suggests that abnormalities in the fronto-limbic system, including the prefrontal cortex, the hippocampus, and the parahippocampal gyrus, may contribute towards both neuropsychological disturbances in schizophrenia and violent behavior. Since the behavioral and clinical consequences of disturbed fronto-limbic circuitry appear to differ in schizophrenia and violence, it may be argued that patients with schizophrenia who exhibit violent behavior would demonstrate different structural abnormalities compared to their non-violent counterparts. However, the neurobiological basis underlying homicide offenders with schizophrenia remains unclear and little is known regarding the cross-cultural applicability of the findings. Using a 2 x 2 factorial design on a total Chinese sample of 92 males and females, we found reduced gray matter volume in the hippocampus and parahippocampal gyrus in murderers with schizophrenia, in the parahippocampal gyrus in murderers without schizophrenia, and in the prefrontal cortex in non-violent schizophrenia compared to normal controls. Results provide initial evidence demonstrating cross-cultural generalizability of prior fronto-limbic findings on violent schizophrenia. Future studies examining subtle morphological changes in frontal and limbic structures in association with clinical and behavioral characteristics may help further clarify the neurobiological basis of violent behavior. Copyright @ 2009 Elsevier Ireland Ltd. All rights reserved.

  1. Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Ericksen Mielle Borba

    2016-12-01

    Full Text Available Background/Aims: Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD pathology. Serum brain-derived neurotrophic factor (BDNF reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]. Methods: Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. Results: MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. Discussion: The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.

  2. Brain-Derived Neurotrophic Factor Serum Levels and Hippocampal Volume in Mild Cognitive Impairment and Dementia due to Alzheimer Disease.

    Science.gov (United States)

    Borba, Ericksen Mielle; Duarte, Juliana Avila; Bristot, Giovana; Scotton, Ellen; Camozzato, Ana Luiza; Chaves, Márcia Lorena Fagundes

    2016-01-01

    Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.

  3. The MRI study of hippocampal volume and shape in the youth and older

    International Nuclear Information System (INIS)

    Li Yuefeng; Jiang Ping; Tong Xinkang; Wang Dongqing; Peng Weibin; Wei Chuanshe; Yin Ruigen; Zhao Liang; Sun Weibin; Wang Zhengchao

    2009-01-01

    Objective: In the base of the landmarks of the hippocampus identified with neighborhood structures, to measure volumes and shape of normal older age group and youth group's hippocampus and hippocampal head, body, tail. Methods: Thirty younger people (age 20-29 years, youth group) and thirty older people (above 60 years, older age group) were scanned by MR, anatomic landmarks were found, which were constancy and easy to be recognized for segmentation hippocampus. The hippocampal volumes, average areas and number of the hippocampal layer were measured, the interclass data of two groups, different gender and sides were compared with statistics methods of t test and the hippocampal model were made with the three-dimensional reconstruction. Results: All landmarks of 60 subjects could be distinguished clearly, such as uncal recess, triangle of the lateral ventricle, uncal apex et al. The discrepancies of two groups volumes of gender had not statistical significance. The youth groups volumes of left hippocampus, head, body and tail were (1250±174), (653±115), (372±116), (2277±109) mm 3 , and the right were (1255±147), (657±129), (386±105), (2298±213) mm 3 . There was no statistical significance between left and right (t=0.08,0.10,0.33,0.35, P>0.05). The older age groups volumes of left hippocampus, head, body and tail were (660 + 109), (472 -+92), (181 -+73), (1313 + 163) mm 3 ,and the right were (717±116), (474±95), (240±75), (1432±171) mm 3 . Older hippocampal volumes were obviously bigger in right tail than in left (t=2.21, P 0.05). There were manifest statistical significance between two groups left volumes of hippocampus and each parts(t=15.78,6.71,7.70,20.83, P 2 and the right were (73±22), (58±19) mm 2 . Both two groups had manifest statistical significance (t=3.33,2.81, P<0.01). The number of layers of youth and older groups were (11.1± 3.2), (7.9±3.9) layers, and the right were (11.5±3.7), (8.2±3.1) layers. Both two groups had manifest

  4. Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Glenthøj, Birte; Rasmussen, Hans

    2010-01-01

    of a false discovery rate correction (p brain structure volumes. We grouped patients as those with (n = 9) or without (n = 29) any lifetime substance abuse to examine the possible effects of substance abuse. RESULTS: We found......BACKGROUND: Enlarged ventricles and reduced hippocampal volume are consistently found in patients with first-episode schizophrenia. Studies investigating brain structure in antipsychotic-naive patients have generally focused on the striatum. In this study, we examined whether ventricular...... healthy controls by use of a 3-T scanner. We warped the brain images to each other by use of a high-dimensional intersubject registration algorithm. We performed voxel-wise group comparisons with permutation tests. We performed small volume correction for the hippocampus, caudate and ventricles by use...

  5. Does white matter structure or hippocampal volume mediate associations between cortisol and cognitive ageing?

    Science.gov (United States)

    Cox, Simon R.; MacPherson, Sarah E.; Ferguson, Karen J.; Royle, Natalie A.; Maniega, Susana Muñoz; Hernández, Maria del C. Valdés; Bastin, Mark E.; MacLullich, Alasdair M.J.; Wardlaw, Joanna M.; Deary, Ian J.

    2015-01-01

    Elevated glucocorticoid (GC) levels putatively damage specific brain regions, which in turn may accelerate cognitive ageing. However, many studies are cross-sectional or have relatively short follow-up periods, making it difficult to relate GCs directly to changes in cognitive ability with increasing age. Moreover, studies combining endocrine, MRI and cognitive variables are scarce, measurement methods vary considerably, and formal tests of the underlying causal hypothesis (cortisol → brain → cognition) are absent. In this study, 90 men, aged 73 years, provided measures of fluid intelligence, processing speed and memory, diurnal and reactive salivary cortisol and two measures of white matter (WM) structure (WM hyperintensity volume from structural MRI and mean diffusivity averaged across 12 major tracts from diffusion tensor MRI), hippocampal volume, and also cognitive ability at age 11. We tested whether negative relationships between cognitive ageing differences (over more than 60 years) and salivary cortisol were significantly mediated by WM and hippocampal volume. Significant associations between reactive cortisol at 73 and cognitive ageing differences between 11 and 73 (r = −.28 to −.36, p cognition associations (cognitive ageing differences from childhood to the early 70s, partly via brain WM structure. PMID:26298692

  6. Hippocampal volume changes in healthy subjects at risk of unipolar depression

    DEFF Research Database (Denmark)

    Baaré, William F C; Vinberg, Maj; Knudsen, Gitte M

    2010-01-01

    Unipolar depression is moderately heritable. It is unclear whether structural brain changes associated with unipolar depression are present in healthy persons at risk of the disorder. Here we investigated whether a genetic predisposition to unipolar depression is associated with structural brain...... changes. A priori, hippocampal volume reductions were hypothesized. Using a high-risk study design, magnetic resonance imaging brain scans were obtained from 59 healthy high-risk subjects having a co-twin with unipolar depression, and 53 healthy low-risk subjects without a first-degree family history...

  7. Alzheimer's disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936.

    Directory of Open Access Journals (Sweden)

    Donald M Lyall

    Full Text Available The APOE ε and TOMM40 rs10524523 ('523' variable length poly-T repeat gene loci have been significantly and independently associated with Alzheimer's disease (AD related phenotypes such as age of clinical onset. Hippocampal atrophy has been significantly associated with memory impairment, a characteristic of AD. The current study aimed to test for independent effects of APOE ε and TOMM40 '523' genotypes on hippocampal volumes as assessed by brain structural MRI in a relatively large sample of community-dwelling older adults. As part of a longitudinal study of cognitive ageing, participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε2/ε3/ε4 status and TOMM40 '523' poly-T repeat length, and detailed structural brain MRI at a mean age of 72.7 years (standard deviation = 0.7, N range = 624 to 636. No significant effects of APOE ε or TOMM40 523 genotype were found on hippocampal volumes when analysed raw, or when adjusted for either intracranial or total brain tissue volumes. In summary, in a large community-dwelling sample of older adults, we found no effects of APOE ε or TOMM40 523 genotypes on hippocampal volumes. This is discrepant with some previous reports of significant association between APOE and left/right hippocampal volumes, and instead echoes other reports that found no association. Previous significant findings may partly reflect type 1 error. Future studies should carefully consider: 1 their specific techniques in adjusting for brain size; 2 assessing more detailed sub-divisions of the hippocampal formation; and 3 testing whether significant APOE-hippocampal associations are independent of generalised brain atrophy.

  8. Berberine prevents nigrostriatal dopaminergic neuronal loss and suppresses hippocampal apoptosis in mice with Parkinson's disease.

    Science.gov (United States)

    Kim, Mia; Cho, Ki-Ho; Shin, Mal-Soon; Lee, Jae-Min; Cho, Han-Sam; Kim, Chang-Ju; Shin, Dong-Hoon; Yang, Hyeon Jeong

    2014-04-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of nigral dopaminergic neurons and a reduction in striatal dopaminergic fibers, which result in tremors, rigidity, bradykinesia and gait disturbance. In addition to motor dysfunction, dementia is a widely recognized symptom of patients with PD. Berberine, an isoquinoline alkaloid isolated from Berberis vulgaris L., is known to exert anxiolytic, analgesic, anti-inflammatory, antipsychotic, antidepressant and anti-amnesic effects. In the present study, we investigated the effects of berberine on short-term memory in relation to dopamine depletion and hippocampal neurogenesis using a mouse model of PD, induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/P) treatment. Mice in the berberine-treated groups were orally administered berberine once a day for a total of 5 weeks. Our results revealed that the injection of MPTP/P induced dopaminergic neuronal death in the substantia nigra and fiber loss in the striatum. This resulted in impaired motor balance and coordination, as assessed by the beam walking test. We further demonstrated that MPTP/P-induced apoptosis in the hippocampus deteriorated short-term memory, as shown by the step-down avoidance task. By contrast, neurogenesis in the hippocampal dentate gyrus, which is a compensatory adaptive response to excessive apoptosis, was increased upon PD induction. However, treatment with berberine enhanced motor balance and coordination by preventing dopaminergic neuronal damage. Treatment with berberine also improved short-term memory by inhibiting apoptosis in the hippocampus. Berberine demonstrated maximal potency at 50 mg/kg. Based on these data, treatment with berberine may serve as a potential therapeutic strategy for the alleviation of memory impairment and motor dysfunction in patients with PD.

  9. Test-retest reliability and longitudinal analysis of automated hippocampal subregion volumes in healthy ageing and Alzheimer's disease populations.

    Science.gov (United States)

    Worker, Amanda; Dima, Danai; Combes, Anna; Crum, William R; Streffer, Johannes; Einstein, Steven; Mehta, Mitul A; Barker, Gareth J; C R Williams, Steve; O'daly, Owen

    2018-04-01

    The hippocampal formation is a complex brain structure that is important in cognitive processes such as memory, mood, reward processing and other executive functions. Histological and neuroimaging studies have implicated the hippocampal region in neuropsychiatric disorders as well as in neurodegenerative diseases. This highly plastic limbic region is made up of several subregions that are believed to have different functional roles. Therefore, there is a growing interest in imaging the subregions of the hippocampal formation rather than modelling the hippocampus as a homogenous structure, driving the development of new automated analysis tools. Consequently, there is a pressing need to understand the stability of the measures derived from these new techniques. In this study, an automated hippocampal subregion segmentation pipeline, released as a developmental version of Freesurfer (v6.0), was applied to T1-weighted magnetic resonance imaging (MRI) scans of 22 healthy older participants, scanned on 3 separate occasions and a separate longitudinal dataset of 40 Alzheimer's disease (AD) patients. Test-retest reliability of hippocampal subregion volumes was assessed using the intra-class correlation coefficient (ICC), percentage volume difference and percentage volume overlap (Dice). Sensitivity of the regional estimates to longitudinal change was estimated using linear mixed effects (LME) modelling. The results show that out of the 24 hippocampal subregions, 20 had ICC scores of 0.9 or higher in both samples; these regions include the molecular layer, granule cell layer of the dentate gyrus, CA1, CA3 and the subiculum (ICC > 0.9), whilst the hippocampal fissure and fimbria had lower ICC scores (0.73-0.88). Furthermore, LME analysis of the independent AD dataset demonstrated sensitivity to group and individual differences in the rate of volume change over time in several hippocampal subregions (CA1, molecular layer, CA3, hippocampal tail, fissure and presubiculum

  10. Hippocampal subfield volumes: Age, vascular risk, and correlation with associative memory

    Directory of Open Access Journals (Sweden)

    Yee Lee eShing

    2011-02-01

    Full Text Available Aging and age-related diseases have negative impact on the hippocampus (HC, which is crucial for such age-sensitive functions as memory formation, maintenance, and retrieval. We examined age differences in hippocampal subfield volumes in 10 younger and 19 older adults, and association of those volumes with memory performance in the older participants. We manually measured volumes of HC regions CA1 and CA2 (CA1-2, sectors CA3 and CA4 plus dentate gyrus (CA3-4/DG, subiculum and the entorhinal cortex using a contrast-optimized high-resolution PD-weighted MRI sequence. Although, as in previous reports, the volume of one region (CA1-2 was larger in the young, the difference was due to the presence of hypertensive subjects among the older adults. Among older participants, increased false alarm (FA rate in an associative recognition memory task was linked to reduced CA3-4/DG volume. We discuss the role of the dentate gyrus in pattern separation and the formation of discrete memory representations.

  11. Amygdalar, hippocampal, and thalamic volumes in youth at high risk for development of bipolar disorder.

    Science.gov (United States)

    Karchemskiy, Asya; Garrett, Amy; Howe, Meghan; Adleman, Nancy; Simeonova, Diana I; Alegria, Dylan; Reiss, Allan; Chang, Kiki

    2011-12-30

    Children of parents with bipolar disorder (BD), especially those with attention deficit hyperactivity disorder (ADHD) and symptoms of depression or mania, are at significantly high risk for developing BD. As we have previously shown amygdalar reductions in pediatric BD, the current study examined amygdalar volumes in offspring of parents (BD offspring) who have not yet developed a full manic episode. Youth participating in the study included 22 BD offspring and 22 healthy controls of comparable age, gender, handedness, and IQ. Subjects had no history of a manic episode, but met criteria for ADHD and moderate mood symptoms. MRI was performed on a 3T GE scanner, using a 3D volumetric spoiled gradient echo series. Amygdalae were manually traced using BrainImage Java software on positionally normalized brain stacks. Bipolar offspring had similar amygdalar volumes compared to the control group. Exploratory analyses yielded no differences in hippocampal or thalamic volumes. Bipolar offspring do not show decreased amygdalar volume, possibly because these abnormalities occur after more prolonged illness rather than as a preexisting risk factor. Longitudinal studies are needed to determine whether amygdalar volumes change during and after the development of BD. 2011 Elsevier Ireland Ltd. All rights reserved.

  12. DPP6 Loss Impacts Hippocampal Synaptic Development and Induces Behavioral Impairments in Recognition, Learning and Memory

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    Lin Lin

    2018-03-01

    Full Text Available DPP6 is well known as an auxiliary subunit of Kv4-containing, A-type K+ channels which regulate dendritic excitability in hippocampal CA1 pyramidal neurons. We have recently reported, however, a novel role for DPP6 in regulating dendritic filopodia formation and stability, affecting synaptic development and function. These results are notable considering recent clinical findings associating DPP6 with neurodevelopmental and intellectual disorders. Here we assessed the behavioral consequences of DPP6 loss. We found that DPP6 knockout (DPP6-KO mice are impaired in hippocampus-dependent learning and memory. Results from the Morris water maze and T-maze tasks showed that DPP6-KO mice exhibit slower learning and reduced memory performance. DPP6 mouse brain weight is reduced throughout development compared with WT, and in vitro imaging results indicated that DPP6 loss affects synaptic structure and motility. Taken together, these results show impaired synaptic development along with spatial learning and memory deficiencies in DPP6-KO mice.

  13. Relationship between Interleukin-6 gene polymorphism and hippocampal volume in antipsychotic-naïve schizophrenia: evidence for differential susceptibility?

    Directory of Open Access Journals (Sweden)

    Sunil Vasu Kalmady

    Full Text Available Various lines of evidence including epidemiological, genetic and foetal pathogenetic models suggest a compelling role for Interleukin-6 (IL-6 in the pathogenesis of schizophrenia. IL-6 mediated inflammatory response triggered by maternal infection or stress induces disruption of prenatal hippocampal development which might contribute towards psychopathology during adulthood. There is a substantial lack of knowledge on how genetic predisposition to elevated IL-6 expression effects hippocampal structure in schizophrenia patients. In this first-time study, we evaluated the relationship between functional polymorphism rs1800795 of IL-6 and hippocampal gray matter volume in antipsychotic-naïve schizophrenia patients in comparison with healthy controls.We examined antipsychotic-naïve schizophrenia patients [N = 28] in comparison with healthy controls [N = 37] group matched on age, sex and handedness. Using 3 Tesla - MRI, bilateral hippocampi were manually segmented by blinded raters with good inter-rater reliability using a valid method. Additionally, Voxel-based Morphometry (VBM analysis was performed using hippocampal mask. The IL-6 level was measured in blood plasma using ELISA technique. SNP rs1800795 was genotyped using PCR and DNA sequencing. Psychotic symptoms were assessed using Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms.Schizophrenia patients had significantly deficient left and right hippocampal volumes after controlling for the potential confounding effects of age, sex and total brain volume. Plasma IL-6 levels were significantly higher in patients than controls. There was a significant diagnosis by rs1800795 genotype interaction involving both right and left hippocampal volumes. Interestingly, this effect was significant only in men but not in women.Our first time observations suggest a significant relationship between IL-6 rs1800795 and reduced hippocampal volume in antipsychotic

  14. Partial volume effect-corrected FDG PET and grey matter volume loss in patients with mild Alzheimer's disease

    International Nuclear Information System (INIS)

    Samuraki, Miharu; Yanase, Daisuke; Yamada, Masahito; Matsunari, Ichiro; Chen, Wei-Ping; Yajima, Kazuyoshi; Fujikawa, Akihiko; Takeda, Nozomi; Nishimura, Shintaro; Matsuda, Hiroshi

    2007-01-01

    Although 18 F-fluorodeoxyglucose (FDG) PET is an established imaging technique to assess brain glucose utilisation, accurate measurement of tracer concentration is confounded by the presence of partial volume effect (PVE) due to the limited spatial resolution of PET, which is particularly true in atrophic brains such as those encountered in patients with Alzheimer's disease (AD). Our aim was to investigate the effects of PVE correction on FDG PET in conjunction with voxel-based morphometry (VBM) in patients with mild AD. Thirty-nine AD patients and 73 controls underwent FDG PET and MRI. The PVE-corrected grey matter PET images were obtained using an MRI-based three-compartment method. Additionally, the results of PET were compared with grey matter loss detected by VBM. Before PVE correction, reduced FDG uptake was observed in posterior cingulate gyri (PCG) and parieto-temporal lobes (PTL) in AD patients, which persisted after PVE correction. Notably, PVE correction revealed relatively preserved FDG uptake in hippocampal areas, despite the grey matter loss in medial temporal lobe (MTL) revealed by VBM. FDG uptake in PCG and PTL is reduced in AD regardless of whether or not PVE correction is applied, supporting the notion that the reduced FDG uptake in these areas is not the result of atrophy. Furthermore, FDG uptake by grey matter tissue in the MTL, including hippocampal areas, is relatively preserved, suggesting that compensatory mechanisms may play a role in patients with mild AD. (orig.)

  15. The influence of negative life events on hippocampal and amygdala volumes in old age: a life-course perspective

    NARCIS (Netherlands)

    Gerritsen, L.; Kalpouzos, G.; Westman, E.; Simmons, A.; Wahlund, L.O.; Backman, L.; Fratiglioni, L.; Wang, H.X.

    2015-01-01

    Background. Psychosocial stress has been related to changes in the nervous system, with both adaptive and maladaptive consequences. The aim of this study was to examine the relationship of negative events experienced throughout the entire lifespan and hippocampal and amygdala volumes in older

  16. Effects of Erythropoietin on Hippocampal Volume and Memory in Mood Disorders

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla Woznica; Vinberg, Maj; Macoveanu, Julian

    2015-01-01

    study assessed the neuroanatomical basis for these effects. METHODS: Patients with TRD who were moderately depressed or BD in partial remission were randomized to 8 weekly EPO (40,000 IU) or saline infusions in a double-blind, parallel-group design. Patients underwent magnetic resonance imaging, memory...... with FMRIB Software Library tools. Memory change was analyzed with repeated-measures analysis of covariance adjusted for depression symptoms, diagnosis, age, and gender. RESULTS: Eighty-four patients were randomized; 1 patient withdrew and data collection was incomplete for 14 patients; data were thus...... analyzed for 69 patients (EPO: n = 35, saline: n = 34). Compared with saline, EPO was associated with mood-independent memory improvement and reversal of brain matter loss in the left hippocampal cornu ammonis 1 to cornu ammonis 3 and subiculum. Using the entire sample, memory improvement was associated...

  17. Amount of lifetime video gaming is positively associated with entorhinal, hippocampal and occipital volume.

    Science.gov (United States)

    Kühn, S; Gallinat, J

    2014-07-01

    Playing video games is a popular leisure activity among children and adults, and may therefore potentially influence brain structure. We have previously shown a positive association between probability of gray matter (GM) volume in the ventral striatum and frequent video gaming in adolescence. Here we set out to investigate structural correlates of video gaming in adulthood, as the effects observed in adolescents may reflect only a fraction of the potential neural long-term effects seen in adults. On magnetic resonance imaging (MRI) scans of 62 male adults, we computed voxel-based morphometry to explore the correlation of GM with the lifetime amount of video gaming (termed joystick years). We found a significant positive association between GM in bilateral parahippocamal region (entorhinal cortex) and left occipital cortex/inferior parietal lobe and joystick years (Pvideo game genres played, such as logic/puzzle games and platform games contributing positively, and action-based role-playing games contributing negatively. Furthermore, joystick years were positively correlated with hippocampus volume. The association of lifetime amount of video game playing with bilateral entorhinal cortex, hippocampal and occipital GM volume could reflect adaptive neural plasticity related to navigation and visual attention.

  18. Cortisol and Hippocampal Volume as Predictors of Active Suicidal Behavior in Major Depressive Disorder: Case Report

    Directory of Open Access Journals (Sweden)

    Theodor Moica

    2016-12-01

    Full Text Available Background: Suicide is frequently encountered in patients suffering from major depressive disorder (MDD. Since only a third of treated depressed patients are able to achieve remission, in the last few years, new theories have been proposed to better understand the mechanism of this illness. Our paper analyzes the interrelation between cortisol as a marker of neuroendocrine theory as a response to stress, and hippocampal volume subfields in depression as a marker of neurogenesis and neuroplasticity theory. Case Report: Here we present the case of a 52-year-old male patient with known history of MDD, who died as a result of completed suicide by hanging. The patient had been recently discharged from a psychiatric clinic, after being hospitalized for a major depressive episode (MDE. The result of the autopsy, medical records, laboratory analysis and a magnetic resonance image (MRI of the patient were analyzed. Both the right and left volumes of the hippocampus were found to be smaller when compared to normal values reported in the literature. The morning level of cortisol was higher than the normal value. Conclusion: In a depressed patient with an acute stressful event, high levels of cortisol associated with decreased volume of the hippocampus could represent predictors for an increased risk of suicide

  19. The SEMA5A gene is associated with hippocampal volume, and their interaction is associated with performance on Raven's Progressive Matrices.

    Science.gov (United States)

    Zhu, Bi; Chen, Chuansheng; Xue, Gui; Moyzis, Robert K; Dong, Qi; Chen, Chunhui; Li, Jin; He, Qinghua; Lei, Xuemei; Wang, Yunxin; Lin, Chongde

    2014-03-01

    The Allen Brain Atlas shows that the semaphorin 5A (SEMA5A) gene, which encodes an important protein for neurogenesis and neuronal apoptosis, is predominantly expressed in the human hippocampus. Structural and functional neuroimaging studies have further shown that the hippocampus plays an important role in the performance on Raven's Progressive Matrices (RPM), a measure of reasoning ability and general fluid intelligence. Thus far, however, no study has examined the relationships between the SEMA5A gene polymorphism, hippocampal volume, and RPM performance. The current study collected both structural MRI, genetic, and behavioral data in 329 healthy Chinese adults, and examined associations between SEMA5A variants, hippocampal volume, and performance on RAPM (the advanced form of RPM). After controlling for intracranial volume (ICV), sex, and age, SEMA5A genetic polymorphism at the SNP rs42352 had the strongest association with hippocampal volume (p=0.00000552 and 0.000103 for right and left hippocampal volumes, respectively), with TT homozygotes having higher hippocampal volume than the other genotypes. Furthermore, there was a high correlation between right hippocampal volume and RAPM performance (r=0.42, p=0.0000509) for SEMA5A rs42352 TT homozygotes. This study provides the first evidence for the involvement of the SEMA5A gene in hippocampal structure and their interaction on RAPM performance. Future studies of the hippocampus-RPM associations should consider genetic factors as potential moderators. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Microstructural white matter alterations and hippocampal volumes are associated with cognitive deficits in craniopharyngioma.

    Science.gov (United States)

    Fjalldal, S; Follin, C; Svärd, D; Rylander, L; Gabery, S; Petersén, Å; van Westen, D; Sundgren, P C; Björkman-Burtscher, I M; Lätt, J; Ekman, B; Johanson, A; Erfurth, E M

    2018-06-01

    Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown. To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP. A cross-sectional study with a median follow-up time of 22 (6-49) years after operation. The South Medical Region of Sweden (2.5 million inhabitants). Included were 41 patients (24 women, ≥17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HL was found in 23 patients. Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry. Right uncinate fasciculus was significantly altered ( P  ≤ 0.01). Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge ( P  = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory. A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP. © 2018 The authors.

  1. Lack of hippocampal volume differences in primary insomnia and good sleeper controls: an MRI volumetric study at 3 Tesla.

    Science.gov (United States)

    Winkelman, John W; Benson, Kathleen L; Buxton, Orfeu M; Lyoo, In Kyoon; Yoon, Sujung; O'Connor, Shawn; Renshaw, Perry F

    2010-06-01

    A recent pilot study reported that hippocampal volume (HV) was reduced in patients with primary insomnia (PI) relative to normal sleepers. Loss of HV in PI might be due to chronic hyperarousal and/or chronic sleep debt. The aim of this study was to replicate the earlier pilot report while employing a larger sample, more rigorous screening criteria, and objective sleep data. This cross-sectional design included community recruits meeting DSM-IV criteria for PI (n=20, 10 males, mean age 39.3+/-8.7) or good sleeper controls (n=15, 9 males, mean age 38.8+/-5.3). All subjects were unmedicated and rigorously screened to exclude comorbid psychiatric and medical illness. PI subjects underwent overnight polysomnography to screen for sleep-related breathing and movement disorders. HV and total brain volumes were derived by MRI employing a Siemens/Trio scanner operating at 3 Tesla. Data also included 2 weeks of sleep diaries and wrist actigraphy. Mean HV was 4322.0+/-299.7 mm(3) for the good sleeper controls and 4601.55+/-537.4 mm(3) for the PI group. The dependent variable, HV, was analyzed by ANCOVA. Main effects were diagnosis and gender; whole brain volume served as the covariate. Although the overall model was significant (F=6.3, p=0.001), the main effects of diagnosis (F=2.14) and gender (F=0.04) were not significant. The covariate of whole brain volume was significant (F=5.74, p=0.023) as was the interaction of diagnosis with gender (F=10.22, p=0.003), with male insomniacs having larger HVs than male controls. This study did not replicate a previously published report of HV loss in primary insomnia. Differences between our finding and the previous report might be due to sample composition and method of MRI assessment. Furthermore, we demonstrated no objective differences between the controls and PIs in actigraphic measures of sleep maintenance. Within the PIs, however, actigraphic measures of poor sleep maintenance were associated with smaller HV. Copyright 2010

  2. Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

    International Nuclear Information System (INIS)

    Lee, Katrina; Lenards, Nishele; Holson, Janice

    2016-01-01

    The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.

  3. Nox-2-mediated phenotype loss of hippocampal parvalbumin interneurons might contribute to postoperative cognitive decline in aging mice

    Directory of Open Access Journals (Sweden)

    lili qiu

    2016-10-01

    Full Text Available Postoperative cognitive decline (POCD is a common complication following anesthesia and surgery, especially in elderly patients; however, the precise mechanisms of POCD remain unclear. Here, we investigated whether nicotinamide adenine dinucleotide phosphate (NADPH oxidase mediated-abnormalities in parvalbumin (PV interneurons play an important role in the pathophysiology of POCD. The animal model was established using isoflurane anesthesia and exploratory laparotomy in sixteen-month-old male C57BL/6 mice. For interventional experiments, mice were chronically treated with the NADPH oxidase inhibitor apocynin (APO. Open field and fear conditioning behavioral tests were performed on day 6 and 7 post-surgery, respectively. In a separate experiment, brain tissue was harvested and subjected to biochemical analysis. Primary hippocampal neurons challenged with lipopolysaccharide in vitro were used to investigate the mechanisms underlying the oxidative stress-induced abnormalities in PV interneurons. Our results showed that anesthesia and surgery induced significant hippocampus-dependent memory impairment, which was accompanied by PV interneuron phenotype loss and increased expression of interleukin-1β, markers of oxidative stress, and NADPH oxidase 2 (Nox2 in the hippocampus. In addition, lipopolysaccharide exposure increased Nox2 level and decreased the expression of PV and the number of excitatory synapses onto PV interneurons in the primary hippocampal neurons. Notably, treatment with APO reversed these abnormalities. Our study suggests that Nox2-derived ROS production triggers, at least in part, anesthesia- and surgery-induced hippocampal PV interneuron phenotype loss and consequent cognitive impairment in aging mice.

  4. Pathological changes in hippocampal neuronal circuits underlie age-associated neurodegeneration and memory loss: positive clue toward SAD.

    Science.gov (United States)

    Moorthi, P; Premkumar, P; Priyanka, R; Jayachandran, K S; Anusuyadevi, M

    2015-08-20

    Among vertebrates hippocampus forms the major component of the brain in consolidating information from short-term memory to long-term memory. Aging is considered as the major risk factor for memory impairment in sporadic Alzheimer's disease (SAD) like pathology. Present study thus aims at investigating whether age-specific degeneration of neuronal-circuits in hippocampal formation (neural-layout of Subiculum-hippocampus proper-dentate gyrus (DG)-entorhinal cortex (EC)) results in cognitive impairment. Furthermore, the neuroprotective effect of Resveratrol (RSV) was attempted to study in the formation of hippocampal neuronal-circuits. Radial-Arm-Maze was conducted to evaluate hippocampal-dependent spatial and learning memory in control and experimental rats. Nissl staining of frontal cortex (FC), subiculum, hippocampal-proper (CA1→CA2→CA3→CA4), DG, amygdala, cerebellum, thalamus, hypothalamus, layers of temporal and parietal lobe of the neocortex were examined for pathological changes in young and aged wistar rats, with and without RSV. Hippocampal trisynaptic circuit (EC layerII→DG→CA3→CA1) forming new memory and monosynaptic circuit (EC→CA1) that strengthen old memories were found disturbed in aged rats. Loss of Granular neuron observed in DG and polymorphic cells of CA4 can lead to decreased mossy fibers disturbing neural-transmission (CA4→CA3) in perforant pathway. Further, intensity of nissl granules (stratum lacunosum moleculare (SLM)-SR-SO) of CA3 pyramidal neurons was decreased, disturbing the communication in schaffer collaterals (CA3-CA1) during aging. We also noticed disarranged neuronal cell layer in Subiculum (presubiculum (PrS)-parasubiculum (PaS)), interfering output from hippocampus to prefrontal cortex (PFC), EC, hypothalamus, and amygdala that may result in interruption of thought processes. We conclude from our observations that poor memory performance of aged rats as evidenced through radial arm maze (RAM) analysis was due to the

  5. Hippocampal volume MRI and 1H-MRS study in chronic alcohol dependent patients

    International Nuclear Information System (INIS)

    Miao Huanmin; Chen Jun; Zha Yunfei; Zhang Yu; Liu Changsheng; Pan Ewu

    2010-01-01

    Objective: To observe the changes of the bilateral hippocampal volume (BHV) and 1 H- MRS appearance of chronic alcohol dependent (CAD) patients and to provide quantitative information for the clinical diagnosis of CAD. Methods: The conventional MR imaging including three-dimensional fast spoiled gradient recalled echo (3D-FSPGR) and 1 H-MRS were performed on 16 patients with CAD (CAD group) and 18 cases of volunteer (control group). The BHV were measured in both groups and the standardized BHV in CAD group and control group were compared. 1 H-MRS metabolites including N-acetylaspartate (NAA), Choline compounds (Cho), Creatine (Cr), and myoinositol (mI) of the bilateral cephalic hippocampus were acquired. The ratios of Cho/Ci, Cho/NAA, NAA/Cr and mI/Ci within the bilateral cephalic hippocampus of the two groups were compared. The t test was used to compare the BHV and the ratios of 1 H-MRS in the bilateral cephalic hippocampus between the two groups. Results: In CAD group, the left and the right hippocampal volume were 1.881±0.292, 2.139±0.328 respectively while they were 2.106±0.245 and 2.267±0.271 respectively in the control group. The BHV had no significant difference between the left and the right in either the CAD group or the control group (t=0.232, 0.147 respectively, P>0.05). The BHV had no significant difference between the CAD group and control group (t=0.424, 0.131 respectively, P>0.05). The Cho/Cr and NAA/Cr in the right cephalic hippocampus of the CAD group were 1.225±0.210 and 1.145±0.034 respectively, while they were 1.429±0.286, 1.612±0.444 respectively in the control group (t=0.321, 0.408, P 1 H-MRS could potentially provide early diagnostic evidence for CAD patients before the onset of cerebral morphological changes. (authors)

  6. Validation of hippocampal volumes measured using a manual method and two automated methods (FreeSurfer and IBASPM) in chronic major depressive disorder

    Energy Technology Data Exchange (ETDEWEB)

    Tae, Woo Suk; Lee, Kang Uk; Nam, Eui-Cheol; Kim, Keun Woo [Kangwon National University College of Medicine, Neuroscience Research Institute, Kangwon (Korea); Kim, Sam Soo [Kangwon National University College of Medicine, Neuroscience Research Institute, Kangwon (Korea); Kangwon National University Hospital, Department of Radiology, Kangwon-do (Korea)

    2008-07-15

    To validate the usefulness of the packages available for automated hippocampal volumetry, we measured hippocampal volumes using one manual and two recently developed automated volumetric methods. The study included T1-weighted magnetic resonance imaging (MRI) of 21 patients with chronic major depressive disorder (MDD) and 20 normal controls. Using coronal turbo field echo (TFE) MRI with a slice thickness of 1.3 mm, the hippocampal volumes were measured using three methods: manual volumetry, surface-based parcellation using FreeSurfer, and individual atlas-based volumetry using IBASPM. In addition, the intracranial cavity volume (ICV) was measured manually. The absolute left hippocampal volume of the patients with MDD measured using all three methods was significantly smaller than the left hippocampal volume of the normal controls (manual P=0.029, FreeSurfer P=0.035, IBASPM P=0.018). After controlling for the ICV, except for the right hippocampal volume measured using FreeSurfer, both measured hippocampal volumes of the patients with MDD were significantly smaller than the measured hippocampal volumes of the normal controls (right manual P=0.019, IBASPM P=0.012; left manual P=0.003, FreeSurfer P=0.010, IBASPM P=0.002). In the intrarater reliability test, the intraclass correlation coefficients (ICCs) were all excellent (manual right 0.947, left 0.934; FreeSurfer right 1.000, left 1.000; IBASPM right 1.000, left 1.000). In the test of agreement between the volumetric methods, the ICCs were right 0.846 and left 0.848 (manual and FreeSurfer), and right 0.654 and left 0.717 (manual and IBASPM). The automated hippocampal volumetric methods showed good agreement with manual hippocampal volumetry, but the volume measured using FreeSurfer was 35% larger and the agreement was questionable with IBASPM. Although the automated methods could detect hippocampal atrophy in the patients with MDD, the results indicate that manual hippocampal volumetry is still the gold standard

  7. Validation of hippocampal volumes measured using a manual method and two automated methods (FreeSurfer and IBASPM) in chronic major depressive disorder

    International Nuclear Information System (INIS)

    Tae, Woo Suk; Lee, Kang Uk; Nam, Eui-Cheol; Kim, Keun Woo; Kim, Sam Soo

    2008-01-01

    To validate the usefulness of the packages available for automated hippocampal volumetry, we measured hippocampal volumes using one manual and two recently developed automated volumetric methods. The study included T1-weighted magnetic resonance imaging (MRI) of 21 patients with chronic major depressive disorder (MDD) and 20 normal controls. Using coronal turbo field echo (TFE) MRI with a slice thickness of 1.3 mm, the hippocampal volumes were measured using three methods: manual volumetry, surface-based parcellation using FreeSurfer, and individual atlas-based volumetry using IBASPM. In addition, the intracranial cavity volume (ICV) was measured manually. The absolute left hippocampal volume of the patients with MDD measured using all three methods was significantly smaller than the left hippocampal volume of the normal controls (manual P=0.029, FreeSurfer P=0.035, IBASPM P=0.018). After controlling for the ICV, except for the right hippocampal volume measured using FreeSurfer, both measured hippocampal volumes of the patients with MDD were significantly smaller than the measured hippocampal volumes of the normal controls (right manual P=0.019, IBASPM P=0.012; left manual P=0.003, FreeSurfer P=0.010, IBASPM P=0.002). In the intrarater reliability test, the intraclass correlation coefficients (ICCs) were all excellent (manual right 0.947, left 0.934; FreeSurfer right 1.000, left 1.000; IBASPM right 1.000, left 1.000). In the test of agreement between the volumetric methods, the ICCs were right 0.846 and left 0.848 (manual and FreeSurfer), and right 0.654 and left 0.717 (manual and IBASPM). The automated hippocampal volumetric methods showed good agreement with manual hippocampal volumetry, but the volume measured using FreeSurfer was 35% larger and the agreement was questionable with IBASPM. Although the automated methods could detect hippocampal atrophy in the patients with MDD, the results indicate that manual hippocampal volumetry is still the gold standard

  8. Preoperative MR imaging-based volume measurements of the hippocampal formation and anterior temporal lobe in epileptic patients

    International Nuclear Information System (INIS)

    Jack, C.R.; Sharbrough, F.W.; Twomey, C.; Zinsmeister, A.R.; Cascino, G.D.; Hirschorn, K.A.; Marsh, W.R.

    1989-01-01

    MR-based volume measurements of the anterior temporal lobe and hippocampal formation were performed in 36 patients who subsequently underwent surgery for medically refractory temporal lobe epilepsy. Seizure lateralization was based on standard clinical and electroencephalographic criteria. No surgical pathologic specimens contained structural lesions; epilepsy in these patients was therefore presumably due to mesial sclerosis. The right-minus-left hippocampal formation volume difference was greater than 0 in all 20 patients operated on the left side and less than 0 in all 16 patients operated on the right side. This difference completely separated the two surgical groups, while the same measurement in a group of 35 normal controls fell between the two surgical groups. Measurements of the anterior temporal to be showed a similar trend but incompletely separated controls, right- and left-sided epileptics. These results suggest that in a significant percentage of cases, MR-based volume measurements correctly identify the unilateral hippocampal atrophy that is known to occur in cases of mesial temporal sclerosis

  9. Correlation between Peripheral Levels of Brain-Derived Neurotrophic Factor and Hippocampal Volume in Children and Adolescents with Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Tatiana Lauxen Peruzzolo

    2015-01-01

    Full Text Available Pediatric bipolar disorder (PBD is a serious mental disorder that affects the development and emotional growth of affected patients. The brain derived neurotrophic factor (BDNF is recognized as one of the possible markers of the framework and its evolution. Abnormalities in BDNF signaling in the hippocampus could explain the cognitive decline seen in patients with TB. Our aim with this study was to evaluate possible changes in hippocampal volume in children and adolescents with BD and associate them to serum BDNF. Subjects included 30 patients aged seven to seventeen years from the ProCAB (Program for Children and Adolescents with Bipolar Disorder. We observed mean right and left hippocampal volumes of 41910.55 and 41747.96 mm3, respectively. No statistically significant correlations between peripheral BDNF levels and hippocampal volumes were found. We believe that the lack of correlation observed in this study is due to the short time of evolution of BD in children and adolescents. Besides studies with larger sample sizes to confirm the present findings and longitudinal assessments, addressing brain development versus a control group and including drug-naive patients in different mood states may help clarify the role of BDNF in the brain changes consequent upon BD.

  10. Hippocampal volume and auditory attention on a verbal memory task with adult survivors of pediatric brain tumor.

    Science.gov (United States)

    Jayakar, Reema; King, Tricia Z; Morris, Robin; Na, Sabrina

    2015-03-01

    We examined the nature of verbal memory deficits and the possible hippocampal underpinnings in long-term adult survivors of childhood brain tumor. 35 survivors (M = 24.10 ± 4.93 years at testing; 54% female), on average 15 years post-diagnosis, and 59 typically developing adults (M = 22.40 ± 4.35 years, 54% female) participated. Automated FMRIB Software Library (FSL) tools were used to measure hippocampal, putamen, and whole brain volumes. The California Verbal Learning Test-Second Edition (CVLT-II) was used to assess verbal memory. Hippocampal, F(1, 91) = 4.06, ηp² = .04; putamen, F(1, 91) = 11.18, ηp² = .11; and whole brain, F(1, 92) = 18.51, ηp² = .17, volumes were significantly lower for survivors than controls (p memory indices of auditory attention list span (Trial 1: F(1, 92) = 12.70, η² = .12) and final list learning (Trial 5: F(1, 92) = 6.01, η² = .06) were significantly lower for survivors (p attention, but none of the other CVLT-II indices. Secondary analyses for the effect of treatment factors are presented. Volumetric differences between survivors and controls exist for the whole brain and for subcortical structures on average 15 years post-diagnosis. Treatment factors seem to have a unique effect on subcortical structures. Memory differences between survivors and controls are largely contingent upon auditory attention list span. Only hippocampal volume is associated with the auditory attention list span component of verbal memory. These findings are particularly robust for survivors treated with radiation. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  11. Medial prefrontal-hippocampal connectivity during emotional memory encoding predicts individual differences in the loss of associative memory specificity.

    Science.gov (United States)

    Berkers, Ruud M W J; Klumpers, Floris; Fernández, Guillén

    2016-10-01

    Emotionally charged items are often remembered better, whereas a paradoxical loss of specificity is found for associative emotional information (specific memory). The balance between specific and generalized emotional memories appears to show large individual differences, potentially related to differences in (the risk for) affective disorders that are characterized by 'overgeneralized' emotional memories. Here, we investigate the neural underpinnings of individual differences in emotional associative memory. A large group of healthy male participants were scanned while encoding associations of face-photographs and written occupational identities that were of either neutral ('driver') or negative ('murderer') valence. Subsequently, memory was tested by prompting participants to retrieve the occupational identities corresponding to each face. Whereas in both valence categories a similar amount of faces was labeled correctly with 'neutral' and 'negative' identities, (gist memory), specific associations were found to be less accurately remembered when the occupational identity was negative compared to neutral (specific memory). This pattern of results suggests reduced memory specificity for associations containing a negatively valenced component. The encoding of these negative associations was paired with a selective increase in medial prefrontal cortex activity and medial prefrontal-hippocampal connectivity. Individual differences in valence-specific neural connectivity were predictive of valence-specific reduction of memory specificity. The relationship between loss of emotional memory specificity and medial prefrontal-hippocampal connectivity is in line with the hypothesized role of a medial prefrontal-hippocampal circuit in regulating memory specificity, and warrants further investigations in individuals displaying 'overgeneralized' emotional memories. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Maternal vitamin C deficiency does not reduce hippocampal volume and beta-tubulin III intensity in prenatal Guinea pigs

    DEFF Research Database (Denmark)

    Hansen, Stine Normann; Schjoldager, Janne Gram; Paidi, Maya Devi

    2016-01-01

    Marginal vitamin C (vitC) deficiency affects 5% to 10% of adults including subpopulations such as pregnant women and newborns. Animal studies link vitC deficiency to deleterious effects on the developing brain, but exactly how the brain adapts to vitC deficiency and the mechanisms behind...... the observed deficits remain largely unknown. We hypothesized that vitC deficiency in utero may lead to a decreased neuronal maturation and increased cellular death giving rise to alterations of the hippocampal morphology in a guinea pig model. Brains from prenatal guinea pig pups (n = 9-10 in each group......) subjected to either a sufficient (918 mg vitC/kg feed) or deficient (100 mg vitC/kg feed) maternal dietary regimen were assessed with regards to hippocampal volume and beta-tubulin isotype III staining intensity at 2 gestational time points (45 and 56). We found a distinct differential regional growth...

  13. Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Katrina, E-mail: Trinabena23@gmail.com; Lenards, Nishele; Holson, Janice

    2016-04-01

    The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.

  14. Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study.

    Science.gov (United States)

    Lee, Katrina; Lenards, Nishele; Holson, Janice

    2016-01-01

    The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient׳s neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient׳s data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  15. Major depressive episodes over the course of 7 years and hippocampal subfield volumes at 7 tesla MRI: the PREDICT-MR study.

    Science.gov (United States)

    Wisse, L E M; Biessels, G J; Stegenga, B T; Kooistra, M; van der Veen, P H; Zwanenburg, J J M; van der Graaf, Y; Geerlings, M I

    2015-04-01

    Smaller hippocampal volumes have been associated with major depressive disorder (MDD). The hippocampus consists of several subfields that may be differentially related to MDD. We investigated the association of occurrence of major depressive episodes (MDEs), assessed five times over seven years, with hippocampal subfield and entorhinal cortex volumes at 7 tesla MRI. In this prospective study of randomly selected general practice attendees, MDEs according to DSM-IV-R criteria were assessed at baseline and after 6, 12, 39 and 84 months follow-up. At the last follow-up, a T2 (0.7 mm(3)) 7 tesla MRI scan was obtained in 47 participants (60±10 years). The subiculum, cornu ammonis (CA) 1 to 3, dentate gyrus&CA4 and entorhinal cortex volumes were manually segmented according a published protocol. Of the 47 participants, 13 had one MDE and 5 had multiple MDEs. ANCOVAs, adjusted for age, sex, education and intracranial volume, revealed no significant differences in hippocampal subfield or entorhinal cortex volumes between participants with and without an MDE in the preceding 84 months. Multiple episodes were associated with smaller subiculum volumes (B=-0.03 mL/episode; 95% CI -0.06; -0.003), but not with the other hippocampal subfield volumes, entorhinal cortex, or total hippocampal volume. A limitation of this study is the small sample size which makes replication necessary. In this exploratory study, we found that an increasing number of major depressive episodes was associated with smaller subiculum volumes in middle-aged and older persons, but not with smaller volumes in other hippocampal subfields or the entorhinal cortex. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. A cross-sectional study of hormone treatment and hippocampal volume in postmenopausal women: evidence for a limited window of opportunity.

    Science.gov (United States)

    Erickson, Kirk I; Voss, Michelle W; Prakash, Ruchika S; Chaddock, Laura; Kramer, Arthur F

    2010-01-01

    The influence of hormone treatment on brain and cognition in postmenopausal women has been a controversial topic. Contradictory patterns of results have prompted speculation that a critical period, or limited window of opportunity, exists for hormone treatment to protect against neurocognitive. In this cross-sectional study of 102 postmenopausal women, we examined whether hippocampal, amygdala, or caudate nucleus volumes and spatial memory performance were related to the interval between menopause and the initiation of hormone treatment. Consistent with a critical period hypothesis, we found that shorter intervals between menopause and the initiation of hormone treatment were associated with larger hippocampal volumes compared with longer intervals between menopause and treatment initiation. Initiation of hormone treatment at the time of menopause was also associated with larger hippocampal volumes when compared with peers who had never used hormone treatment. Furthermore, these effects were independent from potentially confounding factors such as age, years of education, the duration of hormone treatment, current or past use of hormone therapy, the type of therapy, and age at menopause. Larger hippocampal volumes in women who initiated hormone treatment at the time of menopause failed to translate to improved spatial memory performance. There was no relationship between timing of hormone initiation, spatial memory performance, and amygdala or caudate nucleus volume. Our results provide support for a limited window of opportunity for hormone treatment to influence hippocampal volume, yet the degree to which these effects translate to improved memory performance is uncertain. Copyright 2009 APA, all rights reserved.

  17. Loss of CDKL5 in Glutamatergic Neurons Disrupts Hippocampal Microcircuitry and Leads to Memory Impairment in Mice.

    Science.gov (United States)

    Tang, Sheng; Wang, I-Ting Judy; Yue, Cuiyong; Takano, Hajime; Terzic, Barbara; Pance, Katarina; Lee, Jun Y; Cui, Yue; Coulter, Douglas A; Zhou, Zhaolan

    2017-08-02

    Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a neurodevelopmental disorder characterized by epileptic seizures, severe intellectual disability, and autistic features. Mice lacking CDKL5 display multiple behavioral abnormalities reminiscent of the disorder, but the cellular origins of these phenotypes remain unclear. Here, we find that ablating CDKL5 expression specifically from forebrain glutamatergic neurons impairs hippocampal-dependent memory in male conditional knock-out mice. Hippocampal pyramidal neurons lacking CDKL5 show decreased dendritic complexity but a trend toward increased spine density. This morphological change is accompanied by an increase in the frequency of spontaneous miniature EPSCs and interestingly, miniature IPSCs. Using voltage-sensitive dye imaging to interrogate the evoked response of the CA1 microcircuit, we find that CA1 pyramidal neurons lacking CDKL5 show hyperexcitability in their dendritic domain that is constrained by elevated inhibition in a spatially and temporally distinct manner. These results suggest a novel role for CDKL5 in the regulation of synaptic function and uncover an intriguing microcircuit mechanism underlying impaired learning and memory. SIGNIFICANCE STATEMENT Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a severe neurodevelopmental disorder caused by mutations in the CDKL5 gene. Although Cdkl5 constitutive knock-out mice have recapitulated key aspects of human symptomatology, the cellular origins of CDKL5 deficiency-related phenotypes are unknown. Here, using conditional knock-out mice, we show that hippocampal-dependent learning and memory deficits in CDKL5 deficiency have origins in glutamatergic neurons of the forebrain and that loss of CDKL5 results in the enhancement of synaptic transmission and disruptions in neural circuit dynamics in a spatially and temporally specific manner. Our findings demonstrate that CDKL5 is an important regulator of synaptic function in glutamatergic neurons and

  18. Visit-to-Visit Blood Pressure Variability in Young Adulthood and Hippocampal Volume and Integrity at Middle Age: The CARDIA Study (Coronary Artery Risk Development in Young Adults).

    Science.gov (United States)

    Yano, Yuichiro; Reis, Jared P; Levine, Deborah A; Bryan, R Nick; Viera, Anthony J; Shimbo, Daichi; Tedla, Yacob G; Allen, Norrina B; Schreiner, Pamela J; Bancks, Michael P; Sidney, Stephen; Pletcher, Mark J; Liu, Kiang; Greenland, Philip; Lloyd-Jones, Donald M; Launer, Lenore J

    2017-12-01

    The aims of this study are to assess the relationships of visit-to-visit blood pressure (BP) variability in young adulthood to hippocampal volume and integrity at middle age. We used data over 8 examinations spanning 25 years collected in the CARDIA study (Coronary Artery Risk Development in Young Adults) of black and white adults (age, 18-30 years) started in 1985 to 1986. Visit-to-visit BP variability was defined as by SD BP and average real variability (ARV BP , defined as the absolute differences of BP between successive BP measurements). Hippocampal tissue volume standardized by intracranial volume (%) and integrity assessed by fractional anisotropy were measured by 3-Tesla magnetic resonance imaging at the year-25 examination (n=545; mean age, 51 years; 54% women and 34% African Americans). Mean systolic BP (SBP)/diastolic BP levels were 110/69 mm Hg at year 0 (baseline), 117/73 mm Hg at year 25, and ARV SBP and SD SBP were 7.7 and 7.9 mm Hg, respectively. In multivariable-adjusted linear models, higher ARV SBP was associated with lower hippocampal volume (unstandardized regression coefficient [standard error] with 1-SD higher ARV SBP : -0.006 [0.003]), and higher SD SBP with lower hippocampal fractional anisotropy (-0.02 [0.01]; all P young adulthood may be useful in assessing the potential risk for reductions in hippocampal volume and integrity in midlife. © 2017 American Heart Association, Inc.

  19. Egocentric and allocentric visuospatial working memory in premotor Huntington's disease: A double dissociation with caudate and hippocampal volumes.

    Science.gov (United States)

    Possin, Katherine L; Kim, Hosung; Geschwind, Michael D; Moskowitz, Tacie; Johnson, Erica T; Sha, Sharon J; Apple, Alexandra; Xu, Duan; Miller, Bruce L; Finkbeiner, Steven; Hess, Christopher P; Kramer, Joel H

    2017-07-01

    Our brains represent spatial information in egocentric (self-based) or allocentric (landmark-based) coordinates. Rodent studies have demonstrated a critical role for the caudate in egocentric navigation and the hippocampus in allocentric navigation. We administered tests of egocentric and allocentric working memory to individuals with premotor Huntington's disease (pmHD), which is associated with early caudate nucleus atrophy, and controls. Each test had 80 trials during which subjects were asked to remember 2 locations over 1-sec delays. The only difference between these otherwise identical tests was that locations could only be coded in self-based or landmark-based coordinates. We applied a multiatlas-based segmentation algorithm and computed point-wise Jacobian determinants to measure regional variations in caudate and hippocampal volumes from 3T MRI. As predicted, the pmHD patients were significantly more impaired on egocentric working memory. Only egocentric accuracy correlated with caudate volumes, specifically the dorsolateral caudate head, right more than left, a region that receives dense efferents from dorsolateral prefrontal cortex. In contrast, only allocentric accuracy correlated with hippocampal volumes, specifically intermediate and posterior regions that connect strongly with parahippocampal and posterior parietal cortices. These results indicate that the distinction between egocentric and allocentric navigation applies to working memory. The dorsolateral caudate is important for egocentric working memory, which can explain the disproportionate impairment in pmHD. Allocentric working memory, in contrast, relies on the hippocampus and is relatively spared in pmHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. A pilot study of hippocampal volume and N-acetylaspartate (NAA) as response biomarkers in riluzole-treated patients with GAD.

    Science.gov (United States)

    Abdallah, Chadi G; Coplan, Jeremy D; Jackowski, Andrea; Sato, João R; Mao, Xiangling; Shungu, Dikoma C; Mathew, Sanjay J

    2013-04-01

    Anxiolytic benefit following chronic treatment with the glutamate modulating agent riluzole in patients with generalized anxiety disorder (GAD) was previously associated with differential changes in hippocampal NAA concentrations. Here, we investigated the association between hippocampal volume and hippocampal NAA in the context of riluzole response in GAD. Eighteen medication-free adult patients with GAD received 8-week of open-label riluzole. Ten healthy subjects served as a comparison group. Participants underwent magnetic resonance imaging and spectroscopy at baseline and at the end of Week 8. GAD patients who completed all interventions were classified as remitters (n=7) or non-remitters (n=6), based on final Hamilton Anxiety Rating Scale (HAM-A) scores ≤7. At baseline, GAD patients had a significant reduction in total hippocampal volume compared to healthy subjects (F(1,21)=6.55, p=0.02). This reduction was most pronounced in the remitters, compared to non-remitters and healthy subjects. Delta (final-baseline) hippocampal volume was positively correlated with delta NAA in GAD. This positive association was highly significant in the right hippocampus in GAD [r=0.81, p=0.002], with no significant association in healthy subjects [Fisher r-to-z p=0.017]. Across all GAD patients, delta hippocampal volume was positively associated with improvement in HAM-A (rspearman=0.62, p=0.03). These preliminary findings support hippocampal NAA and volume as neural biomarkers substantially associated with therapeutic response to a glutamatergic drug. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

  1. Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume.

    NARCIS (Netherlands)

    Carmichael, O.; Xie, J.; Fletcher, E.; Singh, B.; DeCarli, C.; Olde Rikkert, M.; et al.,

    2012-01-01

    Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures

  2. Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume

    NARCIS (Netherlands)

    Carmichael, Owen; Xie, Jing; Fletcher, Evan; Singh, Baljeet; Decarli, Charles; A, Saradha; Abdi, Hervé; Abdul Hadi, Normi; Abdulkadir, Ahmed; Abdullah, Afnizanfaizal; Achuthan, Anusha; Adluru, Nagesh; Aggarwal, Namita; Aghajanian, Jania; Agyemang, Alex; Ahdidan, Jamila; Ahmad, Duaa; Ahmed, Shiek; Ahmed, Fareed; Ahmed, Fayeza; Akbarifar, Roshanak; Akhondi-Asl, Alireza; Aksu, Yaman; Alcauter, Sarael; Daniel, Alexander; Alin, Aylin; Alshuft, Hamza; Alvarez-Linera, Juan; Amin-Mansour, Ali; Anderson, Dallas; Anderson, Jeff; Andorn, Anne; Ang, Amma; Angersbach, Steve; Ansarian, Reza; Appaji, Abhishek; Appannah, Arti; Arfanakis, Konstantinos; Armentrout, Steven; Arrighi, Michael; Arumughababu, S. Vethanayaki; Arunagiri, Vidhya; Ashe-McNalley, Cody; Ashford, Wes; Aurelie, Le Page; Avants, Brian; Aviv, Richard; Avula, Ramesh; Richard, Edo; Schmand, Ben

    2012-01-01

    Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures

  3. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment.

    Science.gov (United States)

    Papma, Janne M; Smits, Marion; de Groot, Marius; Mattace Raso, Francesco U; van der Lugt, Aad; Vrooman, Henri A; Niessen, Wiro J; Koudstaal, Peter J; van Swieten, John C; van der Veen, Frederik M; Prins, Niels D

    2017-09-01

    Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. • PCC functioning during episodic memory relates to hippocampal functioning in MCI. • PCC functioning during episodic memory does not relate to hippocampal structure in MCI. • Functional network changes are an important predictor of PCC functioning in MCI.

  4. Stress, depression and hippocampal damage

    Indian Academy of Sciences (India)

    Amongst the prime targets of stress in the brain is the hippocampus, which has high receptor ... effects on different hippocampal subfields (McEwen 1999). ... disorders, and decreases in hippocampal volume have been observed in patients of ...

  5. Transiently increasing cAMP levels selectively in hippocampal excitatory neurons during sleep deprivation prevents memory deficits caused by sleep loss

    NARCIS (Netherlands)

    Havekes, Robbert; Bruinenberg, Vibeke M.; Tudor, Jennifer C.; Ferri, Sarah L.; Baumann, Arnd; Meerlo, Peter; Abel, Ted

    2014-01-01

    The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the

  6. Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder.

    LENUS (Irish Health Repository)

    Frodl, T

    2012-01-01

    Neuroplasticity may have a core role in the pathophysiology of major depressive disorder (MDD), a concept supported by experimental studies that found that excessive cortisol secretion and\\/or excessive production of inflammatory cytokines impairs neuronal plasticity and neurogenesis in the hippocampus. The objective of this study was to examine how changes in the glucocorticoid and inflammatory systems may affect hippocampal volumes in MDD. A multimodal approach with structural neuroimaging of hippocampus and amygdala, measurement of peripheral inflammatory proteins interleukin (IL)-6 and C-reactive protein (CRP), glucocorticoid receptor (GR) mRNA expression, and expression of glucocorticoid-inducible genes (glucocorticoid-inducible genes Leucin Zipper (GILZ) and glucocorticoid-inducible kinase-1 (SGK-1)) was used in 40 patients with MDD and 43 healthy controls (HC). Patients with MDD showed smaller hippocampal volumes and increased inflammatory proteins IL-6 and CRP compared with HC. Childhood maltreatment was associated with increased CRP. Patients with MDD, who had less expression of the glucocorticoid-inducible genes GILZ or SGK-1 had smaller hippocampal volumes. Regression analysis showed a strong positive effect of GILZ and SGK-1 mRNA expression, and further inverse effects of IL-6 concentration, on hippocampal volumes. These findings suggest that childhood maltreatment, peripheral inflammatory and glucocorticoid markers and hippocampal volume are interrelated factors in the pathophysiology of MDD. Glucocorticoid-inducible genes GILZ and SGK-1 might be promising candidate markers for hippocampal volume changes relevant for diseases like MDD. Further studies need to explore the possible clinical usefulness of such a blood biomarker, for example, for diagnosis or prediction of therapy response.

  7. Loss of catecholaminergic neuromodulation of persistent forms of hippocampal synaptic plasticity with increasing age

    Directory of Open Access Journals (Sweden)

    Hannah Twarkowski

    2016-09-01

    Full Text Available Neuromodulation by means of the catecholaminergic system is a key component of motivation-driven learning and behaviorally modulated hippocampal synaptic plasticity. In particular, dopamine acting on D1/D5 receptors and noradrenaline acting on beta-adrenergic receptors exert a very potent regulation of forms of hippocampal synaptic plasticity that last for very long-periods of time (>24h, and occur in conjunction with novel spatial learning. Antagonism of these receptors not only prevents long-term potentiation (LTP and long-term depression (LTD, but prevents the memory of the spatial event that, under normal circumstances, leads to the perpetuation of these plasticity forms. Spatial learning behavior that normally comes easily to rats, such as object-place learning and spatial reference learning, becomes increasingly impaired with aging. Middle-aged animals display aging-related deficits of specific, but not all, components of spatial learning, and one possibility is that this initial manifestation of decrements in learning ability that become manifest in middle-age relate to changes in motivation, attention and/or the regulation by neuromodulatory systems of these behavioral states.Here, we compared the regulation by dopaminergic D1/D5 and beta-adrenergic receptors of persistent LTP in young (2-4 month old and middle-aged (8-14 month old rats. We observed in young rats, that weak potentiation that typically lasts for ca. 2h could be strengthened into persistent (>24h LTP by pharmacological activation of either D1/D5 or beta-adrenergic receptors. By contrast, no such facilitation occurred in middle-aged rats. This difference was not related to an ostensible learning deficit: a facilitation of weak potentiation into LTP by spatial learning was possible both in young and middle-aged rats. It was also not directly linked to deficits in LTP: strong afferent stimulation resulted in equivalent LTP in both age groups. We postulate that this change in

  8. A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Andreas Stomby

    2017-12-01

    Full Text Available Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders. Diet and exercise may potentially reverse these impairments. In this study, sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were randomized to a Paleolithic diet (PD, n = 12 with and without high intensity exercise (PDEX, n = 12 for 12 weeks. Episodic memory function, associated functional brain responses and hippocampal gray matter volume was measured by magnetic resonance imaging. A matched, but not randomized, non-interventional group was included as a reference (n = 6. The PD included a high intake of unsaturated fatty acids and protein, and excluded the intake of dairy products, grains, refined sugar and salt. The exercise intervention consisted of 180 min of supervised aerobic and resistance exercise per week. Both interventions induced a significant weight loss, improved insulin sensitivity and increased peak oxygen uptake without any significant group differences. Furthermore, both interventions were associated with increased functional brain responses within the right anterior hippocampus, right inferior occipital gyrus and increased volume of the right posterior hippocampus. There were no changes in memory performance. We conclude that life-style modification may improve neuronal plasticity in brain areas linked to cognitive function in type 2 diabetes. Putative long-term effects on cognitive functions including decreased risk of dementing disorders await further studies. Clinical trials registration number: Clinicaltrials. gov NCT01513798.

  9. Hippocampal sclerosis in children younger than 2 years

    Energy Technology Data Exchange (ETDEWEB)

    Kadom, Nadja [Children' s National Medical Center, Department of Diagnostic Imaging and Radiology, Washington, DC (United States); Tsuchida, Tammy; Gaillard, William D. [Children' s National Medical Center, Department of Neurology, Washington, DC (United States)

    2011-10-15

    Hippocampal sclerosis (HS) is rarely considered as a diagnosis in children younger than 2 years. To describe imaging features in conjunction with clinical information in patients with hippocampal sclerosis who are younger than 2 years. We retrospectively reviewed MR brain imaging and clinical information in five children in whom the diagnosis of HS was made both clinically and by MRI prior to 2 years of age. Imaging features establishing the diagnosis of hippocampal sclerosis were bright T2 signal and volume loss, while the internal architecture of the hippocampal formation was preserved in almost all children. Clinically, all children had an infectious trigger. It is necessary for radiologists to consider HS in children with certain clinical features to plan an MRI protocol that is appropriate for detection of hippocampal pathology. (orig.)

  10. Hippocampal sclerosis in children younger than 2 years

    International Nuclear Information System (INIS)

    Kadom, Nadja; Tsuchida, Tammy; Gaillard, William D.

    2011-01-01

    Hippocampal sclerosis (HS) is rarely considered as a diagnosis in children younger than 2 years. To describe imaging features in conjunction with clinical information in patients with hippocampal sclerosis who are younger than 2 years. We retrospectively reviewed MR brain imaging and clinical information in five children in whom the diagnosis of HS was made both clinically and by MRI prior to 2 years of age. Imaging features establishing the diagnosis of hippocampal sclerosis were bright T2 signal and volume loss, while the internal architecture of the hippocampal formation was preserved in almost all children. Clinically, all children had an infectious trigger. It is necessary for radiologists to consider HS in children with certain clinical features to plan an MRI protocol that is appropriate for detection of hippocampal pathology. (orig.)

  11. Human immunodeficiency virus-1 protein Tat induces excitotoxic loss of presynaptic terminals in hippocampal cultures.

    Science.gov (United States)

    Shin, Angela H; Thayer, Stanley A

    2013-05-01

    Human immunodeficiency virus (HIV) infection of the CNS produces dendritic damage that correlates with cognitive decline in patients with HIV-associated neurocognitive disorders (HAND). HIV-induced neurotoxicity results in part from viral proteins shed from infected cells, including the HIV transactivator of transcription (Tat). We previously showed that Tat binds to the low density lipoprotein receptor-related protein (LRP), resulting in overactivation of NMDA receptors, activation of the ubiquitin-proteasome pathway, and subsequent loss of postsynaptic densities. Here, we show that Tat also induces a loss of presynaptic terminals. The number of presynaptic terminals was quantified using confocal imaging of synaptophysin fused to green fluorescent protein (Syn-GFP). Tat-induced loss of presynaptic terminals was secondary to excitatory postsynaptic mechanisms because treatment with an LRP antagonist or an NMDA receptor antagonist inhibited this loss. Treatment with nutlin-3, an E3 ligase inhibitor, prevented Tat-induced loss of presynaptic terminals. These data suggest that Tat-induced loss of presynaptic terminals is a consequence of excitotoxic postsynaptic activity. We previously found that ifenprodil, an NR2B subunit-selective NMDA receptor antagonist, induced recovery of postsynaptic densities. Here we show that Tat-induced loss of presynaptic terminals was reversed by ifenprodil treatment. Thus, Tat-induced loss of presynaptic terminals is reversible, and this recovery can be initiated by inhibiting a subset of postsynaptic NMDA receptors. Understanding the dynamics of synaptic changes in response to HIV infection of the CNS may lead to the design of improved pharmacotherapies for HAND patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats

    Directory of Open Access Journals (Sweden)

    Yonglu Tian

    2017-08-01

    Full Text Available Fragile X syndrome (FXS is a neurodevelopmental disorder caused by mutations in the FMR1 gene that inactivate expression of the gene product, the fragile X mental retardation 1 protein (FMRP. In this study, we used clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated protein 9 (Cas9 technology to generate Fmr1 knockout (KO rats by disruption of the fourth exon of the Fmr1 gene. Western blotting analysis confirmed that the FMRP was absent from the brains of the Fmr1 KO rats (Fmr1exon4-KO. Electrophysiological analysis revealed that the theta-burst stimulation (TBS–induced long-term potentiation (LTP and the low-frequency stimulus (LFS–induced long-term depression (LTD were decreased in the hippocampal Schaffer collateral pathway of the Fmr1exon4-KO rats. Short-term plasticity, measured as the paired-pulse ratio, remained normal in the KO rats. The synaptic strength mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR was also impaired. Consistent with previous reports, the Fmr1exon4-KO rats demonstrated an enhanced 3,5-dihydroxyphenylglycine (DHPG–induced LTD in the present study, and this enhancement is insensitive to protein translation. In addition, the Fmr1exon4-KO rats showed deficits in the probe trial in the Morris water maze test. These results demonstrate that deletion of the Fmr1 gene in rats specifically impairs long-term synaptic plasticity and hippocampus-dependent learning in a manner resembling the key symptoms of FXS. Furthermore, the Fmr1exon4-KO rats displayed impaired social interaction and macroorchidism, the results consistent with those observed in patients with FXS. Thus, Fmr1exon4-KO rats constitute a novel rat model of FXS that complements existing mouse models.

  13. Ipsilateral hippocampal atrophy is associated with long-term memory dysfunction after ischemic stroke in young adults

    NARCIS (Netherlands)

    Schaapsmeerders, P.; Uden, I.W.M. van; Tuladhar, A.M.; Maaijwee, N.A.M.M.; Dijk, E.J. van; Rutten-Jacobs, L.C.A.; Arntz, R.M.; Schoonderwaldt, H.C.; Dorresteijn, L.D.A.; Leeuw, H.F. de; Kessels, R.P.C.

    2015-01-01

    Memory impairment after stroke in young adults is poorly understood. In elderly stroke survivors memory impairments and the concomitant loss of hippocampal volume are usually explained by coexisting neurodegenerative disease (e.g., amyloid pathology) in interaction with stroke. However,

  14. Hippocampal volume change measurement: Quantitative assessment of the reproducibility of expert manual outlining and the automated methods FreeSurfer and FIRST

    NARCIS (Netherlands)

    Mulder, E.R.; de Jong, R.A.; Knol, D.L.; van Schijndel, R.A.; Cover, K.S.; Visser, P.J.; Barkhof, F.; Vrenken, H.

    2014-01-01

    Background: To measure hippocampal volume change in Alzheimer's disease (AD) or mild cognitive impairment (MCI), expert manual delineation is often used because of its supposed accuracy. It has been suggested that expert outlining yields poorer reproducibility as compared to automated methods, but

  15. Smaller Hippocampal Volume in Posttraumatic Stress Disorder : A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia

    NARCIS (Netherlands)

    Logue, Mark W.; van Rooij, Sanne J H; Dennis, Emily L.; Davis, Sarah L.; Hayes, Jasmeet P.; Stevens, Jennifer S.; Densmore, Maria; Haswell, Courtney C.; Ipser, Jonathan; Koch, Saskia B.J.; Korgaonkar, Mayuresh; Lebois, Lauren A.M.; Peverill, Matthew; Baker, Justin T.; Boedhoe, Premika S W; Frijling, Jessie L.; Gruber, Staci A.; Harpaz-Rotem, Ilan; Jahanshad, Neda; Koopowitz, Sheri; Levy, Ifat; Nawijn, Laura; O'Connor, Lauren; Olff, Miranda; Salat, David H.; Sheridan, Margaret A.; Spielberg, Jeffrey M.; van Zuiden, Mirjam; Winternitz, Sherry R.; Wolff, Jonathan D.; Wolf, Erika J.; Wang, Xin; Wrocklage, Kristen; Abdallah, Chadi G.; Bryant, Richard A.; Geuze, Elbert; Jovanovic, Tanja; Kaufman, Milissa L.; King, Anthony P.; Krystal, John H.; Lagopoulos, Jim; Bennett, Maxwell; Lanius, Ruth; Liberzon, Israel; McGlinchey, Regina E.; McLaughlin, Katie A.; Milberg, William P.; Miller, Mark W.; Ressler, Kerry J; Veltman, Dick J.; Stein, Dan J; Thomaes, Kathleen; Thompson, Paul M.; Morey, Rajendra A.

    2018-01-01

    Background Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium

  16. Systematic comparison of different techniques to measure hippocampal subfield volumes in ADNI2

    DEFF Research Database (Denmark)

    Mueller, Susanne G.; Yushkevich, Paul A.; Das, Sandhitsu

    2018-01-01

    regression analyses were used to calculate effect sizes (ES) for group, amyloid positivity in controls, and associations with cognitive/memory performance for each approach. Results Subfield volumetry was better than whole hippocampal volumetry for the detection of the mild atrophy differences between...... and T1 subfield approaches. None of the different T2-HghRes methods tested had a clear advantage over the other methods. Each has strengths and weaknesses that need to be taken into account when deciding which one to use to get the best results from subfield volumetry....

  17. Changes in hippocampal volume and neuron number co-occur with memory decline in old homing pigeons (Columba livia).

    Science.gov (United States)

    Coppola, Vincent J; Kanyok, Nate; Schreiber, Austin J; Flaim, Mary E; Bingman, Verner P

    2016-05-01

    The mammalian hippocampus is particularly susceptible to age-related structural changes, which have been used to explain, in part, age-related memory decline. These changes are generally characterized by atrophy (e.g., a decrease in volume and number of synaptic contacts). Recent studies have reported age-related spatial memory deficits in older pigeons similar to those seen in older mammals. However, to date, little is known about any co-occurring changes in the aging avian hippocampal formation (HF). In the current study, it was found that the HF of older pigeons was actually larger and contained more neurons than the HF of younger pigeons, a finding that suggests that the pattern of structural changes during aging in the avian HF is different from that seen in the mammalian hippocampus. A working hypothesis for relating the observed structural changes with spatial-cognitive decline is offered. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Behavioral Inhibition System activity is associated with increased amygdala and hippocampal gray matter volume: A voxel-based morphometry study.

    Science.gov (United States)

    Barrós-Loscertales, A; Meseguer, V; Sanjuán, A; Belloch, V; Parcet, M A; Torrubia, R; Avila, C

    2006-11-15

    Recent research has examined anxiety and hyperactivity in the amygdala and the anterior hippocampus while processing aversive stimuli. In order to determine whether these functional differences have a structural basis, optimized voxel-based morphometry was used to study the relationship between gray matter concentration in the brain and scores on a Behavioral Inhibition System measure (the Sensitivity to Punishment scale) in a sample of 63 male undergraduates. Results showed a positive correlation between Sensitivity to Punishment scores and gray matter volume in the amygdala and the hippocampal formation, that is, in areas that Gray, J.A., and McNaughton, N.J. (2000). The neuropsychology of anxiety. Oxford: Oxford Medical Publications. associated with the Behavioral Inhibition System.

  19. Hippocampal atrophy on MRI is predictive of histopathological patterns and surgical prognosis in mesial temporal lobe epilepsy with hippocampal sclerosis.

    Science.gov (United States)

    Jardim, Anaclara Prada; Corso, Jeana Torres; Garcia, Maria Teresa Fernandes Castilho; Gaça, Larissa Botelho; Comper, Sandra Mara; Lancellotti, Carmen Lúcia Penteado; Centeno, Ricardo Silva; Carrete, Henrique; Cavalheiro, Esper Abrão; Scorza, Carla Alessandra; Yacubian, Elza Márcia Targas

    2016-12-01

    To correlate hippocampal volumes obtained from brain structural imaging with histopathological patterns of hippocampal sclerosis (HS), in order to predict surgical outcome. Patients with mesial temporal lobe epilepsy (MTLE) with HS were selected. Clinical data were assessed pre-operatively and surgical outcome in the first year post surgery. One block of mid hippocampal body was selected for HS classification according to ILAE criteria. NeuN-immunoreactive cell bodies were counted within hippocampal subfields, in four randomly visual fields, and cell densities were transformed into z-score values. FreeSurfer processing of 1.5T brain structural images was used for subcortical and cortical volumetric estimation of the ipsilateral hippocampus. Univariate analysis of variance and Pearson's correlation test were applied for statistical analyses. Sixty-two cases (31 female, 32 right HS) were included. ILAE type 1 HS was identified in 48 patients, type 2 in eight, type 3 in two, and four had no-HS. Better results regarding seizure control, i.e. ILAE 1, were achieved by patients with type 1 HS (58.3%). Patients with types 1 and 2 had smaller hippocampal volumes compared to those with no-HS (p<0.001 and p=0.004, respectively). Positive correlation was encountered between hippocampal volumes and CA1, CA3, CA4, and total estimated neuronal densities. CA2 was the only sector which did not correlate its neuronal density with hippocampal volume (p=0.390). This is the first study correlating hippocampal volume on MRI submitted to FreeSurfer processing with ILAE patterns of HS and neuronal loss within each hippocampal subfield, a fundamental finding to anticipate surgical prognosis for patients with drug-resistant MTLE and HS. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Progressive Decline in Hippocampal CA1 Volume in Individuals at Ultra-High-Risk for Psychosis Who Do Not Remit: Findings from the Longitudinal Youth at Risk Study.

    Science.gov (United States)

    Ho, New Fei; Holt, Daphne J; Cheung, Mike; Iglesias, Juan Eugenio; Goh, Alex; Wang, Mingyuan; Lim, Joseph Kw; de Souza, Joshua; Poh, Joann S; See, Yuen Mei; Adcock, Alison R; Wood, Stephen J; Chee, Michael Wl; Lee, Jimmy; Zhou, Juan

    2017-05-01

    Most individuals identified as ultra-high-risk (UHR) for psychosis do not develop frank psychosis. They continue to exhibit subthreshold symptoms, or go on to fully remit. Prior work has shown that the volume of CA1, a subfield of the hippocampus, is selectively reduced in the early stages of schizophrenia. Here we aimed to determine whether patterns of volume change of CA1 are different in UHR individuals who do or do not achieve symptomatic remission. Structural MRI scans were acquired at baseline and at 1-2 follow-up time points (at 12-month intervals) from 147 UHR and healthy control subjects. An automated method (based on an ex vivo atlas of ultra-high-resolution hippocampal tissue) was used to delineate the hippocampal subfields. Over time, a greater decline in bilateral CA1 subfield volumes was found in the subgroup of UHR subjects whose subthreshold symptoms persisted (n=40) and also those who developed clinical psychosis (n=12), compared with UHR subjects who remitted (n=41) and healthy controls (n=54). No baseline differences in volumes of the overall hippocampus or its subfields were found among the groups. Moreover, the rate of volume decline of CA1, but not of other hippocampal subfields, in the non-remitters was associated with increasing symptom severity over time. Thus, these findings indicate that there is deterioration of CA1 volume in persistently symptomatic UHR individuals in proportion to symptomatic progression.

  1. No loss of hippocampal hilar somatostatinergic neurons after repeated electroconvulsive shock

    DEFF Research Database (Denmark)

    Dalby, Nils Ole; Tønder, N; Wolby, D P

    1996-01-01

    Electrically induced seizures with anesthesia and muscle relaxation (ECT) is commonly used in the therapy of psychotic depression in humans. Unmodified electroshock (ECS) is used as a model for epilepsy in the rat. In several seizure models of epilepsy, in particular the dentate hilar somatostatin......-containing (SSergic) neurons have been found to undergo degeneration. To assess the potential loss of SSergic hilar neurons after repeated ECS, 10 rats were given 110 ECS, one per day, 5 days a week. One day after the last ECS the rats were anesthesized, perfused, the brains cut on a vibratome and prepared...... for nonradioactive in situ hybridization for somatostatin along with five control rats. Like rats given 10-36 ECS in earlier studies, the ECS-treated rats displayed a markedly increased neuronal hybridization labeling when compared with control rats. The total number of dentate hilar SSergic neurons of each rat...

  2. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

    International Nuclear Information System (INIS)

    Papma, Janne M.; Koudstaal, Peter J.; Swieten, John C. van; Smits, Marion; Lugt, Aad van der; Groot, Marius de; Vrooman, Henri A.; Mattace Raso, Francesco U.; Niessen, Wiro J.; Veen, Frederik M. van der; Prins, Niels D.

    2017-01-01

    Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. (orig.)

  3. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

    Energy Technology Data Exchange (ETDEWEB)

    Papma, Janne M.; Koudstaal, Peter J.; Swieten, John C. van [Erasmus MC - University Medical Center Rotterdam, Department of Neurology, Rotterdam (Netherlands); Smits, Marion; Lugt, Aad van der [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, Rotterdam (Netherlands); Groot, Marius de; Vrooman, Henri A. [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, Rotterdam (Netherlands); Erasmus MC - University Medical Center Rotterdam, Department of Medical Informatics, Rotterdam (Netherlands); Mattace Raso, Francesco U. [Erasmus MC - University Medical Center Rotterdam, Department of Geriatrics, Rotterdam (Netherlands); Niessen, Wiro J. [Erasmus MC - University Medical Center Rotterdam, Department of Radiology, Rotterdam (Netherlands); Erasmus MC - University Medical Center Rotterdam, Department of Medical Informatics, Rotterdam (Netherlands); Delft University of Technology, Faculty of Applied Sciences, Delft (Netherlands); Veen, Frederik M. van der [Erasmus University Rotterdam, Institute of Psychology, Rotterdam (Netherlands); Prins, Niels D. [VU University Medical Center, Alzheimer Center, Department of Neurology, Amsterdam (Netherlands)

    2017-09-15

    Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. (orig.)

  4. Hippocampal Atrophy Is Associated with Altered Hippocampus-Posterior Cingulate Cortex Connectivity in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

    Science.gov (United States)

    Shih, Y C; Tseng, C E; Lin, F-H; Liou, H H; Tseng, W Y I

    2017-03-01

    = 0.045). In left mesial temporal lobe epilepsy with hippocampal sclerosis, the left inferior cingulum bundle undergoes degeneration in tandem with the left hippocampal volume, whereas intrinsic functional connectivity seems to react by compensating the loss of connectivity. Such insight might be helpful in understanding the development of the epileptic network in left mesial temporal lobe epilepsy with hippocampal sclerosis. © 2017 by American Journal of Neuroradiology.

  5. Lateralization of temporal lobe epilepsy using a novel uncertainty analysis of MR diffusion in hippocampus, cingulum, and fornix, and hippocampal volume and FLAIR intensity.

    Science.gov (United States)

    Nazem-Zadeh, Mohammad-Reza; Schwalb, Jason M; Elisevich, Kost V; Bagher-Ebadian, Hassan; Hamidian, Hajar; Akhondi-Asl, Ali-Reza; Jafari-Khouzani, Kourosh; Soltanian-Zadeh, Hamid

    2014-07-15

    To analyze the utility of a quantitative uncertainty analysis approach for evaluation and comparison of various MRI findings for the lateralization of epileptogenicity in mesial temporal lobe epilepsy (mTLE), including novel diffusion-based analyses. We estimated the hemispheric variation uncertainty (HVU) of hippocampal T1 volumetry and FLAIR (Fluid Attenuated Inversion Recovery) intensity. Using diffusion tensor images of 23 nonepileptic subjects, we estimated the HVU levels of mean diffusivity (MD) in the hippocampus, and fractional anisotropy (FA) in the posteroinferior cingulum and crus of fornix. Imaging from a retrospective cohort of 20 TLE patients who had undergone surgical resection with Engel class I outcomes was analyzed to determine whether asymmetry of preoperative volumetrics, FLAIR intensities, and MD values in hippocampi, as well as FA values in posteroinferior cingula and fornix crura correctly predicted laterality of seizure onset. Ten of the cohort had pathologically proven mesial temporal sclerosis (MTS). Seven of these patients had undergone extraoperative electrocorticography (ECoG) for lateralization or to rule out extra-temporal foci. HVU was estimated to be 3.1×10(-5) for hippocampal MD, 0.027 for FA in posteroinferior cingulum, 0.018 for FA in crus of fornix, 0.069 for hippocampal normalized volume, and 0.099 for hippocampal normalized FLAIR intensity. Using HVU analysis, a higher hippocampal MD value, lower FA within the posteroinferior cingulum and crus of fornix, shrinkage in hippocampal volume, and higher hippocampal FLAIR intensity were observed beyond uncertainty on the side ipsilateral to seizure onset for 10, 10, 9, 9, and 10 out of 10 pathology-proven MTS patients, respectively. Considering all 20 TLE patients, these numbers were 18, 15, 14, 13, and 16, respectively. However, consolidating the lateralization results of HVU analysis on these quantities by majority voting has detected the epileptogenic side for 19 out of 20 cases

  6. Hippocampal Volume Is Reduced in Schizophrenia and Schizoaffective Disorder But Not in Psychotic Bipolar I Disorder Demonstrated by Both Manual Tracing and Automated Parcellation (FreeSurfer)

    Science.gov (United States)

    Arnold, Sara J. M.; Ivleva, Elena I.; Gopal, Tejas A.; Reddy, Anil P.; Jeon-Slaughter, Haekyung; Sacco, Carolyn B.; Francis, Alan N.; Tandon, Neeraj; Bidesi, Anup S.; Witte, Bradley; Poudyal, Gaurav; Pearlson, Godfrey D.; Sweeney, John A.; Clementz, Brett A.; Keshavan, Matcheri S.; Tamminga, Carol A.

    2015-01-01

    This study examined hippocampal volume as a putative biomarker for psychotic illness in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) psychosis sample, contrasting manual tracing and semiautomated (FreeSurfer) region-of-interest outcomes. The study sample (n = 596) included probands with schizophrenia (SZ, n = 71), schizoaffective disorder (SAD, n = 70), and psychotic bipolar I disorder (BDP, n = 86); their first-degree relatives (SZ-Rel, n = 74; SAD-Rel, n = 62; BDP-Rel, n = 88); and healthy controls (HC, n = 145). Hippocampal volumes were derived from 3Tesla T1-weighted MPRAGE images using manual tracing/3DSlicer3.6.3 and semiautomated parcellation/FreeSurfer5.1,64bit. Volumetric outcomes from both methodologies were contrasted in HC and probands and relatives across the 3 diagnoses, using mixed-effect regression models (SAS9.3 Proc MIXED); Pearson correlations between manual tracing and FreeSurfer outcomes were computed. SZ (P = .0007–.02) and SAD (P = .003–.14) had lower hippocampal volumes compared with HC, whereas BDP showed normal volumes bilaterally (P = .18–.55). All relative groups had hippocampal volumes not different from controls (P = .12–.97) and higher than those observed in probands (P = .003–.09), except for FreeSurfer measures in bipolar probands vs relatives (P = .64–.99). Outcomes from manual tracing and FreeSurfer showed direct, moderate to strong, correlations (r = .51–.73, P schizoaffective disorder, but not for psychotic bipolar I disorder, and may reflect a cumulative effect of divergent primary disease processes and/or lifetime medication use. Manual tracing and semiautomated parcellation regional volumetric approaches may provide useful outcomes for defining measurable biomarkers underlying severe mental illness. PMID:24557771

  7. The impact of aging, hearing loss, and body weight on mouse hippocampal redox state, measured in brain slices using fluorescence imaging.

    Science.gov (United States)

    Stebbings, Kevin A; Choi, Hyun W; Ravindra, Aditya; Llano, Daniel Adolfo

    2016-06-01

    The relationships between oxidative stress in the hippocampus and other aging-related changes such as hearing loss, cortical thinning, or changes in body weight are not yet known. We measured the redox ratio in a number of neural structures in brain slices taken from young and aged mice. Hearing thresholds, body weight, and cortical thickness were also measured. We found striking aging-related increases in the redox ratio that were isolated to the stratum pyramidale, while such changes were not observed in thalamus or cortex. These changes were driven primarily by changes in flavin adenine dinucleotide, not nicotinamide adenine dinucleotide hydride. Multiple regression analysis suggested that neither hearing threshold nor cortical thickness independently contributed to this change in hippocampal redox ratio. However, body weight did independently contribute to predicted changes in hippocampal redox ratio. These data suggest that aging-related changes in hippocampal redox ratio are not a general reflection of overall brain oxidative state but are highly localized, while still being related to at least one marker of late aging, weight loss at the end of life. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Interaction between BDNF rs6265 Met allele and low family cohesion is associated with smaller left hippocampal volume in pediatric bipolar disorder.

    Science.gov (United States)

    Zeni, Cristian Patrick; Mwangi, Benson; Cao, Bo; Hasan, Khader M; Walss-Bass, Consuelo; Zunta-Soares, Giovana; Soares, Jair C

    2016-01-01

    Genetic and environmental factors are implicated in the onset and evolution of pediatric bipolar disorder, and may be associated to structural brain abnormalities. The aim of our study was to assess the impact of the interaction between the Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism and family functioning on hippocampal volumes of children and adolescents with bipolar disorder, and typically-developing controls. We evaluated the family functioning cohesion subscale using the Family Environment Scale-Revised, genotyped the BDNF rs6265 polymorphism, and performed structural brain imaging in 29 children and adolescents with bipolar disorder, and 22 healthy controls. We did not find significant differences between patients with BD or controls in left or right hippocampus volume (p=0.44, and p=0.71, respectively). However, we detected a significant interaction between low scores on the cohesion subscale and the presence of the Met allele at BNDF on left hippocampal volume of patients with bipolar disorder (F=3.4, p=0.043). None of the factors independently (BDNF Val66Met, cohesion scores) was significantly associated with hippocampal volume differences. small sample size, cross-sectional study. These results may lead to a better understanding of the impact of the interaction between genes and environment factors on brain structures associated to bipolar disorder and its manifestations. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Automated cross-sectional and longitudinal hippocampal volume measurement in mild cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Leung, Kelvin K; Barnes, Josephine; Ridgway, Gerard R; Bartlett, Jonathan W; Clarkson, Matthew J; Macdonald, Kate; Schuff, Norbert; Fox, Nick C; Ourselin, Sebastien

    2010-07-15

    Volume and change in volume of the hippocampus are both important markers of Alzheimer's disease (AD). Delineation of the structure on MRI is time-consuming and therefore reliable automated methods are required. We describe an improvement (multiple-atlas propagation and segmentation (MAPS)) to our template library-based segmentation technique. The improved technique uses non-linear registration of the best-matched templates from our manually segmented library to generate multiple segmentations and combines them using the simultaneous truth and performance level estimation (STAPLE) algorithm. Change in volume over 12months (MAPS-HBSI) was measured by applying the boundary shift integral using MAPS regions. Methods were developed and validated against manual measures using subsets from Alzheimer's Disease Neuroimaging Initiative (ADNI). The best method was applied to 682 ADNI subjects, at baseline and 12-month follow-up, enabling assessment of volumes and atrophy rates in control, mild cognitive impairment (MCI) and AD groups, and within MCI subgroups classified by subsequent clinical outcome. We compared our measures with those generated by Surgical Navigation Technologies (SNT) available from ADNI. The accuracy of our volumes was one of the highest reported (mean(SD) Jaccard Index 0.80(0.04) (N=30)). Both MAPS baseline volume and MAPS-HBSI atrophy rate distinguished between control, MCI and AD groups. Comparing MCI subgroups (reverters, stable and converters): volumes were lower and rates higher in converters compared with stable and reverter groups (pmethods give accurate and reliable volumes and atrophy rates across the clinical spectrum from healthy aging to AD. Copyright 2010 Elsevier Inc. All rights reserved.

  10. Moderating effects of sex on the impact of diagnosis and amyloid positivity on verbal memory and hippocampal volume.

    Science.gov (United States)

    Caldwell, Jessica Z K; Berg, Jody-Lynn; Cummings, Jeffrey L; Banks, Sarah J

    2017-09-12

    Alzheimer's disease (AD) impacts men and women differently, but the effect of sex on predementia stages is unclear. The objective of this study was to examine whether sex moderates the impact of florbetapir positron emission tomography (PET) amyloid positivity (A + ) on verbal learning and memory performance and hippocampal volume (HV) in normal cognition (NC) and early mild cognitive impairment (eMCI). Seven hundred forty-two participants with NC and participants with eMCI from the Alzheimer's Disease Neuroimaging Initiative (second cohort [ADNI2] and Grand Opportunity Cohort [ADNI-GO]) were included. All had baseline florbetapir PET measured, and 526 had screening visit HV measured. Regression moderation models were used to examine whether A + effects on Rey Auditory Verbal Learning Test learning and delayed recall and right and left HV (adjusted for total intracranial volume) were moderated by diagnosis and sex. Age, cognition at screening, education, and apolipoprotein E ε4 carrier status were controlled. Women with A + , but not those with florbetapir PET amyloid negative (A-),eMCI showed poorer learning. For women with NC, there was no relationship of A + with learning. In contrast, A + men trended toward poorer learning regardless of diagnosis. A similar trend was found for verbal delayed recall: Women with A + , but not A-, eMCI trended toward reduced delayed recall; no effects were observed for women with NC or for men. Hippocampal analyses indicated that women with A + , but not those with A - , eMCI, trended toward smaller right HV; no significant A + effects were observed for women with NC. Men showed similar, though nonsignificant, patterns of smaller right HV in A + eMCI, but not in men with A - eMCI or NC. No interactive effects of sex were noted for left HV. Women with NC showed verbal learning and memory scores robust to A + , and women with A + eMCI lost this advantage. In contrast, A + impacted men's scores less significantly or not at all, and

  11. Structural hippocampal network alterations during healthy aging: A multi-modal MRI study

    Directory of Open Access Journals (Sweden)

    Amandine ePelletier

    2013-12-01

    Full Text Available While hippocampal atrophy has been described during healthy aging, few studies have examined its relationship with the integrity of White Matter (WM connecting tracts of the limbic system. This investigation examined WM structural damage specifically related to hippocampal atrophy in healthy aging subjects (n=129, using morphological MRI to assess hippocampal volume and Diffusion Tensor Imaging (DTI to assess WM integrity. Subjects with Mild Cognitive Impairment (MCI or dementia were excluded from the analysis. In our sample, increasing age was significantly associated with reduced hippocampal volume and reduced Fractional Anisotropy (FA at the level of the fornix and the cingulum bundle. The findings also demonstrate that hippocampal atrophy was specifically associated with reduced FA of the fornix bundle, but it was not related to alteration of the cingulum bundle. Our results indicate that the relationship between hippocampal atrophy and fornix FA values is not due to an independent effect of age on both structures. A recursive regression procedure was applied to evaluate sequential relationships between the alterations of these two brain structures. When both hippocampal atrophy and fornix FA values were included in the same model to predict age, fornix FA values remained significant whereas hippocampal atrophy was no longer significantly associated with age. According to this latter finding, hippocampal atrophy in healthy aging could be mediated by a loss of fornix connections. Structural alterations of this part of the limbic system, which have been associated with neurodegeneration in Alzheimer’s disease, result at least in part from the aging process.

  12. Persistent Adult Neuroimmune Activation and Loss of Hippocampal Neurogenesis Following Adolescent Ethanol Exposure: Blockade by Exercise and the Anti-inflammatory Drug Indomethacin

    Directory of Open Access Journals (Sweden)

    Ryan P. Vetreno

    2018-03-01

    Full Text Available Alcohol abuse and binge drinking are common during adolescence, a developmental period characterized by heightened neuroplasticity. Animal studies reveal that adolescent ethanol exposure decreases hippocampal neurogenesis that persists into adulthood, but the mechanism remains to be fully elucidated. Using a rodent model of adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-days on/2-days off from postnatal day [P]25 to P55, we tested the hypothesis that AIE-induced upregulation of neuroimmune signaling contributes to the loss of hippocampal neurogenesis in adulthood. We found that AIE caused upregulation of multiple proinflammatory Toll-like receptors (TLRs, increased expression of phosphorylated NF-κB p65 (pNF-κB p65 and the cell death marker cleaved caspase 3, and reduced markers of neurogenesis in the adult (P80 hippocampus, which is consistent with persistently increased neuroimmune signaling reducing neurogenesis. We observed a similar increase of pNF-κB p65-immunoreactive cells in the post-mortem human alcoholic hippocampus, an effect that was negatively correlated with age of drinking onset. Voluntary wheel running from P24 to P80 prevented the AIE-induced loss of neurogenesis markers (i.e., nestin and doublecortin in the adult hippocampus that was paralleled by blockade of increased expression of the cell death marker cleaved caspase 3. Wheel running also prevented the AIE-induced increase of hippocampal pNF-κB p65 and induction of neuroimmune NF-κB target genes, including TNFα and IκBα in the adult brain. Administration of the anti-inflammatory drug indomethacin during AIE prevented the loss of neurogenesis markers (i.e., nestin and doublecortin and the concomitant increase of cleaved caspase 3, an effect that was accompanied by blockade of the increase of pNF-κB p65. Similarly, administration of the proinflammatory TLR4 activator lipopolysaccharide resulted in a loss of doublecortin that was paralleled by increased

  13. Hippocampal volume change measurement: quantitative assessment of the reproducibility of expert manual outlining and the automated methods FreeSurfer and FIRST.

    Science.gov (United States)

    Mulder, Emma R; de Jong, Remko A; Knol, Dirk L; van Schijndel, Ronald A; Cover, Keith S; Visser, Pieter J; Barkhof, Frederik; Vrenken, Hugo

    2014-05-15

    To measure hippocampal volume change in Alzheimer's disease (AD) or mild cognitive impairment (MCI), expert manual delineation is often used because of its supposed accuracy. It has been suggested that expert outlining yields poorer reproducibility as compared to automated methods, but this has not been investigated. To determine the reproducibilities of expert manual outlining and two common automated methods for measuring hippocampal atrophy rates in healthy aging, MCI and AD. From the Alzheimer's Disease Neuroimaging Initiative (ADNI), 80 subjects were selected: 20 patients with AD, 40 patients with mild cognitive impairment (MCI) and 20 healthy controls (HCs). Left and right hippocampal volume change between baseline and month-12 visit was assessed by using expert manual delineation, and by the automated software packages FreeSurfer (longitudinal processing stream) and FIRST. To assess reproducibility of the measured hippocampal volume change, both back-to-back (BTB) MPRAGE scans available for each visit were analyzed. Hippocampal volume change was expressed in μL, and as a percentage of baseline volume. Reproducibility of the 1-year hippocampal volume change was estimated from the BTB measurements by using linear mixed model to calculate the limits of agreement (LoA) of each method, reflecting its measurement uncertainty. Using the delta method, approximate p-values were calculated for the pairwise comparisons between methods. Statistical analyses were performed both with inclusion and exclusion of visibly incorrect segmentations. Visibly incorrect automated segmentation in either one or both scans of a longitudinal scan pair occurred in 7.5% of the hippocampi for FreeSurfer and in 6.9% of the hippocampi for FIRST. After excluding these failed cases, reproducibility analysis for 1-year percentage volume change yielded LoA of ±7.2% for FreeSurfer, ±9.7% for expert manual delineation, and ±10.0% for FIRST. Methods ranked the same for reproducibility of 1

  14. Developmental Differences in Relations between Episodic Memory and Hippocampal Subregion Volume during Early Childhood

    Science.gov (United States)

    Riggins, Tracy; Blankenship, Sarah L.; Mulligan, Elizabeth; Rice, Katherine; Redcay, Elizabeth

    2015-01-01

    Episodic memory shows striking improvement during early childhood. However, neural contributions to these behavioral changes are not well understood. This study examined associations between episodic memory and volume of subregions (head, body, and tail) of the hippocampus--a structure known to support episodic memory in school-aged children and…

  15. Hippocampal volume is positively associated with behavioural inhibition (BIS) in a large community-based sample of mid-life adults: the PATH through life study.

    Science.gov (United States)

    Cherbuin, Nicolas; Windsor, Tim D; Anstey, Kaarin J; Maller, Jerome J; Meslin, Chantal; Sachdev, Perminder S

    2008-09-01

    The fields of personality research and neuropsychology have developed with very little overlap. Gray and McNaughton were among the first to recognize that personality traits must have neurobiological correlates and developed models relating personality factors to brain structures. Of particular note was their description of associations between conditioning, inhibition and activation of behaviours, and specific neural structures such as the hippocampus, amygdala and the prefrontal cortex. The aim of this study was to determine whether personality constructs representing the behavioural inhibition and activation systems (BIS/BAS) were associated with volumetric measures of the hippocampus and amygdala in humans. Amygdalar and hippocampal volumes were measured in 430 brain scans of cognitively intact community-based volunteers. Linear associations between brain volumes and the BIS/BAS measures were assessed using multiple regression, controlling for age, sex, education, intra-cranial and total brain volume. Results showed that hippocampal volumes were positively associated with BIS sensitivity and to a lesser extent with BAS sensitivity. No association was found between amygdalar volume and either the BIS or BAS. These findings add support to the model of Gray and McNaughton, which proposes a role of the hippocampus in the regulation of defensive/approach behaviours and trait anxiety but suggest an absence of associations between amygdala volume and BIS/BAS measures.

  16. Changes in Search Path Complexity and Length During Learning of a Virtual Water Maze: Age Differences and Differential Associations with Hippocampal Subfield Volumes.

    Science.gov (United States)

    Daugherty, Ana M; Bender, Andrew R; Yuan, Peng; Raz, Naftali

    2016-06-01

    Impairment of hippocampus-dependent cognitive processes has been proposed to underlie age-related deficits in navigation. Animal studies suggest a differential role of hippocampal subfields in various aspects of navigation, but that hypothesis has not been tested in humans. In this study, we examined the association between volume of hippocampal subfields and age differences in virtual spatial navigation. In a sample of 65 healthy adults (age 19-75 years), advanced age was associated with a slower rate of improvement operationalized as shortening of the search path over 25 learning trials on a virtual Morris water maze task. The deficits were partially explained by greater complexity of older adults' search paths. Larger subiculum and entorhinal cortex volumes were associated with a faster decrease in search path complexity, which in turn explained faster shortening of search distance. Larger Cornu Ammonis (CA)1-2 volume was associated with faster distance shortening, but not in path complexity reduction. Age differences in regional volumes collectively accounted for 23% of the age-related variance in navigation learning. Independent of subfield volumes, advanced age was associated with poorer performance across all trials, even after reaching the asymptote. Thus, subiculum and CA1-2 volumes were associated with speed of acquisition, but not magnitude of gains in virtual maze navigation. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. [Hippocampal subfield volume alteration in post-traumatic stress disorder: a magnetic resonance imaging study].

    Science.gov (United States)

    Lu, Lu; Zhang, Lianqing; Hu, Xinyu; Hu, Xiaoxiao; Li, Lingjiang; Gong, Qiyong; Huang, Xiaoqi

    2018-04-01

    In the current study, we aim to investigate whether post-traumatic stress disorder (PTSD) is associated with structural alterations in specific subfields of hippocampus comparing with trauma-exposed control (TC) in a relatively large sample. We included 67 PTSD patients who were diagnosed under Diagnostic and Statistical Manual of Mental Disorders (4th Edition) (DSM-Ⅳ) criteria and 78 age- and sex-matched non-PTSD adult survivors who experienced similar stressors. High resolution T1 weighted images were obtained via a GE 3.0 T scanner. The structural data was automatically segmented using FreeSurfer software, and volume of whole hippocampus and subfield including CA1, CA2-3, CA4-DG, fimbria, presubiculum, subiculum and fissure were extracted. Volume differences between the two groups were statistically compared with age, years of education, duration from the events and intracranial volume (ICV) as covariates. Hemisphere, sex and diagnosis were entered as fixed factors. Relationship between morphometric measurements with Clinician-Administered PTSD Scale (CAPS) score and illness duration were performed using Pearson's correlation with SPSS. Comparing to TC, PTSD patients showed no statistically significant alteration in volumes of the whole hippocampus and all the subfields ( P > 0.05). In male patients, there were significant correlations between CAPS score and volume of right CA2-3 ( R 2 = 0.197, P = 0.034), right subiculum ( R 2 = 0.245, P = 0.016), and duration statistically correlated with right fissure ( R 2 = 0.247, P = 0.016). In female patients, CAPS scores significant correlated with volume of left presubiculum ( R 2 = 0.095, P = 0.042), left subiculum ( R 2 = 0.090, P = 0.048), and left CA4-DG ( R 2 = 0.099, P = 0.037). The main findings of the current study suggest that stress event causes non-selective damage to hippocampus in both PTSD patients and TC, and gender-specific lateralization may underlie PTSD pathology.

  18. Verbal and visual memory performance and hippocampal volumes, measured by 3-Tesla magnetic resonance imaging, in patients with Cushing's syndrome.

    Science.gov (United States)

    Resmini, Eugenia; Santos, Alicia; Gómez-Anson, Beatriz; Vives, Yolanda; Pires, Patricia; Crespo, Iris; Portella, Maria J; de Juan-Delago, Manel; Barahona, Maria-José; Webb, Susan M

    2012-02-01

    Cushing's syndrome (CS) affects cognition and memory. Our objective was to evaluate memory and hippocampal volumes (HV) on 3-tesla magnetic resonance imaging (3T MRI) in CS patients and controls. Thirty-three CS patients (11 active, 22 cured) and 34 controls matched for age, sex, and education underwent Rey Auditory Verbal Learning Test and Rey-Osterrieth Complex Figure memory tests. Gray matter and HV were calculated on 3T MRI, using FreeSurfer image analyses software. No differences in HV were observed between active and cured CS or controls. Memory performance was worse in CS patients than controls (P visual memory (P = 0.04) than controls. In 12 CS patients, memory was below normative cutoff values for verbal (n = 6, cured), visual memory (n = 10, six cured) or both (n = 4); these patients with severe memory impairments showed smaller HV compared with their matched controls (P = 0.02 with verbal impairment; P = 0.03 with visual impairment). They were older (P = 0.04), had shorter education (P = 0.02), and showed a trend toward longer duration of hypercortisolism (P = 0.07) than the remaining CS patients. Total (P = 0.004) and cortical (P = 0.03) brain gray matter volumes were decreased in CS compared with controls, indicating brain atrophy, whereas subcortical gray matter (which includes HV) was reduced only in the 12 patients with severe memory impairment. Verbal and visual memory is worse in CS patients than controls, even after biochemical cure. HV was decreased only in those whose memory scores were below normative cutoff values.

  19. Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults.

    Science.gov (United States)

    Maass, Anne; Düzel, Sandra; Brigadski, Tanja; Goerke, Monique; Becke, Andreas; Sobieray, Uwe; Neumann, Katja; Lövdén, Martin; Lindenberger, Ulman; Bäckman, Lars; Braun-Dullaeus, Rüdiger; Ahrens, Dörte; Heinze, Hans-Jochen; Müller, Notger G; Lessmann, Volkmar; Sendtner, Michael; Düzel, Emrah

    2016-05-01

    Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here. Copyright © 2015 The Authors

  20. Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Seibert, Tyler M.; Karunamuni, Roshan [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Bartsch, Hauke [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Kaifi, Samar [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Krishnan, Anitha Priya [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Dalia, Yoseph; Burkeen, Jeffrey; Murzin, Vyacheslav; Moiseenko, Vitali [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States); Kuperman, Joshua; White, Nathan S. [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Brewer, James B. [Department of Radiology, University of California, San Diego, La Jolla, California (United States); Department of Neurosciences, University of California, San Diego, La Jolla, California (United States); Farid, Nikdokht [Department of Radiology, University of California, San Diego, La Jolla, California (United States); McDonald, Carrie R. [Department of Psychiatry, University of California, San Diego, La Jolla, California (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California (United States)

    2017-02-01

    Purpose: After radiation therapy (RT) to the brain, patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved by efficient in vivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy. Methods and Materials: Hippocampal volume was measured with magnetic resonance imaging (MRI) in 52 patients who underwent fractionated, partial brain RT for primary brain tumors. Study patients had high-resolution, 3-dimensional volumetric MRI before and 1 year after RT. Images were processed using software with clearance from the US Food and Drug Administration and Conformité Européene marking for automated measurement of hippocampal volume. Automated results were inspected visually for accuracy. Tumor and surgical changes were censored. Mean hippocampal dose was tested for correlation with hippocampal atrophy 1 year after RT. Average hippocampal volume change was also calculated for hippocampi receiving high (>40 Gy) or low (<10 Gy) mean RT dose. A multivariate analysis was conducted with linear mixed-effects modeling to evaluate other potential predictors of hippocampal volume change, including patient (random effect), age, hemisphere, sex, seizure history, and baseline volume. Statistical significance was evaluated at α = 0.05. Results: Mean hippocampal dose was significantly correlated with hippocampal volume loss (r=−0.24, P=.03). Mean hippocampal volume was significantly reduced 1 year after high-dose RT (mean −6%, P=.009) but not after low-dose RT. In multivariate analysis, both RT dose and patient age were significant predictors of hippocampal atrophy (P<.01). Conclusions: The hippocampus demonstrates radiation dose–dependent atrophy after treatment for brain

  1. BDNF Val66Met in preclinical Alzheimer's disease is associated with short-term changes in episodic memory and hippocampal volume but not serum mBDNF.

    Science.gov (United States)

    Lim, Yen Ying; Rainey-Smith, Stephanie; Lim, Yoon; Laws, Simon M; Gupta, Veer; Porter, Tenielle; Bourgeat, Pierrick; Ames, David; Fowler, Christopher; Salvado, Olivier; Villemagne, Victor L; Rowe, Christopher C; Masters, Colin L; Zhou, Xin Fu; Martins, Ralph N; Maruff, Paul

    2017-11-01

    The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36-54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months. Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ- or Aβ+. At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ- Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF. While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.

  2. Sex differences in cell genesis, hippocampal volume and behavioral outcomes in a rat model of neonatal HI.

    Science.gov (United States)

    Waddell, Jaylyn; Hanscom, Marie; Shalon Edwards, N; McKenna, Mary C; McCarthy, Margaret M

    2016-01-01

    Hypoxia-ischemia (HI) of the brain in near-term and term infants is a leading cause of infant mortality and lifelong disability but current therapeutic approaches remain limited. Males consistently display greater vulnerability to the deleterious consequences of HI in both humans and animal models. Neurogenesis increases after neonatal HI and offers a potential therapeutic target for recovery. The steroid hormone estradiol has been extensively explored as a neuroprotectant in adult models of stroke but with mixed results. Less consideration has been afforded to this naturally occurring agent in the developing brain, which has unique challenges from the adult. Using a model of term HI in the rat we have explored the impact of this insult on cell genesis in the hippocampus of males and females and the ability of estradiol treatment immediately after insult to restore function. Both short-term (3 days) and long-term (7 days) post-injury were assessed and revealed that only females had markedly increased cell genesis on the short-term but both sexes were increased long-term. A battery of behavioral tests revealed motor impairment in males and compromised episodic memory while both sexes were modestly impaired in spatial memory. Juvenile social play was also depressed in both sexes after HI. Estradiol therapy improved behavioral performance in both sexes but did not reverse a deficit in hippocampal volume ipsilateral to the insult. Thus the effects of estradiol do not appear to be via cell death or proliferation but rather involve other components of neural functioning. Published by Elsevier Inc.

  3. Sex differences in cell genesis, hippocampal volume and behavioral outcomes in a rat model of neonatal HI

    Science.gov (United States)

    Waddell, Jaylyn; Hanscom, Marie; Edwards, N. Shalon; McKenna, Mary C.; McCarthy, Margaret M.

    2015-01-01

    Hypoxia ischemia (HI) of the brain in near-term and term infants is a leading cause of infant mortality and lifelong disability but current therapeutic approaches remain limited. Males consistently display greater vulnerability to the deleterious consequences of HI in both humans and animal models. Neurogenesis increases after neonatal HI and offers a potential therapeutic target for recovery. The steroid hormone estradiol has been extensively explored as a neuroprotectant in adult models of stroke but with mixed results. Less consideration has been afforded to this naturally occurring agent in the developing brain, which has unique challenges from the adult. Using a model of term HI in the rat we have explored the impact of this insult on cell genesis in the hippocampus of males and females and the ability of estradiol treatment immediately after insult to restore function. Both short-term (3 days) and long-term (7 days) post-injury were assessed and revealed that only females had markedly increased cell genesis on the short-term but both sexes were increased long-term. A battery of behavioral tests revealed motor impairment in males and compromised episodic memory while both sexes were modestly impaired in spatial memory. Juvenile social play was also depressed in both sexes after HI. Estradiol therapy improved behavioral performance in both sexes but did not reverse a deficit in hippocampal volume ipsilateral to the insult. Thus the effects of estradiol do not appear to be via cell death or proliferation but rather involve other components of neural functioning. PMID:26376217

  4. Early maternal alcohol consumption alters hippocampal DNA methylation, gene expression and volume in a mouse model.

    Directory of Open Access Journals (Sweden)

    Heidi Marjonen

    Full Text Available The adverse effects of alcohol consumption during pregnancy are known, but the molecular events that lead to the phenotypic characteristics are unclear. To unravel the molecular mechanisms, we have used a mouse model of gestational ethanol exposure, which is based on maternal ad libitum ingestion of 10% (v/v ethanol for the first 8 days of gestation (GD 0.5-8.5. Early neurulation takes place by the end of this period, which is equivalent to the developmental stage early in the fourth week post-fertilization in human. During this exposure period, dynamic epigenetic reprogramming takes place and the embryo is vulnerable to the effects of environmental factors. Thus, we hypothesize that early ethanol exposure disrupts the epigenetic reprogramming of the embryo, which leads to alterations in gene regulation and life-long changes in brain structure and function. Genome-wide analysis of gene expression in the mouse hippocampus revealed altered expression of 23 genes and three miRNAs in ethanol-exposed, adolescent offspring at postnatal day (P 28. We confirmed this result by using two other tissues, where three candidate genes are known to express actively. Interestingly, we found a similar trend of upregulated gene expression in bone marrow and main olfactory epithelium. In addition, we observed altered DNA methylation in the CpG islands upstream of the candidate genes in the hippocampus. Our MRI study revealed asymmetry of brain structures in ethanol-exposed adult offspring (P60: we detected ethanol-induced enlargement of the left hippocampus and decreased volume of the left olfactory bulb. Our study indicates that ethanol exposure in early gestation can cause changes in DNA methylation, gene expression, and brain structure of offspring. Furthermore, the results support our hypothesis of early epigenetic origin of alcohol-induced disorders: changes in gene regulation may have already taken place in embryonic stem cells and therefore can be seen in

  5. A bayesian nework based risk model for volume loss in soft soils in mechanized bored tunnels

    NARCIS (Netherlands)

    Chivatá Cárdenas, Ibsen; Al-Jibouri, Saad H.S.; Halman, Johannes I.M.

    2012-01-01

    Volume loss is one of the most important risks when boring a tunnel. This is particularly true when a tunnel is being constructed in soft soils. The risk of excessive volume loss, if materialised can lead to large consequences such as damage in buildings on the surface. This paper describes the

  6. Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.

    Directory of Open Access Journals (Sweden)

    Dennis Hernaus

    Full Text Available In the development of psychotic symptoms, environmental and genetic factors may both play a role. The reported association between childhood trauma and psychotic symptoms could therefore be moderated by single nucleotide polymorphisms (SNPs associated with the stress response, such as FK506-binding protein 5 (FKBP5 and brain-derived neurotrophic factor (BDNF. Recent studies investigating childhood trauma by SNP interactions have inconsistently found the hippocampus to be a potential target underlying these interactions. Therefore, more detailed modelling of these effects, using appropriate covariates, is required. We examined whether BDNF/FKBP5 and childhood trauma interactions affected two proxies of hippocampal integrity: (i hippocampal volume and (ii cognitive performance on a block design (BD and delayed auditory verbal task (AVLT. We also investigated whether the putative interaction was different for patients with a psychotic disorder (n = 89 compared to their non-psychotic siblings (n = 95, in order to elicit possible group-specific protective/vulnerability effects. SNPs were rs9296158, rs4713916, rs992105, rs3800373 (FKBP5 and rs6265 (BDNF. In the combined sample, no BDNF/FKBP5 by childhood trauma interactions were apparent for either outcome, and BDNF/FKBP5 by childhood trauma interactions were not different for patients and siblings. The omission of drug use and alcohol consumption sometimes yielded false positives, greatly affected explained error and influenced p-values. The consistent absence of any significant BDNF/FKBP5 by childhood trauma interactions on assessments of hippocampal integrity suggests that the effect of these interactions on psychotic symptoms is not mediated by hippocampal integrity. The importance of appropriate statistical designs and inclusion of relevant covariates should be carefully considered.

  7. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-12-01

    Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

  8. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke–Korsakoff syndrome

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-01-01

    Patients with severe Wernicke–Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation. PMID:27576603

  9. Persistent deficits in hippocampal synaptic plasticity accompany losses of hippocampus-dependent memory in a rodent model of psychosis

    Directory of Open Access Journals (Sweden)

    Valentina eWiescholleck

    2013-03-01

    Full Text Available Irreversible N-methyl-D-aspartate receptor (NMDAR antagonism is known to provoke symptoms of psychosis and schizophrenia in healthy humans. NMDAR hypofunction is believed to play a central role in the pathophysiology of both disorders and in an animal model of psychosis, that is based on irreversible antagonism of NMDARs, pronounced deficits in hippocampal synaptic plasticity have been reported shortly after antagonist treatment. Here, we examined the long-term consequences for long-term potentiation (LTP of a single acute treatment with an irreversible antagonist and investigated whether deficits are associated with memory impairments.The ability to express long-term potentiation (LTP at the perforant pathway – dentate gyrus synapse, as well as object recognition memory was assessed 1, 2, 3 and 4 weeks after a single -treatment of the antagonist, MK801. Here, LTP in freely behaving rats was significantly impaired at all time-points compared to control LTP before treatment. Object recognition memory was also significantly poorer in MK801-treated compared to vehicle-treated animals for several weeks after treatment. Histological analysis revealed no changes in brain tissue.Taken together, these data support that acute treatment with an irreversible NMDAR antagonist persistently impairs hippocampal functioning on behavioral, as well as synaptic levels. The long-term deficits in synaptic plasticity may underlie the cognitive impairments that are associated with schizophrenia-spectrum disorders.

  10. Distinct Trajectories of Cortisol Response to Prolonged Acute Stress Are Linked to Affective Responses and Hippocampal Gray Matter Volume in Healthy Females.

    Science.gov (United States)

    Admon, Roee; Treadway, Michael T; Valeri, Linda; Mehta, Malavika; Douglas, Samuel; Pizzagalli, Diego A

    2017-08-16

    The development of robust laboratory procedures for acute stress induction over the last decades has greatly advanced our understanding of stress responses in humans and their underlying neurobiological mechanisms. Nevertheless, attempts to uncover linear relationships among endocrine, neural, and affective responses to stress have generally yielded inconsistent results. Here, 79 healthy females completed a well established laboratory procedure of acute stress induction that was modified to prolong its effect. Endocrinological and subjective affect assessments revealed stress-induced increases in cortisol release and negative affect that persisted 65 and 100 min after stress onset, respectively, confirming a relatively prolonged acute stress induction. Applying latent class linear mixed modeling on individuals' patterns of cortisol responses identified three distinct trajectories of cortisol response: the hyper-response ( n = 10), moderate-response ( n = 21), and mild-response ( n = 48) groups. Notably, whereas all three groups exhibited a significant stress-induced increase in cortisol release and negative affect, the hyper-response and mild-response groups both reported more negative affect relative to the moderate-response group. Structural MRI revealed no group differences in hippocampal and amygdala volumes, yet a continuous measure of cortisol response (area under the curve) showed that high and low levels of stress-induced cortisol release were associated with less hippocampal gray matter volume compared with moderate cortisol release. Together, these results suggest that distinct trajectories of cortisol response to prolonged acute stress among healthy females may not be captured by conventional linear analyses; instead, quadratic relations may better describe links between cortisol response to stress and affective responses, as well as hippocampal structural variability. SIGNIFICANCE STATEMENT Despite substantial research, it is unclear whether and how

  11. Effects of low-level sarin and cyclosarin exposure on hippocampal microstructure in Gulf War Veterans.

    Science.gov (United States)

    Chao, Linda L; Zhang, Yu

    2018-05-04

    In early March 1991, shortly after the end of the Gulf War (GW), a munitions dump was destroyed at Khamisiyah, Iraq. Later, in 1996, the dump was found to have contained the organophosphorus (OP) nerve agents sarin and cyclosarin. We previously reported evidence of smaller hippocampal volumes in GW veterans with predicted exposure to the Khamisiyah plume compared to unexposed GW veterans. To investigate whether these macroscopic hippocampal volume changes are accompanied by microstructural alterations in the hippocampus, the current study acquired diffusion-tensor imaging (DTI), T1-, and T2-weighted images from 170 GW veterans (mean age: 53 ± 7 years), 81 of whom had predicted exposure to the Khamisiyah plume according to Department of Defense (DOD) plume modeling. We examined fractional anisotropy (FA), mean diffusivity (MD), and grey matter (GM) density from a hippocampal region of interest (ROI). Results indicate that, even after accounting for total hippocampal GM density (or hippocampal volume), age, sex, apolipoprotein ε4 genotype, and potential confounding OP pesticide exposures, hippocampal MD significantly predicted Khamisiyah exposure status (model p = 0.005, R 2  = 0.215, standardized coefficient β = 0.26, t = 2.85). Hippocampal MD was also inversely correlated with verbal memory learning performance in the entire study sample (p = 0.001). There were no differences in hippocampal FA or GM density; however, veterans with predicted Khamisiyah exposure had smaller hippocampal volumes compared to unexposed veterans. Because MD is sensitive to general microstructural disruptions that lead to increased extracellular spaces due to neuronal death, inflammation and gliosis, and/or to axonal loss or demyelination, these findings suggest that low-level exposure to the Khamisiyah plume has a detrimental, lasting effects on both macro- and micro-structure of the hippocampus. Copyright © 2018. Published by Elsevier Inc.

  12. Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures.

    Science.gov (United States)

    Weston, Matthew C; Chen, Hongmei; Swann, John W

    2014-01-01

    The Pten and Tsc1 genes both encode proteins that repress mechanistic target of rapamycin (mTOR) signaling. Disruption of either gene in the brain results in epilepsy and autism-like symptoms in humans and mouse models, therefore it is important to understand the molecular and physiological events that lead from gene disruption to disease phenotypes. Given the similar roles these two molecules play in the regulation of cellular growth and the overlap in the phenotypes that result from their loss, we predicted that the deletion of either the Pten or Tsc1 gene from autaptic hippocampal neurons would have similar effects on neuronal morphology and synaptic transmission. Accordingly, we found that loss of either Pten or Tsc1 caused comparable increases in soma size, dendrite length and action potential properties. However, the effects of Pten and Tsc1 loss on synaptic transmission were different. Loss of Pten lead to an increase in both excitatory and inhibitory neurotransmission, while loss of Tsc1 did not affect excitatory neurotransmission and reduced inhibitory transmission by decreasing mIPSC amplitude. Although the loss of Pten or Tsc1 both increased downstream mTORC1 signaling, phosphorylation of Akt was increased in Pten-ko and decreased in Tsc1-ko neurons, potentially accounting for the different effects on synaptic transmission. Despite the different effects at the synaptic level, our data suggest that loss of Pten or Tsc1 may both lead to an increase in the ratio of excitation to inhibition at the network level, an effect that has been proposed to underlie both epilepsy and autism.

  13. Ultra Low Loss Optical Fiber Cable Assemblies. Volume 2.

    Science.gov (United States)

    1983-06-07

    AND CABLE ASSEMBLY TEST PLAN I Part 1: CABLE TEST PLAN for U. S. ARMY CORADCOM Fort Monmouth, New Jersey 9~Contract # DA -A B07-78-C-29ZZ * Prepared by...VICES$ 1TEST OArg sMATED UTZx ccwITE I INSERTION LOSS £P40,,T PdA. "AT1 NO. ’we Uva ITS R.H. REQUECZ=ENT: The insertion loss of a mated =ai.r of...16(m separation between the rear of the con- nectar and the first turn on the mandrel. After which the plug and receptacle were mated, the mounting

  14. Preliminary evidence for obesity and elevations in fasting insulin mediating associations between cortisol awakening response and hippocampal volumes and frontal atrophy.

    Science.gov (United States)

    Ursache, Alexandra; Wedin, William; Tirsi, Aziz; Convit, Antonio

    2012-08-01

    Recent studies have demonstrated alterations in the cortisol awakening response (CAR) and brain abnormalities in adults with obesity and type 2 diabetes mellitus (T2DM). While adolescents with T2DM exhibit similar brain abnormalities, less is known about whether brain impairments and hypothalamic-pituitary-adrenal (HPA) axis abnormalities are already present in adolescents with pre-diabetic conditions such as insulin resistance (IR). This study included 33 adolescents with IR and 20 without IR. Adolescents with IR had a blunted CAR, smaller hippocampal volumes, and greater frontal lobe atrophy compared to controls. Mediation analyses indicated pathways whereby a smaller CAR was associated with higher BMI which was in turn associated with fasting insulin levels, which in turn was related to smaller hippocampal volume and greater frontal lobe atrophy. While we had hypothesized that HPA dysregulation may result from brain abnormalities, our findings suggest that HPA dysregulation may also impact brain structures through associations with metabolic abnormalities. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Chronic copper exposure causes spatial memory impairment, selective loss of hippocampal synaptic proteins, and activation of PKR/eIF2α pathway in mice.

    Science.gov (United States)

    Ma, Quan; Ying, Ming; Sui, Xiaojing; Zhang, Huimin; Huang, Haiyan; Yang, Linqing; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun; Yang, Xifei

    2015-01-01

    Copper is an essential element for human growth and development; however, excessive intake of copper could contribute to neurotoxicity. Here we show that chronic exposure to copper in drinking water impaired spatial memory with simultaneous selective loss of hippocampal pre-synaptic protein synapsin 1, and post-synaptic density protein (PSD)-93/95 in mice. Copper exposure was shown to elevate the levels of nitrotyrosine and 8-hydroxydeoxyguanosine (8-OHdG) in hippocampus, two markers of oxidative stress. Concurrently, we also found that copper exposure activated double stranded RNA-dependent protein kinase (PKR) as evidenced by increased ratio of phosphorylated PKR at Thr451 and total PKR and increased the phosphorylation of its downstream signaling molecule eukaryotic initiation factor 2α (eIF2α) at Ser51 in hippocampus. Consistent with activation of PKR/eIF2α signaling pathway which was shown to mediate synaptic deficit and cognitive impairment, the levels of activating transcription factor 4 (ATF-4), a downstream signaling molecule of eIF2α and a repressor of CREB-mediated gene expression, were significantly increased, while the activity of cAMP response elements binding protein (CREB) was inactivated as suggested by decreased phosphorylation of CREB at Ser133 by copper exposure. In addition, the expression of the pro-apoptotic target molecule C/EBP homology protein (CHOP) of ATF-4 was upregulated and hippocampal neuronal apoptosis was induced by copper exposure. Taken together, we propose that chronic copper exposure might cause spatial memory impairment, selective loss of synaptic proteins, and neuronal apoptosis through the mechanisms involving activation of PKR/eIF2α signaling pathway.

  16. Detection the changes of hippocampal volume and the lateral ventricle vein in the patients with depression with susceptibility weighted imaging and morphological measurement

    International Nuclear Information System (INIS)

    Song Huihui; Li Yuefeng; Wang Dongqing; Wei Chuanshe; Duan Ruigen; Zhao Tian; Zhao Liang; Jiang Ping

    2013-01-01

    Objective: To study the hippocampal structure in the patients with depression in varying degrees of severity with the combination of the susceptibility weighted imaging (SWI) and morphological measurement. Methods: Sixty patients (divided equally into mild, moderate and major group as the conditions of the severity of depression) and 20 healthy controls were scanned using the three dimensional fast low angle shot imaging sequence (3D-FLASH) and SWI. Then the morphological images were manually segmented and delineated by three doctors. The hippocampal volumes were calculated and standardized. The maximum diameter, length and the branching numbers of the Inferior ventricular vein which were clear demonstrated in the SWI were measured. The changes in the venous system and morphology among the three different degrees of severity in depression and the healthy controls were contrastively analyzed by the one-way analysis of variance. Results: Left and right hippocampal volumes: the mild group were 2246 ± 147, 2271 ± 151; the moderate group were 2028 ± 65, 2038 ± 57; the major group were 1965 ± 129, 1962 ± 110; the healthy control were 2287 ± 160, 2305 ± 171. There were statistically significant differences among the four groups (F = 7.45, 8.55, P 0.05). The diameter,length and branch numbers of the lateral ventricle vein: the mild group were (0.94 ± 0.09) mm, (12.0 ± 1.07) mm and 3.67 ± 1.03 ; the moderate group were (0.81 ± 0.04) mm, (10.2 ± 1.25) mm and 2.00 ± 0.89 ; the major group were (0.70 ± 0.08) mm, (8.6 ± 1.40) mm and 1.83 ± 0.75 ; the healthy control were (1.15 ± 0.14) mm, (14.2 ± 0.90) mm and 3.33 ± 0.82. There were statistically significant differences among the four groups (F = 17.07, 25.20, 6.65, P 0.05). As the progressive of the depression, the reduction in the length, diameter and branch numbers of the lateral ventricle vein showed more evident (the Dunnett-t of the moderate were -10.20, -11.50, -2.88, P < 0.05 ; the Dunnett-t of the

  17. Volume loss as a tool to assess kiln drying of eucalyptus wood

    Directory of Open Access Journals (Sweden)

    Djeison Cesar Batista

    Full Text Available In this study, we aimed to analyze the kiln drying quality of Eucalyptus grandis, Eucalyptus saligna and Eucalyptus dunnii woods with respect to volume loss. Wood from the three species was kiln dried together with the same drying schedule and conditions in a conventional-temperature pilot kiln. Three kinds of volume loss were evaluated: total - from saturated (initial to machined (final condition; shrinkage - from saturated to 10% moisture content; and machining - from 10% moisture content to machined condition. Eucalyptus grandis wood was the most dimensionally stable and presented the smallest volume loss due to shrinkage. Although they had different shrinkage behaviors, Eucalyptus grandis and Eucalyptus saligna woods presented the same drying quality regarding machining and total volume losses. These species can be considered the same for kiln drying. Eucalyptus dunnii wood presented the worst quality in drying, and should not be kiln dried in the same batch with the other species.

  18. Volume loss as a tool to assess kiln drying of eucalyptus wood

    OpenAIRE

    Batista,Djeison Cesar; Klitzke,Ricardo Jorge; Rocha,Márcio Pereira da; Muñiz,Graciela Inez Bolzon de; Batista,Tharcia Ribeiro

    2013-01-01

    In this study, we aimed to analyze the kiln drying quality of Eucalyptus grandis, Eucalyptus saligna and Eucalyptus dunnii woods with respect to volume loss. Wood from the three species was kiln dried together with the same drying schedule and conditions in a conventional-temperature pilot kiln. Three kinds of volume loss were evaluated: total - from saturated (initial) to machined (final) condition; shrinkage - from saturated to 10% moisture content; and machining - from 10% moisture content...

  19. A grading system for hippocampal sclerosis based on the degree of hippocampal mossy fiber sprouting

    NARCIS (Netherlands)

    Gispen, W.H.; Proper, E.A.; Jansen, G.H.; Veelen, C.W. van; Rijen, P.C. van; Graan, P.N.E. de

    2001-01-01

    Abstract. In patients suffering from temporal lobe epilepsy (TLE) a highly variable degree of hippocampal sclerosis (HS) can be observed. For standard neuropathological evaluation after hippocampal resection, neuronal cell loss in the hippocampal subareas is assessed (Wyler score 0-4) [Wyler et al.

  20. Hippocampal volumes in patients exposed to low-dose radiation to the basal brain. A case–control study in long-term survivors from cancer in the head and neck region

    International Nuclear Information System (INIS)

    Olsson, Erik; Löfdahl, Elisabet; Malmgren, Helge; Eckerström, Carl; Berg, Gertrud; Borga, Magnus; Ekholm, Sven; Johannsson, Gudmundur; Ribbelin, Susanne; Starck, Göran; Wysocka, Anna

    2012-01-01

    An earlier study from our group of long time survivors of head and neck cancer who had received a low radiation dose to the hypothalamic-pituitary region, with no signs of recurrence or pituitary dysfunction, had their quality of life (QoL) compromised as compared with matched healthy controls. Hippocampal changes have been shown to accompany several psychiatric conditions and the aim of the present study was to test whether the patients’ lowered QoL was coupled to a reduction in hippocampal volume. Patients (11 men and 4 women, age 31–65) treated for head and neck cancer 4–10 years earlier and with no sign of recurrence or pituitary dysfunction, and 15 matched controls were included. The estimated radiation doses to the basal brain including the hippocampus (1.5 – 9.3 Gy) had been calculated in the earlier study. The hippocampal volumetry was done on coronal sections from a 1.5 T MRI scanner. Measurements were done by two independent raters, blinded to patients and controls, using a custom method for computer assisted manual segmentation. The volumes were normalized for intracranial volume which was also measured manually. The paired t test and Wilcoxon’s signed rank test were used for the main statistical analysis. There was no significant difference with respect to left, right or total hippocampal volume between patients and controls. All mean differences were close to zero, and the two-tailed 95% confidence interval for the difference in total, normalized volume does not include a larger than 8% deficit in the patients. The study gives solid evidence against the hypothesis that the patients’ lowered quality of life was due to a major reduction of hippocampal volume

  1. Medial prefrontal-hippocampal connectivity during emotional memory encoding predicts individual differences in the loss of associative memory specificity

    NARCIS (Netherlands)

    Berkers, R.M.W.J.; Klumpers, F.; Fernandez, G.S.E.

    2016-01-01

    Emotionally charged items are often remembered better, whereas a paradoxical loss of specificity is found for associative emotional information (specific memory). The balance between specific and generalized emotional memories appears to show large individual differences, potentially related to

  2. Medial prefrontal–hippocampal connectivity during emotional memory encoding predicts individual differences in the loss of associative memory specificity

    NARCIS (Netherlands)

    Berkers, R.M.W.J.; Klumpers, F.; Fernandez, G.S.E.

    2016-01-01

    Emotionally charged items are often remembered better, whereas a paradoxical loss of specificity is found for associative emotional information (specific memory). The balance between specific and generalized emotional memories appears to show large individual differences, potentially related to

  3. Grey matter volume loss is associated with specific clinical motor signs in Huntington's disease.

    Science.gov (United States)

    Coppen, Emma M; Jacobs, Milou; van den Berg-Huysmans, Annette A; van der Grond, Jeroen; Roos, Raymund A C

    2018-01-01

    Motor disturbances are clinical hallmarks of Huntington's disease (HD) and involve chorea, dystonia, hypokinesia and visuomotor dysfunction. Investigating the association between specific motor signs and different regional volumes is important to understand the heterogeneity of HD. To investigate the motor phenotype of HD and associations with subcortical and cortical grey matter volume loss. Structural T1-weighted MRI scans of 79 HD patients and 30 healthy controls were used to calculate volumes of seven subcortical structures including the nucleus accumbens, hippocampus, thalamus, caudate nucleus, putamen, pallidum and amygdala. Multiple linear regression analyses, corrected for age, gender, CAG, MRI scan protocol and normalized brain volume, were performed to assess the relationship between subcortical volumes and different motor subdomains (i.e. eye movements, chorea, dystonia, hypokinesia/rigidity and gait/balance). Voxel-based morphometry analysis was used to investigate the relationship between cortical volume changes and motor signs. Subcortical volume loss of the accumbens nucleus, caudate nucleus, putamen, and pallidum were associated with higher chorea scores. No other subcortical region was significantly associated with motor symptoms after correction for multiple comparisons. Voxel-based cortical grey matter volume reductions in occipital regions were related with an increase in eye movement scores. In HD, chorea is mainly associated with subcortical volume loss, while eye movements are more related to cortical volume loss. Both subcortical and cortical degeneration has an impact on motor impairment in HD. This implies that there is a widespread contribution of different brain regions resulting in the clinical motor presentation seen in HD patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro.

    Science.gov (United States)

    Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C; Mennerick, Steven

    2015-08-05

    Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (-astrocyte) within the same culture dish. -Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal

  5. A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes

    DEFF Research Database (Denmark)

    Stomby, Andreas; Otten, Julia; Ryberg, Mats

    2017-01-01

    Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders. Diet and exercise may potentially reverse these impairments. In this study, sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were randomized...... to a Paleolithic diet (PD, n = 12) with and without high intensity exercise (PDEX, n = 12) for 12 weeks. Episodic memory function, associated functional brain responses and hippocampal gray matter volume was measured by magnetic resonance imaging. A matched, but not randomized, non-interventional group...... was included as a reference (n = 6). The PD included a high intake of unsaturated fatty acids and protein, and excluded the intake of dairy products, grains, refined sugar and salt. The exercise intervention consisted of 180 min of supervised aerobic and resistance exercise per week. Both interventions induced...

  6. Hippocampal MR volumetry

    Science.gov (United States)

    Haller, John W.; Botteron, K.; Brunsden, Barry S.; Sheline, Yvette I.; Walkup, Ronald K.; Black, Kevin J.; Gado, Mokhtar; Vannier, Michael W.

    1994-09-01

    Goal: To estimate hippocampal volumes from in vivo 3D magnetic resonance (MR) brain images and determine inter-rater and intra- rater repeatability. Objective: The precision and repeatability of hippocampal volume estimates using stereologic measurement methods is sought. Design: Five normal control and five schizophrenic subjects were MR scanned using a MPRAGE protocol. Fixed grid stereologic methods were used to estimate hippocampal volumes on a graphics workstation. The images were preprocessed using histogram analysis to standardize 3D MR image scaling from 16 to 8 bits and image volumes were interpolated to 0.5 mm3 isotropic voxels. The following variables were constant for the repeated stereologic measures: grid size, inter-slice distance (1.5 mm), voxel dimensions (0.5 mm3), number of hippocampi measured (10), total number of measurements per rater (40), and number of raters (5). Two grid sizes were tested to determine the coefficient of error associated with the number of sampled 'hits' (approximately 140 and 280) on the hippocampus. Starting slice and grid position were randomly varied to assure unbiased volume estimates. Raters were blind to subject identity, diagnosis, and side of the brain from which the image volumes were extracted and the order of subject presentation was randomized for each of the raters. Inter- and intra-rater intraclass correlation coefficients (ICC) were determined. Results: The data indicate excellent repeatability of fixed grid stereologic hippocampal volume measures when using an inter-slice distance of 1.5 mm and a 6.25 mm2 grid (inter-rater ICCs equals 0.86 - 0.97, intra- rater ICCs equals 0.85 - 0.97). One major advantage of the current study was the use of 3D MR data which significantly improved visualization of hippocampal boundaries by providing the ability to access simultaneous orthogonal views while counting stereological marks within the hippocampus. Conclusion: Stereological estimates of 3D volumes from 2D MR

  7. Volume regulated anion channel currents of rat hippocampal neurons and their contribution to oxygen-and-glucose deprivation induced neuronal death.

    Directory of Open Access Journals (Sweden)

    Huaqiu Zhang

    2011-02-01

    Full Text Available Volume-regulated anion channels (VRAC are widely expressed chloride channels that are critical for the cell volume regulation. In the mammalian central nervous system, the physiological expression of neuronal VRAC and its role in cerebral ischemia are issues largely unknown. We show that hypoosmotic medium induce an outwardly rectifying chloride conductance in CA1 pyramidal neurons in rat hippocampal slices. The induced chloride conductance was sensitive to some of the VRAC inhibitors, namely, IAA-94 (300 µM and NPPB (100 µM, but not to tamoxifen (10 µM. Using oxygen-and-glucose deprivation (OGD to simulate ischemic conditions in slices, VRAC activation appeared after OGD induced anoxic depolarization (AD that showed a progressive increase in current amplitude over the period of post-OGD reperfusion. The OGD induced VRAC currents were significantly inhibited by inhibitors for glutamate AMPA (30 µM NBQX and NMDA (40 µM AP-5 receptors in the OGD solution, supporting the view that induction of AD requires an excessive Na(+-loading via these receptors that in turn to activate neuronal VRAC. In the presence of NPPB and DCPIB in the post-OGD reperfusion solution, the OGD induced CA1 pyramidal neuron death, as measured by TO-PRO-3-I staining, was significantly reduced, although DCPIB did not appear to be an effective neuronal VRAC blocker. Altogether, we show that rat hippocampal pyramidal neurons express functional VRAC, and ischemic conditions can initial neuronal VRAC activation that may contribute to ischemic neuronal damage.

  8. Investigation of neutrophil-to-lymphocyte ratio and mean platelet volume in sudden hearing loss,

    Directory of Open Access Journals (Sweden)

    Rauf Oguzhan Kum

    2015-12-01

    Full Text Available ABSTRACT INTRODUCTION: Several theories attempt to explain the pathophysiology of sudden hearing loss. OBJECTIVE: The objective of this study was to investigate the possible role of inflammation and atherothrombosis in sudden hearing loss patients through the neutrophil-to-lymphocyte ratio and mean platelet volume. METHODS: Study design - retrospective cross-sectional historical cohort. This study was conducted on two groups: one with 59 individuals diagnosed with sudden hearing loss, and other with 59 healthy individuals with the same characteristics of gender and age distribution, neutrophil-to-lymphocyte ratio and mean platelet volume levels were measured in patients diagnosed with sudden hearing loss as well as in the control group, and it was verified whether these results interfered for a better or worse prognosis with treatment of sudden deafness. RESULTS: Neutrophil-to-lymphocyte ratio levels are much higher in patients diagnosed with sudden hearing loss compared to the control group. Similarly, mean levels of neutrophil-to-lymphocyte ratio are higher in non-recovered versus recovered patients (p = 0.001. However, we could not find a correlation with mean platelet volume levels (p > 0.05. CONCLUSION: Neutrophil-to-lymphocyte ratio is a quick and reliable indicator regarding diagnosis and prognosis of sudden hearing loss; on the other hand, mean platelet volume may be considered a less important indicator in this aspect.

  9. Loss aversion is associated with bilateral insula volume. A voxel based morphometry study.

    Science.gov (United States)

    Markett, S; Heeren, G; Montag, C; Weber, B; Reuter, M

    2016-04-21

    Loss aversion is a decision bias, reflecting a greater sensitivity to losses than to gains in a decision situation. Recent neuroscientific research has shown that mesocorticolimbic structures like ventromedial prefrontal cortex and the ventral striatum constitute a bidirectional neural system that processes gains and losses and exhibits a neural basis of loss aversion. On a functional and structural level, the amygdala and insula also seem to play an important role in the processing of loss averse behavior. By applying voxel-based morphometry to structural brain images in N=41 healthy participants, the current study provides further evidence for the relationship of brain structure and loss aversion. The results show a negative correlation of gray matter volume in bilateral posterior insula as well as left medial frontal gyrus with individual loss aversion. Hence, higher loss aversion is associated with lower gray matter volume in these brain areas. Both structures have been discussed to play important roles in the brain's salience network, where the posterior insula is involved in interoception and the detection of salience. The medial frontal gyrus might impact decision making through its dense connections with the anterior cingulate cortex. A possible explanation for the present finding is that structural differences in these regions alter the processing of losses and salience, possibly biasing decision making towards avoidance of negative outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. BDNF polymorphisms are linked to poorer working memory performance, reduced cerebellar and hippocampal volumes and differences in prefrontal cortex in a Swedish elderly population.

    Directory of Open Access Journals (Sweden)

    Samantha J Brooks

    Full Text Available BACKGROUND: Brain-derived neurotrophic factor (BDNF links learning, memory and cognitive decline in elderly, but evidence linking BDNF allele variation, cognition and brain structural differences is lacking. METHODS: 367 elderly Swedish men (n = 181 and women (n = 186 from Prospective Investigation of the Vasculature in Uppsala seniors (PIVUS were genotyped and the BDNF functional rs6265 SNP was further examined in subjects who completed the Trail Making Task (TMT, verbal fluency task, and had a magnetic resonance imaging (MRI scan. Voxel-based morphometry (VBM examined brain structure, cognition and links with BDNF. RESULTS: The functional BDNF SNP (rs6265, predicted better working memory performance on the TMT with positive association of the Met rs6265, and was linked with greater cerebellar, precuneus, left superior frontal gyrus and bilateral hippocampal volume, and reduced brainstem and bilateral posterior cingulate volumes. CONCLUSIONS: The functional BDNF polymorphism influences brain volume in regions associated with memory and regulation of sensorimotor control, with the Met rs6265 allele potentially being more beneficial to these functions in the elderly.

  11. Restoration of hippocampal growth hormone reverses stress-induced hippocampal impairment

    Directory of Open Access Journals (Sweden)

    Caitlin M. Vander Weele

    2013-06-01

    Full Text Available Though growth hormone (GH is synthesized by hippocampal neurons, where its expression is influenced by stress exposure, its function is poorly characterized. Here, we show that a regimen of chronic stress that impairs hippocampal function in rats also leads to a profound decrease in hippocampal GH levels. Restoration of hippocampal GH in the dorsal hippocampus via viral-mediated gene transfer completely reversed stress-related impairment of two hippocampus-dependent behavioral tasks, auditory trace fear conditioning and contextual fear conditioning, without affecting hippocampal function in unstressed control rats. GH overexpression reversed stress-induced decrements in both fear acquisition and long-term fear memory. These results suggest that loss of hippocampal GH contributes to hippocampal dysfunction following prolonged stress and demonstrate that restoring hippocampal GH levels following stress can promote stress resilience.

  12. Western High-Fat Diet Consumption during Adolescence Increases Susceptibility to Traumatic Stress while Selectively Disrupting Hippocampal and Ventricular Volumes

    Science.gov (United States)

    Kalyan-Masih, Priya; Vega-Torres, Julio David; Haddad, Elizabeth; Rainsbury, Sabrina; Baghchechi, Mohsen

    2016-01-01

    Abstract Psychological trauma and obesity co-occur frequently and have been identified as major risk factors for psychiatric disorders. Surprisingly, preclinical studies examining how obesity disrupts the ability of the brain to cope with psychological trauma are lacking. The objective of this study was to determine whether an obesogenic Western-like high-fat diet (WD) predisposes rats to post-traumatic stress responsivity. Adolescent Lewis rats (postnatal day 28) were fed ad libitum for 8 weeks with either the experimental WD diet (41.4% kcal from fat) or the control diet (16.5% kcal from fat). We modeled psychological trauma by exposing young adult rats to a cat odor threat. The elevated plus maze and the open field test revealed increased psychological trauma-induced anxiety-like behaviors in the rats that consumed the WD when compared with control animals 1 week after undergoing traumatic stress (p < 0.05). Magnetic resonance imaging showed significant hippocampal atrophy (20% reduction) and lateral ventricular enlargement (50% increase) in the animals fed the WD when compared with controls. These volumetric abnormalities were associated with behavioral indices of anxiety, increased leptin and FK506-binding protein 51 (FKBP51) levels, and reduced hippocampal blood vessel density. We found asymmetric structural vulnerabilities to the WD, particularly the ventral and left hippocampus and lateral ventricle. This study highlights how WD consumption during adolescence impacts key substrates implicated in post-traumatic stress disorder. Understanding how consumption of a WD affects the developmental trajectories of the stress neurocircuitry is critical, as stress susceptibility imposes a marked vulnerability to neuropsychiatric disorders. PMID:27844058

  13. Why and how to spare the hippocampus during brain radiotherapy: the developing role of hippocampal avoidance in cranial radiotherapy

    International Nuclear Information System (INIS)

    Kazda, Tomas; Slampa, Pavel; Laack, Nadia N; Jancalek, Radim; Pospisil, Petr; Sevela, Ondrej; Prochazka, Tomas; Vrzal, Miroslav; Burkon, Petr; Slavik, Marek; Hynkova, Ludmila

    2014-01-01

    The goal of this review is to summarize the rationale for and feasibility of hippocampal sparing techniques during brain irradiation. Radiotherapy is the most effective non-surgical treatment of brain tumors and with the improvement in overall survival for these patients over the last few decades, there is an effort to minimize potential adverse effects leading to possible worsening in quality of life, especially worsening of neurocognitive function. The hippocampus and associated limbic system have long been known to be important in memory formation and pre-clinical models show loss of hippocampal stem cells with radiation as well as changes in architecture and function of mature neurons. Cognitive outcomes in clinical studies are beginning to provide evidence of cognitive effects associated with hippocampal dose and the cognitive benefits of hippocampal sparing. Numerous feasibility planning studies support the feasibility of using modern radiotherapy systems for hippocampal sparing during brain irradiation. Although results of the ongoing phase II and phase III studies are needed to confirm the benefit of hippocampal sparing brain radiotherapy on neurocognitive function, it is now technically and dosimetrically feasible to create hippocampal sparing treatment plans with appropriate irradiation of target volumes. The purpose of this review is to provide a brief overview of studies that provide a rationale for hippocampal avoidance and provide summary of published feasibility studies in order to help clinicians prepare for clinical usage of these complex and challenging techniques

  14. Quantifying Standing Dead Tree Volume and Structural Loss with Voxelized Terrestrial Lidar Data

    Science.gov (United States)

    Popescu, S. C.; Putman, E.

    2017-12-01

    Standing dead trees (SDTs) are an important forest component and impact a variety of ecosystem processes, yet the carbon pool dynamics of SDTs are poorly constrained in terrestrial carbon cycling models. The ability to model wood decay and carbon cycling in relation to detectable changes in tree structure and volume over time would greatly improve such models. The overall objective of this study was to provide automated aboveground volume estimates of SDTs and automated procedures to detect, quantify, and characterize structural losses over time with terrestrial lidar data. The specific objectives of this study were: 1) develop an automated SDT volume estimation algorithm providing accurate volume estimates for trees scanned in dense forests; 2) develop an automated change detection methodology to accurately detect and quantify SDT structural loss between subsequent terrestrial lidar observations; and 3) characterize the structural loss rates of pine and oak SDTs in southeastern Texas. A voxel-based volume estimation algorithm, "TreeVolX", was developed and incorporates several methods designed to robustly process point clouds of varying quality levels. The algorithm operates on horizontal voxel slices by segmenting the slice into distinct branch or stem sections then applying an adaptive contour interpolation and interior filling process to create solid reconstructed tree models (RTMs). TreeVolX estimated large and small branch volume with an RMSE of 7.3% and 13.8%, respectively. A voxel-based change detection methodology was developed to accurately detect and quantify structural losses and incorporated several methods to mitigate the challenges presented by shifting tree and branch positions as SDT decay progresses. The volume and structural loss of 29 SDTs, composed of Pinus taeda and Quercus stellata, were successfully estimated using multitemporal terrestrial lidar observations over elapsed times ranging from 71 - 753 days. Pine and oak structural loss rates

  15. Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia

    Science.gov (United States)

    Logue, Mark W.; van Rooij, Sanne J.H.; Dennis, Emily L.; Davis, Sarah L.; Hayes, Jasmeet P.; Stevens, Jennifer S.; Densmore, Maria; Haswell, Courtney C.; Ipser, Jonathan; Koch, Saskia B.J.; Korgaonkar, Mayuresh; Lebois, Lauren A.M.; Peverill, Matthew; Baker, Justin T.; Boedhoe, Premika S.W.; Frijling, Jessie L.; Gruber, Staci A.; Harpaz-Rotem, Ilan; Jahanshad, Neda; Koopowitz, Sheri; Levy, Ifat; Nawijn, Laura; O’Connor, Lauren; Olff, Miranda; Salat, David H.; Sheridan, Margaret A.; Spielberg, Jeffrey M.; van Zuiden, Mirjam; Winternitz, Sherry R.; Wolff, Jonathan D.; Wolf, Erika J.; Wang, Xin; Wrocklage, Kristen; Abdallah, Chadi G.; Bryant, Richard A.; Geuze, Elbert; Jovanovic, Tanja; Kaufman, Milissa L.; King, Anthony P.; Krystal, John H.; Lagopoulos, Jim; Bennett, Maxwell; Lanius, Ruth; Liberzon, Israel; McGlinchey, Regina E.; McLaughlin, Katie A.; Milberg, William P.; Miller, Mark W.; Ressler, Kerry J.; Veltman, Dick J.; Stein, Dan J.; Thomaes, Kathleen; Thompson, Paul M.; Morey, Rajendra A.

    2018-01-01

    BACKGROUND Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)–Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. METHODS We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. RESULTS In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen’s d = −0.17, p = .00054), and smaller amygdalae (d = −0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063). CONCLUSIONS Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain’s response to trauma. PMID:29217296

  16. Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia.

    Science.gov (United States)

    Logue, Mark W; van Rooij, Sanne J H; Dennis, Emily L; Davis, Sarah L; Hayes, Jasmeet P; Stevens, Jennifer S; Densmore, Maria; Haswell, Courtney C; Ipser, Jonathan; Koch, Saskia B J; Korgaonkar, Mayuresh; Lebois, Lauren A M; Peverill, Matthew; Baker, Justin T; Boedhoe, Premika S W; Frijling, Jessie L; Gruber, Staci A; Harpaz-Rotem, Ilan; Jahanshad, Neda; Koopowitz, Sheri; Levy, Ifat; Nawijn, Laura; O'Connor, Lauren; Olff, Miranda; Salat, David H; Sheridan, Margaret A; Spielberg, Jeffrey M; van Zuiden, Mirjam; Winternitz, Sherry R; Wolff, Jonathan D; Wolf, Erika J; Wang, Xin; Wrocklage, Kristen; Abdallah, Chadi G; Bryant, Richard A; Geuze, Elbert; Jovanovic, Tanja; Kaufman, Milissa L; King, Anthony P; Krystal, John H; Lagopoulos, Jim; Bennett, Maxwell; Lanius, Ruth; Liberzon, Israel; McGlinchey, Regina E; McLaughlin, Katie A; Milberg, William P; Miller, Mark W; Ressler, Kerry J; Veltman, Dick J; Stein, Dan J; Thomaes, Kathleen; Thompson, Paul M; Morey, Rajendra A

    2018-02-01

    Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)-Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen's d = -0.17, p = .00054), and smaller amygdalae (d = -0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063). Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain's response to trauma. Published by Elsevier Inc.

  17. Stem volume losses in grand firs topkilled by western spruce budworm in Idaho

    Science.gov (United States)

    George T. Ferrell; Robert F. Scharpf

    1982-01-01

    Mature grand firs (Abies grandis [Dougl. ex D. Don] Lindl.) were sampled in two stands, one cutover and one virgin, in the Little Salmon River drainage in west-central Idaho, to estimate stem volume losses associated with topkilling. Damage to the stands resulted from three outbreaks of western spruce budworm (Choristoneura occidentalis...

  18. Comparing Volume Loss in Neuroanatomical Regions of Emotion versus Regions of Cognition in Healthy Aging.

    Science.gov (United States)

    Pressman, Peter S; Noniyeva, Yuliana; Bott, Nick; Dutt, Shubir; Sturm, Virginia; Miller, Bruce L; Kramer, Joel H

    2016-01-01

    Many emotional functions are relatively preserved in aging despite declines in several cognitive domains and physical health. High levels of happiness exist even among centenarians. To address the hypothesis of whether preservation of emotional function in healthy aging may relate to different rates of age-related volume loss across brain structures, we performed two volumetric analyses on structural magnetic resonance neuroimaging of a group of healthy aging research participants using Freesurfer version 5.1. Volumes selected as supporting cognition included bilateral midfrontal and lateral frontal gyri, lateral parietal and temporal cortex, and medial temporal lobes. Volumes supporting emotion included bilateral amygdala, rostral anterior cingulate, insula, orbitofrontal cortex, and nucleus accumbens. A cross-sectional analysis was performed using structural MRI scans from 258 subjects. We found no difference in proportional change between groups. A longitudinal mixed effects model was used to compare regional changes over time in a subset of 84 subjects. Again, there was no difference in proportional change over time. While our results suggest that aging does not collectively target cognitive brain regions more than emotional regions, subgroup analysis suggests relative preservation of the anterior cingulate cortex, with greater volume loss in the nucleus accumbens. Implications of these relative rates of age-related volume loss in healthy aging are discussed and merit further research.

  19. Magnitude of Myocutaneous Flaps and Factors Associated With Loss of Volume in Oral Cancer Reconstructive Surgery.

    Science.gov (United States)

    Sakamoto, Yuki; Yanamoto, Souichi; Ota, Yoshihide; Furudoi, Shungo; Komori, Takahide; Umeda, Masahiro

    2016-03-01

    Myocutaneous flaps are often used to repair oral and maxillofacial defects after surgery for oral cancer; however, their volume decreases during the postoperative period. To facilitate treatment planning, the authors measured the extent of such postoperative flap volume loss and identified associated factors in patients who underwent oral reconstruction with myocutaneous flaps. The authors designed and performed a retrospective observational study of patients who underwent reconstructive procedures involving rectus abdominal myocutaneous (RAM) or pectoralis major myocutaneous (PMMC) flaps at Tokai University Hospital, Kobe University Hospital, or Nagasaki University Hospital from April 2009 through March 2013. Flap type and other clinical variables were examined as potential predictors of flap loss. The primary outcome was flap loss at 6 months postoperatively. Correlations between each potential predictor and the primary outcome were examined using multiple regression analysis. The subjects were 75 patients whose oral defects were reconstructed with RAM flaps (n = 57) or PMMC flaps (n = 18). RAM flaps exhibited a mean volume shrinkage of 22% at 6 months postoperatively, which was less than the 27.5% displayed by the PMMC flaps, but the difference was not important. Renal failure, previous surgery of the oral region, postoperative radiotherapy, and postoperative serum albumin level were found to be meaningful risk factors for postoperative flap volume loss. The results of this study suggest that larger flaps should be used in patients who possess these risk factors or are scheduled to undergo postoperative radiotherapy. Future studies should examine the utility of postoperative nutritional management for preventing flap volume loss. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  20. MEMANTINE ATTENUATES THE OKADAIC ACID INDUCED SHORT-TERM SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS IN RATS.

    Science.gov (United States)

    Dashniani, M; Chighladze, M; Burjanadze, M; Beselia, G; Kruashvili, L

    2016-03-01

    In the present study, the possible beneficial effect of memantine on the Okadaic Acid (OA) induced spatial short-term memory impairment was examined in spatial alternation task, and the neuroprotective potential of memantine on OA-induced structural changes in the hippocampus was evaluated by Nissl staining. OA was dissolved in artificial cerebrospinal fluid (aCSF) and injected intracerebroventriculary (ICV) 200 ng in a volume of 10 μl bilaterally. Vehicle control received aCSF ICV bilaterally. Control and OA injected rats were divided into 2 subgroups injected i.p. with saline or memantine (5 mg/kg). Memantine or saline were given daily for 13 days starting from the day of OA injection. Behavioral study showed that bilateral ICV microinjection of OA induced impairment in spatial short-term memory. Nissl staining in the present study showed that the ICV microinjection of OA significantly decreased the number of surviving pyramidal neurons in the CA1 region of the hippocampus. Chronic administration of memantine effectively attenuated OA induced spatial short-term memory impairment and the OA-induced neuropathological changes in the hippocampus. Therefore, ICV injection of OA can be used as an experimental model to study mechanisms of neurodegeneration and define novel therapeutics targets for AD pathology.

  1. Induction of the Wnt antagonist Dickkopf-1 is involved in stress-induced hippocampal damage.

    Directory of Open Access Journals (Sweden)

    Francesco Matrisciano

    Full Text Available The identification of mechanisms that mediate stress-induced hippocampal damage may shed new light into the pathophysiology of depressive disorders and provide new targets for therapeutic intervention. We focused on the secreted glycoprotein Dickkopf-1 (Dkk-1, an inhibitor of the canonical Wnt pathway, involved in neurodegeneration. Mice exposed to mild restraint stress showed increased hippocampal levels of Dkk-1 and reduced expression of β-catenin, an intracellular protein positively regulated by the canonical Wnt signalling pathway. In adrenalectomized mice, Dkk-1 was induced by corticosterone injection, but not by exposure to stress. Corticosterone also induced Dkk-1 in mouse organotypic hippocampal cultures and primary cultures of hippocampal neurons and, at least in the latter model, the action of corticosterone was reversed by the type-2 glucocorticoid receptor antagonist mifepristone. To examine whether induction of Dkk-1 was causally related to stress-induced hippocampal damage, we used doubleridge mice, which are characterized by a defective induction of Dkk-1. As compared to control mice, doubleridge mice showed a paradoxical increase in basal hippocampal Dkk-1 levels, but no Dkk-1 induction in response to stress. In contrast, stress reduced Dkk-1 levels in doubleridge mice. In control mice, chronic stress induced a reduction in hippocampal volume associated with neuronal loss and dendritic atrophy in the CA1 region, and a reduced neurogenesis in the dentate gyrus. Doubleridge mice were resistant to the detrimental effect of chronic stress and, instead, responded to stress with increases in dendritic arborisation and neurogenesis. Thus, the outcome of chronic stress was tightly related to changes in Dkk-1 expression in the hippocampus. These data indicate that induction of Dkk-1 is causally related to stress-induced hippocampal damage and provide the first evidence that Dkk-1 expression is regulated by corticosteroids in the central

  2. Baseline Gray- and White Matter Volume Predict Successful Weight Loss in the Elderly

    Science.gov (United States)

    Mokhtari, Fatemeh; Paolini, Brielle M.; Burdette, Jonathan H.; Marsh, Anthony P.; Rejeski, W. Jack; Laurienti, Paul J.

    2016-01-01

    Objective The purpose of this study is to investigate if structural brain phenotypes can be used to predict weight loss success following behavioral interventions in older adults that are overweight or obese and have cardiometabolic dysfunction. Methods A support vector machine (SVM) with a repeated random subsampling validation approach was used to classify participants into the upper and lower halves of the weight loss distribution following 18 months of a weight loss intervention. Predictions were based on baseline brain gray matter (GM) and white matter (WM) volume from 52 individuals that completed the intervention and a magnetic resonance imaging session. Results The SVM resulted in an average classification accuracy of 72.62 % based on GM and WM volume. A receiver operating characteristic analysis indicated that classification performance was robust based on an area under the curve of 0.82. Conclusions Our findings suggest that baseline brain structure is able to predict weight loss success following 18 months of treatment. The identification of brain structure as a predictor of successful weight loss is an innovative approach to identifying phenotypes for responsiveness to intensive lifestyle interventions. This phenotype could prove useful in future research focusing on the tailoring of treatment for weight loss. PMID:27804273

  3. Improving volume loss estimates of the northwestern Greenland Ice Sheet 2002-2010

    DEFF Research Database (Denmark)

    Korsgaard, Niels Jákup; Khan, Shfaqat Abbas; Kjeldsen, Kristian Kjellerup

    Studies have been carried out using various methods to estimate the Greenland ice sheet mass balance. Remote sensing techniques used to determine the ice sheet volume includes airborne and satellite radar and laser methods and measurements of ice flow of outlet glaciers use InSAR satellite radar......) does not work on sloping surfaces and is affected by radar penetration into the snow. InSAR estimates require knowledge of outlet glacier thickness. GRACE has limited spatial resolution and is affected by mass variations not just from ice changes, but also from hydrologic and ocean mass variability...... and mass redistribution within the solid Earth. The accuracy of ice mass and ice volume estimates can be assessed by comparing results from different techniques. Here, we focus on volume loss estimates from ICESat, ATM and LVIS data. We estimate catchment-wide ice volume change in northwest Greenland...

  4. Abnormalities of hippocampal-cortical connectivity in temporal lobe epilepsy patients with hippocampal sclerosis

    Science.gov (United States)

    Li, Wenjing; He, Huiguang; Lu, Jingjing; Wang, Chunheng; Li, Meng; Lv, Bin; Jin, Zhengyu

    2011-03-01

    Hippocampal sclerosis (HS) is the most common damage seen in the patients with temporal lobe epilepsy (TLE). In the present study, the hippocampal-cortical connectivity was defined as the correlation between the hippocampal volume and cortical thickness at each vertex throughout the whole brain. We aimed to investigate the differences of ipsilateral hippocampal-cortical connectivity between the unilateral TLE-HS patients and the normal controls. In our study, the bilateral hippocampal volumes were first measured in each subject, and we found that the ipsilateral hippocampal volume significantly decreased in the left TLE-HS patients. Then, group analysis showed significant thinner average cortical thickness of the whole brain in the left TLE-HS patients compared with the normal controls. We found significantly increased ipsilateral hippocampal-cortical connectivity in the bilateral superior temporal gyrus, the right cingulate gyrus and the left parahippocampal gyrus of the left TLE-HS patients, which indicated structural vulnerability related to the hippocampus atrophy in the patient group. However, for the right TLE-HS patients, no significant differences were found between the patients and the normal controls, regardless of the ipsilateral hippocampal volume, the average cortical thickness or the patterns of hippocampal-cortical connectivity, which might be related to less atrophies observed in the MRI scans. Our study provided more evidence for the structural abnormalities in the unilateral TLE-HS patients.

  5. Autopsy-confirmed hippocampal-sparing Alzheimer's disease with delusional jealousy as initial manifestation.

    Science.gov (United States)

    Fujishiro, Hiroshige; Iritani, Shuji; Hattori, Miho; Sekiguchi, Hirotaka; Matsunaga, Shinji; Habuchi, Chikako; Torii, Youta; Umeda, Kentaro; Ozaki, Norio; Yoshida, Mari; Fujita, Kiyoshi

    2015-09-01

    Alzheimer's disease (AD) is clinically characterized by gradual onset over years with worsening of cognition. The initial and most prominent cognitive deficit is commonly memory dysfunction. However, a subset of AD cases has less hippocampal atrophy than would be expected relative to the predominance of cortical atrophy. These hippocampal-sparing cases have distinctive clinical features, including the presence of focal cortical clinical syndromes. Given that previous studies have indicated that severe hippocampal atrophy corresponds to prominent loss of episodic memory, it is likely that memory impairment is initially absent in hippocampal-sparing AD cases. Here, we report on a patient with an 8-year history of delusional jealousy with insidious onset who was clinically diagnosed as possible AD and pathologically confirmed to have AD with relatively preserved neurons in the hippocampus. This patient had delusional jealousy with a long pre-dementia stage, which initially was characterized by lack of memory impairment. Head magnetic resonance imaging findings showed preserved hippocampal volume with bilateral enlarged ventricles and mild-to-moderate cortical atrophy. Head single-photon emission computed tomography revealed severely decreased regional cerebral blood flow in the right temporal lobe. The resolution of the delusion was attributed to pharmacotherapy by an acetylcholinesterase inhibitor, suggesting that the occurrence of delusional jealousy was due to the disease process of AD. Although the neural basis of delusional jealousy remains unclear, this hippocampal-sparing AD case may be classified as an atypical presentation of AD. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

  6. Detection of Low-volume Blood Loss: Compensatory Reserve Versus Traditional Vital Signs

    Science.gov (United States)

    2014-01-01

    follows: heart rate (HR), blood pressure (BP), respiratory rate, and oxygen saturation. These vital signs are, however, notoriously unreliable.2,3 As...additional tests using specific equipment.22 Base deficit (BD) is a rapidly and widely available serum laboratory marker of systemic acidosis that...and mortality.23,24 BD can increase, however, because of any derangement causing metabolic acidosis and is not limited to intravascular volume loss

  7. Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury

    Science.gov (United States)

    Jolly, Amy; de Simoni, Sara; Bourke, Niall; Patel, Maneesh C; Scott, Gregory; Sharp, David J

    2018-01-01

    Abstract Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the

  8. Production and loss of H- and D- in the volume of a plasma

    International Nuclear Information System (INIS)

    Hamilton, G.W.; Bacal, M.

    1981-01-01

    The study of the production and loss of negative ions, H - and D - , in the volume of a plasma has received considerable attention since the measurement of anomalously high densities of H - in 1977. The most probable mechanism for production is dissociative attachment (DA) to vibrationally highly-excited hydrogen molecules. New diagnostics developed for this purpose are photodetachment and the extension of coherent anti-Stokes Raman scattering (CARS) systems to the sensitivity required for low-pressure gases. Measurements and calculations indicate that the important loss mechanisms are diffusion to the walls at low densities and collisional destruction of several types at plasma densities above 10 10 cm -3 . Production mechanisms must be highly efficient to compete with the losses. It appears to be straightforward to extrapolate measurements and theory to the densities above 10 12 cm -3 that are required for an intense source of D - for neutral beam injection into magnetically-confined fusion devices

  9. Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia.

    Science.gov (United States)

    La Joie, Renaud; Perrotin, Audrey; de La Sayette, Vincent; Egret, Stéphanie; Doeuvre, Loïc; Belliard, Serge; Eustache, Francis; Desgranges, Béatrice; Chételat, Gaël

    2013-01-01

    Hippocampal atrophy is a well-known feature of Alzheimer's disease (AD), but sensitivity and specificity of hippocampal volumetry are limited. Neuropathological studies have shown that hippocampal subfields are differentially vulnerable to AD; hippocampal subfield volumetry may thus prove to be more accurate than global hippocampal volumetry to detect AD. CA1, subiculum and other subfields were manually delineated from 40 healthy controls, 18 AD, 17 amnestic Mild Cognitive Impairment (aMCI), and 8 semantic dementia (SD) patients using a previously developed high resolution MRI procedure. Non-parametric group comparisons and receiver operating characteristic (ROC) analyses were conducted. Complementary analyses were conducted to evaluate differences of hemispheric asymmetry and anterior-predominance between AD and SD patients and to distinguish aMCI patients with or without β-amyloid deposition as assessed by Florbetapir-TEP. Global hippocampi were atrophied in all three patient groups and volume decreases were maximal in the CA1 subfield (22% loss in aMCI, 27% in both AD and SD; all p volumetry was more accurate than global hippocampal measurement to distinguish patients from controls (areas under the ROC curve = 0.88 and 0.76, respectively; p = 0.05) and preliminary analyses suggest that it was independent from the presence of β-amyloid deposition. In patients with SD, whereas the degree of CA1 and subiculum atrophy was similar to that found in AD patients, hemispheric and anterior-posterior asymmetry were significantly more marked than in AD with greater involvement of the left and anterior hippocampal subfields. The findings suggest that CA1 measurement is more sensitive than global hippocampal volumetry to detect structural changes at the pre-dementia stage, although the predominance of CA1 atrophy does not appear to be specific to AD pathophysiological processes.

  10. Global and regional annual brain volume loss rates in physiological aging.

    Science.gov (United States)

    Schippling, Sven; Ostwaldt, Ann-Christin; Suppa, Per; Spies, Lothar; Manogaran, Praveena; Gocke, Carola; Huppertz, Hans-Jürgen; Opfer, Roland

    2017-03-01

    The objective is to estimate average global and regional percentage brain volume loss per year (BVL/year) of the physiologically ageing brain. Two independent, cross-sectional single scanner cohorts of healthy subjects were included. The first cohort (n = 248) was acquired at the Medical Prevention Center (MPCH) in Hamburg, Germany. The second cohort (n = 316) was taken from the Open Access Series of Imaging Studies (OASIS). Brain parenchyma (BP), grey matter (GM), white matter (WM), corpus callosum (CC), and thalamus volumes were calculated. A non-parametric technique was applied to fit the resulting age-volume data. For each age, the BVL/year was derived from the age-volume curves. The resulting BVL/year curves were compared between the two cohorts. For the MPCH cohort, the BVL/year curve of the BP was an increasing function starting from 0.20% at the age of 35 years increasing to 0.52% at 70 years (corresponding values for GM ranged from 0.32 to 0.55%, WM from 0.02 to 0.47%, CC from 0.07 to 0.48%, and thalamus from 0.25 to 0.54%). Mean absolute difference between BVL/year trajectories across the age range of 35-70 years was 0.02% for BP, 0.04% for GM, 0.04% for WM, 0.11% for CC, and 0.02% for the thalamus. Physiological BVL/year rates were remarkably consistent between the two cohorts and independent from the scanner applied. Average BVL/year was clearly age and compartment dependent. These results need to be taken into account when defining cut-off values for pathological annual brain volume loss in disease models, such as multiple sclerosis.

  11. Deep gray matter volume loss drives disability worsening in multiple sclerosis

    Science.gov (United States)

    Prados, Ferran; Brownlee, Wallace J.; Altmann, Daniel R.; Tur, Carmen; Cardoso, M. Jorge; De Angelis, Floriana; van de Pavert, Steven H.; Cawley, Niamh; De Stefano, Nicola; Stromillo, M. Laura; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A.; Rovira, Alex; Sastre‐Garriga, Jaume; Vrenken, Hugo; Leurs, Cyra E.; Killestein, Joep; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Wheeler‐Kingshott, Claudia A.M. Gandini; Chard, Declan; Thompson, Alan J.; Alexander, Daniel C.; Barkhof, Frederik; Ciccarelli, Olga

    2018-01-01

    Objective Gray matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS. Methods We analyzed 3,604 brain high‐resolution T1‐weighted magnetic resonance imaging scans from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome [CIS], 708 relapsing‐remitting [RRMS], 128 secondary‐progressive [SPMS], and 125 primary‐progressive [PPMS]), over an average follow‐up of 2.41 years (standard deviation [SD] = 1.97), and 203 healthy controls (HCs; average follow‐up = 1.83 year; SD = 1.77), attending seven European centers. Disability was assessed with the Expanded Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem, and cerebral white matter. Hierarchical mixed models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time‐to‐EDSS progression. Results SPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time‐to‐EDSS progression (hazard ratio = 0.73; 95% confidence interval, 0.65, 0.82; p < 0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow‐up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (–1.45%), PPMS (–1.66%), and RRMS (–1.34%) than CIS (–0.88%) and HCs (–0.94%; p < 0.01). The rate of temporal GM atrophy in SPMS (–1.21%) was significantly faster than RRMS (–0.76%), CIS (–0.75%), and HCs (–0.51%). Similarly, the rate of parietal GM atrophy in SPMS (–1.24‐%) was faster than CIS (–0.63%) and HCs (–0.23%; all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated

  12. Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury.

    Science.gov (United States)

    Cole, James H; Jolly, Amy; de Simoni, Sara; Bourke, Niall; Patel, Maneesh C; Scott, Gregory; Sharp, David J

    2018-01-04

    Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the follow

  13. Quantifying volume loss from ice cliffs on debris-covered glaciers using high-resolution terrestrial and aerial photogrammetry

    NARCIS (Netherlands)

    Brun, Fanny; Buri, Pascal; Miles, Evan S.; Wagnon, Patrick; Steiner, J.F.; Berthier, Etienne; Ragettli, S.; Kraaijenbrink, P.D.A.; Immerzeel, W.W.; Pellicciotti, Francesca

    Mass losses originating from supraglacial ice cliffs at the lower tongues of debris-covered glaciers are a potentially large component of the mass balance, but have rarely been quantified. In this study, we develop a method to estimate ice cliff volume losses based on high-resolution topographic

  14. Three-Dimensional Photography for Quantitative Assessment of Penile Volume-Loss Deformities in Peyronie's Disease.

    Science.gov (United States)

    Margolin, Ezra J; Mlynarczyk, Carrie M; Mulhall, John P; Stember, Doron S; Stahl, Peter J

    2017-06-01

    Non-curvature penile deformities are prevalent and bothersome manifestations of Peyronie's disease (PD), but the quantitative metrics that are currently used to describe these deformities are inadequate and non-standardized, presenting a barrier to clinical research and patient care. To introduce erect penile volume (EPV) and percentage of erect penile volume loss (percent EPVL) as novel metrics that provide detailed quantitative information about non-curvature penile deformities and to study the feasibility and reliability of three-dimensional (3D) photography for measurement of quantitative penile parameters. We constructed seven penis models simulating deformities found in PD. The 3D photographs of each model were captured in triplicate by four observers using a 3D camera. Computer software was used to generate automated measurements of EPV, percent EPVL, penile length, minimum circumference, maximum circumference, and angle of curvature. The automated measurements were statistically compared with measurements obtained using water-displacement experiments, a tape measure, and a goniometer. Accuracy of 3D photography for average measurements of all parameters compared with manual measurements; inter-test, intra-observer, and inter-observer reliabilities of EPV and percent EPVL measurements as assessed by the intraclass correlation coefficient. The 3D images were captured in a median of 52 seconds (interquartile range = 45-61). On average, 3D photography was accurate to within 0.3% for measurement of penile length. It overestimated maximum and minimum circumferences by averages of 4.2% and 1.6%, respectively; overestimated EPV by an average of 7.1%; and underestimated percent EPVL by an average of 1.9%. All inter-test, inter-observer, and intra-observer intraclass correlation coefficients for EPV and percent EPVL measurements were greater than 0.75, reflective of excellent methodologic reliability. By providing highly descriptive and reliable measurements of

  15. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

    NARCIS (Netherlands)

    Papma, Janne M.; Smits, Marion; De Groot, Marius; Mattace-Raso, Francesco U. S.; van der Lugt, Aad; Vrooman, Henri A.; Niessen, W.J.; Koudstaal, Peter J.; van Swieten, John C.; van der Veen, Frederik M.; Prins, Niels D.

    2017-01-01

    Objectives: Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the

  16. The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment

    NARCIS (Netherlands)

    J.M. Papma (Janne); M. Smits (Marion); M. de Groot (Mirthe); F.U.S. Mattace Raso (Francesco); A. van der Lugt (Aad); H.A. Vrooman (Henri); W.J. Niessen (Wiro); P.J. Koudstaal (Peter Jan); J.C. van Swieten (John); F.M. van der Veen (Frederik); N.D. Prins (Niels)

    2017-01-01

    textabstractObjectives: Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer’s disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the

  17. The anatomy of the aging face: volume loss and changes in 3-dimensional topography.

    Science.gov (United States)

    Coleman, Sydney R; Grover, Rajiv

    2006-01-01

    Facial aging reflects the dynamic, cumulative effects of time on the skin, soft tissues, and deep structural components of the face, and is a complex synergy of skin textural changes and loss of facial volume. Many of the facial manifestations of aging reflect the combined effects of gravity, progressive bone resorption, decreased tissue elasticity, and redistribution of subcutaneous fullness. A convenient method for assessing the morphological effects of aging is to divide the face into the upper third (forehead and brows), middle third (midface and nose), and lower third (chin, jawline, and neck). The midface is an important factor in facial aesthetics because perceptions of facial attractiveness are largely founded on the synergy of the eyes, nose, lips, and cheek bones (central facial triangle). For aesthetic purposes, this area should be considered from a 3-dimensional rather than a 2-dimensional perspective, and restoration of a youthful 3-dimensional facial topography should be regarded as the primary goal in facial rejuvenation. Recent years have seen a significant increase in the number of nonsurgical procedures performed for facial rejuvenation. Patients seeking alternatives to surgical procedures include those who require restoration of lost facial volume, those who wish to enhance normal facial features, and those who want to correct facial asymmetry. Important factors in selecting a nonsurgical treatment option include the advantages of an immediate cosmetic result and a short recovery time.

  18. A cross-sectional MRI study of brain regional atrophy and clinical characteristics of temporal lobe epilepsy with hippocampal sclerosis.

    LENUS (Irish Health Repository)

    2012-02-01

    PURPOSE: Applying a cross-sectional design, we set out to further characterize the significance of extrahippocampal brain atrophy in a large sample of \\'sporadic\\' mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS). By evaluating the influence of epilepsy chronicity on structural atrophy, this work represents an important step towards the characterization of MRI-based volumetric measurements as genetic endophenotypes for this condition. METHODS: Using an automated brain segmentation technique, MRI-based volume measurements of several brain regions were compared between 75 patients with \\'sporadic\\' MTLE+HS and 50 healthy controls. Applying linear regression models, we examined the relationship between structural atrophy and important clinical features of MTLE+HS, including disease duration, lifetime number of partial and generalized seizures, and history of initial precipitating insults (IPIs). RESULTS: Significant volume loss was detected in ipsilateral hippocampus, amygdala, thalamus, and cerebral white matter (WM). In addition, contralateral hippocampal and bilateral cerebellar grey matter (GM) volume loss was observed in left MTLE+HS patients. Hippocampal, amygdalar, and cerebral WM volume loss correlated with duration of epilepsy. This correlation was stronger in patients with prior IPIs history. Further, cerebral WM, cerebellar GM, and contralateral hippocampal volume loss correlated with lifetime number of generalized seizures. CONCLUSION: Our findings confirm that multiple brain regions beyond the hippocampus are involved in the pathogenesis of MTLE+HS. IPIs are an important factor influencing the rate of regional atrophy but our results also support a role for processes related to epilepsy chronicity. The consequence of epilepsy chronicity on candidate brain regions has important implications on their application as genetic endophenotypes.

  19. Incentive loss and hippocampal gene expression in inbred Roman high- (RHA-I) and Roman low- (RLA-I) avoidance rats.

    Science.gov (United States)

    Sabariego, Marta; Morón, Ignacio; Gómez, M José; Donaire, Rocío; Tobeña, Adolf; Fernández-Teruel, Alberto; Martínez-Conejero, José A; Esteban, Francisco J; Torres, Carmen

    2013-11-15

    Two recent microarray and qRT-PCR studies showed that inbred Roman high- (RHA-I, low anxiety and frustration vulnerability) and low-avoidance (RLA-I, high anxiety and frustration vulnerability) rats, psychogenetically selected on the basis of their divergence in two-way avoidance performance, differed in basal whole-brain and hippocampal expression of genes related to neurotransmission, emotion, stress, aversive learning, and drug seeking behavior. We have extended these studies by analyzing strain differences in hippocampal gene expression following a frustrative experience involving reward downshift, i.e. instrumental successive negative contrast (iSNC), a phenomenon in which the sudden reduction of an expected reward induces frustration/anxiety. Food-deprived male Roman rats were exposed to a reduction in the amount of solid food presented in the goal of a straight alley (from 12 pellets in "training" trials - i.e. preshift trials- to 2 pellets in "frustration testing" trials - i.e. postshift trials-). The iSNC effect, as measured by response latencies in the "postshift" trials, appeared only in RLA-I rats (i.e. higher response latencies in the 12-2 RLA-I group as compared to the 2-2 RLA-I control group in postshift trials). Two and a half hours after the "postshift" behavioral test, hippocampi were removed and stored (-80°C) until analysis. Microarray analysis of these hippocampi showed that four differentially-expressed, and qRT-PCR-validated genes (TAAR2, THAP1, PKD2L1, NANOS), have relevance for brain function and behavior, including schizophrenia, depression, anxiety, and drug addiction, thus showing the usefulness of Roman strains as a genetic model for research on the neurogenetic basis of frustration. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Evidence for regional hippocampal damage in patients with schizophrenia

    International Nuclear Information System (INIS)

    Singh, Sadhana; Khushu, Subash; Kumar, Pawan; Goyal, Satnam; Bhatia, Triptish; Deshpande, Smita N.

    2018-01-01

    Schizophrenia patients show cognitive and mood impairments, including memory loss and depression, suggesting damage in the brain regions. The hippocampus is a brain structure that is significantly involved in memory and mood function and shows impairment in schizophrenia. In the present study, we examined the regional hippocampal changes in schizophrenia patients using voxel-based morphometry (VBM), Freesurfer, and proton magnetic resonance spectroscopy ( 1 H MRS) procedures. 1 H MRS and high-resolution T1-weighted magnetic resonance imaging were collected in both healthy control subjects (N = 28) and schizophrenia patients (N = 28) using 3-Tesla whole body MRI system. Regional hippocampal volume was analyzed using VBM and Freesufer procedures. The relative ratios of the neurometabolites were calculated using linear combination model (LCModel). Compared to controls, schizophrenia patients showed significantly decreased gray matter volume in the hippocampus. Schizophrenia patients also showed significantly reduced glutamate (Glu) and myo-inositol (mI) ratios in the hippocampus. Additionally, significant positive correlation between gray matter volume and Glu/tCr was also observed in the hippocampus in schizophrenia. Our findings provide an evidence for a possible association between structural deficits and metabolic alterations in schizophrenia patients. (orig.)

  1. Evidence for regional hippocampal damage in patients with schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Sadhana; Khushu, Subash; Kumar, Pawan [DRDO, NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi (India); Goyal, Satnam; Bhatia, Triptish; Deshpande, Smita N. [RML Hospital, Post Graduate Institute of Medical Education and Research (PGIMER), New Delhi (India)

    2018-02-15

    Schizophrenia patients show cognitive and mood impairments, including memory loss and depression, suggesting damage in the brain regions. The hippocampus is a brain structure that is significantly involved in memory and mood function and shows impairment in schizophrenia. In the present study, we examined the regional hippocampal changes in schizophrenia patients using voxel-based morphometry (VBM), Freesurfer, and proton magnetic resonance spectroscopy ({sup 1}H MRS) procedures. {sup 1}H MRS and high-resolution T1-weighted magnetic resonance imaging were collected in both healthy control subjects (N = 28) and schizophrenia patients (N = 28) using 3-Tesla whole body MRI system. Regional hippocampal volume was analyzed using VBM and Freesufer procedures. The relative ratios of the neurometabolites were calculated using linear combination model (LCModel). Compared to controls, schizophrenia patients showed significantly decreased gray matter volume in the hippocampus. Schizophrenia patients also showed significantly reduced glutamate (Glu) and myo-inositol (mI) ratios in the hippocampus. Additionally, significant positive correlation between gray matter volume and Glu/tCr was also observed in the hippocampus in schizophrenia. Our findings provide an evidence for a possible association between structural deficits and metabolic alterations in schizophrenia patients. (orig.)

  2. Temporal lobe developmental malformations and epilepsy: dual pathology and bilateral hippocampal abnormalities.

    Science.gov (United States)

    Ho, S S; Kuzniecky, R I; Gilliam, F; Faught, E; Morawetz, R

    1998-03-01

    Temporal lobe developmental malformations (TLDM) with focal cortical dysplasia and balloon cells may coexist with mesial temporal sclerosis. The true incidence of this dual pathology is unknown. Our aim was to assess the frequency of amygdala (AM)-hippocampal abnormality in a homogeneous population with this specific developmental malformation. MRI-based volumetry of the AM and hippocampal formation (HF) in 30 patients with unilateral TLDM and intractable partial epilepsy was performed. A volume normalization process defined a normal range of HF and AM volumes in control subjects, and enabled the detection of bilateral volume loss. Normalized volumes detected HF atrophy in 26 patients (nine unilateral and 17 bilateral) and AM atrophy in 18 patients (three unilateral and 15 bilateral). Visual analysis detected unilateral HF abnormality in 21 patients and bilateral abnormality in two. When compared with a group of patients with temporal lobe epilepsy and pure hippocampal sclerosis (N = 92), where volumetry revealed bilateral HF atrophy in 18%, a significant difference in the frequency of bilateral HF atrophy was found (p Dual pathology is frequent in patients with TLDM (87%), and the AM-HF abnormality is often bilateral (57%). Our data suggest that more widespread and potentially epileptogenic lesions coexist with visibly detectable unilateral TLDM. This has implications for the selection of patients for temporal lobe surgery and may influence surgical strategies.

  3. Dynamics of a hot (T∼107 K) gas cloud with volume energy losses

    International Nuclear Information System (INIS)

    Suchkov, A.A.; Berman, V.G.; Mishurov, Yu.N.

    1987-01-01

    The dynamics of a hot (T=10 6 -5x10 7 K) gas cloud with volume energy losses is investigated by numerical integration of gas dynamics equations. The dynamics is governed by a spherically symmetric gravitational field of the cloud and additional ''hidden'' mass. The cloud mass is taken in the range M 0 =10 10 -10 12 M sun , its radius R 0 =50-200 kpc, the ''hidden'' mass M ν =10 11 -3x10 13 M sun . The results show that in such sytems a structure can develop in the form of a dense compact nucleus with a radius R s 0 , and an extended rarefied hot envelope with a radius R X ∼ R 0 . Among the models involved are those where the gas cloud is either entirely blown up or entirely collapses; in some models, after the phase of initial expansion, part of the gas mass returns back into the system to form a nucleus and an envelope, and the other part leaves the system. The results are discussed in connection with the formation and early evolution of galaxies, the history of star formation and chemical evolution of galaxies, the origin of hot gas in galaxies and clusters of galaxies. It is suggested that in the real history of galaxies, formation of the nucleus and envelope corresponds to formation of galactic stellar component and X-ray halo

  4. Volume Attenuation and High Frequency Loss as Auditory Depth Cues in Stereoscopic 3D Cinema

    Science.gov (United States)

    Manolas, Christos; Pauletto, Sandra

    2014-09-01

    Assisted by the technological advances of the past decades, stereoscopic 3D (S3D) cinema is currently in the process of being established as a mainstream form of entertainment. The main focus of this collaborative effort is placed on the creation of immersive S3D visuals. However, with few exceptions, little attention has been given so far to the potential effect of the soundtrack on such environments. The potential of sound both as a means to enhance the impact of the S3D visual information and to expand the S3D cinematic world beyond the boundaries of the visuals is large. This article reports on our research into the possibilities of using auditory depth cues within the soundtrack as a means of affecting the perception of depth within cinematic S3D scenes. We study two main distance-related auditory cues: high-end frequency loss and overall volume attenuation. A series of experiments explored the effectiveness of these auditory cues. Results, although not conclusive, indicate that the studied auditory cues can influence the audience judgement of depth in cinematic 3D scenes, sometimes in unexpected ways. We conclude that 3D filmmaking can benefit from further studies on the effectiveness of specific sound design techniques to enhance S3D cinema.

  5. Ipsilateral hippocampal atrophy is associated with long-term memory dysfunction after ischemic stroke in young adults.

    Science.gov (United States)

    Schaapsmeerders, Pauline; van Uden, Inge W M; Tuladhar, Anil M; Maaijwee, Noortje A M; van Dijk, Ewoud J; Rutten-Jacobs, Loes C A; Arntz, Renate M; Schoonderwaldt, Hennie C; Dorresteijn, Lucille D A; de Leeuw, Frank-Erik; Kessels, Roy P C

    2015-07-01

    Memory impairment after stroke in young adults is poorly understood. In elderly stroke survivors memory impairments and the concomitant loss of hippocampal volume are usually explained by coexisting neurodegenerative disease (e.g., amyloid pathology) in interaction with stroke. However, neurodegenerative disease, such as amyloid pathology, is generally absent at young age. Accumulating evidence suggests that infarction itself may cause secondary neurodegeneration in remote areas. Therefore, we investigated the relation between long-term memory performance and hippocampal volume in young patients with first-ever ischemic stroke. We studied all consecutive first-ever ischemic stroke patients, aged 18-50 years, admitted to our academic hospital center between 1980 and 2010. Episodic memory of 173 patients was assessed using the Rey Auditory Verbal Learning Test and the Rey Complex Figure and compared with 87 stroke-free controls. Hippocampal volume was determined using FSL-FIRST, with manual correction. On average 10 years after stroke, patients had smaller ipsilateral hippocampal volumes compared with controls after left-hemispheric stroke (5.4%) and right-hemispheric stroke (7.7%), with most apparent memory dysfunctioning after left-hemispheric stroke. A larger hemispheric stroke was associated with a smaller ipsilateral hippocampal volume (b=-0.003, Pstroke (b=-0.028 ml, P=0.002) and right-hemispheric stroke (b=-0.015 ml, P=0.03). Our results suggest that infarction is associated with remote injury to the hippocampus, which may lower or expedite the threshold for cognitive impairment or even dementia later in life. © 2015 Wiley Periodicals, Inc.

  6. Hippocampal sclerosis in advanced age: clinical and pathological features.

    Science.gov (United States)

    Nelson, Peter T; Schmitt, Frederick A; Lin, Yushun; Abner, Erin L; Jicha, Gregory A; Patel, Ela; Thomason, Paula C; Neltner, Janna H; Smith, Charles D; Santacruz, Karen S; Sonnen, Joshua A; Poon, Leonard W; Gearing, Marla; Green, Robert C; Woodard, John L; Van Eldik, Linda J; Kryscio, Richard J

    2011-05-01

    Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer's disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer's Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n=106). For individuals aged≥95 years at death (n=179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of 'definite' Alzheimer's disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n=10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar degeneration TAR

  7. Electroencephalography reveals lower regional blood perfusion and atrophy of the temporoparietal network associated with memory deficits and hippocampal volume reduction in mild cognitive impairment due to Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Moretti DV

    2015-02-01

    Full Text Available Davide Vito MorettiNational Institute for the research and cure of Alzheimer’s disease, S. John of God, Fatebenefratelli, Brescia, Italy Background: An increased electroencephalographic (EEG upper/lower alpha power ratio has been associated with less regional blood perfusion, atrophy of the temporoparietal region of the brain, and reduction of hippocampal volume in subjects affected by mild cognitive impairment due to Alzheimer’s disease as compared with subjects who do not develop the disease. Moreover, EEG theta frequency activity is quite different in these groups. This study investigated the correlation between biomarkers and memory performance.Methods: EEG α3/α2 power ratio and cortical thickness were computed in 74 adult subjects with prodromal Alzheimer’s disease. Twenty of these subjects also underwent assessment of blood perfusion by single-photon emission computed tomography (SPECT. Pearson’s r was used to assess the correlation between cortical thinning, brain perfusion, and memory impairment.Results: In the higher α3/α2 frequency power ratio group, greater cortical atrophy and lower regional perfusion in the temporoparietal cortex was correlated with an increase in EEG theta frequency. Memory impairment was more pronounced in the magnetic resonance imaging group and SPECT groups.Conclusion: A high EEG upper/low alpha power ratio was associated with cortical thinning and less perfusion in the temporoparietal area. Moreover, atrophy and less regional perfusion were significantly correlated with memory impairment in subjects with prodromal Alzheimer’s disease. The EEG upper/lower alpha frequency power ratio could be useful for identifying individuals at risk for progression to Alzheimer’s dementia and may be of value in the clinical context.Keywords: electroencephalography, perfusion, atrophy, temporoparietal network, memory deficits, hippocampal volume, mild cognitive impairment, Alzheimer’s disease

  8. Hippocampal Neuron Number Is Unchanged 1 Year After Fractionated Whole-Brain Irradiation at Middle Age

    International Nuclear Information System (INIS)

    Shi Lei; Molina, Doris P.; Robbins, Michael E.; Wheeler, Kenneth T.; Brunso-Bechtold, Judy K.

    2008-01-01

    Purpose: To determine whether hippocampal neurons are lost 12 months after middle-aged rats received a fractionated course of whole-brain irradiation (WBI) that is expected to be biologically equivalent to the regimens used clinically in the treatment of brain tumors. Methods and Materials: Twelve-month-old Fischer 344 X Brown Norway male rats were divided into WBI and control (CON) groups (n = 6 per group). Anesthetized WBI rats received 45 Gy of 137 Cs γ rays delivered as 9 5-Gy fractions twice per week for 4.5 weeks. Control rats were anesthetized but not irradiated. Twelve months after WBI completion, all rats were anesthetized and perfused with paraformaldehyde, and hippocampal sections were immunostained with the neuron-specific antibody NeuN. Using unbiased stereology, total neuron number and the volume of the neuronal and neuropil layers were determined in the dentate gyrus, CA3, and CA1 subregions of hippocampus. Results: No differences in tissue integrity or neuron distribution were observed between the WBI and CON groups. Moreover, quantitative analysis demonstrated that neither total neuron number nor the volume of neuronal or neuropil layers differed between the two groups for any subregion. Conclusions: Impairment on a hippocampal-dependent learning and memory test occurs 1 year after fractionated WBI at middle age. The same WBI regimen, however, does not lead to a loss of neurons or a reduction in the volume of hippocampus

  9. Comparison with hippocampal atrophy and hypoperfusion in Alzheimer's disease

    International Nuclear Information System (INIS)

    Chung, YA; Kim, SH; Chung, SK; Juh, RH; Sohn, HS; Suh, TS; Choe, BY

    2004-01-01

    Objective: Hypoperfusion and hippocampal atropy of the medial temporal lobe are peculiarity of Alzheimer's disease (AD). The manual ROI (region of interest) technique for hippocampal volume estimation is specific and sensitive for the detection of hippocampal atrophy. In patients with AD reported a significant correlation between hippocampal volume and hypoperfusion. This study investigated correlations between atrophy distinct medial temporal lobe structure and hypoperfusion in hippocampal volumetry. Methods: The hippocampi were individually outlined on Tl-weighted volumetry MRI and calculated with MATLAB in 12 patients with AD. All volume measurements were performed by a segmentation technique with a combination of tracing and thresholding. The volume of a given structure in each slice was obtained by automatically counting the number of pixels within the segmented regions and multiplying the number by a voxel size. In order to permit direct regional comparisons, both of each patient's Tc- 99m ECD SPECT was then registered to the patient's MRI. Delineation continued anteriorly in each contiguous slice reaching the head of the hippocampus, which was distinguished from the overlying amygdala by the presence of the alveus or uncal recess. The right hippocampus (RH) was measured first, followed by the left hippocampus (LH). The accuracy of registration was investigated in a validation study with developed brain phantom. Results:The mean total intracranial volume of the AD was significantly smaller volume (1492.9 cm 3 ) and hypo perfused than those in normal subjects. The mean hippocampal volumes were 2.01 cm 3 and l.99 cm 3 for the RH and LH. The correlations between volume and hypoperfusion in the affected hippocampi were found to be significant; especially the medial temporal lobe is markedly hypo perfused. Conclusion: Volumetry is the most sensitive tool for the detection of hippocampal abnormality in AD, and significant correlation between asymmetry in

  10. Cognitive decline in temporal lobe epilepsy due to unilateral hippocampal sclerosis.

    Science.gov (United States)

    Marques, Carolina Mattos; Caboclo, Luís Otávio Sales Ferreira; da Silva, Tatiana Indelicato; Noffs, Maria Helena da Silva; Carrete, Henrique; Lin, Katia; Lin, Jaime; Sakamoto, Américo Ceiki; Yacubian, Elza Márcia Targas

    2007-05-01

    We assessed the cognitive performance of patients with temporal lobe epilepsy (TLE) caused by unilateral hippocampal sclerosis (HS), in comparison with that of matched, healthy controls. We report the relationship between cognitive measures and duration of epilepsy, correlating with hippocampal volumes, and the impact of educational level on cognitive decline. This study involved 61 outpatients (40 with 8 years of formal education) with unilateral HS and 61 controls. Volumetric MRI was performed on all patients and 10 controls. The results (mean, SD) of the neuropsychological tests of healthy subjects and patients were compared using the Student t and Mann-Whitney tests. Patients performed worse than controls in the neuropsychological evaluation. When adjusted z scores were used to calculate the impairment index, patients had a greater percentage of abnormal tests compared with controls. The cognitive decline, assessed through the impairment index, correlated with duration of epilepsy. Higher level of education did not protect against this decline, thus not supporting the hypothesis of cerebral reserve in this population. A significant correlation between hippocampal volumetric measures and duration of epilepsy was observed only in patients with left HS. Patients with TLE caused by HS present with cognitive morbidity that extends beyond memory deficits. Cognitive decline is associated with duration of epilepsy, and in patients with left-sided HS, duration may correlate with volumetric hippocampal loss.

  11. Automated volumetry for unilateral hippocampal sclerosis detection in patients with temporal lobe epilepsy.

    Science.gov (United States)

    Martins, Cristina; Moreira da Silva, Nadia; Silva, Guilherme; Rozanski, Verena E; Silva Cunha, Joao Paulo

    2016-08-01

    Hippocampal sclerosis (HS) is the most common cause of temporal lobe epilepsy (TLE) and can be identified in magnetic resonance imaging as hippocampal atrophy and subsequent volume loss. Detecting this kind of abnormalities through simple radiological assessment could be difficult, even for experienced radiologists. For that reason, hippocampal volumetry is generally used to support this kind of diagnosis. Manual volumetry is the traditional approach but it is time consuming and requires the physician to be familiar with neuroimaging software tools. In this paper, we propose an automated method, written as a script that uses FSL-FIRST, to perform hippocampal segmentation and compute an index to quantify hippocampi asymmetry (HAI). We compared the automated detection of HS (left or right) based on the HAI with the agreement of two experts in a group of 19 patients and 15 controls, achieving 84.2% sensitivity, 86.7% specificity and a Cohen's kappa coefficient of 0.704. The proposed method is integrated in the "Advanced Brain Imaging Lab" (ABrIL) cloud neurocomputing platform. The automated procedure is 77% (on average) faster to compute vs. the manual volumetry segmentation performed by an experienced physician.

  12. 40 CFR 63.2854 - How do I determine the weighted average volume fraction of HAP in the actual solvent loss?

    Science.gov (United States)

    2010-07-01

    ... volume fraction of HAP in the actual solvent loss? 63.2854 Section 63.2854 Protection of Environment... AIR POLLUTANTS FOR SOURCE CATEGORIES National Emission Standards for Hazardous Air Pollutants: Solvent... average volume fraction of HAP in the actual solvent loss? (a) This section describes the information and...

  13. Hippocampal multimodal structural changes and subclinical depression in healthy individuals.

    Science.gov (United States)

    Spalletta, Gianfranco; Piras, Fabrizio; Caltagirone, Carlo; Fagioli, Sabrina

    2014-01-01

    Several neuroimaging studies report reduced hippocampal volume in depressed patients. However, it is still unclear if hippocampal changes in healthy individuals can be considered a risk factor for progression to clinical depression. Here, we investigated subclinical depression and its hippocampal correlates in a non-clinical sample of healthy individuals, with particular regard to gender differences. One-hundred-two participants underwent a comprehensive clinical assessment, a high-resolution T1-weighted magnetic resonance imaging and diffusion tensor imaging protocol using a 3T MRI scanner. Data of macro-(volume) and micro-(mean diffusivity, MD) structural changes of the hippocampus were analyzed with reference to the Beck Depression Inventory score. Results of multivariate regression analyses revealed reduced bilateral volume, along with increased bilateral MD in hippocampal formation predicting subclinical depressive phenomenology only in healthy males. Conversely, subclinical depressive phenomenology in healthy female was accounted for by only lower educational level, in the absence of any hippocampal structure variations. To date, this is the only evidence reporting a relationship between subclinical depressive phenomenology and changes in hippocampal formation in healthy individuals. Our findings demonstrated that reduced volume, along with increased MD in hippocampal formation, is significantly associated with subclinical depressive phenomenology in healthy males. This encourages to study the hypothesis that early macro- and microstructural changes in hippocampi associated with subclinical depression may constitute a risk factor of developing depressive disorders in males. © 2013 Elsevier B.V. All rights reserved.

  14. Hippocampal Abnormalities after Prolonged Febrile Convulsions

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-11-01

    Full Text Available Hippocampal volume and T2 relaxation times were determined in an MRI study of 14 children with prolonged febrile convulsions (PFC who were investigated, 1 within 5 days of a PFC, and 2 at follow-up 4-8 months after the acute study, at the Institute of Child Health, University College, and Great Ormond Street Hospital, London, UK.

  15. The effect of amyloid pathology and glucose metabolism on cortical volume loss over time in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Adriaanse, Sofie M. [VU University Medical Center, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); VU University Medical Center, Department of Radiology and Nuclear Medicine, Alzheimer Center, Neuroscience Campus Amsterdam, P.O. Box 7057, Amsterdam (Netherlands); Van Dijk, Koene R.A. [Harvard University, Department of Psychology, Center for Brain Science, Cambridge, MA (United States); Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA (United States); Ossenkoppele, Rik; Tolboom, Nelleke; Zwan, Marissa D.; Barkhof, Frederik; Berckel, Bart N.M. van [VU University Medical Center, Department of Radiology and Nuclear Medicine, Alzheimer Center, Neuroscience Campus Amsterdam, Amsterdam (Netherlands); Reuter, Martin [Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA (United States); Massachusetts Institute of Technology, Computer Science and Artificial Intelligence Laboratory, Division of Health Sciences and Technology, Cambridge, MA (United States); Yaqub, Maqsood; Boellaard, Ronald; Windhorst, Albert D.; Lammertsma, Adriaan A. [VU University Medical Center, Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, Amsterdam (Netherlands); Flier, Wiesje M. van der; Scheltens, Philip [VU University Medical Center, Department of Neurology, Alzheimer Center, Neuroscience Campus Amsterdam, Amsterdam (Netherlands)

    2014-06-15

    The present multimodal neuroimaging study examined whether amyloid pathology and glucose metabolism are related to cortical volume loss over time in Alzheimer's disease (AD) patients and healthy elderly controls. Structural MRI scans of eleven AD patients and ten controls were available at baseline and follow-up (mean interval 2.5 years). Change in brain structure over time was defined as percent change of cortical volume within seven a-priori defined regions that typically show the strongest structural loss in AD. In addition, two PET scans were performed at baseline: [{sup 11}C]PIB to assess amyloid-β plaque load and [{sup 18}F]FDG to assess glucose metabolism. [{sup 11}C]PIB binding and [{sup 18}F]FDG uptake were measured in the precuneus, a region in which both amyloid deposition and glucose hypometabolism occur early in the course of AD. While amyloid-β plaque load at baseline was not related to cortical volume loss over time in either group, glucose metabolism within the group of AD patients was significantly related to volume loss over time (rho = 0.56, p < 0.05). The present study shows that in a group of AD patients amyloid-β plaque load as measured by [{sup 11}C]PIB behaves as a trait marker (i.e., all AD patients showed elevated levels of amyloid, not related to subsequent disease course), whilst hypometabolism as measured by [{sup 18}F]FDG changed over time indicating that it could serve as a state marker that is predictive of neurodegeneration. (orig.)

  16. Reduced cortical distribution volume of iodine-123 iomazenil in Alzheimer's disease as a measure of loss of synapses

    DEFF Research Database (Denmark)

    Soricelli, A; Postiglione, A; Grivet-Fojaja, M R

    1996-01-01

    Iodine-123 labelled iomazenil (IMZ) is a specific tracer for the GABAA receptor, the dominant inhibitory synapse of the brain. The cerebral distribution volume (Vd) of IMZ may be taken as a quantitative measure of these synapses in Alzheimer's disease (AD), where synaptic loss tends indiscriminat...... simultaneously. Reduced values were found in all regions except in the occipital (visual) cortex. In particular, temporal and parietal cortex Vd was significantly (P...

  17. Cerebral gray matter volume losses in essential tremor: A case-control study using high resolution tissue probability maps.

    Science.gov (United States)

    Cameron, Eric; Dyke, Jonathan P; Hernandez, Nora; Louis, Elan D; Dydak, Ulrike

    2018-03-10

    Essential tremor (ET) is increasingly recognized as a multi-dimensional disorder with both motor and non-motor features. For this reason, imaging studies are more broadly examining regions outside the cerebellar motor loop. Reliable detection of cerebral gray matter (GM) atrophy requires optimized processing, adapted to high-resolution magnetic resonance imaging (MRI). We investigated cerebral GM volume loss in ET cases using automated segmentation of MRI T1-weighted images. MRI was acquired on 47 ET cases and 36 controls. Automated segmentation and voxel-wise comparisons of volume were performed using Statistical Parametric Mapping (SPM) software. To improve upon standard protocols, the high-resolution International Consortium for Brain Mapping (ICBM) 2009a atlas and tissue probability maps were used to process each subject image. Group comparisons were performed: all ET vs. Controls, ET with head tremor (ETH) vs. Controls, and severe ET vs. An analysis of variance (ANOVA) was performed between ET with and without head tremor and controls. Age, sex, and Montreal Cognitive Assessment (MoCA) score were regressed out from each comparison. We were able to consistently identify regions of cerebral GM volume loss in ET and in ET subgroups in the posterior insula, superior temporal gyri, cingulate cortex, inferior frontal gyri and other occipital and parietal regions. There were no significant increases in GM volume in ET in any comparisons with controls. This study, which uses improved methodologies, provides evidence that GM volume loss in ET is present beyond the cerebellum, and in fact, is widespread throughout the cerebrum as well. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis.

    Science.gov (United States)

    Miller, Thomas D; Chong, Trevor T-J; Aimola Davies, Anne M; Ng, Tammy W C; Johnson, Michael R; Irani, Sarosh R; Vincent, Angela; Husain, Masud; Jacob, Saiju; Maddison, Paul; Kennard, Christopher; Gowland, Penny A; Rosenthal, Clive R

    2017-05-01

    Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P 3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  19. 4-containing GABA receptors at the hippocampal CA1 spines is a biomarker for resilience to food restriction-evoked excessive exercise and weight loss of adolescent female rats

    Science.gov (United States)

    Aoki, Chiye; Wable, Gauri; Chowdhury, Tara G.; Sabaliauskas, Nicole A.; Laurino, Kevin; Barbarich-Marsteller, Nicole C.

    2014-01-01

    Anorexia nervosa (AN) is a psychiatric illness characterized by restricted eating and an intense fear of gaining weight. Most individuals with AN are females, diagnosed first during adolescence, 40% to 80% of whom exhibit excessive exercise, and an equally high number with a history of anxiety disorder. We sought to determine the cellular basis for individual differences in AN vulnerability by using an animal model, activity-based anorexia (ABA), that is induced by combining food restriction (FR) with access to a running wheel that allows voluntary exercise. Previously, we showed that by the 4th day of FR, the ABA group of adolescent female rats exhibit > 500% greater levels of non-synaptic α4βδ−GABAARs at the plasma membrane of hippocampal CA1 pyramidal cell spines, relative to the levels found in age-matched controls that are not FR and without wheel access. Here, we show that the ABA group exhibits individual differences in body weight loss, with some losing nearly 30%, while others lose only 15%. The individual differences in weight loss are ascribable to individual differences in wheel activity that both precedes and concurs with days of FR. Moreover, the increase in activity during FR correlates strongly and negatively with α4βδ−GABAAR levels (R= - 0.9, p<0.01). This negative correlation is evident within 2 days of FR, before body weight loss approaches life-threatening levels for any individual. These findings suggest that increased shunting inhibition by α4βδ−GABAARs in spines of CA1 pyramidal neurons may participate in the protection against the ABA-inducing environmental factors of severe weight loss by suppressing excitability of the CA1 pyramidal neurons which, in turn, is related indirectly to suppression of excessive exercise. The data also indicate that, although exercise has many health benefits, it can be maladaptive to individuals with low levels of α4βδ−GABAARs in the CA1, particularly when combined with FR. PMID:24444828

  20. Predicting memory performance in normal ageing using different measures of hippocampal size

    International Nuclear Information System (INIS)

    Lye, T.C.; Creasey, H.; Kril, J.J.; Grayson, D.A.; Piguet, O.; Bennett, H.P.; Ridley, L.J.; Broe, G.A.

    2006-01-01

    A number of different methods have been employed to correct hippocampal volumes for individual variation in head size. Researchers have previously used qualitative visual inspection to gauge hippocampal atrophy. The purpose of this study was to determine the best measure(s) of hippocampal size for predicting memory functioning in 102 community-dwelling individuals over 80 years of age. Hippocampal size was estimated using magnetic resonance imaging (MRI) volumetry and qualitative visual assessment. Right and left hippocampal volumes were adjusted by three different estimates of head size: total intracranial volume (TICV), whole-brain volume including ventricles (WB+V) and a more refined measure of whole-brain volume with ventricles extracted (WB). We compared the relative efficacy of these three volumetric adjustment methods and visual ratings of hippocampal size in predicting memory performance using linear regression. All four measures of hippocampal size were significant predictors of memory performance. TICV-adjusted volumes performed most poorly in accounting for variance in memory scores. Hippocampal volumes adjusted by either measure of whole-brain volume performed equally well, although qualitative visual ratings of the hippocampus were at least as effective as the volumetric measures in predicting memory performance in community-dwelling individuals in the ninth or tenth decade of life. (orig.)

  1. The effect of blood volume loss on cardiovascular response to lower body negative pressure using a mathematical model

    Science.gov (United States)

    Karam, E. H.; Srinivasan, R. S.; Charles, J. B.; Fortney, S. M.

    1994-01-01

    Different mathematical models of varying complexity have been proposed in recent years to study the cardiovascular (CV) system. However, only a few of them specifically address the response to lower body negative pressure (LBNP), a stress that can be applied in weightlessness to predict changes in orthostatic tolerance. Also, the simulated results produced by these models agree only partially with experimental observations. In contrast, the model proposed by Melchior et al., and modified by Karam et al. is a simple representation of the CV system capable of accurately reproducing observed LBNP responses up to presyncopal levels. There are significant changes in LBNP response due to a loss of blood volume and other alterations that occur in weightlessness and related one-g conditions such as bedrest. A few days of bedrest can cause up to 15% blood volume loss (BVL), with consequent decreases in both stroke volume and cardiac output, and increases in heart rate, mean arterial pressure, and total peripheral resistance. These changes are more pronounced at higher levels of LBNP. This paper presents the results of a simulation study using our CV model to examine the effect of BVL on LBNP response.

  2. Hippocampal damage and memory impairment in congenital cyanotic heart disease.

    Science.gov (United States)

    Muñoz-López, Mónica; Hoskote, Aparna; Chadwick, Martin J; Dzieciol, Anna M; Gadian, David G; Chong, Kling; Banks, Tina; de Haan, Michelle; Baldeweg, Torsten; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2017-04-01

    Neonatal hypoxia can lead to hippocampal atrophy, which can lead, in turn, to memory impairment. To test the generalizability of this causal sequence, we examined a cohort of 41 children aged 8-16, who, having received the arterial switch operation to correct for transposition of the great arteries, had sustained significant neonatal cyanosis but were otherwise neurodevelopmentally normal. As predicted, the cohort had significant bilateral reduction of hippocampal volumes relative to the volumes of 64 normal controls. They also had significant, yet selective, impairment of episodic memory as measured by standard tests of memory, despite relatively normal levels of intelligence, academic attainment, and verbal fluency. Across the cohort, degree of memory impairment was correlated with degree of hippocampal atrophy suggesting that even as early as neonatal life no other structure can fully compensate for hippocampal injury and its special role in serving episodic long term memory. © 2017 Wiley Periodicals, Inc. © 2017 The Authors. Hippocampus Published by Wiley Periodicals, Inc.

  3. Desmin loss and mitochondrial damage precede left ventricular systolic failure in volume overload heart failure.

    Science.gov (United States)

    Guichard, Jason L; Rogowski, Michael; Agnetti, Giulio; Fu, Lianwu; Powell, Pamela; Wei, Chih-Chang; Collawn, James; Dell'Italia, Louis J

    2017-07-01

    Heart failure due to chronic volume overload (VO) in rats and humans is characterized by disorganization of the cardiomyocyte desmin/mitochondrial network. Here, we tested the hypothesis that desmin breakdown is an early and continuous process throughout VO. Male Sprague-Dawley rats had aortocaval fistula (ACF) or sham surgery and were examined 24 h and 4 and 12 wk later. Desmin/mitochondrial ultrastructure was examined by transmission electron microscopy (TEM) and immunohistochemistry (IHC). Protein and kinome analysis were performed in isolated cardiomyocytes, and desmin cleavage was assessed by mass spectrometry in left ventricular (LV) tissue. Echocardiography demonstrated a 40% decrease in the LV mass-to-volume ratio with spherical remodeling at 4 wk with ACF and LV systolic dysfunction at 12 wk. Starting at 24 h and continuing to 4 and 12 wk, with ACF there is TEM evidence of extensive mitochondrial clustering, IHC evidence of disorganization associated with desmin breakdown, and desmin protein cleavage verified by Western blot analysis and mass spectrometry. IHC results revealed that ACF cardiomyocytes at 4 and 12 wk had perinuclear translocation of αB-crystallin from the Z disk with increased α, β-unsaturated aldehyde 4-hydroxynonelal. Use of protein markers with verification by TUNEL staining and kinome analysis revealed an absence of cardiomyocyte apoptosis at 4 and 12 wk of ACF. Significant increases in protein indicators of mitophagy were countered by a sixfold increase in p62/sequestosome-1, which is indicative of an inability to complete autophagy. An early and continuous disruption of the desmin/mitochondrial architecture, accompanied by oxidative stress and inhibition of apoptosis and mitophagy, suggests its causal role in LV dilatation and systolic dysfunction in VO. NEW & NOTEWORTHY This study provides new evidence of early onset (24 h) and continuous (4-12 wk) desmin misarrangement and disruption of the normal sarcomeric and mitochondrial

  4. Loss of benefits resulting from nuclear power plant outages. Volume 2. Appendixes

    International Nuclear Information System (INIS)

    Buehring, W.A.; Peerenboom, J.P.

    1982-03-01

    Appendices are presented which contain information concerning the loss of benefits resulting from a hypothetical derating or shutdown of Zion-1, Zion-2, Oconee-1, Oconee-2, Oconee-3, Prairie Island-1, Prairie Island-2, Browns Ferry-1, Browns Ferry-2, and Browns Ferry-3 reactors; review of the General Accounting Office's analysis of the economic impact of closing the Indian Point-1, Indian Point-2, and Indian Point-3 reactors; and review of the General Accounting Office's analysis of the financial effects of the Three Mile Island-2 reactor accident

  5. Preliminary evidence of hippocampal damage in chronic users of ecstasy.

    Science.gov (United States)

    den Hollander, Bjørnar; Schouw, Marieke; Groot, Paul; Huisman, Henk; Caan, Matthan; Barkhof, Frederik; Reneman, Liesbeth

    2012-01-01

    Various studies have shown that ecstasy (3,4-methylenedioxymethamphetamine) users display significant memory impairments, whereas their performance on other cognitive tests is generally normal. The hippocampus plays an essential role in short-term memory. There are, however, no structural human data on the effects of ecstasy on the hippocampus. The objective of this study was to investigate whether the hippocampal volume of chronic ecstasy users is reduced when compared with healthy polydrug-using controls, as an indicator of hippocampal damage. The hippocampus was manually outlined in volumetric MRI scans in 10 male ecstasy users (mean age 25.4 years) and seven healthy age- and gender-matched control subjects (21.3 years). Other than the use of ecstasy, there were no statistically significant differences between both groups in exposure to other drugs of abuse and alcohol. The ecstasy users were on average drug-free for more than 2 months and had used on average 281 tablets over the past six and a half years. The hippocampal volume in the ecstasy using group was on average 10.5% smaller than the hippocampal volume in the control group (p=0.032). These data provide preliminary evidence that ecstasy users may be prone to incurring hippocampal damage, in line with previous reports of acute hippocampal sclerosis and subsequent atrophy in chronic users of this drug.

  6. Evidence of Hippocampal Structural Alterations in Gulf War Veterans With Predicted Exposure to the Khamisiyah Plume.

    Science.gov (United States)

    Chao, Linda L; Raymond, Morgan R; Leo, Cynthia K; Abadjian, Linda R

    2017-10-01

    To replicate and expand our previous findings of smaller hippocampal volumes in Gulf War (GW) veterans with predicted exposure to the Khamisiyah plume. Total hippocampal and hippocampal subfield volumes were quantified from 3 Tesla magnetic resonance images in 113 GW veterans, 62 of whom had predicted exposure as per the Department of Defense exposure models. Veterans with predicted exposure had smaller total hippocampal and CA3/dentate gyrus volumes compared with unexposed veterans, even after accounting for potentially confounding genetic and clinical variables. Among veterans with predicted exposure, memory performance was positively correlated with hippocampal volume and negatively correlated with estimated exposure levels and self-reported memory difficulties. These results replicate and extend our previous finding that low-level exposure to chemical nerve agents from the Khamisiyah pit demolition has detrimental, lasting effects on brain structure and function.

  7. Reduced cortical distribution volume of iodine-123 iomazenil in Alzheimer's disease as a measure of loss of synapses

    International Nuclear Information System (INIS)

    Soricelli, A.; Postiglione, A.; Grivet-Fojaja, M.R.; Mainenti, P.P.; Discepolo, A.; Varrone, A.; Salvatore, M.; Lassen, N.A.

    1996-01-01

    Iodine-123 labelled iomazenil (IMZ) is a specific tracer for the GABA A receptor, the dominant inhibitory synapse of the brain. The cerebral distribution volume (V d ) of IMZ may be taken as a quantitative measure of these synapses in Alzheimer's disease (AD), where synaptic loss tends indiscriminately to affect all cortical neurons, albeit more so in some areas than in others. In this pilot study we measured V d in six patients with probable AD and in five age-matched controls using a brain-dedicated single-photon emission tomography scanner allowing all cortical levels to be sampled simultaneously. Reduced values were found in all regions except in the occipital (visual) cortex. In particular, temporal and parietal cortex V d was significantly (P d averaged 69 ml/ml in normals and 51 ml/ml in AD, and parietal V d averaged 71 ml/ml in normals and 48 ml/ml in AD. These results accord well with emission tomographic studies of blood flow or labelled glucose. This supports the idea that while only measuring a subpopulation of synapses, the IMZ method reflects synaptic loss and hence functional loss in AD. The method constitutes an in vivo version of synaptic quantitation that in histopathological studies has been shown to correlated closely with the mental deterioration in AD. (orig.)

  8. Abnormalities of hippocampal signal intensity in patients with familial mesial temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Coan A.C.

    2004-01-01

    Full Text Available Mesial temporal lobe epilepsy (MTLE is associated with hippocampal atrophy and hippocampal signal abnormalities. In our series of familial MTLE (FMTLE, we found a high proportion of hippocampal abnormalities. To quantify signal abnormalities in patients with FMTLE we studied 152 individuals (46 of them asymptomatic with FMTLE. We used NIH-Image® for volumetry and signal quantification in coronal T1 inversion recovery and T2 for all cross-sections of the hippocampus. Values diverging by 2 or more SD from the control mean were considered abnormal. T2 hippocampal signal abnormalities were found in 52% of all individuals: 54% of affected subjects and 48% of asymptomatic subjects. T1 hippocampal signal changes were found in 34% of all individuals: 42.5% of affected subjects and 15% of asymptomatic subjects. Analysis of the hippocampal head (first three slices revealed T2 abnormalities in 73% of all individuals (74% of affected subjects and 72% of asymptomatic subjects and T1 abnormalities in 59% (67% of affected subjects and 41% of asymptomatic subjects. Affected individuals had smaller volumes than controls (P < 0.0001. There was no difference in hippocampal volumes between asymptomatic subjects and controls, although 39% of asymptomatic patients had hippocampal atrophy. Patients with an abnormal hippocampal signal (133 individuals had smaller ipsilateral volume, but no linear correlation could be determined. Hippocampal signal abnormalities in FMTLE were more frequently found in the hippocampal head in both affected and asymptomatic family members, including those with normal volumes. These results indicate that subtle abnormalities leading to an abnormal hippocampal signal in FMTLE are not necessarily related to seizures and may be determined by genetic factors.

  9. Loss of benefits resulting from nuclear-power-plant outages. Volume 1. Approach and analysis

    International Nuclear Information System (INIS)

    Buehring, W.A.; Peerenboom, J.P.

    1982-03-01

    This report discusses and analyzes some of the important consequences of nuclear-power-plant unavailability, and quantifies a number of technical measures of loss of benefits that may help the Nuclear Regulatory Commission make decisions involving nuclear-power-plant licensing and operation. The consequences include increased costs of system generation, increased demand for nonnuclear and often scarce fuels, and reduced system reliability. Argonne National Laboratory (ANL) developed case studies to investigate the effects of hypothetical nuclear-plant shutdowns. The studies developed quantitative measures of both short- and long-term economic, fuel use, and reliability effects that could result from the unavailability of nuclear generating units. Results showed that production costs (fuel costs plus operation and maintenance costs) increase significantly whenever an operating reactor is shut down. Production-cost increases ranged from less than 10% to over 60%; the normalized increases for the first year of reactor outage ranged from $0.125 million per MWe-year to $0.33 million per MWe-year

  10. Extent of hippocampal atrophy predicts degree of deficit in recall.

    Science.gov (United States)

    Patai, Eva Zita; Gadian, David G; Cooper, Janine M; Dzieciol, Anna M; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2015-10-13

    Which specific memory functions are dependent on the hippocampus is still debated. The availability of a large cohort of patients who had sustained relatively selective hippocampal damage early in life enabled us to determine which type of mnemonic deficit showed a correlation with extent of hippocampal injury. We assessed our patient cohort on a test that provides measures of recognition and recall that are equated for difficulty and found that the patients' performance on the recall tests correlated significantly with their hippocampal volumes, whereas their performance on the equally difficult recognition tests did not and, indeed, was largely unaffected regardless of extent of hippocampal atrophy. The results provide new evidence in favor of the view that the hippocampus is essential for recall but not for recognition.

  11. Roles of hippocampal subfields in verbal and visual episodic memory.

    Science.gov (United States)

    Zammit, Andrea R; Ezzati, Ali; Zimmerman, Molly E; Lipton, Richard B; Lipton, Michael L; Katz, Mindy J

    2017-01-15

    Selective hippocampal (HC) subfield atrophy has been reported in older adults with mild cognitive impairment and Alzheimer's disease. The goal of this study was to investigate the associations between the volume of hippocampal subfields and visual and verbal episodic memory in cognitively normal older adults. This study was conducted on a subset of 133 participants from the Einstein Aging Study (EAS), a community-based study of non-demented older adults systematically recruited from the Bronx, N.Y. All participants completed comprehensive EAS neuropsychological assessment. Visual episodic memory was assessed using the Complex Figure Delayed Recall subtest from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Verbal episodic memory was assessed using Delayed Recall from the Free and Cued Selective Reminding Test (FCSRT). All participants underwent 3T MRI brain scanning with subsequent automatic measurement of the hemispheric hippocampal subfield volumes (CA1, CA2-CA3, CA4-dente gyrus, presubiculum, and subiculum). We used linear regressions to model the association between hippocampal subfield volumes and visual and verbal episodic memory tests while adjusting for age, sex, education, and total intracranial volume. Participants had a mean age of 78.9 (SD=5.1) and 60.2% were female. Total hippocampal volume was associated with Complex Figure Delayed Recall (β=0.31, p=0.001) and FCSRT Delayed Recall (β=0.27, p=0.007); subiculum volume was associated with Complex Figure Delayed Recall (β=0.27, p=0.002) and FCSRT Delayed Recall (β=0.24, p=0.010); CA1 was associated with Complex Figure Delayed Recall (β=0.26, pepisodic memory. Our results suggest that hippocampal subfields have sensitive roles in the process of visual and verbal episodic memory. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Hippocampal sclerosis in advanced age: clinical and pathological features

    Science.gov (United States)

    Schmitt, Frederick A.; Lin, Yushun; Abner, Erin L.; Jicha, Gregory A.; Patel, Ela; Thomason, Paula C.; Neltner, Janna H.; Smith, Charles D.; Santacruz, Karen S.; Sonnen, Joshua A.; Poon, Leonard W.; Gearing, Marla; Green, Robert C.; Woodard, John L.; Van Eldik, Linda J.; Kryscio, Richard J.

    2011-01-01

    Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer’s disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer’s Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n = 106). For individuals aged ≥95 years at death (n = 179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of ‘definite’ Alzheimer’s disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n = 10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar

  13. Abnormal Hippocampal Morphology in Dissociative Identity Disorder and Post-Traumatic Stress Disorder Correlates with Childhood Trauma and Dissociative Symptoms

    NARCIS (Netherlands)

    Chalavi, Sima; Vissia, Eline M.; Giesen, Mechteld E.; Nijenhuis, Ellert R. S.; Draijer, Nel; Cole, James H.; Dazzan, Paola; Pariante, Carmine M.; Madsen, Sarah K.; Rajagopalan, Priya; Thompson, Paul M.; Toga, Arthur W.; Veltman, Dick J.; Reinders, Antje A. T. S.

    Smaller hippocampal volume has been reported in individuals with post-traumatic stress disorder (PTSD) and dissociative identity disorder (DID), but the regional specificity of hippocampal volume reductions and the association with severity of dissociative symptoms and/or childhood traumatization

  14. Abnormal Hippocampal Morphology in Dissociative Identity Disorder and Post-Traumatic Stress Disorder Correlates with Childhood Trauma and Dissociative Symptoms

    NARCIS (Netherlands)

    Chalavi, S.; Vissia, E.M.; Giesen, M.E.; Nijenhuis, E.R.S.; Draijer, N.; Cole, J.H.; Dazzan, P.; Pariante, C.M.; Madsen, S.K.; Rajagopalan, P.; Thompson, P.M.; Toga, A.W.; Veltman, D.J.; Reinders, A.A.T.S

    2015-01-01

    Smaller hippocampal volume has been reported in individuals with post-traumatic stress disorder (PTSD) and dissociative identity disorder (DID), but the regional specificity of hippocampal volume reductions and the association with severity of dissociative symptoms and/or childhood traumatization

  15. Episodic autobiographical memory is associated with variation in the size of hippocampal subregions.

    Science.gov (United States)

    Palombo, Daniela J; Bacopulos, Agnes; Amaral, Robert S C; Olsen, Rosanna K; Todd, Rebecca M; Anderson, Adam K; Levine, Brian

    2018-02-01

    Striking individual differences exist in the human capacity to recollect past events, yet, little is known about the neural correlates of such individual differences. Studies investigating hippocampal volume in relation to individual differences in laboratory measures of episodic memory in young adults suggest that whole hippocampal volume is unrelated (or even negatively associated) with episodic memory. However, anatomical and functional specialization across hippocampal subregions suggests that individual differences in episodic memory may be linked to particular hippocampal subregions, as opposed to whole hippocampal volume. Given that the DG/CA 2/3 circuitry is thought to be especially critical for supporting episodic memory in humans, we predicted that the volume of this region would be associated with individual variability in episodic memory. This prediction was supported using high-resolution MRI of the hippocampal subfields and measures of real-world (autobiographical) episodic memory. In addition to the association with DG/CA 2/3 , we further observed a relationship between episodic autobiographical memory and subiculum volume, whereas no association was observed with CA 1 or with whole hippocampal volume. These findings provide insight into the possible neural substrates that mediate individual differences in real-world episodic remembering in humans. © 2017 Wiley Periodicals, Inc.

  16. Cholinergic denervation of the hippocampal formation does not produce long-term changes in glucose metabolism

    International Nuclear Information System (INIS)

    Harrell, L.E.; Davis, J.N.

    1984-01-01

    Decreased glucose metabolism is found in Alzheimer's disease associated with a loss of cholinergic neurons. The relationship between the chronic cholinergic denervation produced by medial septal lesions and glucose metabolism was studied using 2-deoxy-D-[ 3 H]glucose in the rat hippocampal formation. Hippocampal glucose metabolism was increased 1 week after medial septal lesions. Three weeks after lesions, glucose metabolism was profoundly suppressed in all regions. By 3 months, intraregional hippocampal glucose metabolism had returned to control values. Our results demonstrate that chronic cholinergic denervation of the hippocampal formation does not result in permanent alterations of metabolic activity

  17. Prediction of dementia by hippocampal shape analysis

    DEFF Research Database (Denmark)

    Achterberg, Hakim C.; van der Lijn, Fedde; den Heijer, Tom

    2010-01-01

    This work investigates the possibility of predicting future onset of dementia in subjects who are cognitively normal, using hippocampal shape and volume information extracted from MRI scans. A group of 47 subjects who were non-demented normal at the time of the MRI acquisition, but were diagnosed...... with dementia during a 9 year follow-up period, was selected from a large population based cohort study. 47 Age and gender matched subjects who stayed cognitively intact were selected from the same cohort study as a control group. The hippocampi were automatically segmented and all segmentations were inspected...... and, if necessary, manually corrected by a trained observer. From this data a statistical model of hippocampal shape was constructed, using an entropy-based particle system. This shape model provided the input for a Support Vector Machine classifier to predict dementia. Cross validation experiments...

  18. Hippocampal MRI volumetry at 3 Tesla: reliability and practical guidance.

    Science.gov (United States)

    Jeukens, Cécile R L P N; Vlooswijk, Mariëlle C G; Majoie, H J Marian; de Krom, Marc C T F M; Aldenkamp, Albert P; Hofman, Paul A M; Jansen, Jacobus F A; Backes, Walter H

    2009-09-01

    Although volumetry of the hippocampus is considered to be an established technique, protocols reported in literature are not described in great detail. This article provides a complete and detailed protocol for hippocampal volumetry applicable to T1-weighted magnetic resonance (MR) images acquired at 3 Tesla, which has become the standard for structural brain research. The protocol encompasses T1-weighted image acquisition at 3 Tesla, anatomic guidelines for manual hippocampus delineation, requirements of delineation software, reliability measures, and criteria to assess and ensure sufficient reliability. Moreover, the validity of the correction for total intracranial volume size was critically assessed. The protocol was applied by 2 readers to the MR images of 36 patients with cryptogenic localization-related epilepsy, 4 patients with unilateral hippocampal sclerosis, and 20 healthy control subjects. The uncorrected hippocampal volumes were 2923 +/- 500 mm3 (mean +/- SD) (left) and 3120 +/- 416 mm3 (right) for the patient group and 3185 +/- 411 mm3 (left) and 3302 +/- 411 mm3 (right) for the healthy control group. The volume of the 4 pathologic hippocampi of the patients with unilateral hippocampal sclerosis was 2980 +/- 422 mm3. The inter-reader reliability values were determined: intraclass-correlation-coefficient (ICC) = 0.87 (left) and 0.86 (right), percentage volume difference (VD) = 7.0 +/- 4.7% (left) and 6.0 +/- 3.8% (right), and overlap ratio (OR) = 0.82 +/- 0.04 (left) and 0.82 +/- 0.03 (right). The positive Pearson correlation between hippocampal volume and total intracranial volume was found to be low: r = 0.48 (P = 0.03, left) and r = 0.62 (P = 0.004, right) and did not significantly reduce the volumetric variances, showing the limited benefit of the brain size correction. A protocol was described to determine hippocampal volumes based on 3 Tesla MR images with high inter-reader reliability. Although the reliability of hippocampal volumetry at 3 Tesla

  19. 3D Volumetry and its Correlation Between Postoperative Gastric Volume and Excess Weight Loss After Sleeve Gastrectomy.

    Science.gov (United States)

    Hanssen, Andrés; Plotnikov, Sergio; Acosta, Geylor; Nuñez, José Tomas; Haddad, José; Rodriguez, Carmen; Petrucci, Claudia; Hanssen, Diego; Hanssen, Rafael

    2018-03-01

    The volume of the postoperative gastric remnant is a key factor in excess weight loss (EWL) after sleeve gastrectomy (SG). Traditional methods to estimate gastric volume (GV) after bariatric procedures are often inaccurate; usually conventional biplanar contrast studies are used. Thirty patients who underwent SG were followed prospectively and evaluated at 6 months after the surgical procedure, performing 3D CT reconstruction and gastric volumetry, to establish its relationship with EWL. The gastric remnant was distended with effervescent sodium bicarbonate given orally. Helical CT images were acquired and reconstructed; GV was estimated with the software of the CT device. The relationship between GV and EWL was analyzed. The study allowed estimating the GV in all patients. A dispersion diagram showed an inverse relationship between GV and %EWL. 55.5% of patients with GV ≤ 100 ml had %EWL 25-75% and 38.8% had an %EWL above 75% and patients with GV ≥ 100 ml had an %EWL under 25% (50% of patients) or between 25 and 75% (50% of this group). The Pearson's correlation coefficient was R = 6.62, with bilateral significance (p ≤ .01). The Chi-square result correlating GV and EWL showed a significance of .005 (p ≤ .01). The 3D reconstructions showed accurately the shape and anatomic details of the gastric remnant. 3D volumetry CT scans accurately estimate GV after SG. A significant relationship between GV and EWL 6 months after SG was established, seeming that GV ≥ 100 ml at 6 months of SG is associated with poor EWL.

  20. Hippocampal ''gliosis only'' on MR imaging represents a distinct entity in epilepsy patients

    Energy Technology Data Exchange (ETDEWEB)

    Hattingen, Elke; Enkirch, Simon Jonas; Jurcoane, Alina; Kruse, Maximilian [University Clinics Bonn, Neuroradiology, Department of Radiology, Bonn (Germany); Delev, Daniel [University Clinics Bonn, Department of Neurosurgery, Bonn (Germany); University Clinics Freiburg, Department of Neurosurgery, Freiburg (Germany); Grote, Alexander [University Clinics Bonn, Department of Neurosurgery, Bonn (Germany); Evangelic Hospital of Bethel, Department of Neurosurgery, Bielefeld (Germany); Becker, Albert [University Clinics Bonn, Institute of Neuropathology, Bonn (Germany)

    2018-02-15

    The purpose of this study is to evaluate whether patients with drug-resistant mesial temporal lobe epilepsy (TLE) due to hippocampal ''gliosis only'' have different MRI features than those with hippocampal sclerosis (HS). Most TLE patients have HS corresponding to severe neuronal loss and gliosis, but a few have ''gliosis only'' without significant reduction of neuronal density. We analyzed the morphology of cerebral 3 T MRIs (T1, T2, and FLAIR) of 103 patients with HS and 20 with ''gliosis only'' concerning hippocampal and amygdala aspect, volumes, and signal intensity (SI) using Fisher's exact test, Student's t test, and principal component analysis. Visually, the ipsilateral hippocampus was hyperintense in both groups, but SI was markedly increased in 74% of HS and in 25% of ''gliosis only'' patients; the ipsilateral hippocampus was smaller in 92% of HS and in 50% of ''gliosis only'' patients, and its internal architecture was lost in 57% of HS and 5% of ''gliosis only'' patients; the contralateral hippocampal SI was altered in 25% of HS and in 70% of ''gliosis only'' patients (all p < 0.001). Ipsilateral hippocampus of HS patients had lower volume (mean ± SD 2.86 ± 0.87 ml) compared with that of ''gliosis only'' patients (3.4 ± 1.02 ml) and had higher SI than the contralateral hippocampus of HS patients and then the hippocampus of ''gliosis only'' patients (all p < 0.01). ''Gliosis only'' has different MRI hippocampal characteristics than HS: less volume loss, less increase of the T2-w signal intensity, preservation of internal architecture, and more contralateral affection. (orig.)

  1. Hippocampal ''gliosis only'' on MR imaging represents a distinct entity in epilepsy patients

    International Nuclear Information System (INIS)

    Hattingen, Elke; Enkirch, Simon Jonas; Jurcoane, Alina; Kruse, Maximilian; Delev, Daniel; Grote, Alexander; Becker, Albert

    2018-01-01

    The purpose of this study is to evaluate whether patients with drug-resistant mesial temporal lobe epilepsy (TLE) due to hippocampal ''gliosis only'' have different MRI features than those with hippocampal sclerosis (HS). Most TLE patients have HS corresponding to severe neuronal loss and gliosis, but a few have ''gliosis only'' without significant reduction of neuronal density. We analyzed the morphology of cerebral 3 T MRIs (T1, T2, and FLAIR) of 103 patients with HS and 20 with ''gliosis only'' concerning hippocampal and amygdala aspect, volumes, and signal intensity (SI) using Fisher's exact test, Student's t test, and principal component analysis. Visually, the ipsilateral hippocampus was hyperintense in both groups, but SI was markedly increased in 74% of HS and in 25% of ''gliosis only'' patients; the ipsilateral hippocampus was smaller in 92% of HS and in 50% of ''gliosis only'' patients, and its internal architecture was lost in 57% of HS and 5% of ''gliosis only'' patients; the contralateral hippocampal SI was altered in 25% of HS and in 70% of ''gliosis only'' patients (all p < 0.001). Ipsilateral hippocampus of HS patients had lower volume (mean ± SD 2.86 ± 0.87 ml) compared with that of ''gliosis only'' patients (3.4 ± 1.02 ml) and had higher SI than the contralateral hippocampus of HS patients and then the hippocampus of ''gliosis only'' patients (all p < 0.01). ''Gliosis only'' has different MRI hippocampal characteristics than HS: less volume loss, less increase of the T2-w signal intensity, preservation of internal architecture, and more contralateral affection. (orig.)

  2. Observations of Recent Arctic Sea Ice Volume Loss and Its Impact on Ocean-Atmosphere Energy Exchange and Ice Production

    Science.gov (United States)

    Kurtz, N. T.; Markus, T.; Farrell, S. L.; Worthen, D. L.; Boisvert, L. N.

    2011-01-01

    Using recently developed techniques we estimate snow and sea ice thickness distributions for the Arctic basin through the combination of freeboard data from the Ice, Cloud, and land Elevation Satellite (ICESat) and a snow depth model. These data are used with meteorological data and a thermodynamic sea ice model to calculate ocean-atmosphere heat exchange and ice volume production during the 2003-2008 fall and winter seasons. The calculated heat fluxes and ice growth rates are in agreement with previous observations over multiyear ice. In this study, we calculate heat fluxes and ice growth rates for the full distribution of ice thicknesses covering the Arctic basin and determine the impact of ice thickness change on the calculated values. Thinning of the sea ice is observed which greatly increases the 2005-2007 fall period ocean-atmosphere heat fluxes compared to those observed in 2003. Although there was also a decline in sea ice thickness for the winter periods, the winter time heat flux was found to be less impacted by the observed changes in ice thickness. A large increase in the net Arctic ocean-atmosphere heat output is also observed in the fall periods due to changes in the areal coverage of sea ice. The anomalously low sea ice coverage in 2007 led to a net ocean-atmosphere heat output approximately 3 times greater than was observed in previous years and suggests that sea ice losses are now playing a role in increasing surface air temperatures in the Arctic.

  3. Presbycusis: a human temporal bone study of individuals with flat audiometric patterns of hearing loss using a new method to quantify stria vascularis volume.

    Science.gov (United States)

    Nelson, Erik G; Hinojosa, Raul

    2003-10-01

    The purpose of this study was to determine the prevalence of stria vascularis atrophy in individuals with presbycusis and flat audiometric patterns of hearing loss. Individuals with presbycusis have historically been categorized by the shape of their audiograms, and flat audiometric thresholds have been reported to be associated with atrophy of the stria vascularis. Stria vascularis volume was not measured in these studies. Retrospective case review. Archival human temporal bones from individuals with presbycusis were selected on the basis of strict audiometric criteria for flat audiometric thresholds. Six temporal bones that met these criteria were identified and compared with 10 temporal bones in individuals with normal hearing. A unique quantitative method was developed to measure the stria vascularis volume in these temporal bones. The hair cell and spiral ganglion cell populations also were quantitatively evaluated. Only one of the six individuals with presbycusis and flat audiometric thresholds had significant atrophy of the stria vascularis. This individual with stria vascularis atrophy also had reduced inner hair cell, outer hair cell, and ganglion cell populations. Three of the individuals with presbycusis had spiral ganglion cell loss, three individuals had inner hair cell loss, and all six individuals had outer hair cell loss. The results of this investigation suggest that individuals with presbycusis and flat audiometric patterns of hearing loss infrequently have stria vascularis atrophy. Outer hair cell loss alone or in combination with inner hair cell or ganglion cell loss may be the cause of flat audiometric thresholds in individuals with presbycusis.

  4. Adult Hippocampal Neurogenesis is Impaired by Transient and Moderate Developmental Thyroid Hormone Disruption

    Science.gov (United States)

    Severe thyroid hormone (TH) deprivation during development impairs neurogenesis throughout the brain. The hippocampus also maintains a capacity for neurogenesis throughout life which is reduced in adult-onset hypothyroidism. This study examined hippocampal volume in the neonate a...

  5. A Model for Estimating Current and Future Timber Volume Loss from Stem Decay Caused by Heterobasidion annosum and Other Fungi in Stands of True Fir

    Science.gov (United States)

    Gregory M. Filip

    1989-01-01

    In 1979, an equation was developed to estimate the percentage of current and future timber volume loss due to stem decay caused by Heterobasidion annosum and other fungi in advance regeneration stands of grand and white fir in eastern Oregon and Washington. Methods for using and testing the equation are presented. Extensive testing in 1988 showed the...

  6. The Sensitivity of Arctic Ozone Loss to Polar Stratospheric Cloud Volume and Chlorine and Bromine Loading in a Chemistry and Transport Model

    Science.gov (United States)

    Douglass, A. R.; Stolarski, R. S.; Strahan, S. E.; Polansky, B. C.

    2006-01-01

    The sensitivity of Arctic ozone loss to polar stratospheric cloud volume (V(sub PSC)) and chlorine and bromine loading is explored using chemistry and transport models (CTMs). A simulation using multi-decadal output from a general circulation model (GCM) in the Goddard Space Flight Center (GSFC) CTM complements one recycling a single year s GCM output in the Global Modeling Initiative (GMI) CTM. Winter polar ozone loss in the GSFC CTM depends on equivalent effective stratospheric chlorine (EESC) and polar vortex characteristics (temperatures, descent, isolation, polar stratospheric cloud amount). Polar ozone loss in the GMI CTM depends only on changes in EESC as the dynamics repeat annually. The GSFC CTM simulation reproduces a linear relationship between ozone loss and Vpsc derived from observations for 1992 - 2003 which holds for EESC within approx.85% of its maximum (approx.1990 - 2020). The GMI simulation shows that ozone loss varies linearly with EESC for constant, high V(sub PSC).

  7. Qualitative and Quantitative Hippocampal MRI Assessments in Intractable Epilepsy

    Directory of Open Access Journals (Sweden)

    Paramdeep Singh

    2013-01-01

    Full Text Available Aims. To acquire normative data of hippocampal volumes and T2 relaxation times, to evaluate and compare qualitative and quantitative assessments in evaluating hippocampi in patients with different durations of intractable epilepsy, and to propose an imaging protocol based on performance of these techniques. Methods. MRI analysis was done in 50 nonepileptic controls and 30 patients with intractable epilepsy on 1.5T scanner. Visual assessment and hippocampal volumetry were done on oblique coronal IR/T2W and T1W MP-RAGE images, respectively. T2 relaxation times were measured using 16-echo Carr-Purcell-Meiboom-Gill sequence. Volumetric data was normalized for variation in head size between individuals. Patients were divided into temporal ( and extratemporal ( groups based on clinical and EEG localization. Results. In controls, right hippocampal volume was slightly more than the left with no effect of age or gender. In TLE patients, hippocampal volumetry provided maximum concordance with EEG. Visual assessment of unilateral pathology concurred well with measured quantitative values but poorly in cases with bilateral pathologies. There were no significant differences of mean values between extratemporal group and controls group. Quantitative techniques detected mild abnormalities, undetected on visual assessment. Conclusions. Quantitative techniques are more sensitive to diagnose bilateral and mild unilateral hippocampal abnormalities.

  8. Hippocampal atrophy in people with memory deficits: results from the population-based IPREA study.

    Science.gov (United States)

    Ferrarini, Luca; van Lew, Baldur; Reiber, Johan H C; Gandin, Claudia; Galluzzo, Lucia; Scafato, Emanuele; Frisoni, Giovanni B; Milles, Julien; Pievani, Michela

    2014-07-01

    Clinical studies have shown that hippocampal atrophy is present before dementia in people with memory deficits and can predict dementia development. The question remains whether this association holds in the general population. This is of interest for the possible use of hippocampal atrophy to screen population for preventive interventions. The aim of this study was to assess hippocampal volume and shape abnormalities in elderly adults with memory deficits in a cross-sectional population-based study. We included individuals participating in the Italian Project on the Epidemiology of Alzheimer Disease (IPREA) study: 75 cognitively normal individuals (HC), 31 individuals with memory deficits (MEM), and 31 individuals with memory deficits not otherwise specified (MEMnos). Hippocampal volumes and shape were extracted through manual tracing and the growing and adaptive meshes (GAMEs) shape-modeling algorithm. We investigated between-group differences in hippocampal volume and shape, and correlations with memory deficits. In MEM participants, hippocampal volumes were significantly smaller than in HC and were mildly associated with worse memory scores. Memory-associated shape changes mapped to the anterior hippocampus. Shape-based analysis detected no significant difference between MEM and HC, while MEMnos showed shape changes in the posterior hippocampus compared with HC and MEM groups. These findings support the discriminant validity of hippocampal volumetry as a biomarker of memory impairment in the general population. The detection of shape changes in MEMnos but not in MEM participants suggests that shape-based biomarkers might lack sensitivity to detect Alzheimer's-like pathology in the general population.

  9. Early detection of Alzheimer's disease using MRI hippocampal texture

    DEFF Research Database (Denmark)

    Sørensen, Lauge; Igel, Christian; Hansen, Naja Liv

    2016-01-01

    the receiver operating characteristic curve [AUC] 0.74 vs 0.67; DeLong test, p = 0.005), and provided even better prognostic results in AIBL (AUC 0.83). Hippocampal texture, but not volume, correlated with Addenbrooke's cognitive examination score (Pearson correlation, r = −0.25, p ...

  10. Association Between Pain at Sites Outside the Knee and Knee Cartilage Volume Loss in Elderly People Without Knee Osteoarthritis: A Prospective Study.

    Science.gov (United States)

    Pan, Feng; Laslett, Laura; Tian, Jing; Cicuttini, Flavia; Winzenberg, Tania; Ding, Changhai; Jones, Graeme

    2017-05-01

    Pain is common in the elderly. Knee pain may predict knee cartilage loss, but whether generalized pain is associated with knee cartilage loss is unclear. This study, therefore, aimed to determine whether pain at multiple sites predicts knee cartilage volume loss among community-dwelling older adults, and, if so, to explore potential mechanisms. Data from the prospective Tasmanian Older Adult Cohort study was utilized (n = 394, mean age 63 years, range 52-79 years). Experience of pain at multiple sites was assessed using a questionnaire at baseline. T1-weighted fat-saturated magnetic resonance imaging of the right knee was performed to assess the cartilage volume at baseline and after 2.6 years. Linear regression modeling was used with adjustment for potential confounders. The median number of painful sites was 3 (range 0-7). There was a dose-response relationship between the number of painful sites and knee cartilage volume loss in the lateral and total tibiofemoral compartments (lateral β = -0.28% per annum; total β = -0.25% per annum, both P for trend knee osteoarthritis (OA) (P pain medication, and knee structural abnormalities. The number of painful sites independently predicts knee cartilage volume loss, especially in people without knee OA, suggesting that widespread pain may be an early marker of more rapid knee cartilage loss in those without radiographic knee OA. The underlying mechanism is unclear, but it is independent of anthropometrics, physical activity, and knee structural abnormalities. © 2016, American College of Rheumatology.

  11. Gradient COUP-TFI Expression Is Required for Functional Organization of the Hippocampal Septo-Temporal Longitudinal Axis.

    Science.gov (United States)

    Flore, Gemma; Di Ruberto, Giuseppina; Parisot, Joséphine; Sannino, Sara; Russo, Fabio; Illingworth, Elizabeth A; Studer, Michèle; De Leonibus, Elvira

    2017-02-01

    The hippocampus (HP), a medial cortical structure, is subdivided into a distinct dorsal (septal) and ventral (temporal) portion, which is separated by an intermediate region lying on a longitudinal curvature. While the dorsal portion is more dedicated to spatial navigation and memory, the most ventral part processes emotional information. Genetic factors expressed in gradient during development seem to control the size and correct positioning of the HP along its longitudinal axis; however, their roles in regulating differential growth and in supporting its anatomical and functional dissociation remain unexplored. Here, we challenge the in vivo function of the nuclear receptor COUP-TFI (chicken ovalbumin upstream promoter transcription factor 1) in controlling the hippocampal, anatomical, and functional properties along its longitudinal axis. Loss of cortical COUP-TFI function results in a dysmorphic HP with altered shape, volume, and connectivity, particularly in its dorsal and intermediate regions. Notably, topographic inputs from the entorhinal cortex are strongly impaired in the dorsal portion of COUP-TFI mutants. These severe morphological changes are associated with selective spatial learning and memory impairment. These findings identify a novel transcriptional regulator required in the functional organization along the hippocampal septo-temporal axis supporting a genetic basis of the hippocampal volumetric growth with its final shape, circuit, and type of memory function. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

    Energy Technology Data Exchange (ETDEWEB)

    Squitieri, Ferdinando; Orobello, Sara; Cannella, Milena; Martino, Tiziana [IRCCS Neuromed, Neurogenetics Unit and Centre for Rare Disease, Pozzilli (Italy); Romanelli, Pantaleo [IRCCS Neuromed, Department of Neurosurgery, Pozzilli (Italy); Giovacchini, Giampiero; Ciarmiello, Andrea [S. Andrea Hospital, Unit of Nuclear Medicine, La Spezia (Italy); Frati, Luigi [University ' ' Sapienza' ' , Department of Experimental Medicine, Rome (Italy); Mansi, Luigi [Second University of Naples, Department of Nuclear Medicine, Naples (Italy)

    2009-07-15

    Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and {sup 18}F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD. (orig.)

  13. Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

    International Nuclear Information System (INIS)

    Squitieri, Ferdinando; Orobello, Sara; Cannella, Milena; Martino, Tiziana; Romanelli, Pantaleo; Giovacchini, Giampiero; Ciarmiello, Andrea; Frati, Luigi; Mansi, Luigi

    2009-01-01

    Huntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and 18 F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p<0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD. (orig.)

  14. Hippocampus and amygdala volumes in children and young adults at high-risk of schizophrenia: research synthesis.

    Science.gov (United States)

    Ganzola, Rossana; Maziade, Michel; Duchesne, Simon

    2014-06-01

    Studies have reported hippocampal and amygdala volume abnormalities in schizophrenic patients. It is necessary to explore the potential for these structures as early disease markers in subjects at high risk (HR) of schizophrenia. We performed a review of 29 magnetic resonance imaging (MRI) studies measuring hippocampal and amygdala volumes in subjects at HR for schizophrenia. We reclassified subjects in 3 new HR categories: presence of only risk symptoms (psychotic moderate symptoms), presence of only risk factors (genetic, developmental or environmental), and presence of combined risk symptoms/factors. Hippocampal volume reductions were detected in subjects with first episode (FE) of psychosis, in all young adults and in adolescents at HR of schizophrenia. The loss of tissue was mainly located in the posterior part of hippocampus and the right side seems more vulnerable in young adults with only risk symptoms. Instead, the anterior sector seems more involved in HR subjects with genetic risks. Abnormal amygdala volumes were found in FE subjects, in children with combined risk symptoms/factors and in older subjects using different inclusion criteria, but not in young adults. Hippocampal and amygdala abnormalities may be present before schizophrenia onset. Further studies should be conducted to clarify whether these abnormalities are causally or effectually related to neurodevelopment. Shape analysis could clarify the impact of environmental, genetic, and developmental factors on the medial temporal structures during the evolution of this disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Volume of the human hippocampus and clinical response following electroconvulsive therapy

    DEFF Research Database (Denmark)

    Oltedal, Leif; Narr, Katherine L.; Abbott, Christopher

    2018-01-01

    Background: Hippocampal enlargements are commonly reported following electroconvulsive therapy (ECT). To clarify mechanisms, we examined if ECT induced hippocampal volume change relates to dose (number of ECT sessions and electrode placement) and acts as a biomarker of clinical outcome. Methods...

  16. Features of amygdala in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: An MRI volumetric and histopathological study.

    Science.gov (United States)

    Nakayama, Yoko; Masuda, Hiroshi; Shirozu, Hiroshi; Ito, Yosuke; Higashijima, Takefumi; Kitaura, Hiroki; Fujii, Yukihiko; Kakita, Akiyoshi; Fukuda, Masafumi

    2017-09-01

    It is well-known that there is a correlation between the neuropathological grade of hippocampal sclerosis (HS) and neuroradiological atrophy of the hippocampus in mesial temporal lobe epilepsy (mTLE) patients. However, there is no strict definition or criterion regarding neuron loss and atrophy of the amygdala neighboring the hippocampus. We examined the relationship between HS and neuronal loss in the amygdala. Nineteen mTLE patients with neuropathological proof of HS were assigned to Group A, while seven mTLE patients without HS were assigned to Group B. We used FreeSurfer software to measure amygdala volume automatically based on pre-operation magnetic resonance images. Neurons observed using Klüver-Barrera (KB) staining in resected amygdala tissue were counted. and the extent of immunostaining with stress marker antibodies was semiquantitatively evaluated. There was no significant difference in amygdala volume between the two groups (Group A: 1.41±0.24; Group B: 1.41±0.29cm 3 ; p=0.98), nor in the neuron cellularity of resected amygdala specimens (Group A: 3.98±0.97; Group B: 3.67±0.67 10× -4 number of neurons/μm 2 ; p=0.40). However, the HSP70 level, representing acute stress against epilepsy, in Group A patients was significantly larger than that in Group B. There was no significant difference in the level of Bcl-2, which is known as a protein that inhibits cell death, between the two groups. Neuronal loss and volume loss in the amygdala may not necessarily follow hippocampal sclerosis. From the analysis of stress proteins, epileptic attacks are as likely to damage the amygdala as the hippocampus but do not lead to neuronal death in the amygdala. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Abnormal Hippocampal Morphology in Dissociative Identity Disorder and Posttraumatic Stress Disorder Correlates with Childhood Trauma and Dissociative Symptoms

    Science.gov (United States)

    Chalavi, Sima; Vissia, Eline M.; Giesen, Mechteld E.; Nijenhuis, Ellert R.S.; Draijer, Nel; Cole, James H.; Dazzan, Paola; Pariante, Carmine M.; Madsen, Sarah K.; Rajagopalan, Priya; Thompson, Paul M.; Toga, Arthur W.; Veltman, Dick J.; Reinders, Antje A.T.S.

    2015-01-01

    Smaller hippocampal volume has been reported in individuals with posttraumatic stress disorder (PTSD) and dissociative identity disorder (DID), but the regional specificity of hippocampal volume reductions and the association with severity of dissociative symptoms and/or childhood traumatization are still unclear. Brain structural MRI scans were analyzed for 33 outpatients (17 with DID and 16 with PTSD only) and 28 healthy controls (HC), all matched for age, sex, and education. DID patients met criteria for PTSD (PTSD-DID). Hippocampal global and subfield volumes and shape measurements were extracted. We found that global hippocampal volume was significantly smaller in all 33 patients (left: 6.75%; right: 8.33%) compared to HC. PTSD-DID (left: 10.19%; right: 11.37%) and PTSD-only with a history of childhood traumatization (left: 7.11%; right: 7.31%) had significantly smaller global hippocampal volume relative to HC. PTSD-DID had abnormal shape and significantly smaller volume in the CA2-3, CA4-DG and (pre)subiculum compared to HC. In the patient groups, smaller global and subfield hippocampal volumes significantly correlated with higher severity of childhood traumatization and dissociative symptoms. These findings support a childhood trauma-related etiology for abnormal hippocampal morphology in both PTSD and DID and can further the understanding of neurobiological mechanisms involved in these disorders. PMID:25545784

  18. Abnormal hippocampal morphology in dissociative identity disorder and post-traumatic stress disorder correlates with childhood trauma and dissociative symptoms.

    Science.gov (United States)

    Chalavi, Sima; Vissia, Eline M; Giesen, Mechteld E; Nijenhuis, Ellert R S; Draijer, Nel; Cole, James H; Dazzan, Paola; Pariante, Carmine M; Madsen, Sarah K; Rajagopalan, Priya; Thompson, Paul M; Toga, Arthur W; Veltman, Dick J; Reinders, Antje A T S

    2015-05-01

    Smaller hippocampal volume has been reported in individuals with post-traumatic stress disorder (PTSD) and dissociative identity disorder (DID), but the regional specificity of hippocampal volume reductions and the association with severity of dissociative symptoms and/or childhood traumatization are still unclear. Brain structural magnetic resonance imaging scans were analyzed for 33 outpatients (17 with DID and 16 with PTSD only) and 28 healthy controls (HC), all matched for age, sex, and education. DID patients met criteria for PTSD (PTSD-DID). Hippocampal global and subfield volumes and shape measurements were extracted. We found that global hippocampal volume was significantly smaller in all 33 patients (left: 6.75%; right: 8.33%) compared with HC. PTSD-DID (left: 10.19%; right: 11.37%) and PTSD-only with a history of childhood traumatization (left: 7.11%; right: 7.31%) had significantly smaller global hippocampal volume relative to HC. PTSD-DID had abnormal shape and significantly smaller volume in the CA2-3, CA4-DG and (pre)subiculum compared with HC. In the patient groups, smaller global and subfield hippocampal volumes significantly correlated with higher severity of childhood traumatization and dissociative symptoms. These findings support a childhood trauma-related etiology for abnormal hippocampal morphology in both PTSD and DID and can further the understanding of neurobiological mechanisms involved in these disorders. © 2014 Wiley Periodicals, Inc.

  19. Examining the Efficacy of Calcium Hydroxylapatite Filler With Integral Lidocaine in Correcting Volume Loss of the Jawline-A Pilot Study.

    Science.gov (United States)

    Juhász, Margit L W; Marmur, Ellen S

    2018-04-19

    Patients seek 3-dimensional volume restoration of the jawline to obtain a "defined" line. Injection of filler into the jawline is not approved by the Food and Drug Administration; however, dermatologists have injected this area with positive results, minimal adverse events, and high patient satisfaction. This study explores the efficacy of premixed calcium hydroxylapatite filler with integral lidocaine [CaHA(+)] to correct volume defects of the jawline. It examines the longevity, safety, and patient satisfaction (up to 12 months) of CaHA(+) for jawline volume loss correction. This is a single-investigator, nonblinded study. Twenty subjects received CaHA(+) filler injection in the jawline, with follow-up evaluations conducted at 14 days, 6 weeks, and 3, 6, 9, and 12 months. CaHA(+) injection in the jawline results in statistically significant restoration in volume and improvement in appearance lasting up to 12 months. Overall, subjects report "moderate" improvement on the Global Aesthetic Improvement Scale. It is important for cosmetic surgeons and dermatologists to have access to data on the efficacy and safety of injectables. The data obtained in this study show that CaHA(+) is an effective and safe option to correct jawline volume loss and is associated with high patient satisfaction.

  20. The BDNF val-66-met Polymorphism Affects Neuronal Morphology and Synaptic Transmission in Cultured Hippocampal Neurons from Rett Syndrome Mice

    Directory of Open Access Journals (Sweden)

    Xin Xu

    2017-07-01

    Full Text Available Brain-derived neurotrophic factor (Bdnf has been implicated in several neurological disorders including Rett syndrome (RTT, an X-linked neurodevelopmental disorder caused by loss-of-function mutations in the transcriptional modulator methyl-CpG-binding protein 2 (MECP2. The human BDNF gene has a single nucleotide polymorphism (SNP—a methionine (met substitution for valine (val at codon 66—that affects BDNF’s trafficking and activity-dependent release and results in cognitive dysfunction. Humans that are carriers of the met-BDNF allele have subclinical memory deficits and reduced hippocampal volume and activation. It is still unclear whether this BDNF SNP affects the clinical outcome of RTT individuals. To evaluate whether this BDNF SNP contributes to RTT pathophysiology, we examined the consequences of expression of either val-BDNF or met-BDNF on dendrite and dendritic spine morphology, and synaptic function in cultured hippocampal neurons from wildtype (WT and Mecp2 knockout (KO mice. Our findings revealed that met-BDNF does not increase dendritic growth and branching, dendritic spine density and individual spine volume, and the number of excitatory synapses in WT neurons, as val-BDNF does. Furthermore, met-BDNF reduces dendritic complexity, dendritic spine volume and quantal excitatory synaptic transmission in Mecp2 KO neurons. These results suggest that the val-BDNF variant contributes to RTT pathophysiology, and that BDNF-based therapies should take into consideration the BDNF genotype of the RTT individuals.

  1. An initial abstraction and constant loss model, and methods for estimating unit hydrographs, peak streamflows, and flood volumes for urban basins in Missouri

    Science.gov (United States)

    Huizinga, Richard J.

    2014-01-01

    Streamflow data, basin characteristics, and rainfall data from 39 streamflow-gaging stations for urban areas in and adjacent to Missouri were used by the U.S. Geological Survey in cooperation with the Metropolitan Sewer District of St. Louis to develop an initial abstraction and constant loss model (a time-distributed basin-loss model) and a gamma unit hydrograph (GUH) for urban areas in Missouri. Study-specific methods to determine peak streamflow and flood volume for a given rainfall event also were developed.

  2. Effects of Early-Life Adversity on Hippocampal Structures and Associated HPA Axis Functions.

    Science.gov (United States)

    Dahmen, Brigitte; Puetz, Vanessa B; Scharke, Wolfgang; von Polier, Georg G; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2018-01-01

    Early-life adversity (ELA) is one of the major risk factors for serious mental and physical health risks later in life. ELA has been associated with dysfunctional neurodevelopment, especially in brain structures such as the hippocampus, and with dysfunction of the stress system, including the hypothalamic-pituitary-adrenal (HPA) axis. Children who have experienced ELA are also more likely to suffer from mental health disorders such as depression later in life. The exact interplay of aberrant neurodevelopment and HPA axis dysfunction as risks for psychopathology is not yet clear. We investigated volume differences in the bilateral hippocampus and in stress-sensitive hippocampal subfields, behavior problems, and diurnal cortisol activity in 24 children who had experienced documented ELA (including out-of-home placement) in a circumscribed duration of adversity only in their first 3 years of life in comparison to data on 25 control children raised by their biological parents. Hippocampal volumes and stress-sensitive hippocampal subfields (Cornu ammonis [CA]1, CA3, and the granule-cell layer of the dentate gyrus [GCL-DG]) were significantly smaller in children who had experienced ELA, taking psychiatric diagnoses and dimensional psychopathological symptoms into account. ELA moderated the relationship between left hippocampal volume and cortisol: in the control group, hippocampal volumes were not related to diurnal cortisol, while in ELA children, a positive linear relationship between left hippocampal volume and diurnal cortisol was present. Our findings show that ELA is associated with altered development of the hippocampus, and an altered relationship between hippocampal volume and HPA axis activity in youth in care, even after they have lived in stable and caring foster family environments for years. Altered hippocampal development after ELA could thus be associated with a risk phenotype for the development of psychiatric disorders later in life. © 2017 S. Karger

  3. Porencephaly in dogs and cats: relationships between magnetic resonance imaging (MRI) features and hippocampal atrophy.

    Science.gov (United States)

    Hori, Ai; Hanazono, Kiwamu; Miyoshi, Kenjirou; Nakade, Tetsuya

    2015-07-01

    Porencephaly is the congenital cerebral defect and a rare malformation and described few MRI reports in veterinary medicine. MRI features of porencephaly are recognized the coexistence with the unilateral/bilateral hippocampal atrophy, caused by the seizure symptoms in human medicine. We studied 2 dogs and 1 cat with congenital porencephaly to characterize the clinical signs and MRI, and to discuss the associated MRI with hippocampal atrophy. The main clinical sign was the seizure symptoms, and all had hippocampal atrophy at the lesion side or the larger defect side. There is association between hippocampal atrophy or the cyst volume and the severe of clinical signs, and it is suggested that porencephaly coexists with hippocampal atrophy as well as humans in this study.

  4. Hippocampal dosimetry correlates with the change in neurocognitive function after hippocampal sparing during whole brain radiotherapy: a prospective study

    International Nuclear Information System (INIS)

    Tsai, Ping-Fang; Yang, Chi-Cheng; Chuang, Chi-Cheng; Huang, Ting-Yi; Wu, Yi-Ming; Pai, Ping-Ching; Tseng, Chen-Kan; Wu, Tung-Ho; Shen, Yi-Liang; Lin, Shinn-Yn

    2015-01-01

    Whole brain radiotherapy (WBRT) has been the treatment of choice for patients with brain metastases. However, change/decline of neurocognitive functions (NCFs) resulting from impaired hippocampal neurogenesis might occur after WBRT. It is reported that conformal hippocampal sparing would provide the preservation of NCFs. Our study aims to investigate the hippocampal dosimetry and to demonstrate the correlation between hippocampal dosimetry and neurocognitive outcomes in patients receiving hippocampal sparing during WBRT (HS-WBRT). Forty prospectively recruited cancer patients underwent HS-WBRT for therapeutic or prophylactic purposes. Before receiving HS-WBRT, all participants received a battery of baseline neurocognitive assessment, including memory, executive functions and psychomotor speed. The follow-up neurocognitive assessment at 4 months after HS-WBRT was also performed. For the delivery of HS-WBRT, Volumetric Modulated Arc Therapy (VMAT) with two full arcs and two non-coplanar partial arcs was employed. For each treatment planning, dose volume histograms were generated for left hippocampus, right hippocampus, and the composite hippocampal structure respectively. Biologically equivalent doses in 2-Gy fractions (EQD 2 ) assuming an alpha/beta ratio of 2 Gy were computed. To perform analyses addressing the correlation between hippocampal dosimetry and the change in scores of NCFs, pre- and post-HS-WBRT neurocognitive assessments were available in 24 patients in this study. Scores of NCFs were quite stable before and after HS-WBRT in terms of hippocampus-dependent memory. Regarding verbal memory, the corresponding EQD 2 values of 0, 10, 50, 80 % irradiating the composite hippocampal structure with <12.60 Gy, <8.81, <7.45 Gy and <5.83 Gy respectively were significantly associated with neurocognitive preservation indicated by the immediate recall of Word List Test of Wechsler Memory Scale-III. According to logistic regression analyses, it was noted that

  5. Effects of Estradiol on Learned Helplessness and Associated Remodeling of Hippocampal Spine Synapses in Female Rats

    Science.gov (United States)

    Hajszan, Tibor; Szigeti-Buck, Klara; Sallam, Nermin L; Bober, Jeremy; Parducz, Arpad; MacLusky, Neil J; Leranth, Csaba; Duman, Ronald S

    2009-01-01

    Background Despite the fact that women are twice as likely to develop depression as men, our understanding of depression neurobiology in females is limited. We have recently reported in male rats that development of helpless behavior is associated with a severe loss of hippocampal spine synapses, which is reversed by treatment with the antidepressant, desipramine. Considering the fact that estradiol has a hippocampal synaptogenic effect similar to those of antidepressants, the presence of estradiol during the female reproductive life may influence behavioral and synaptic responses to stress and depression. Methods Using electron microscopic stereology, we analyzed hippocampal spine synapses in association with helpless behavior in ovariectomized female rats (n=70), under different conditions of estradiol exposure. Results Stress induced an acute and persistent loss of hippocampal spine synapses, while subchronic treatment with desipramine reversed the stress-induced synaptic loss. Estradiol supplementation given either prior to stress or prior to escape testing of nonstressed animals both increased the number of hippocampal spine synapses. Correlation analysis demonstrated a statistically significant negative correlation between the severity of helpless behavior and hippocampal spine synapse numbers. Conclusions These findings suggest that hippocampal spine synapse remodeling may be a critical factor underlying learned helplessness and, possibly, the neurobiology of depression. PMID:19811775

  6. Left main bronchus compression as a result of tuberculous lymphnode compression of the right-sided airways with right lung volume loss in children.

    Science.gov (United States)

    Andronikou, S; Van Wyk, M J; Goussard, P; Gie, R P

    2014-03-01

    The superior mediastinal space is confined by the sterno-manubrium anteriorly and the vertebral column posterior. An abnormal relationship between the superior mediastinal structures may result in compression of the left main bronchus. In patients with right-sided pneumonectomy an exaggerated compensatory response may lead to stretching and compression of the remainder of the intra-thoracic airway. Lymphobronchial TB mimics pneumonectomy when it causes compression of the bronchus intermedius, between nodal lymphnode groups with resultant volume loss in the right lung and displacement of the mediastinum to the right. The left main bronchus may be at risk of compression due to rotation and displacement of the major vessels. To report pediatric cases of right-sided lymphobronchial TB with volume loss, demonstrate the use of angle measurements to quantify mediastinal dynamics and support a pathogenetic theory for left main bronchus compression. CT scans in children with TB and right lung volume loss, were compared retrospectively with controls using angle measurements based on descriptions of the aorta-carinal syndrome and the post-pneumonectomy syndrome. The Mann-Whitney U-test was used to compare groups. The "Pulmonary bifurcation angle" between the main pulmonary arteries reached statistical significance (P = 0.025). The "Pulmonary outflow tract rotation" angle (pulmonary trunk with the mid sagittal plane) approached statistical significance (P = 0.078). The left main bronchus ranged from complete obliteration in two patients to 0.7 cm. In 16 of 30 patients the size was reduced to less than 75% of expected. In children with right lung volume loss from TB, the compression of the contralateral bronchus is due to narrowing of the pulmonary artery bifurcation angle as the main trunk rotates towards the midline. This is comparable to the post-pneumonectomy syndrome. © 2012 Wiley Periodicals, Inc.

  7. Associations between hippocampal morphometry and neuropathologic markers of Alzheimer's disease using 7 T MRI

    Directory of Open Access Journals (Sweden)

    Anna E. Blanken

    2017-01-01

    Full Text Available Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9 Alzheimer's dementia (AD and 7 cognitively normal (NC subjects. Brains were scanned post-mortem at 7 Tesla. We extracted hippocampal volumes and radial distances using automated segmentation techniques. Hippocampal slices were stained for amyloid beta (Aβ, tau, and cresyl violet to evaluate neuronal counts. The hippocampal subfields, CA1, CA2, CA3, CA4, and subiculum were manually traced so that the neuronal counts, Aβ, and tau burden could be obtained for each region. We used linear regression to detect associations between hippocampal atrophy in 3D, clinical diagnosis and total as well as subfield pathology burden measures. As expected, we found significant correlations between hippocampal radial distance and mean neuronal count, as well as diagnosis. There were subfield specific associations between hippocampal radial distance and tau in CA2, and cresyl violet neuronal counts in CA1 and subiculum. These results provide further validation for the European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP.

  8. Smaller Dentate Gyrus and CA2 and CA3 Volumes Are Associated with Kynurenine Metabolites in Collegiate Football Athletes.

    Science.gov (United States)

    Meier, Timothy B; Savitz, Jonathan; Singh, Rashmi; Teague, T Kent; Bellgowan, Patrick S F

    2016-07-15

    An imbalance in kynurenine pathway metabolism is hypothesized to be associated with dysregulated glutamatergic neurotransmission, which has been proposed as a mechanism underlying the hippocampal volume loss observed in a variety of neurological disorders. Pre-clinical models suggest that the CA2-3 and dentate gyrus hippocampal subfields are particularly susceptible to excitotoxicity after experimental traumatic brain injury. We tested the hypothesis that smaller hippocampal volumes in collegiate football athletes with (n = 25) and without (n = 24) a concussion history would be most evident in the dentate gyrus and CA2-3 subfields relative to nonfootball healthy controls (n = 27). Further, we investigated whether the concentration of peripheral levels of kynurenine metabolites are altered in football athletes. Football athletes with and without a self-reported concussion history had smaller dentate gyrus (p Football athletes with and without a concussion history had a trend toward lower (p history had greater levels of quinolinic acid compared with athletes without a concussion history (p football athletes with a concussion history (p football athletes without a concussion history (p < 0.05). Our results raise the possibility that abnormalities of the kynurenine metabolic pathway constitute a mechanism for hippocampal volume differences in the context of sports-related brain injury.

  9. Hummingbirds have a greatly enlarged hippocampal formation.

    Science.gov (United States)

    Ward, Brian J; Day, Lainy B; Wilkening, Steven R; Wylie, Douglas R; Saucier, Deborah M; Iwaniuk, Andrew N

    2012-08-23

    Both field and laboratory studies demonstrate that hummingbirds (Apodiformes, Trochilidae) have exceptional spatial memory. The complexity of spatial-temporal information that hummingbirds must retain and use daily is probably subserved by the hippocampal formation (HF), and therefore, hummingbirds should have a greatly expanded HF. Here, we compare the relative size of the HF in several hummingbird species with that of other birds. Our analyses reveal that the HF in hummingbirds is significantly larger, relative to telencephalic volume, than any bird examined to date. When expressed as a percentage of telencephalic volume, the hummingbird HF is two to five times larger than that of caching and non-caching songbirds, seabirds and woodpeckers. This HF expansion in hummingbirds probably underlies their ability to remember the location, distribution and nectar content of flowers, but more detailed analyses are required to determine the extent to which this arises from an expansion of HF or a decrease in size of other brain regions.

  10. Deficits in memory and visuospatial learning correlate with regional hippocampal atrophy in MS.

    Science.gov (United States)

    Longoni, Giulia; Rocca, Maria A; Pagani, Elisabetta; Riccitelli, Gianna C; Colombo, Bruno; Rodegher, Mariaemma; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

    2015-01-01

    The hippocampus has a critical role in episodic memory and visuospatial learning and consolidation. We assessed the patterns of whole and regional hippocampal atrophy in a large group of multiple sclerosis (MS) patients, and their correlations with neuropsychological impairment. From 103 MS patients and 28 healthy controls (HC), brain dual-echo and high-resolution 3D T1-weighted images were acquired using a 3.0-Tesla scanner. All patients underwent a neuropsychological assessment of hippocampal-related cognitive functions, including Paired Associate Word Learning, Short Story, delayed recall of Rey-Osterrieth Complex Figure and Paced Auditory Serial Attention tests. The hippocampi were manually segmented and volumes derived. Regional atrophy distribution was assessed using a radial mapping analysis. Correlations between hippocampal atrophy and clinical, neuropsychological and MRI metrics were also evaluated. Hippocampal volume was reduced in MS patients vs HC (p right and hippocampus). In MS patients, radial atrophy affected CA1 subfield and subiculum of posterior hippocampus, bilaterally. The dentate hilus (DG:H) of the right hippocampal head was also affected. Regional hippocampal atrophy correlated with brain T2 and T1 lesion volumes, while no correlation was found with disability. Damage to the CA1 and subiculum was significantly correlated to the performances at hippocampal-targeted neuropsychological tests. These results show that hippocampal subregions have a different vulnerability to MS-related damage, with a relative sparing of the head of the left hippocampus. The assessment of regional hippocampal atrophy may help explain deficits of specific cognitive functions in MS patients, including memory and visuospatial abilities.

  11. Subregional Hippocampal Morphology and Psychiatric Outcome in Adolescents Who Were Born Very Preterm and at Term.

    Directory of Open Access Journals (Sweden)

    James H Cole

    Full Text Available The hippocampus has been reported to be structurally and functionally altered as a sequel of very preterm birth (<33 weeks gestation, possibly due its vulnerability to hypoxic-ischemic damage in the neonatal period. We examined hippocampal volumes and subregional morphology in very preterm born individuals in mid- and late adolescence and their association with psychiatric outcome.Structural brain magnetic resonance images were acquired at two time points (baseline and follow-up from 65 ex-preterm adolescents (mean age = 15.5 and 19.6 years and 36 term-born controls (mean age=15.0 and 19.0 years. Hippocampal volumes and subregional morphometric differences were measured from manual tracings and with three-dimensional shape analysis. Psychiatric outcome was assessed with the Rutter Parents' Scale at baseline, the General Health Questionnaire at follow-up and the Peters Delusional Inventory at both time points.In contrast to previous studies we did not find significant difference in the cross-sectional or longitudinal hippocampal volumes between individuals born preterm and controls, despite preterm individual having significantly smaller whole brain volumes. Shape analysis at baseline revealed subregional deformations in 28% of total bilateral hippocampal surface, reflecting atrophy, in ex-preterm individuals compared to controls, and in 22% at follow-up. In ex-preterm individuals, longitudinal changes in hippocampal shape accounted for 11% of the total surface, while in controls they reached 20%. In the whole sample (both groups larger right hippocampal volume and bilateral anterior surface deformations at baseline were associated with delusional ideation scores at follow-up.This study suggests a dynamic association between cross-sectional hippocampal volumes, longitudinal changes and surface deformations and psychosis proneness.

  12. Lower Ipsilateral Hippocampal Integrity after Ischemic Stroke in Young Adults: A Long-Term Follow-Up Study

    NARCIS (Netherlands)

    Schaapsmeerders, P.; Tuladhar, A.M.; Maaijwee, N.A.M.M.; Rutten-Jacobs, L.C.A.; Arntz, R.M.; Schoonderwaldt, H.C.; Dorresteijn, L.D.A.; Dijk, E.J. van; Kessels, R.P.C.; Leeuw, H.F. de

    2015-01-01

    Background and purpose Memory impairment after stroke is poorly understood as stroke rarely occurs in the hippocampus. Previous studies have observed smaller ipsilateral hippocampal volumes after stroke compared with controls. Possibly, these findings on macroscopic level are not the first

  13. Lower Ipsilateral Hippocampal Integrity after Ischemic Stroke in Young Adults: A Long-Term Follow-Up Study

    NARCIS (Netherlands)

    Schaapsmeerders, P.; Tuladhar, A.M.; Maaijwee, N.A.M.M.; Rutten-Jacobs, L.C.A.; Arntz, R.M.; Schoonderwaldt, H.C.; Dorresteijn, L.D.; Dijk, E.J. van; Kessels, R.P.C.; Leeuw, F.E. de

    2015-01-01

    BACKGROUND AND PURPOSE: Memory impairment after stroke is poorly understood as stroke rarely occurs in the hippocampus. Previous studies have observed smaller ipsilateral hippocampal volumes after stroke compared with controls. Possibly, these findings on macroscopic level are not the first

  14. Food restriction reduces neurogenesis in the avian hippocampal formation.

    Directory of Open Access Journals (Sweden)

    Barbara-Anne Robertson

    Full Text Available The mammalian hippocampus is particularly vulnerable to chronic stress. Adult neurogenesis in the dentate gyrus is suppressed by chronic stress and by administration of glucocorticoid hormones. Post-natal and adult neurogenesis are present in the avian hippocampal formation as well, but much less is known about its sensitivity to chronic stressors. In this study, we investigate this question in a commercial bird model: the broiler breeder chicken. Commercial broiler breeders are food restricted during development to manipulate their growth curve and to avoid negative health outcomes, including obesity and poor reproductive performance. Beyond knowing that these chickens are healthier than fully-fed birds and that they have a high motivation to eat, little is known about how food restriction impacts the animals' physiology. Chickens were kept on a commercial food-restricted diet during the first 12 weeks of life, or released from this restriction by feeding them ad libitum from weeks 7-12 of life. To test the hypothesis that chronic food restriction decreases the production of new neurons (neurogenesis in the hippocampal formation, the cell proliferation marker bromodeoxyuridine was injected one week prior to tissue collection. Corticosterone levels in blood plasma were elevated during food restriction, even though molecular markers of hypothalamic-pituitary-adrenal axis activation did not differ between the treatments. The density of new hippocampal neurons was significantly reduced in the food-restricted condition, as compared to chickens fed ad libitum, similar to findings in rats at a similar developmental stage. Food restriction did not affect hippocampal volume or the total number of neurons. These findings indicate that in birds, like in mammals, reduction in hippocampal neurogenesis is associated with chronically elevated corticosterone levels, and therefore potentially with chronic stress in general. This finding is consistent with the

  15. Studies on hippocampal sclerosis by 1H MRS and MRI

    International Nuclear Information System (INIS)

    Qi Jing; Du Xiangke; Luan Guoming; Wang Dehang

    2000-01-01

    Objective: To determine the relative utility of 1 H MRS and MRI for pre-surgical diagnosis of hippocampal sclerosis by the study on metabolic abnormalities and anatomical alterations in the brain of patients with temporal lobe epilepsy (TLE). Methods: 1 H MRS and MRI were performed on 8 patients with pathologically confirmed hippocampal sclerosis and 8 healthy volunteers on 2.0 T 1 H MRS/MRI system. The values of NAA, Cr and Cho were calculated by integration of their peaks and the ratios of NAA/Cr, NAA/(Cr + Cho), and Cho/Cr were measured. The volumes of both hippocampal formations in every case were observed and the differences of hippocampal formation (DHF) were analyzed. Results: The ratios of NAA/Cr, NAA/(Cr + Cho), and Cho/Cr in ipsilateral side were 0.55, 1.77 and 1.38, and in control subjects were 0.77, 1.38 and 1.06 separately. The ratios of NAA/Cr and NAA/(Cr + Cho) were decreased on ipsilateral side (t = 2.15, 4.83 separately, P 1 H MRS and MRI, seven of eight cases could be lateralized. Conclusion: 1 H MRS is sensitive to the diagnosis of neuron abnormality and coincident well with the pathological results 1 H MRS and MRI correctly lateralize most patients with hippocampal sclerosis and complement each other in final lateralization. The combination of 1 H MRS and MRI can provide useful information for pre-surgical diagnosis of hippocampal sclerosis

  16. Hippocampal Structure Predicts Statistical Learning and Associative Inference Abilities during Development.

    Science.gov (United States)

    Schlichting, Margaret L; Guarino, Katharine F; Schapiro, Anna C; Turk-Browne, Nicholas B; Preston, Alison R

    2017-01-01

    Despite the importance of learning and remembering across the lifespan, little is known about how the episodic memory system develops to support the extraction of associative structure from the environment. Here, we relate individual differences in volumes along the hippocampal long axis to performance on statistical learning and associative inference tasks-both of which require encoding associations that span multiple episodes-in a developmental sample ranging from ages 6 to 30 years. Relating age to volume, we found dissociable patterns across the hippocampal long axis, with opposite nonlinear volume changes in the head and body. These structural differences were paralleled by performance gains across the age range on both tasks, suggesting improvements in the cross-episode binding ability from childhood to adulthood. Controlling for age, we also found that smaller hippocampal heads were associated with superior behavioral performance on both tasks, consistent with this region's hypothesized role in forming generalized codes spanning events. Collectively, these results highlight the importance of examining hippocampal development as a function of position along the hippocampal axis and suggest that the hippocampal head is particularly important in encoding associative structure across development.

  17. Wildlife Loss Estimates and Summary of Previous Mitigation Related to Hydroelectric Projects in Montana, Volume Three, Hungry Horse Project.

    Energy Technology Data Exchange (ETDEWEB)

    Casey, Daniel

    1984-10-01

    This assessment addresses the impacts to the wildlife populations and wildlife habitats due to the Hungry Horse Dam project on the South Fork of the Flathead River and previous mitigation of theses losses. In order to develop and focus mitigation efforts, it was first necessary to estimate wildlife and wildlife hatitat losses attributable to the construction and operation of the project. The purpose of this report was to document the best available information concerning the degree of impacts to target wildlife species. Indirect benefits to wildlife species not listed will be identified during the development of alternative mitigation measures. Wildlife species incurring positive impacts attributable to the project were identified.

  18. Distinguishing Depressive Pseudodementia from Alzheimer Disease: A Comparative Study of Hippocampal Volumetry and Cognitive Tests

    Directory of Open Access Journals (Sweden)

    Sevki Sahin

    2017-07-01

    Full Text Available Background and Aim: Depressive pseudodementia (DPD is a condition which may develop secondary to depression. The aim of this study was to contribute to the differential diagnosis between Alzheimer disease (AD and DPD by comparing the neurocognitive tests and hippocampal volume. Materials and Methods: Patients who met criteria of AD/DPD were enrolled in the study. All patients were assessed using the Wechsler Memory Scale (WMS, clock-drawing test, Stroop test, Benton Facial Recognition Test (BFRT, Boston Naming Test, Mini-Mental State Examination (MMSE, and Geriatric Depression Scale (GDS. Hippocampal volume was measured by importing the coronal T1-weighted magnetic resonance images to the Vitrea 2 workstation. Results: A significant difference was found between the AD and DPD groups on the WMS test, clock-drawing test, Stroop test, Boston Naming Test, MMSE, GDS, and left hippocampal volume. A significant correlation between BFRT and bilateral hippocampal volumes was found in the AD group. No correlation was found among parameters in DPD patients. Conclusions: Our results suggest that evaluation of facial recognition and left hippocampal volume may provide more reliable evidence for distinguishing DPD from AD. Further investigations combined with functional imaging techniques including more patients are needed.

  19. The Effect of Radioactive Lantern Mantle Powder and Bentonite-Zeoloite Minerals on the Volume of Blood Loss, Bleeding and Clotting Time

    Directory of Open Access Journals (Sweden)

    M Atefi

    2009-04-01

    Full Text Available ABSTRACT Introduction & Objective: Over the past decade the US army has widely studied new technologies for stopping sever hemorrhages and has introduced an effective Zeolite based hemostatic agent. On the other hand, Mortazavi and his colleagues previously reported the bio-stimulatory effects of the topical application of radioactive lantern mantle powder on wound healing. Their subsequent studies showed significant changes in some histological parameters concerning healing. In this light, here the bio-stimulatory effect of burned radioactive lantern mantles powder as well as two minerals bentonite and zeolite are presented. Materials & Methods: This experimental study was conducted in the center for radiological studies, Shiraz University of Medical Sciences in 2008. Fifty male Wistar rats were divided randomly into 5 groups of 10 animals each. Following anesthesia, animals’ tails were cut at a thickness of 5 mm by using a surgical scissor. No intervention was made on the animals of the 1st group. The 2nd to 4th group received topical non-radioactive lantern mantle powder, radioactive lantern mantle powder, Bentonite mineral or a mixture of Bentonite-Zeoliteat minerals respectively. After treatment with above mentioned agents, the volume of blood loss was measured using a scaled test-tube. The bleeding time and clotting time were also measured using a chronometer. SPSS software was used for statistical analysis. ANOVA was used for comparing the means of each parameter in the 5 groups. Results: The the volume of blood loss, bleeding and clotting times in control animals were 4.39±1.92 cc, 112.10±39.60 sec and 94.9±54.26 sec, respectively. In the 5th group in which the animals were treated with a mixture of Bentonite-Zeoliteat minerals, the volume of blood loss, bleeding and clotting times were 1.31±0.60 cc, 34.50±4.65 sec and 24.2±4.61 sec, respectively. Conclusion: This is the 1st investigation that studied the alterations of bleeding

  20. Hippocampal and diencephalic pathology in developmental amnesia.

    Science.gov (United States)

    Dzieciol, Anna M; Bachevalier, Jocelyne; Saleem, Kadharbatcha S; Gadian, David G; Saunders, Richard; Chong, W K Kling; Banks, Tina; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2017-01-01

    Developmental amnesia (DA) is a selective episodic memory disorder associated with hypoxia-induced bilateral hippocampal atrophy of early onset. Despite the systemic impact of hypoxia-ischaemia, the resulting brain damage was previously reported to be largely limited to the hippocampus. However, the thalamus and the mammillary bodies are parts of the hippocampal-diencephalic network and are therefore also at risk of injury following hypoxic-ischaemic events. Here, we report a neuroimaging investigation of diencephalic damage in a group of 18 patients with DA (age range 11-35 years), and an equal number of controls. Importantly, we uncovered a marked degree of atrophy in the mammillary bodies in two thirds of our patients. In addition, as a group, patients had mildly reduced thalamic volumes. The size of the anterior-mid thalamic (AMT) segment was correlated with patients' visual memory performance. Thus, in addition to the hippocampus, the diencephalic structures also appear to play a role in the patients' memory deficit. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Ethanol induces MAP2 changes in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Noraberg, J; Zimmer, J

    1998-01-01

    loss of CA3 pyramidal cells and moderate loss of dentate granule cells, as seen in vivo. The results indicate that brain slice cultures combined with immunostaining for cytoskeleton and neuronal markers can be used for studies of ethanol and organic solvent neurotoxicity.......Microtubule-associated protein 2 (MAP2) and neuron-specific protein (NeuN) immunostains were used to demonstrate neurotoxic effects in mature hippocampal slice cultures exposed to ethanol (50, 100, 200 mM) for 4 weeks. At the low dose the density of MAP2 immunostaining in the dentate molecular...... layer was 118% of the control cultures, with no detectable changes in CA1 and CA3. At 100 mM no changes were detected, while 200 mM ethanol significantly reduced the MAP2 density in both dentate (19%) and hippocampal dendritic fields (CA3, 52%; CA1, 55%). At this dose NeuN staining showed considerable...

  2. Magnetic resonance imaging signal reduction may precede volume loss in the pituitary gland of transfusion-dependent beta-thalassemic patients

    Energy Technology Data Exchange (ETDEWEB)

    Hekmatnia, Ali; Rahmani, Ali Asghar; Adibi, Atoosa (Image Processing and Signal Research Center, Dept. of Radiology, Isfahan Univ. of Medical Sciences, Isfahan (Iran)); Radmard, Amir Reza (Dept. of Radiology, Shariati Hospital, Tehran Univ. of Medical Sciences, Tehran (Iran)); Khademi, Hooman (Shariati Hospital, Tehran Univ. of Medical Sciences, Tehran (Iran)), e-mail: radmard@ams.ac.ir

    2010-01-15

    Background: Pituitary iron overload in patients with transfusion-dependent beta-thalassemia may lead to delayed puberty. Magnetic resonance imaging (MRI) has the potential to estimate tissue iron concentration by detecting its paramagnetic effect and hypophyseal damage by measuring its dimensions indirectly. Purpose: To investigate the association of pituitary MRI findings and pubertal status in thalassemic patients as well as to demonstrate any priority in appearance of them. Material and Methods: Twenty-seven beta-thalassemic patients, aged 15-25 years, were divided into 13 with (group A) and 14 without hypogonadism (group B), matched by age, gender, duration of transfusion, and chelation therapy. Thirty-eight age- and sex-adjusted healthy control individuals were also included (group C). All participants underwent pituitary MRI using a 1.5T unit. Pituitary-to-fat signal intensity ratios (SIR) were calculated from coronal T2-weighted images. Estimated pituitary volumes were measured using pituitary height, width, and length on T1-weighted images. Results: The mean values of pituitary-to-fat SIRs were significantly lower in group A as compared with group B (P <0.001), and likewise group B had statistically lower values than group C (P=0.03). The pituitary height and volume were significantly decreased in group A compared to group B (P = 0.006 and P = 0.002, respectively), while these differences did not demonstrate statistically significance between groups B and C. Conclusion: Pituitary MRI findings such as signal intensity reduction and decrease in volume can be useful markers in estimating pituitary dysfunction in beta-thalassemic patients. Compared to healthy controls, lower values of pituitary-to-fat SIRs in thalassemic patients experiencing normal puberty, without marked decrease in volume, indicate that signal reduction may precede volume loss and could be expected first on MRI

  3. Hippocampal development in youth with a history of childhood maltreatment.

    Science.gov (United States)

    Paquola, Casey; Bennett, Maxwell R; Hatton, Sean N; Hermens, Daniel F; Groote, Inge; Lagopoulos, Jim

    2017-08-01

    Childhood maltreatment (CM) is associated with enhanced risk of psychiatric illness and reduced subcortical grey matter in adulthood. The hippocampus and amygdala, due to their involvement in stress and emotion circuitries, have been subject to extensive investigations regarding the effect of CM. However, the complex relationship between CM, subcortical grey matter and mental illness remains poorly understood partially due to a lack of longitudinal studies. Here we used segmentation and linear mixed effect modelling to examine the impact of CM on hippocampal and amygdala development in young people with emerging mental illness. A total of 215 structural magnetic resonance imaging (MRI) scans were acquired from 123 individuals (age: 14-28 years, 79 female), 52 of whom were scanned twice or more. Hippocampal and amygdala volumes increased linearly with age, and their developmental trajectories were not moderated by symptom severity. However, exposure to CM was associated with significantly stunted right hippocampal growth. This finding bridges the gap between child and adult research in the field and provides novel evidence that CM is associated with disrupted hippocampal development in youth. Although CM was associated with worse symptom severity, we did not find evidence that CM-induced structural abnormalities directly underpin psychopathology. This study has important implications for the psychiatric treatment of individuals with CM since they are clinically and neurobiologically distinct from their peers who were not maltreated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Training labels for hippocampal segmentation based on the EADC-ADNI harmonized hippocampal protocol.

    Science.gov (United States)

    Boccardi, Marina; Bocchetta, Martina; Morency, Félix C; Collins, D Louis; Nishikawa, Masami; Ganzola, Rossana; Grothe, Michel J; Wolf, Dominik; Redolfi, Alberto; Pievani, Michela; Antelmi, Luigi; Fellgiebel, Andreas; Matsuda, Hiroshi; Teipel, Stefan; Duchesne, Simon; Jack, Clifford R; Frisoni, Giovanni B

    2015-02-01

    The European Alzheimer's Disease Consortium and Alzheimer's Disease Neuroimaging Initiative (ADNI) Harmonized Protocol (HarP) is a Delphi definition of manual hippocampal segmentation from magnetic resonance imaging (MRI) that can be used as the standard of truth to train new tracers, and to validate automated segmentation algorithms. Training requires large and representative data sets of segmented hippocampi. This work aims to produce a set of HarP labels for the proper training and certification of tracers and algorithms. Sixty-eight 1.5 T and 67 3 T volumetric structural ADNI scans from different subjects, balanced by age, medial temporal atrophy, and scanner manufacturer, were segmented by five qualified HarP tracers whose absolute interrater intraclass correlation coefficients were 0.953 and 0.975 (left and right). Labels were validated as HarP compliant through centralized quality check and correction. Hippocampal volumes (mm(3)) were as follows: controls: left = 3060 (standard deviation [SD], 502), right = 3120 (SD, 897); mild cognitive impairment (MCI): left = 2596 (SD, 447), right = 2686 (SD, 473); and Alzheimer's disease (AD): left = 2301 (SD, 492), right = 2445 (SD, 525). Volumes significantly correlated with atrophy severity at Scheltens' scale (Spearman's ρ = segmentation algorithms. The publicly released labels will allow the widespread implementation of the standard segmentation protocol. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  5. Estradiol and luteinizing hormone regulate recognition memory following subchronic phencyclidine: Evidence for hippocampal GABA action.

    Science.gov (United States)

    Riordan, Alexander J; Schaler, Ari W; Fried, Jenny; Paine, Tracie A; Thornton, Janice E

    2018-05-01

    The cognitive symptoms of schizophrenia are poorly understood and difficult to treat. Estrogens may mitigate these symptoms via unknown mechanisms. To examine these mechanisms, we tested whether increasing estradiol (E) or decreasing luteinizing hormone (LH) could mitigate short-term episodic memory loss in a phencyclidine (PCP) model of schizophrenia. We then assessed whether changes in cortical or hippocampal GABA may underlie these effects. Female rats were ovariectomized and injected subchronically with PCP. To modulate E and LH, animals received estradiol capsules or Antide injections. Short-term episodic memory was assessed using the novel object recognition task (NORT). Brain expression of GAD67 was analyzed via western blot, and parvalbumin-containing cells were counted using immunohistochemistry. Some rats received hippocampal infusions of a GABA A agonist, GABA A antagonist, or GAD inhibitor before behavioral testing. We found that PCP reduced hippocampal GAD67 and abolished recognition memory. Antide restored hippocampal GAD67 and rescued recognition memory in PCP-treated animals. Estradiol prevented PCP's amnesic effect in NORT but failed to restore hippocampal GAD67. PCP did not cause significant differences in number of parvalbumin-expressing cells or cortical expression of GAD67. Hippocampal infusions of a GABA A agonist restored recognition memory in PCP-treated rats. Blocking hippocampal GAD or GABA A receptors in ovx animals reproduced recognition memory loss similar to PCP and inhibited estradiol's protection of recognition memory in PCP-treated animals. In summary, decreasing LH or increasing E can lessen short-term episodic memory loss, as measured by novel object recognition, in a PCP model of schizophrenia. Alterations in hippocampal GABA may contribute to both PCP's effects on recognition memory and the hormones' ability to prevent or reverse them. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Evidence for smaller right amygdala volumes in posttraumatic stress disorder following childhood trauma

    NARCIS (Netherlands)

    Veer, I.M.; Oei, N.Y.L.; van Buchem, M.A.; Spinhoven, Ph.; Elzinga, B.M.; Rombouts, S.A.R.B.

    2015-01-01

    Hippocampus and amygdala volumes in posttraumatic stress disorder (PTSD) related to childhood trauma are relatively understudied, albeit the potential importance to the disorder. Whereas some studies reported smaller hippocampal volumes, little evidence was found for abnormal amygdala volumes. Here

  7. Evaluating Alzheimer's disease progression using rate of regional hippocampal atrophy.

    Directory of Open Access Journals (Sweden)

    Edit Frankó

    Full Text Available Alzheimer's disease (AD is characterized by neurofibrillary tangle and neuropil thread deposition, which ultimately results in neuronal loss. A large number of magnetic resonance imaging studies have reported a smaller hippocampus in AD patients as compared to healthy elderlies. Even though this difference is often interpreted as atrophy, it is only an indirect measurement. A more direct way of measuring the atrophy is to use repeated MRIs within the same individual. Even though several groups have used this appropriate approach, the pattern of hippocampal atrophy still remains unclear and difficult to relate to underlying pathophysiology. Here, in this longitudinal study, we aimed to map hippocampal atrophy rates in patients with AD, mild cognitive impairment (MCI and elderly controls. Data consisted of two MRI scans for each subject. The symmetric deformation field between the first and the second MRI was computed and mapped onto the three-dimensional hippocampal surface. The pattern of atrophy rate was similar in all three groups, but the rate was significantly higher in patients with AD than in control subjects. We also found higher atrophy rates in progressive MCI patients as compared to stable MCI, particularly in the antero-lateral portion of the right hippocampus. Importantly, the regions showing the highest atrophy rate correspond to those that were described to have the highest burden of tau deposition. Our results show that local hippocampal atrophy rate is a reliable biomarker of disease stage and progression and could also be considered as a method to objectively evaluate treatment effects.

  8. PirB regulates asymmetries in hippocampal circuitry.

    Directory of Open Access Journals (Sweden)

    Hikari Ukai

    Full Text Available Left-right asymmetry is a fundamental feature of higher-order brain structure; however, the molecular basis of brain asymmetry remains unclear. We recently identified structural and functional asymmetries in mouse hippocampal circuitry that result from the asymmetrical distribution of two distinct populations of pyramidal cell synapses that differ in the density of the NMDA receptor subunit GluRε2 (also known as NR2B, GRIN2B or GluN2B. By examining the synaptic distribution of ε2 subunits, we previously found that β2-microglobulin-deficient mice, which lack cell surface expression of the vast majority of major histocompatibility complex class I (MHCI proteins, do not exhibit circuit asymmetry. In the present study, we conducted electrophysiological and anatomical analyses on the hippocampal circuitry of mice with a knockout of the paired immunoglobulin-like receptor B (PirB, an MHCI receptor. As in β2-microglobulin-deficient mice, the PirB-deficient hippocampus lacked circuit asymmetries. This finding that MHCI loss-of-function mice and PirB knockout mice have identical phenotypes suggests that MHCI signals that produce hippocampal asymmetries are transduced through PirB. Our results provide evidence for a critical role of the MHCI/PirB signaling system in the generation of asymmetries in hippocampal circuitry.

  9. Necroptosis Mediates TNF-Induced Toxicity of Hippocampal Neurons

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    Shan Liu

    2014-01-01

    Full Text Available Tumor necrosis factor-α (TNF-α is a critical proinflammatory cytokine regulating neuroinflammation. Elevated levels of TNF-α have been associated with various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. However, the signaling events that lead to TNF-α-initiated neurotoxicity are still unclear. Here, we report that RIP3-mediated necroptosis, a form of regulated necrosis, is activated in the mouse hippocampus after intracerebroventricular injection of TNF-α. RIP3 deficiency attenuates TNF-α-initiated loss of hippocampal neurons. Furthermore, we characterized the molecular mechanism of TNF-α-induced neurotoxicity in HT-22 hippocampal neuronal cells. HT-22 cells are sensitive to TNF-α only upon caspase blockage and subsequently undergo necrosis. The cell death is suppressed by knockdown of CYLD or RIP1 or RIP3 or MLKL, suggesting that this necrosis is necroptosis and mediated by CYLD-RIP1-RIP3-MLKL signaling pathway. TNF-α-induced necroptosis of HT-22 cells is largely independent of both ROS accumulation and calcium influx although these events have been shown to be critical for necroptosis in certain cell lines. Taken together, these data not only provide the first in vivo evidence for a role of RIP3 in TNF-α-induced toxicity of hippocampal neurons, but also demonstrate that TNF-α promotes CYLD-RIP1-RIP3-MLKL-mediated necroptosis of hippocampal neurons largely bypassing ROS accumulation and calcium influx.

  10. Hippocampal Sclerosis in Older Patients

    Science.gov (United States)

    Cykowski, Matthew D.; Powell, Suzanne Z.; Schulz, Paul E.; Takei, Hidehiro; Rivera, Andreana L.; Jackson, Robert E.; Roman, Gustavo; Jicha, Gregory A.; Nelson, Peter T.

    2018-01-01

    Context Autopsy studies of the older population (≥65 years of age), and particularly of the “oldest-old” (≥85 years of age), have identified a significant proportion (~20%) of cognitively impaired patients in which hippocampal sclerosis is the major substrate of an amnestic syndrome. Hippocampal sclerosis may also be comorbid with frontotemporal lobar degeneration, Alzheimer disease, and Lewy body disease. Until recently, the terms hippocampal sclerosis of aging or hippocampal sclerosis dementia were applied in this context. Recent discoveries have prompted a conceptual expansion of hippocampal sclerosis of aging because (1) cellular inclusions of TAR DNA-binding protein 43 kDa (TDP-43) are frequent; (2) TDP-43 pathology may be found outside hippocampus; and (3) brain arteriolosclerosis is a common, possibly pathogenic, component. Objective To aid pathologists with recent recommendations for diagnoses of common neuropathologies in older persons, particularly hippocampal sclerosis, and highlight the recent shift in diagnostic terminology from HS-aging to cerebral age-related TDP-43 with sclerosis (CARTS). Data Sources Peer-reviewed literature and 5 autopsy examples that illustrate common age-related neuropathologies, including CARTS, and emphasize the importance of distinguishing CARTS from late-onset frontotemporal lobar degeneration with TDP-43 pathology and from advanced Alzheimer disease with TDP-43 pathology. Conclusions In advanced old age, the substrates of cognitive impairment are often multifactorial. This article demonstrates common and frequently comorbid neuropathologic substrates of cognitive impairment in the older population, including CARTS, to aid those practicing in this area of pathology. PMID:28467211

  11. Carriers of loss-of-function mutations in EXT display impaired pancreatic beta-cell reserve due to smaller pancreas volume.

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    Sophie J Bernelot Moens

    Full Text Available Exotosin (EXT proteins are involved in the chain elongation step of heparan sulfate (HS biosynthesis, which is intricately involved in organ development. Loss of function mutations (LOF in EXT1 and EXT2 result in hereditary exostoses (HME. Interestingly, HS plays a role in pancreas development and beta-cell function, and genetic variations in EXT2 are associated with an increased risk for type 2 diabetes mellitus. We hypothesized that loss of function of EXT1 or EXT2 in subjects with hereditary multiple exostoses (HME affects pancreatic insulin secretion capacity and development. We performed an oral glucose tolerance test (OGTT followed by hyperglycemic clamps to investigate first-phase glucose-stimulated insulin secretion (GSIS in HME patients and age and gender matched non-affected relatives. Pancreas volume was assessed with magnetic resonance imaging (MRI. OGTT did not reveal significant differences in glucose disposal, but there was a markedly lower GSIS in HME subjects during hyperglycemic clamp (iAUC HME: 0.72 [0.46-1.16] vs. controls 1.53 [0.69-3.36] nmol·l-1·min-1, p<0.05. Maximal insulin response following arginine challenge was also significantly attenuated (iAUC HME: 7.14 [4.22-10.5] vs. controls 10.2 [7.91-12.70] nmol·l-1·min-1 p<0.05, indicative of an impaired beta-cell reserve. MRI revealed a significantly smaller pancreatic volume in HME subjects (HME: 72.0±15.8 vs. controls 96.5±26.0 cm3 p = 0.04. In conclusion, loss of function of EXT proteins may affect beta-cell mass and insulin secretion capacity in humans, and render subjects at a higher risk of developing type 2 diabetes when exposed to environmental risk factors.

  12. Subacute normobaric oxygen and hyperbaric oxygen therapy in drowning, reversal of brain volume loss: a case report

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    Paul G Harch

    2017-01-01

    Full Text Available A 2-year-old girl experienced cardiac arrest after cold water drowning. Magnetic resonance imaging (MRI showed deep gray matter injury on day 4 and cerebral atrophy with gray and white matter loss on day 32. Patient had no speech, gait, or responsiveness to commands on day 48 at hospital discharge. She received normobaric 100% oxygen treatment (2 L/minute for 45 minutes by nasal cannula, twice/day since day 56 and then hyperbaric oxygen treatment (HBOT at 1.3 atmosphere absolute (131.7 kPa air/45 minutes, 5 days/week for 40 sessions since day 79; visually apparent and/or physical examination-documented neurological improvement occurred upon initiating each therapy. After HBOT, the patient had normal speech and cognition, assisted gait, residual fine motor and temperament deficits. MRI at 5 months after injury and 27 days after HBOT showed near-normalization of ventricles and reversal of atrophy. Subacute normobaric oxygen and HBOT were able to restore drowning-induced cortical gray matter and white matter loss, as documented by sequential MRI, and simultaneous neurological function, as documented by video and physical examinations.

  13. Effects of low-level sarin and cyclosarin exposure on hippocampal subfields in Gulf War Veterans.

    Science.gov (United States)

    Chao, Linda L; Kriger, Stephen; Buckley, Shannon; Ng, Peter; Mueller, Susanne G

    2014-09-01

    More than 100,000 US troops were potentially exposed to chemical warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at Khamisiyah, Iraq was destroyed during the 1991 Gulf War (GW). We previously reported reduced hippocampal volume in GW veterans with suspected GB/GF exposure relative to matched, unexposed GW veterans estimated from 1.5T magnetic resonance images (MRI). Here we investigate, in a different cohort of GW veterans, whether low-level GB/GF exposure is associated with structural alterations in specific hippocampal subfields, estimated from 4T MRI. The Automatic Segmentation of Hippocampal Subfields (ASHS) technique was used to quantify CA1, CA2, CA3 and dentate gyrus (DG), and subiculum (SUB) subfields volumes from high-resolution T2-weighted images acquired on a 4T MR scanner in 56 GW veterans with suspected GB/GF exposure and 56 "matched" unexposed GW veterans (mean age 49±7 years). GB/GF exposed veterans had smaller CA2 (p=0.003) and CA3/DG (p=0.01) subfield volumes compared to matched, unexposed GW veterans. There were no group difference in total hippocampal volume, quantified with FreeSurfer, and no dose-response relationship between estimated levels of GB/GF exposure and total hippocampal or subfield volume. These findings extend our previous report of structural alterations in the hippocampi of GW veterans with suspected GB/GF exposure to volume changes in the CA2, CA3, and DG hippocampal subfields in a different cohort of GW veterans with suspected GB/GF exposure. Published by Elsevier B.V.

  14. Hippocampal atrophy and altered brain responses to pleasant tastes among obese compared with healthy weight children.

    Science.gov (United States)

    Mestre, Z L; Bischoff-Grethe, A; Eichen, D M; Wierenga, C E; Strong, D; Boutelle, K N

    2017-10-01

    The hippocampus is a key structure implicated in food motivation and intake. Research has shown that the hippocampus is vulnerable to the consumption of a western diet (i.e., high saturated fat and simple carbohydrates). Studies of patients with obesity (OB), compared with healthy weight (HW), show changes in hippocampal volume and response to food cues. Moreover, evidence suggests that OB children, relative to HW, have greater hippocampal response to taste. However, no study has examined the association of hippocampal volume with taste functioning in children. We hypothesized that OB children, relative to HW, would show a significant reduction in hippocampal volume and that decreased volume would be significantly associated with greater activation to taste. Finally, we explored whether hippocampal activation would be associated with measures on eating and eating habits. Twenty-five 8-12-year-old children (i.e., 13 HW, 12 OB) completed a magnetic resonance imaging scan while participating in a taste paradigm (i.e., 1 ml of 10% sucrose or ionic water delivered pseudorandomly every 20 s). Children with OB, relative to HW, showed reduced left hippocampal volume (t=1.994, P=0.03, 95% confidence interval (CI)=-40.23,  755.42), and greater response to taste in three clusters within the left hippocampus (z=3.3, P=0.001, 95% CI=-0.241, -0.041; z=3.3, P=0.001, 95% CI=-0.2711, -0.0469; z=2.7, P=0.007, 95% CI=-0.6032, -0.0268). Activation within the hippocampus was associated with eating in the absence of hunger (EAH%; t=2.408, P=0.025, 95% CI= 1.751708, 23.94109) and two subscales on a measure of eating behaviors (Food responsiveness, t=2.572, P=0.017, 95% CI= 0.9565195, 9.043440; Food enjoyment, t=2.298, P=0.032, 95% CI=0.2256749, 4.531298). As hypothesized, OB children, relative to HW, had significantly reduced hippocampal volume, and greater hippocampal activation to taste. Moreover, hippocampal activation was associated with measures of eating. These results

  15. Remodeling of hippocampal spine synapses in the rat learned helplessness model of depression.

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    Hajszan, Tibor; Dow, Antonia; Warner-Schmidt, Jennifer L; Szigeti-Buck, Klara; Sallam, Nermin L; Parducz, Arpad; Leranth, Csaba; Duman, Ronald S

    2009-03-01

    Although it has been postulated for many years that depression is associated with loss of synapses, primarily in the hippocampus, and that antidepressants facilitate synapse growth, we still lack ultrastructural evidence that changes in depressive behavior are indeed correlated with structural synaptic modifications. We analyzed hippocampal spine synapses of male rats (n=127) with electron microscopic stereology in association with performance in the learned helplessness paradigm. Inescapable footshock (IES) caused an acute and persistent loss of spine synapses in each of CA1, CA3, and dentate gyrus, which was associated with a severe escape deficit in learned helplessness. On the other hand, IES elicited no significant synaptic alterations in motor cortex. A single injection of corticosterone reproduced both the hippocampal synaptic changes and the behavioral responses induced by IES. Treatment of IES-exposed animals for 6 days with desipramine reversed both the hippocampal spine synapse loss and the escape deficit in learned helplessness. We noted, however, that desipramine failed to restore the number of CA1 spine synapses to nonstressed levels, which was associated with a minor escape deficit compared with nonstressed control rats. Shorter, 1-day or 3-day desipramine treatments, however, had neither synaptic nor behavioral effects. These results indicate that changes in depressive behavior are associated with remarkable remodeling of hippocampal spine synapses at the ultrastructural level. Because spine synapse loss contributes to hippocampal dysfunction, this cellular mechanism may be an important component in the neurobiology of stress-related disorders such as depression.

  16. Structural correlates of impaired working memory in hippocampal sclerosis

    Science.gov (United States)

    Winston, Gavin P; Stretton, Jason; Sidhu, Meneka K; Symms, Mark R; Thompson, Pamela J; Duncan, John S

    2013-01-01

    Purpose: Temporal lobe epilepsy (TLE) has been considered to impair long-term memory, whilst not affecting working memory, but recent evidence suggests that working memory is compromised. Functional MRI (fMRI) studies demonstrate that working memory involves a bilateral frontoparietal network the activation of which is disrupted in hippocampal sclerosis (HS). A specific role of the hippocampus to deactivate during working memory has been proposed with this mechanism faulty in patients with HS. Structural correlates of disrupted working memory in HS have not been explored. Methods: We studied 54 individuals with medically refractory TLE and unilateral HS (29 left) and 28 healthy controls. Subjects underwent 3T structural MRI, a visuospatial n-back fMRI paradigm and diffusion tensor imaging (DTI). Working memory capacity assessed by three span tasks (digit span backwards, gesture span, motor sequences) was combined with performance in the visuospatial paradigm to give a global working memory measure. Gray and white matter changes were investigated using voxel-based morphometry and voxel-based analysis of DTI, respectively. Key Findings: Individuals with left or right HS performed less well than healthy controls on all measures of working memory. fMRI demonstrated a bilateral frontoparietal network during the working memory task with reduced activation of the right parietal lobe in both patient groups. In left HS, gray matter loss was seen in the ipsilateral hippocampus and parietal lobe, with maintenance of the gray matter volume of the contralateral parietal lobe associated with better performance. White matter integrity within the frontoparietal network, in particular the superior longitudinal fasciculus and cingulum, and the contralateral temporal lobe, was associated with working memory performance. In right HS, gray matter loss was also seen in the ipsilateral hippocampus and parietal lobe. Working memory performance correlated with the gray matter volume of

  17. The Reduction of Ventrolateral Prefrontal Cortex Gray Matter Volume Correlates with Loss of Economic Rationality in Aging.

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    Chung, Hui-Kuan; Tymula, Agnieszka; Glimcher, Paul

    2017-12-06

    The population of people above 65 years old continues to grow, and there is mounting evidence that as humans age they are more likely to make errors. However, the specific effect of neuroanatomical aging on the efficiency of economic decision-making is poorly understood. We used whole-brain voxel-based morphometry analysis to determine where reduction of gray matter volume in healthy female and male adults over the age of 65 years correlates with a classic measure of economic irrationality: violations of the Generalized Axiom of Revealed Preference. All participants were functionally normal with Mini-Mental State Examination scores ranging between 26 and 30. While our elders showed the previously reported decline in rationality compared with younger subjects, chronological age per se did not correlate with rationality measures within our population of elders. Instead, reduction of gray matter density in ventrolateral prefrontal cortex correlates tightly with irrational behavior. Interestingly, using a large fMRI sample and meta-analytic tool with Neurosynth, we found that this brain area shows strong coactivation patterns with nearly all of the value-associated regions identified in previous studies. These findings point toward a neuroanatomic locus for economic rationality in the aging brain and highlight the importance of understanding both anatomy and function in the study of aging, cognition, and decision-making. SIGNIFICANCE STATEMENT Age is a crucial factor in decision-making, with older individuals making more errors in choices. Using whole-brain voxel-based morphometry analysis, we found that reduction of gray matter density in ventrolateral prefrontal cortex correlates with economic irrationality: reduced gray matter volume in this area correlates with the frequency and severity of violations of the Generalized Axiom of Revealed Preference. Furthermore, this brain area strongly coactivates with other reward-associated regions identified with Neurosynth

  18. Hippocampal Abnormalities and Seizure Recurrence

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    J Gordon Millichap

    2006-08-01

    Full Text Available Hippocampal volumetry and T2 relaxometry were performed on 84 consecutive patients (adolescents and adults with partial epilepsy submitted to antiepileptic drug (AED withdrawal after at least 2 years of seizure control, in a study at State University of Campinas-UNICAMP, Brazil.

  19. Decreased rhythmic GABAergic septal activity and memory-associated theta oscillations after hippocampal amyloid-beta pathology in the rat.

    Science.gov (United States)

    Villette, Vincent; Poindessous-Jazat, Frédérique; Simon, Axelle; Léna, Clément; Roullot, Elodie; Bellessort, Brice; Epelbaum, Jacques; Dutar, Patrick; Stéphan, Aline

    2010-08-18

    The memory deficits associated with Alzheimer's disease result to a great extent from hippocampal network dysfunction. The coordination of this network relies on theta (symbol) oscillations generated in the medial septum. Here, we investigated in rats the impact of hippocampal amyloid beta (Abeta) injections on the physiological and cognitive functions that depend on the septohippocampal system. Hippocampal Abeta injections progressively impaired behavioral performances, the associated hippocampal theta power, and theta frequency response in a visuospatial recognition test. These alterations were associated with a specific reduction in the firing of the identified rhythmic bursting GABAergic neurons responsible for the propagation of the theta rhythm to the hippocampus, but without loss of medial septal neurons. Such results indicate that hippocampal Abeta treatment leads to a specific functional depression of inhibitory projection neurons of the medial septum, resulting in the functional impairment of the temporal network.

  20. Cannabis-related hippocampal volumetric abnormalities specific to subregions in dependent users.

    Science.gov (United States)

    Chye, Yann; Suo, Chao; Yücel, Murat; den Ouden, Lauren; Solowij, Nadia; Lorenzetti, Valentina

    2017-07-01

    Cannabis use is associated with neuroanatomical alterations in the hippocampus. While the hippocampus is composed of multiple subregions, their differential vulnerability to cannabis dependence remains unknown. The objective of the study is to investigate gray matter alteration in each of the hippocampal subregions (presubiculum, subiculum, cornu ammonis (CA) subfields CA1-4, and dentate gyrus (DG)) as associated with cannabis use and dependence. A total of 35 healthy controls (HC), 22 non-dependent (CB-nondep), and 39 dependent (CB-dep) cannabis users were recruited. We investigated group differences in hippocampal subregion volumes between HC, CB-nondep, and CB-dep users. We further explored the association between CB use variables (age of onset of regular use, monthly use, lifetime use) and hippocampal subregions in CB-nondep and CB-dep users separately. The CA1, CA2/3, CA4/DG, as well as total hippocampal gray matter were reduced in volume in CB-dep but not in CB-nondep users, relative to HC. The right CA2/3 and CA4/DG volumes were also negatively associated with lifetime cannabis use in CB-dep users. Our results suggest a regionally and dependence-specific influence of cannabis use on the hippocampus. Hippocampal alteration in cannabis users was specific to the CA and DG regions and confined to dependent users.

  1. Hypothalamic-pituitary-adrenal axis tonus is associated with hippocampal microstructural asymmetry

    DEFF Research Database (Denmark)

    Madsen, Kathrine Skak; Jernigan, Terry L; Iversen, Pernille

    2012-01-01

    It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since there is gr......It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since....... Observed associations raise a number of possibilities, among them an asymmetric role of the hippocampus on HPA-axis regulation, or conversely, that individual variations in secreted cortisol, perhaps associated with stress, may have lateralized effects on hippocampal microstructure. Our results point...

  2. Late-Onset Alzheimer's Disease Polygenic Risk Profile Score Predicts Hippocampal Function.

    Science.gov (United States)

    Xiao, Ena; Chen, Qiang; Goldman, Aaron L; Tan, Hao Yang; Healy, Kaitlin; Zoltick, Brad; Das, Saumitra; Kolachana, Bhaskar; Callicott, Joseph H; Dickinson, Dwight; Berman, Karen F; Weinberger, Daniel R; Mattay, Venkata S

    2017-11-01

    We explored the cumulative effect of several late-onset Alzheimer's disease (LOAD) risk loci using a polygenic risk profile score (RPS) approach on measures of hippocampal function, cognition, and brain morphometry. In a sample of 231 healthy control subjects (19-55 years of age), we used an RPS to study the effect of several LOAD risk loci reported in a recent meta-analysis on hippocampal function (determined by its engagement with blood oxygen level-dependent functional magnetic resonance imaging during episodic memory) and several cognitive metrics. We also studied effects on brain morphometry in an overlapping sample of 280 subjects. There was almost no significant association of LOAD-RPS with cognitive or morphometric measures. However, there was a significant negative relationship between LOAD-RPS and hippocampal function (familywise error [small volume correction-hippocampal region of interest] p risk score based on APOE haplotype, and for a combined LOAD-RPS + APOE haplotype risk profile score (p risk genes on hippocampal function even in healthy volunteers. The effect of LOAD-RPS on hippocampal function in the relative absence of any effect on cognitive and morphometric measures is consistent with the reported temporal characteristics of LOAD biomarkers with the earlier manifestation of synaptic dysfunction before morphometric and cognitive changes. Copyright © 2017 Society of Biological Psychiatry. All rights reserved.

  3. Asymmetry of limbic structure (hippocampal formation and amygdaloidal complex at PTSD

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    Aida Sarač-Hadžihalilović

    2003-05-01

    Full Text Available Defining exact position of weak anatomic function which is find in a base of neurological and psychiatric disorder is just became the subject of intensive research interest. For this purposes it is important to implement structural and functional MRI techniques, also for further lightening and seeing subject of this work, more concretely connected to PTSD. Therefore, exactly MRI gives most sensitive volumetric measuring of hippocampal formation and amygdaloidal complex.The goal of this work was to research asymmetry of hippocampal formation and amygdaloidal complex to the PTSD patients.Results showed that at the axial slice length of hippocampal formation on the left and right side of all patients are significantly asymmetric. At the sagittal slice from the left side of hippocampal formation is in many cases longer than right about 50 %. At the coronal slice, there are no significant differences toward patient proportion according to symm. / asymm. of the hippocampal formation width at the right and left side. Difference in volume average of hippocampal formation between right and left side for axial and coronal slice is not statistically significant, but it is significant for sagittal slice. In about amygdaloidal complex patients with PTSD toward symm. / asymm. Amygdaloidal complex at the right and left side of axial and sagittal slice in all three measurement shows asymmetry, what is especially shown at sagittal slice. Difference in average length of amygdaloidal complex at the right and left side is not statistically significant for no one slice.Therefore, results of a new research that are used MRI, showed smaller hippocampal level at PTSD (researched by Van der Kolka 1996, Pitman 1996, Bremner et al., 1995.. Application of MRI technique in research of asymmetry of hippocampal formation and amygdaloidal complex, which we used in our research, we recommend as a template for future researches in a sense of lightening anatomic function that is

  4. 17β Estradiol increases resilience and improves hippocampal synaptic function in helpless ovariectomized rats

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    Bredemann, Teruko M.; McMahon, Lori L.

    2014-01-01

    Summary Memory impairment is the most commonly reported cognitive symptom associated with major depressive disorder. Decreased hippocampal volume and neurogenesis in depression link hippocampal dysfunction with deficits in memory. Stress decreases hippocampal dendritic spine density and long-term potentiation (LTP) at glutamate synapses, a cellular correlate of learning and memory. However, elevated plasma levels of 17β estradiol (E2) during proestrus increase hippocampal structure and function, directly opposing the negative consequences of stress. In women, significant fluctuations in ovarian hormones likely increase vulnerability of hippocampal circuits to stress, potentially contributing to the greater incidence of depression compared to men. Using the learned helplessness model of depression and ovariectomized female rats, we investigated whether acquisition of helplessness and hippocampal synaptic dysfunction is differentially impacted by the presence or absence of plasma E2. We find that inescapable shock induces a greater incidence of helplessness in vehicle- versus E2-treated OVX rats. In the vehicle-treated group, LTP was absent at CA3-CA1 synapses in slices only from helpless rats, and CA1 spine density was decreased compared to resilient rats. In contrast, significant LTP was observed in slices from E2-treated helpless rats; importantly, spine density was not different between E2-treated helpless and resilient rats, dissociating spine density from the LTP magnitude. We also find that E2 replacement can reverse previously established helpless behavior. Thus, our results show that E2 replacement in OVX rats increases resilience and improves hippocampal plasticity, suggesting that E2 therapy may increase resilience to stress and preserve hippocampal function in women experiencing large fluctuations in plasma estrogen levels. PMID:24636504

  5. Potential hippocampal region atrophy in diabetes mellitus type 2. A voxel-based morphometry VSRAD study

    International Nuclear Information System (INIS)

    Kamiyama, Kazutoshi; Sugihara, Masaki; Wada, Akihiko

    2010-01-01

    Among diabetes mellitus type 2 (DM2) patients, the frequency of cognitive dysfunction is higher and the relative risk of Alzheimer's disease (AD) is approximately twice that of nondiabetics. Cognitive impairment symptoms of AD are induced by limbic system dysfunction, and an early-stage AD brain without dementia has the potential for atrophy in the hippocampal region. In this study, we estimated potential hippocampal region atrophy in DM2 and pursued the association between DM2 and cognitive impairment/AD. Voxel-based morphometry analysis was performed in 28 diabetics (14 men, 14 women; ages 59-79 years, mean 70.7 years) and 28 sex- and age- matched (±1 year) nondiabetics. Severity of gray matter loss in the hippocampal region and whole brain were investigated. Group analysis was performed using two-tailed unpaired t-test; significance was assumed with less than 1% (P<0.01) of the critical rate. There was a significant difference between diabetics and nondiabetics regarding the severity of hippocampal region atrophy and whole-brain atrophy. Only diabetics showed a positive correlation for severity of hippocampal region atrophy and whole-brain atrophy (rs=0.69, P<0.0001). Aged DM2 patients have the potential for hippocampal region atrophy, and its dysfunction can be related to the expression of a cognitive impairment that resembles AD. (author)

  6. A mathematical model of aging-related and cortisol induced hippocampal dysfunction

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    Jones Janette JL

    2009-03-01

    Full Text Available Abstract Background The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD, the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML. We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated. Results The in silicoSBML model reflected the in vivoaging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA, increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation. Conclusion Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitroand in vivostudies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people.

  7. Development of a Modelling to Correlate Site and Diameter of Brain Metastases with Hippocampal Sparing Using Volumetric Modulated Arc Therapy

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    Silvia Chiesa

    2013-01-01

    Full Text Available Purpose. To correlate site and diameter of brain metastases with hippocampal sparing in patients treated by RapidArc (RA technique on whole brain with simultaneously integrated boost (SIB. Methods and Materials. An RA plan was calculated for brain metastases of 1-2-3 cm of diameter. The whole brain dose was 32.25 Gy (15 fractions, and SIB doses to brain metastases were 63 Gy (2 and 3 cm or 70.8 Gy (1 cm. Plans were optimized and evaluated for conformity, target coverage, prescription isodose to target volume, homogeneity index, and hippocampal sparing. Results. Fifteen brain lesions and RA plan were generated. Hippocampal volume was 4.09 cm3, and hippocampal avoidance volume was 17.50 cm3. Related to site of metastases, the mean hippocampal dose was 9.68 Gy2 for occipital lobe, 10.56 Gy2 for frontal lobe, 10.56 Gy2 for parietal lobe, 10.94 Gy2 for deep brain structures, and 40.44 Gy2 for temporal lobe. The mean hippocampal dose was 9.45 Gy2, 10.15 Gy2, and 11.70 Gy2 for diameter’s metastases of 1.2 and 3 cm, respectively, excluding results relative to temporal brain lesions. Conclusions. Location more than size of metastases can adversely influence the hippocampus sparing. Further investigation is necessary to meet definitive considerations.

  8. Regional hippocampal vulnerability in early multiple sclerosis: Dynamic pathological spreading from dentate gyrus to CA1.

    Science.gov (United States)

    Planche, Vincent; Koubiyr, Ismail; Romero, José E; Manjon, José V; Coupé, Pierrick; Deloire, Mathilde; Dousset, Vincent; Brochet, Bruno; Ruet, Aurélie; Tourdias, Thomas

    2018-04-01

    Whether hippocampal subfields are differentially vulnerable at the earliest stages of multiple sclerosis (MS) and how this impacts memory performance is a current topic of debate. We prospectively included 56 persons with clinically isolated syndrome (CIS) suggestive of MS in a 1-year longitudinal study, together with 55 matched healthy controls at baseline. Participants were tested for memory performance and scanned with 3 T MRI to assess the volume of 5 distinct hippocampal subfields using automatic segmentation techniques. At baseline, CA4/dentate gyrus was the only hippocampal subfield with a volume significantly smaller than controls (p < .01). After one year, CA4/dentate gyrus atrophy worsened (-6.4%, p < .0001) and significant CA1 atrophy appeared (both in the stratum-pyramidale and the stratum radiatum-lacunosum-moleculare, -5.6%, p < .001 and -6.2%, p < .01, respectively). CA4/dentate gyrus volume at baseline predicted CA1 volume one year after CIS (R 2  = 0.44 to 0.47, p < .001, with age, T2 lesion-load, and global brain atrophy as covariates). The volume of CA4/dentate gyrus at baseline was associated with MS diagnosis during follow-up, independently of T2-lesion load and demographic variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with memory scores at baseline, CA1 atrophy was an independent correlate of episodic verbal memory performance one year after CIS (ß = 0.87, p < .05). The hippocampal degenerative process spread from dentate gyrus to CA1 at the earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis after CIS and will ultimately impact hippocampal-dependent memory performance. © 2018 Wiley Periodicals, Inc.

  9. Depressive Symptoms in Adolescents: Associations with White Matter Volume and Marijuana Use

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    Medina, Krista Lisdahl; Nagel, Bonnie J.; Park, Ann; McQueeny, Tim; Tapert, Susan F.

    2007-01-01

    Background: Depressed mood has been associated with decreased white matter and reduced hippocampal volumes. However, the relationship between brain structure and mood may be unique among adolescents who use marijuana heavily. The goal of this study was to examine the relationship between white matter and hippocampal volumes and depressive symptoms…

  10. Fully automated atlas-based hippocampal volumetry for detection of Alzheimer's disease in a memory clinic setting.

    Science.gov (United States)

    Suppa, Per; Anker, Ulrich; Spies, Lothar; Bopp, Irene; Rüegger-Frey, Brigitte; Klaghofer, Richard; Gocke, Carola; Hampel, Harald; Beck, Sacha; Buchert, Ralph

    2015-01-01

    Hippocampal volume is a promising biomarker to enhance the accuracy of the diagnosis of dementia due to Alzheimer's disease (AD). However, whereas hippocampal volume is well studied in patient samples from clinical trials, its value in clinical routine patient care is still rather unclear. The aim of the present study, therefore, was to evaluate fully automated atlas-based hippocampal volumetry for detection of AD in the setting of a secondary care expert memory clinic for outpatients. One-hundred consecutive patients with memory complaints were clinically evaluated and categorized into three diagnostic groups: AD, intermediate AD, and non-AD. A software tool based on open source software (Statistical Parametric Mapping SPM8) was employed for fully automated tissue segmentation and stereotactical normalization of high-resolution three-dimensional T1-weighted magnetic resonance images. Predefined standard masks were used for computation of grey matter volume of the left and right hippocampus which then was scaled to the patient's total grey matter volume. The right hippocampal volume provided an area under the receiver operating characteristic curve of 84% for detection of AD patients in the whole sample. This indicates that fully automated MR-based hippocampal volumetry fulfills the requirements for a relevant core feasible biomarker for detection of AD in everyday patient care in a secondary care memory clinic for outpatients. The software used in the present study has been made freely available as an SPM8 toolbox. It is robust and fast so that it is easily integrated into routine workflow.

  11. Survival of mossy cells of the hippocampal dentate gyrus in humans with mesial temporal lobe epilepsy.

    Science.gov (United States)

    Seress, László; Abrahám, Hajnalka; Horváth, Zsolt; Dóczi, Tamás; Janszky, József; Klemm, Joyce; Byrne, Richard; Bakay, Roy A E

    2009-12-01

    Hippocampal sclerosis can be identified in most patients with mesial temporal lobe epilepsy (TLE). Surgical removal of the sclerotic hippocampus is widely performed to treat patients with drug-resistant mesial TLE. In general, both epilepsy-prone and epilepsy-resistant neurons are believed to be in the hippocampal formation. The hilar mossy cells of the hippocampal dentate gyrus are usually considered one of the most vulnerable types of neurons. The aim of this study was to clarify the fate of mossy cells in the hippocampus in epileptic humans. Of the 19 patients included in this study, 15 underwent temporal lobe resection because of drug-resistant TLE. Four patients were used as controls because they harbored tumors that had not invaded the hippocampus and they had experienced no seizures. Histological evaluation of resected hippocampal tissues was performed using immunohistochemistry. Mossy cells were identified in the control as well as the epileptic hippocampi by using cocaine- and amphetamine-regulated transcript peptide immunohistochemistry. In most cases the number of mossy cells was reduced and thorny excrescences were smaller in the epileptic hippocampi than in controls; however, there was a significant loss of pyramidal cells and a partial loss of granule cells in the same epileptic hippocampi in which mossy cell loss was apparent. The loss of mossy cells could be correlated with the extent of hippocampal sclerosis, patient age at seizure onset, duration of epilepsy, and frequency of seizures. In many cases large numbers of mossy cells were present in the hilus of the dentate gyrus when most pyramidal neurons of the CA1 and CA3 areas of the Ammon's horn were lost, suggesting that mossy cells may not be more vulnerable to epileptic seizures than the hippocampal pyramidal neurons.

  12. Impact of preoperative calculation of nephron volume loss on future of partial nephrectomy techniques; planning a strategic roadmap for improving functional preservation and securing oncological safety.

    Science.gov (United States)

    Rha, Koon H; Abdel Raheem, Ali; Park, Sung Y; Kim, Kwang H; Kim, Hyung J; Koo, Kyo C; Choi, Young D; Jung, Byung H; Lee, Sang K; Lee, Won K; Krishnan, Jayram; Shin, Tae Y; Cho, Jin-Seon

    2017-11-01

    To assess the correlation of the resected and ischaemic volume (RAIV), which is a preoperatively calculated volume of nephron loss, with the amount of postoperative renal function (PRF) decline after minimally invasive partial nephrectomy (PN) in a multi-institutional dataset. We identified 348 patients from March 2005 to December 2013 at six institutions. Data on all cases of laparoscopic (n = 85) and robot-assisted PN (n = 263) performed were retrospectively gathered. Univariable and multivariable linear regression analyses were used to identify the associations between various time points of PRF and the RAIV, as a continuous variable. The mean (sd) RAIV was 24.2 (29.2) cm 3 . The mean preoperative estimated glomerular filtration rate (eGFR) and the eGFRs at postoperative day 1, 6 and 36 months after PN were 91.0 and 76.8, 80.2 and 87.7 mL/min/1.73 m 2 , respectively. In multivariable linear regression analysis, the amount of decline in PRF at follow-up was significantly correlated with the RAIV (β 0.261, 0.165, 0.260 at postoperative day 1, 6 and 36 months after PN, respectively). This study has the limitation of its retrospective nature. Preoperatively calculated RAIV significantly correlates with the amount of decline in PRF during long-term follow-up. The RAIV could lead our research to the level of prediction of the amount of PRF decline after PN and thus would be appropriate for assessing the technical advantages of emerging techniques. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  13. MRI volumetric measurement of hippocampal formation based on statistic parametric mapping

    International Nuclear Information System (INIS)

    Hua Jianming; Jiang Biao; Zhou Jiong; Zhang Weimin

    2010-01-01

    Objective: To study MRI volumetric measurement of hippocampal formation using statistic parametric mapping (SPM) software and to discuss the value of the method applied to Alzheimer's disease (AD). Methods: The SPM software was used to divide the three-dimensional MRI brain image into gray matter, white matter and CSF separately. The bilateral hippocampal formations in both AD group and normal control group were delineated and the volumes were measured. The SPM method was compared with conventional method based on region of interest (ROI), which was the gold standard of volume measurement. The time used in measuring the volume by these two methods were respectively recorded and compared by two independent samples't test. Moreover, 7 physicians measured the left hippocampal formation of one same control with both of the two methods. The frequency distribution and dispersion of data acquired with the two methods were evaluated using standard deviation coefficient. Results (1) The volume of the bilateral hippocampal formations with SPM method was (1.88 ± 0.07) cm 3 and (1.93 ± 0.08) cm 3 respectively in the AD group, while was (2.99 ± 0.07) cm 3 and (3.02 ± 0.06) cm 3 in the control group. The volume of bilateral hippocampal formations measured by ROI method was (1.87 ± 0.06) cm 3 and (1.91 ± 0.09) cm 3 in the AD group, while was (2.97 ± 0.08) cm 3 and (3.00 ± 0.05) cm 3 in the control group. There was no significant difference between SPM method and conventional ROI method in the AD group and the control group (t=1.500, 1.617, 1.095, 1.889, P>0.05). However, the time used for delineation and volume measurement was significantly different. The time used in SPM measurement was (38.1 ± 2.0) min, while that in ROI measurement was (55.4 ± 2.4) min (t=-25.918, P 3 respectively. The frequency distribution of hippocampal formation volume measured by SPM method and ROI method was different. The CV SPM was 7% and the CV ROI was 19%. Conclusions: The borders of

  14. Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Robert Nisticò

    Full Text Available Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS and its mouse model, experimental autoimmune encephalomyelitis (EAE. In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP induction was favored over long-term depression (LTD in EAE, as shown by a significant rightward shift in the frequency-synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS.

  15. Inflammation Subverts Hippocampal Synaptic Plasticity in Experimental Multiple Sclerosis

    Science.gov (United States)

    Mandolesi, Georgia; Piccinin, Sonia; Berretta, Nicola; Pignatelli, Marco; Feligioni, Marco; Musella, Alessandra; Gentile, Antonietta; Mori, Francesco; Bernardi, Giorgio; Nicoletti, Ferdinando; Mercuri, Nicola B.; Centonze, Diego

    2013-01-01

    Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE). In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP) induction was favored over long-term depression (LTD) in EAE, as shown by a significant rightward shift in the frequency–synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β) perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC) without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS. PMID:23355887

  16. Hippocampal sclerosis dementia: An amnesic variant of frontotemporal degeneration

    Directory of Open Access Journals (Sweden)

    Chiadi U. Onyike

    Full Text Available ABSTRACT Objective: To describe characteristics of hippocampal sclerosis dementia. Methods: Convenience sample of Hippocampal sclerosis dementia (HSD recruited from the Johns Hopkins University Brain Resource Center. Twenty-four cases with post-mortem pathological diagnosis of hippocampal sclerosis dementia were reviewed for clinical characterization. Results: The cases showed atrophy and neuronal loss localized to the hippocampus, amygdala and entorrhinal cortex. The majority (79.2% had amnesia at illness onset, and many (54.2% showed abnormal conduct and psychiatric disorder. Nearly 42% presented with an amnesic state, and 37.5% presented with amnesia plus abnormal conduct and psychiatric disorder. All eventually developed a behavioral or psychiatric disorder. Disorientation, executive dysfunction, aphasia, agnosia and apraxia were uncommon at onset. Alzheimer disease (AD was the initial clinical diagnosis in 89% and the final clinical diagnosis in 75%. Diagnosis of frontotemporal dementia (FTD was uncommon (seen in 8%. Conclusion: HSD shows pathological characteristics of FTD and clinical features that mimic AD and overlap with FTD. The findings, placed in the context of earlier work, support the proposition that HSD belongs to the FTD family, where it may be identified as an amnesic variant.

  17. Hippocampal sclerosis dementia: an amnesic variant of frontotemporal degeneration

    Science.gov (United States)

    Onyike, Chiadi U.; Pletnikova, Olga; Sloane, Kelly L.; Sullivan, Campbell; Troncoso, Juan C.; Rabins, Peter V.

    2013-01-01

    OBJECTIVE To describe characteristics of hippocampal sclerosis dementia. METHODS Convenience sample of Hippocampal sclerosis dementia (HSD) recruited from the Johns Hopkins University Brain Resource Center. Twenty-four cases with post-mortem pathological diagnosis of hippocampal sclerosis dementia were reviewed for clinical characterization. RESULTS The cases showed atrophy and neuronal loss localized to the hippocampus, amygdala and entorrhinal cortex. The majority (79.2%) had amnesia at illness onset, and many (54.2%) showed abnormal conduct and psychiatric disorder. Nearly 42% presented with an amnesic state, and 37.5% presented with amnesia plus abnormal conduct and psychiatric disorder. All eventually developed a behavioral or psychiatric disorder. Disorientation, executive dysfunction, aphasia, agnosia and apraxia were uncommon at onset. Alzheimer disease (AD) was the initial clinical diagnosis in 89% and the final clinical diagnosis in 75%. Diagnosis of frontotemporal dementia (FTD) was uncommon (seen in 8%). CONCLUSION HSD shows pathological characteristics of FTD and clinical features that mimic AD and overlap with FTD. The findings, placed in the context of earlier work, support the proposition that HSD belongs to the FTD family, where it may be identified as an amnesic variant. PMID:24363834

  18. Effect of dorsal hippocampal lesion compared to dorsal hippocampal blockade by atropine on reference memory in vision deprived rats.

    Science.gov (United States)

    Dhume, R A; Noronha, A; Nagwekar, M D; Mascarenhas, J F

    1989-10-01

    In order to study the primacy of the hippocampus in place learning function 24 male adult albino rats were hippocampally-lesioned in dorsal hippocampus involving fornical damage (group I); sham operated for comparison with group I (group II); cannulated for instillation of atropine sulphate in the same loci as group I (group III); and cannulated for instillation of saline which served as control for group III (group IV). All the animals were enucleated and their reference memory (long-term memory) was tested, using open 4-arm radial maze. There was loss of reference memory in groups I and III. However, hippocampally-lesioned animals, showed recovery of reference memory deficit within a short period of 10 days or so. Whereas atropinized animals showed persistent reference memory deficit as long as the instillation effect continued. The mechanism involved in the recovery of reference memory in hippocampally-lesioned animals and persistent deficit of reference memory in atropinized animals has been postulated to explain the primacy of hippocampus in the place learning function under normal conditions.

  19. Is radiological evaluation as good as computer-based volumetry to assess hippocampal atrophy in Alzheimer's disease?

    International Nuclear Information System (INIS)

    Boutet, Claire; Drier, Aurelie; Dormont, Didier; Lehericy, Stephane; Chupin, Marie; Colliot, Olivier; Sarazin, Marie; Mutlu, Gurkan; Pellot, Audrey

    2012-01-01

    Hippocampus volumetry is a useful surrogate marker for the diagnosis of Alzheimer's disease (AD). Our purpose was to compare visual assessment of medial temporal lobe atrophy made by radiologists with automatic hippocampal volume and to compare their performances for the classification of AD, mild cognitive impairment (MCI) and cognitively normal (CN). We studied 30 CN, 30 MCI and 30 AD subjects. Six radiologists with two levels of expertise performed two readings of medial temporal lobe atrophy. Medial temporal lobe atrophy was evaluated on coronal three-dimensional T1-weighted images using Scheltens scale and compared with hippocampal volume obtained using a fully automatic segmentation method (Spearman's rank coefficient). Visual assessment of medial temporal lobe atrophy was correlated with hippocampal volume (p < 0.01). Classification performances between MCI converter and CN was better using volumetry than visual assessment of non-expert readers whereas classification of AD and CN did not differ between visual assessment and volumetry except for the first reading of one non-expert (p = 0.03). Visual assessment of medial temporal lobe atrophy by radiologists was well correlated with hippocampal volume. Radiological assessment is as good as computer-based volumetry for the classification of AD, MCI non-converter and CN and less good for the classification of MCI converter versus CN. Use of Scheltens scale for assessing hippocampal atrophy in AD seems thus justified in clinical routine. (orig.)

  20. Is radiological evaluation as good as computer-based volumetry to assess hippocampal atrophy in Alzheimer's disease?

    Energy Technology Data Exchange (ETDEWEB)

    Boutet, Claire; Drier, Aurelie; Dormont, Didier; Lehericy, Stephane [Groupe Hospitalier Pitie-Salpetriere, Department of Neuroradiology, AP-HP, Paris Cedex 13 (France); Universite Pierre et Marie Curie-Paris 6, Centre de Recherche de l' Institut du Cerveau et de la Moelle epiniere, UMR-S975, Paris (France); Inserm, Paris (France); CNRS, Paris (France); ICM-Institut du Cerveau et de la Moelle epiniere, Paris (France); Chupin, Marie; Colliot, Olivier [Universite Pierre et Marie Curie-Paris 6, Centre de Recherche de l' Institut du Cerveau et de la Moelle epiniere, UMR-S975, Paris (France); Inserm, Paris (France); CNRS, Paris (France); ICM-Institut du Cerveau et de la Moelle epiniere, Paris (France); Equipe Cogimage-CRICM, Paris Cedex 13 (France); Sarazin, Marie [Universite Pierre et Marie Curie-Paris 6, Centre de Recherche de l' Institut du Cerveau et de la Moelle epiniere, UMR-S975, Paris (France); Inserm, Paris (France); CNRS, Paris (France); ICM-Institut du Cerveau et de la Moelle epiniere, Paris (France); Groupe Hospitalier Pitie-Salpetriere, Department of Neurology, Institut de la Memoire et de la Maladie d' Alzheimer-IM2A, Paris Cedex 13 (France); Mutlu, Gurkan [Groupe Hospitalier Pitie-Salpetriere, Urgences Cerebro-Vasculaires, Universite Pierre et Marie Curie-Paris 6, Paris Cedex 13 (France); Hopital Saint-Louis, Inserm, Universite Paris 7-Denis Diderot, Paris (France); Pellot, Audrey [Groupe Hospitalier Pitie-Salpetriere, Department of Neuroradiology, AP-HP, Paris Cedex 13 (France); Collaboration: And the Alzheimer' s Disease Neuroimaging Initiative

    2012-12-15

    Hippocampus volumetry is a useful surrogate marker for the diagnosis of Alzheimer's disease (AD). Our purpose was to compare visual assessment of medial temporal lobe atrophy made by radiologists with automatic hippocampal volume and to compare their performances for the classification of AD, mild cognitive impairment (MCI) and cognitively normal (CN). We studied 30 CN, 30 MCI and 30 AD subjects. Six radiologists with two levels of expertise performed two readings of medial temporal lobe atrophy. Medial temporal lobe atrophy was evaluated on coronal three-dimensional T1-weighted images using Scheltens scale and compared with hippocampal volume obtained using a fully automatic segmentation method (Spearman's rank coefficient). Visual assessment of medial temporal lobe atrophy was correlated with hippocampal volume (p < 0.01). Classification performances between MCI converter and CN was better using volumetry than visual assessment of non-expert readers whereas classification of AD and CN did not differ between visual assessment and volumetry except for the first reading of one non-expert (p = 0.03). Visual assessment of medial temporal lobe atrophy by radiologists was well correlated with hippocampal volume. Radiological assessment is as good as computer-based volumetry for the classification of AD, MCI non-converter and CN and less good for the classification of MCI converter versus CN. Use of Scheltens scale for assessing hippocampal atrophy in AD seems thus justified in clinical routine. (orig.)

  1. Higher glucose levels associated with lower memory and reduced hippocampal microstructure.

    Science.gov (United States)

    Kerti, Lucia; Witte, A Veronica; Winkler, Angela; Grittner, Ulrike; Rujescu, Dan; Flöel, Agnes

    2013-11-12

    For this cross-sectional study, we aimed to elucidate whether higher glycosylated hemoglobin (HbA1c) and glucose levels exert a negative impact on memory performance and hippocampal volume and microstructure in a cohort of healthy, older, nondiabetic individuals without dementia. In 141 individuals (72 women, mean age 63.1 years ± 6.9 SD), memory was tested using the Rey Auditory Verbal Learning Test. Peripheral levels of fasting HbA1c, glucose, and insulin and 3-tesla MRI scans were acquired to assess hippocampal volume and microstructure, as indicated by gray matter barrier density. Linear regression and simple mediation models were calculated to examine associations among memory, glucose metabolism, and hippocampal parameters. Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. In multiple regression models, HbA1c remained strongly associated with memory performance. Moreover, mediation analyses indicated that beneficial effects of lower HbA1c on memory are in part mediated by hippocampal volume and microstructure. Our results indicate that even in the absence of manifest type 2 diabetes mellitus or impaired glucose tolerance, chronically higher blood glucose levels exert a negative influence on cognition, possibly mediated by structural changes in learning-relevant brain areas. Therefore, strategies aimed at lowering glucose levels even in the normal range may beneficially influence cognition in the older population, a hypothesis to be examined in future interventional trials.

  2. Midlife managerial experience is linked to late life hippocampal morphology and function.

    Science.gov (United States)

    Suo, C; Gates, N; Fiatarone Singh, M; Saigal, N; Wilson, G C; Meiklejohn, J; Sachdev, P; Brodaty, H; Wen, W; Singh, N; Baune, B T; Baker, M; Foroughi, N; Wang, Y; Valenzuela, Michael J

    2017-04-01

    An active cognitive lifestyle has been suggested to have a protective role in the long-term maintenance of cognition. Amongst healthy older adults, more managerial or supervisory experiences in midlife are linked to a slower hippocampal atrophy rate in late life. Yet whether similar links exist in individuals with Mild Cognitive Impairment (MCI) is not known, nor whether these differences have any functional implications. 68 volunteers from the Sydney SMART Trial, diagnosed with non-amnestic MCI, were divided into high and low managerial experience (HME/LME) during their working life. All participants underwent neuropsychological testing, structural and resting-state functional MRI. Group comparisons were performed on hippocampal volume, morphology, hippocampal seed-based functional connectivity, memory and executive function and self-ratings of memory proficiency. HME was linked to better memory function (p = 0.024), mediated by larger hippocampal volume (p = 0.025). More specifically, deformation analysis found HME had relatively more volume in the CA1 sub-region of the hippocampus (p < 0.05). Paradoxically, this group rated their memory proficiency worse (p = 0.004), a result correlated with diminished functional connectivity between the right hippocampus and right prefrontal cortex (p < 0.001). Finally, hierarchical regression modelling substantiated this double dissociation.

  3. Is the type and extent of hippocampal sclerosis measurable on high-resolution MRI?

    Energy Technology Data Exchange (ETDEWEB)

    Urbach, H; Schwarzwald, R [Medical Center University of Freiburg, Dept. of Neuroradiology, Freiburg (Germany); Huppertz, H.J. [Swiss Epilepsy Center, Zurich (Switzerland); Becker, A.J. [Medical Center University of Bonn, Department of Neuropathology, Bonn (Germany); Wagner, J. [Medical Center University of Bonn, Department of Epileptology, Bonn (Germany); Bahri, M. Delsous; Tschampa, H.J. [Medical Center University of Bonn, Department of Radiology/Neuroradiology, Bonn (Germany)

    2014-09-15

    The purpose of this study is to relate hippocampal volume and FLAIR signal intensity to Wyler grading of hippocampal sclerosis (HS). Of 100 consecutive patients with temporal lobe epilepsy and HS as histopathological diagnosis, 32 had high-resolution 3 Tesla MRI and anatomically well-preserved hippocampi following amygdalo-hippocampectomy. Hippocampal volume on 3D T1-weighted gradient echo and signal intensity on coronal FLAIR sequences were determined using FreeSurfer and SPM tools and related to Wyler grading. Seizure outcome was determined after 1 year. Histopathology showed four Wyler II, 19 Wyler III, and 9 Wyler IV HS. Hippocampal volumes were 3.08 ml for Wyler II (Wyler II/contralateral side: p > 0.05), 2.19 ml for Wyler III (p < 0.01), 2.62 ml for Wyler IV (p = 0.01), and 3.08 ml for the contralateral side. Normalized FLAIR signals were 1,354 (p = 0.0004), 1,408 (p < 0.0001), 1,371 (p < 0.04), and 1,296, respectively. Wyler II hippocampi were visually normal. Two of four (50 %) Wyler II, 16/19 (84 %) Wyler III, and 6/9 (66 %) Wyler IV patients achieved Engel I outcome. Combined volumetry and quantitative FLAIR signal analysis clearly identifies Wyler III and IV HS. Quantitative FLAIR signal analysis may be helpful to identify Wyler II HS. (orig.)

  4. Hippocampal Volumetry as a Biomarker for Dementia in People with Low Education.

    Science.gov (United States)

    Mondragón, Jaime D; Celada-Borja, César; Barinagarrementeria-Aldatz, Fernando; Burgos-Jaramillo, Martín; Barragán-Campos, Héctor Manuel

    2016-01-01

    To evaluate the relationship between hippocampal volume and cognitive decline in patients with dementia due to probable Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI) and education, and the possible relationship between cognitive reserve and education in this population. From February 2013 to October 2015, 76 patients (25 men, 51 women) were classified according to the NIA-AA diagnostic criteria. We used two 3.0-tesla MRI scanners and performed manual hippocampal volumetry. Twenty-six patients were found to have AD, 20 aMCI and 30 had normal aging (NA). The mean normalized hippocampal volume in age-, sex- and education (years)-matched subjects was 2.38 ± 0.51 cm 3 in AD (p < 0.001), 2.91 ± 0.78 cm 3 in aMCI (p = 0.019) and 3.07 ± 0.76 cm 3 in NA. Psychometric test (MMSE and MoCA) scores had a good to strong positive correlation with statistically significant differences in the entire population and healthy subjects but not among dementia patients and lower educational level groups. The patients with low education had greater hippocampal volumes, which is in line with the cognitive reserve theory; lower-educated individuals can tolerate less neuropathology and will thus show less atrophy at a similar level of cognitive performance than higher-educated subjects.

  5. Hippocampal sclerosis and status epilepticus: cause or consequence? A MRI study

    International Nuclear Information System (INIS)

    Kuster, Gustavo Wruck; Braga-Neto, Pedro; Santos-Neto, Denizart; Santana, Maria Teresa Garcia; Barsottini, Orlando Graziani; Maia Junior, Antonio Carlos Martins

    2007-01-01

    Background: Transient imaging abnormalities, including changes on diffusion-weighted imaging (DWI), may be seen in status epilepticus. These abnormalities can be followed by hippocampal sclerosis. Case Report: We report a 15-year-old lady with focal non convulsive status epilepticus (NCSE) and focal slowing on EEG. DWI exhibited abnormal hyperintense signals in bilateral temporal and insular cortices. After 3 weeks, MRI performed a localized hippocampal atrophy. Conclusion: The MRI findings indicated vasogenic and cytotoxic edema during seizure activity and subsequent loss of brain parenchyma. (author)

  6. Hippocampal sparing radiotherapy for pediatric medulloblastoma: impact of treatment margins and treatment technique.

    Science.gov (United States)

    Brodin, N Patrik; Munck af Rosenschöld, Per; Blomstrand, Malin; Kiil-Berthlesen, Anne; Hollensen, Christian; Vogelius, Ivan R; Lannering, Birgitta; Bentzen, Søren M; Björk-Eriksson, Thomas

    2014-04-01

    We investigated how varying the treatment margin and applying hippocampal sparing and proton therapy impact the risk of neurocognitive impairment in pediatric medulloblastoma patients compared with current standard 3D conformal radiotherapy. We included 17 pediatric medulloblastoma patients to represent the variability in tumor location relative to the hippocampal region. Treatment plans were generated using 3D conformal radiotherapy, hippocampal sparing intensity-modulated radiotherapy, and spot-scanned proton therapy, using 3 different treatment margins for the conformal tumor boost. Neurocognitive impairment risk was estimated based on dose-response models from pediatric CNS malignancy survivors and compared among different margins and treatment techniques. Mean hippocampal dose and corresponding risk of cognitive impairment were decreased with decreasing treatment margins (P < .05). The largest risk reduction, however, was seen when applying hippocampal sparing proton therapy-the estimated risk of impaired task efficiency (95% confidence interval) was 92% (66%-98%), 81% (51%-95%), and 50% (30%-70%) for 3D conformal radiotherapy, intensity-modulated radiotherapy, and proton therapy, respectively, for the smallest boost margin and 98% (78%-100%), 90% (60%-98%), and 70% (39%-90%) if boosting the whole posterior fossa. Also, the distance between the closest point of the planning target volume and the center of the hippocampus can be used to predict mean hippocampal dose for a given treatment technique. We estimate a considerable clinical benefit of hippocampal sparing radiotherapy. In choosing treatment margins, the tradeoff between margin size and risk of neurocognitive impairment quantified here should be considered.

  7. Electroconvulsive stimulation results in long-term survival of newly generated hippocampal neurons in rats

    DEFF Research Database (Denmark)

    Olesen, Mikkel Vestergaard; Wörtwein, Gitta; Folke, Jonas

    2017-01-01

    Electroconvulsive stimulation (ECS) is one of the strongest stimulators of hippocampal neurogenesis in rodents that represents a plausible mechanism for the efficacy of electroconvulsive therapy (ECT) in major depressive disorder. Using design-based stereological cell counting, we recently...... in neurogenesis facilitates the behavioral outcome of the forced swim test (FST), an animal model of depression. The results showed that ECS in conjunction with CRS stimulates hippocampal neurogenesis, and that a significant quantity of the newly formed hippocampal neurons survives up to 12 months. The new Brd......U-positive neurons showed time-dependent attrition of ∼40% from day 1 to 3 months, with no further decline between 3 and 12 months. ECS did not affect the number of pre-existing dentate granule neurons or the volume of the dentate granule cell layer, suggesting no damaging effect of the treatment. Finally, we found...

  8. Maternal vitamin C deficiency during pregnancy persistently impairs hippocampal neurogenesis in offspring of guinea pigs

    DEFF Research Database (Denmark)

    Tveden-Nyborg, Pernille; Vogt, Lucile; Schjoldager, Janne G

    2012-01-01

    While having the highest vitamin C (VitC) concentrations in the body, specific functions of VitC in the brain have only recently been acknowledged. We have shown that postnatal VitC deficiency in guinea pigs causes impairment of hippocampal memory function and leads to 30% less neurons. This study...... investigates how prenatal VitC deficiency affects postnatal hippocampal development and if any such effect can be reversed by postnatal VitC repletion. Eighty pregnant Dunkin Hartley guinea pig dams were randomized into weight stratified groups receiving High (900 mg) or Low (100 mg) VitC per kg diet. Newborn...... by stereology. Prenatal VitC deficiency resulted in a significant reduction in postnatal hippocampal volume (P...

  9. Depression, depressive symptoms, and rate of hippocampal atrophy in a longitudinal cohort of older men and women.

    Science.gov (United States)

    Elbejjani, M; Fuhrer, R; Abrahamowicz, M; Mazoyer, B; Crivello, F; Tzourio, C; Dufouil, C

    2015-07-01

    Several studies have reported smaller hippocampal volume (HcV) in depression patients; however, the temporality of the association remains unknown. One proposed hypothesis is that depression may cause HcV loss. This study evaluates whether previous depression and recent depressive symptoms are associated with HcV and HcV loss. We used a prospective cohort of older adults (n = 1328; age = 65-80 years) with two cerebral magnetic resonance imaging examinations at baseline and 4-year follow-up. Using multivariable linear regression models, we estimated, in stratified analyses by gender, the association between indicators of history of depression and its severity (age at onset, recurrence, hospitalization for depression), proximal depressive symptoms [Center for Epidemiologic Studies-Depression (CES-D) scale], baseline antidepressant use, and the outcomes: baseline HcV and annual percentage change in HcV. At baseline, women with more depressive symptoms had smaller HcV [-0.05 cm3, 95% confidence interval (CI) -0.1 to -0.01 cm3 per 10-unit increase in CES-D scores]. History of depression was associated with a 0.2% faster annual HcV loss in women (95% CI 0.01-0.36%). More baseline depressive symptoms and worsening of these symptoms were also associated with accelerated HcV loss in women. No associations were observed in men. Treatment for depression was associated with slower HcV loss in women and men. While only concomitant depressive symptoms were associated with HcV, both previous depression and more proximal depressive symptoms were associated with faster HcV loss in women.

  10. Hippocampal Functioning and Verbal Associative Memory in Adolescents with Congenital Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Sarah Marie Wheeler

    2015-10-01

    Full Text Available Thyroid hormone (TH is essential for normal development of the hippocampus, which is critical for memory and particularly for learning and recalling associations between visual and verbal stimuli. Adolescents with congenital hypothyroidism (CH, who lack TH in late gestation and early life, demonstrate weak verbal recall abilities, reduced hippocampal volumes, and abnormal hippocampal functioning for visually associated material. However, it is not known if their hippocampus functions abnormally when remembering verbal associations. Our objective was to assess hippocampal functioning in CH using functional magnetic resonance imaging (fMRI. Fourteen adolescents with CH and 14 typically developing controls (TDC were studied. Participants studied pairs of words and then, during fMRI acquisition, made two types of recognition decisions: in one they judged whether the pairs were the same as when seen originally and in the other, whether individual words were seen before regardless of pairing. Hippocampal activation was greater for pairs than items in both groups, but this difference was only significant in TDC. When we directly compared the groups, the right anterior hippocampus was the primary region in which the TDC and CH groups differed for this pair memory effect. Results signify that adolescents with CH show abnormal hippocampal functioning during verbal memory processing.

  11. TNF-α from hippocampal microglia induces working memory deficits by acute stress in mice.

    Science.gov (United States)

    Ohgidani, Masahiro; Kato, Takahiro A; Sagata, Noriaki; Hayakawa, Kohei; Shimokawa, Norihiro; Sato-Kasai, Mina; Kanba, Shigenobu

    2016-07-01

    The role of microglia in stress responses has recently been highlighted, yet the underlying mechanisms of action remain unresolved. The present study examined disruption in working memory due to acute stress using the water-immersion resistant stress (WIRS) test in mice. Mice were subjected to acute WIRS, and biochemical, immunohistochemical, and behavioral assessments were conducted. Spontaneous alternations (working memory) significantly decreased after exposure to acute WIRS for 2h. We employed a 3D morphological analysis and site- and microglia-specific gene analysis techniques to detect microglial activity. Morphological changes in hippocampal microglia were not observed after acute stress, even when assessing ramification ratios and cell somata volumes. Interestingly, hippocampal tumor necrosis factor (TNF)-α levels were significantly elevated after acute stress, and acute stress-induced TNF-α was produced by hippocampal-ramified microglia. Conversely, plasma concentrations of TNF-α were not elevated after acute stress. Etanercept (TNF-α inhibitor) recovered working memory deficits in accordance with hippocampal TNF-α reductions. Overall, results suggest that TNF-α from hippocampal microglia is a key contributor to early-stage stress-to-mental responses. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Visual performance of pigeons following hippocampal lesions.

    Science.gov (United States)

    Bingman, V P; Hodos, W

    1992-11-15

    The effect of hippocampal lesions on performance in two psychophysical measures of spatial vision (acuity and size-difference threshold) was examined in 7 pigeons. No difference between the preoperative and postoperative thresholds of the experimental birds was found. The visual performance of pigeons in the psychophysical tasks failed to reveal a role of the hippocampal formation in vision. The results argue strongly that the behavioral deficits found in pigeons with hippocampal lesions when tested in a variety of memory-related spatial tasks is not based on a defect in spatial vision but impaired spatial cognition.

  13. Both oophorectomy and obesity impaired solely hippocampal-dependent memory via increased hippocampal dysfunction.

    Science.gov (United States)

    Mantor, Duangkamol; Pratchayasakul, Wasana; Minta, Wanitchaya; Sutham, Wissuta; Palee, Siripong; Sripetchwandee, Jirapas; Kerdphoo, Sasiwan; Jaiwongkum, Thidarat; Sriwichaiin, Sirawit; Krintratun, Warunsorn; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2018-04-17

    Our previous study demonstrated that obesity aggravated peripheral insulin resistance and brain dysfunction in the ovariectomized condition. Conversely, the effect of obesity followed by oophorectomy on brain oxidative stress, brain apoptosis, synaptic function and cognitive function, particularly in hippocampal-dependent and hippocampal-independent memory, has not been investigated. Our hypothesis was that oophorectomy aggravated metabolic impairment, brain dysfunction and cognitive impairment in obese rats. Thirty-two female rats were fed with either a normal diet (ND, n = 16) or a high-fat diet (HFD, n = 16) for a total of 20 weeks. At week 13, rats in each group were subdivided into sham and ovariectomized subgroups (n = 8/subgroup). At week 20, all rats were tested for hippocampal-dependent and hippocampal-independent memory by using Morris water maze test (MWM) and Novel objective recognition (NOR) tests, respectively. We found that the obese-insulin resistant condition occurred in sham-HFD-fed rats (HFS), ovariectomized-ND-fed rats (NDO), and ovariectomized-HFD-fed rats (HFO). Increased hippocampal oxidative stress level, increased hippocampal apoptosis, increased hippocampal synaptic dysfunction, decreased hippocampal estrogen level and impaired hippocampal-dependent memory were observed in HFS, NDO, and HFO rats. However, the hippocampal-independent memory, cortical estrogen levels, cortical ROS production, and cortical apoptosis showed no significant difference between groups. These findings suggested that oophorectomy and obesity exclusively impaired hippocampal-dependent memory, possibly via increased hippocampal dysfunction. Nonetheless, oophorectomy did not aggravate these deleterious effects under conditions of obesity. Copyright © 2017. Published by Elsevier Inc.

  14. Cavernous angioma associated with ipsilateral hippocampal sclerosis

    International Nuclear Information System (INIS)

    Okujava, M.; Ebner, A.; Schmitt, J.; Woermann, F.G.

    2002-01-01

    We report two cases with extratemporal cavernous angioma (CA) and coexisting ipsilateral hippocampal sclerosis. Classically dual pathology is defined as the association of hippocampal sclerosis with an extrahippocampal lesion. Subtle changes in hippocampus might be overlooked in the presence of an unequivocal extrahippocampal abnormality. Seizure outcome after epilepsy surgery in cases with dual pathology is less favourable if only one of the lesions is removed. Dual pathology must always be considered in diagnostic imaging of patients with intractable epilepsy and CA. (orig.)

  15. Cavernous angioma associated with ipsilateral hippocampal sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Okujava, M [Institute of Radiology and Interventional Diagnostics, Tbilisi (Georgia); Ebner, A; Schmitt, J; Woermann, F G [Bethel Epilepsy Centre, Mara Hospital, Bielefeld (Germany)

    2002-07-01

    We report two cases with extratemporal cavernous angioma (CA) and coexisting ipsilateral hippocampal sclerosis. Classically dual pathology is defined as the association of hippocampal sclerosis with an extrahippocampal lesion. Subtle changes in hippocampus might be overlooked in the presence of an unequivocal extrahippocampal abnormality. Seizure outcome after epilepsy surgery in cases with dual pathology is less favourable if only one of the lesions is removed. Dual pathology must always be considered in diagnostic imaging of patients with intractable epilepsy and CA. (orig.)

  16. Morphological Variations of Hippocampal Formation in Epilepsy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-02-01

    Full Text Available Researchers at Hospital Sao Paulo and other centers in Brazil compared the hippocampal formation (HF morphology of healthy asymptomatic individuals (n=30 with that of patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS(n=68, of patients with malformations of cortical development (MCD(n=34, and of patients with morphological HF variations without other structural signs (pure MVHF(n=12.

  17. Less impairment of hemostasis and reduced blood loss in pigs after resuscitation from hemorrhagic shock using the small-volume concept with hypertonic saline/hydroxyethyl starch as compared to administration of 4% gelatin or 6% hydroxyethyl starch solution.

    Science.gov (United States)

    Haas, Thorsten; Fries, Dietmar; Holz, Carmen; Innerhofer, Petra; Streif, Werner; Klingler, Anton; Hanke, Alexander; Velik-Salchner, Corinna

    2008-04-01

    Small-volume resuscitation using hypertonic saline/hydroxyethyl starch 200/0.62 (HS-HES) has been shown to be an effective alternative to the administration of crystalloids or colloids in trauma patients. All i.v. fluids cause dose-related dilutional coagulopathy and show intrinsic effects on the hemostatic system, but only few data refer to functional consequences after small-volume resuscitation. Using thrombelastometry (ROTEM), we studied 30 pigs (weighing 35-45 kg) after withdrawal of 60% of blood volume [1484 mL (1369-1624 mL)] and receiving 4 mL/kg HS-HES for compensation of blood loss or 4% gelatin or 6% HES 130/0.4 in a 1:1 ratio to lost blood volume. To compare the ROTEM variables (coagulation time, clot formation time, alpha angle, clot firmness, and fibrinogen polymerization) with bleeding tendency, a hepatic incision was made and blood loss was measured. Median (25th, 75th percentile) fibrinogen polymerization was significantly higher after HS-HES infusion [11 mm (10, 11), P = 0.0034] when compared with administration of 4% gelatin [4.5 mm (3.0, 5.8)] or HES 130/0.4 [3.5 mm (2.3, 4.0)]. Median blood loss after liver incision was 725 mL (900, 375) after HS-HES, 1625 mL (1275, 1950) after 4% gelatin, and 1600 mL (1500, 1800) after 6% HES 130/0.4 (P = 0.004). Hemodynamic stabilization was traceable in all groups but showed differences regarding filling pressures. Resuscitation from hemorrhagic shock with HS-HES 200/0.62 results in less impairment of clot formation when compared with compensation of blood loss by administering 6% HES 130/0.4 or 4% gelatin.

  18. Hippocampal Sclerosis of Aging Can Be Segmental: Two Cases and Review of the Literature

    Science.gov (United States)

    Ighodaro, Eseosa T.; Jicha, Gregory A.; Schmitt, Frederick A.; Neltner, Janna H.; Abner, Erin L.; Kryscio, Richard J.; Smith, Charles D.; Duplessis, Taylor; Anderson, Sonya; Patel, Ela; Bachstetter, Adam; Van Eldik, Linda J.; Nelson, Peter T.

    2015-01-01

    Hippocampal sclerosis of aging (HS-Aging) is a neurodegenerative disease that mimics Alzheimer disease (AD) clinically and has a prevalence rivaling AD in advanced age. Whereas clinical biomarkers are not yet optimized, HS-Aging has distinctive pathological features that distinguish it from other diseases with “hippocampal sclerosis” pathology, such as epilepsy, cerebrovascular perturbations, and frontotemporal lobar degeneration. By definition, HS-Aging brains show neuronal cell loss and gliosis in the hippocampal formation out of proportion to AD-type pathology; it is strongly associated with aberrant TDP-43 pathology and arteriolosclerosis. Here, we describe 2 cases of “segmental” HS-Aging in which “sclerosis” in the hippocampus was evident only in a subset of brain sections by hematoxylin and eosin (H&E) stain. In these cases, TDP-43 pathology was more widespread on immunostained sections than the neuronal cell loss and gliosis seen in H&E stains. The 2 patients were cognitively intact at baseline and were tracked longitudinally over a decade using cognitive studies with at least 1 neuroimaging scan. We discuss the relevant HS-Aging literature, which indicates the need for a clearer consensus-based delineation of “hippocampal sclerosis” and TDP-43 pathologies in aged subjects. PMID:26083567

  19. Neonatal hypoxia, hippocampal atrophy, and memory impairment: evidence of a causal sequence.

    Science.gov (United States)

    Cooper, Janine M; Gadian, David G; Jentschke, Sebastian; Goldman, Allan; Munoz, Monica; Pitts, Georgia; Banks, Tina; Chong, W Kling; Hoskote, Aparna; Deanfield, John; Baldeweg, Torsten; de Haan, Michelle; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2015-06-01

    Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life. © The Author 2013. Published by Oxford University Press.

  20. Aberrant expression of miR-218 and miR-204 in human mesial temporal lobe epilepsy and hippocampal sclerosis-Convergence on axonal guidance

    DEFF Research Database (Denmark)

    Kaalund, Sanne S; Venø, Morten T; Bak, Mads

    2014-01-01

    OBJECTIVE: Mesial temporal lobe epilepsy (MTLE) is one of the most common types of the intractable epilepsies and is most often associated with hippocampal sclerosis (HS), which is characterized by pronounced loss of hippocampal pyramidal neurons. microRNAs (miRNAs) have been shown...... to be dysregulated in epilepsy and neurodegenerative diseases, and we hypothesized that miRNAs could be involved in the pathogenesis of MTLE and HS. METHODS: miRNA expression was quantified in hippocampal specimens from human patients using miRNA microarray and quantitative real-time polymerase chain reaction RT...

  1. Dietary lipids are differentially associated with hippocampal-dependent relational memory in prepubescent children1234

    Science.gov (United States)

    Khan, Naiman A; Monti, Jim M; Raine, Lauren B; Drollette, Eric S; Moore, R Davis; Scudder, Mark R; Kramer, Arthur F; Hillman, Charles H; Cohen, Neal J

    2014-01-01

    Background: Studies in rodents and older humans have shown that the hippocampus—a brain structure critical to relational/associative memory—has remarkable plasticity as a result of lifestyle factors (eg, exercise). However, the effect of dietary intake on hippocampal-dependent memory during childhood has remained unexamined. Objective: We investigated the cross-sectional relation of dietary components characteristic of the Western diet, including saturated fatty acids (SFAs), omega-3 (n−3) fatty acids, and refined sugar, with hippocampal-dependent relational memory in prepubescent children. Design: Participants aged 7–9 y (n = 52) reported their dietary intake by using the Youth-Adolescent Food-Frequency Questionnaire and completed memory tasks designed to assess relational (hippocampal-dependent) and item (hippocampal-independent) memory. Performance on the memory tasks was assessed with both direct (accuracy) and indirect (eye movement) measures. Results: Partial correlations adjusted for body mass index showed a positive relation between relational memory accuracy and intake of omega-3 fatty acids and a negative relation of both relational and item memory accuracy with intake of SFAs. Potential confounding factors of age, sex, intelligence quotient, socioeconomic status, pubertal timing, and aerobic fitness (maximal oxygen volume) were not significantly related to any of the dietary intake measures. Eye movement measures of relational memory (preferential viewing to the target stimulus) showed a negative relation with intake of added sugar. Conclusions: SFA intake was negatively associated with both forms of memory, whereas omega-3 fatty acid intake was selectively positively associated with hippocampal-dependent relational memory. These findings are among the first to show a link between habitual dietary intake and cognitive health as pertaining to hippocampal function in childhood. The Fitness Improves Thinking Kids (FITKids) and FITKids2 trials were

  2. Dietary lipids are differentially associated with hippocampal-dependent relational memory in prepubescent children.

    Science.gov (United States)

    Baym, Carol L; Khan, Naiman A; Monti, Jim M; Raine, Lauren B; Drollette, Eric S; Moore, R Davis; Scudder, Mark R; Kramer, Arthur F; Hillman, Charles H; Cohen, Neal J

    2014-05-01

    Studies in rodents and older humans have shown that the hippocampus-a brain structure critical to relational/associative memory-has remarkable plasticity as a result of lifestyle factors (eg, exercise). However, the effect of dietary intake on hippocampal-dependent memory during childhood has remained unexamined. We investigated the cross-sectional relation of dietary components characteristic of the Western diet, including saturated fatty acids (SFAs), omega-3 (n-3) fatty acids, and refined sugar, with hippocampal-dependent relational memory in prepubescent children. Participants aged 7-9 y (n = 52) reported their dietary intake by using the Youth-Adolescent Food-Frequency Questionnaire and completed memory tasks designed to assess relational (hippocampal-dependent) and item (hippocampal-independent) memory. Performance on the memory tasks was assessed with both direct (accuracy) and indirect (eye movement) measures. Partial correlations adjusted for body mass index showed a positive relation between relational memory accuracy and intake of omega-3 fatty acids and a negative relation of both relational and item memory accuracy with intake of SFAs. Potential confounding factors of age, sex, intelligence quotient, socioeconomic status, pubertal timing, and aerobic fitness (maximal oxygen volume) were not significantly related to any of the dietary intake measures. Eye movement measures of relational memory (preferential viewing to the target stimulus) showed a negative relation with intake of added sugar. SFA intake was negatively associated with both forms of memory, whereas omega-3 fatty acid intake was selectively positively associated with hippocampal-dependent relational memory. These findings are among the first to show a link between habitual dietary intake and cognitive health as pertaining to hippocampal function in childhood. The Fitness Improves Thinking Kids (FITKids) and FITKids2 trials were registered at www.clinicaltrials.gov as NCT01334359 and NCT

  3. APP Is a Context-Sensitive Regulator of the Hippocampal Presynaptic Active Zone.

    Directory of Open Access Journals (Sweden)

    Melanie Laßek

    2016-04-01

    Full Text Available The hallmarks of Alzheimer's disease (AD are characterized by cognitive decline and behavioral changes. The most prominent brain region affected by the progression of AD is the hippocampal formation. The pathogenesis involves a successive loss of hippocampal neurons accompanied by a decline in learning and memory consolidation mainly attributed to an accumulation of senile plaques. The amyloid precursor protein (APP has been identified as precursor of Aβ-peptides, the main constituents of senile plaques. Until now, little is known about the physiological function of APP within the central nervous system. The allocation of APP to the proteome of the highly dynamic presynaptic active zone (PAZ highlights APP as a yet unknown player in neuronal communication and signaling. In this study, we analyze the impact of APP deletion on the hippocampal PAZ proteome. The native hippocampal PAZ derived from APP mouse mutants (APP-KOs and NexCreAPP/APLP2-cDKOs was isolated by subcellular fractionation and immunopurification. Subsequently, an isobaric labeling was performed using TMT6 for protein identification and quantification by high-resolution mass spectrometry. We combine bioinformatics tools and biochemical approaches to address the proteomics dataset and to understand the role of individual proteins. The impact of APP deletion on the hippocampal PAZ proteome was visualized by creating protein-protein interaction (PPI networks that incorporated APP into the synaptic vesicle cycle, cytoskeletal organization, and calcium-homeostasis. The combination of subcellular fractionation, immunopurification, proteomic analysis, and bioinformatics allowed us to identify APP as structural and functional regulator in a context-sensitive manner within the hippocampal active zone network.

  4. Protective effects of hydroponic Teucrium polium on hippocampal neurodegeneration in ovariectomized rats.

    Science.gov (United States)

    Simonyan, K V; Chavushyan, V A

    2016-10-24

    The hippocampus is a target of ovarian hormones, and is necessary for memory. Ovarian hormone loss is associated with a progressive reduction in synaptic strength and dendritic spine. Teucrium polium has beneficial effects on learning and memory. However, it remains unknown whether Teucrium polium ameliorates hippocampal cells spike activity and morphological impairments induced by estrogen deficiency. In the present study, we investigated the effects of hydroponic Teucrium polium on hippocampal neuronal activity and morpho-histochemistry of bilateral ovariectomized (OVX) rats. Tetanic potentiation or depression with posttetanic potentiation and depression was recorded extracellularly in response to ipsilateral entorhinal cortex high frequency stimulation. In morpho-histochemical study revealing of the activity of Ca 2+ -dependent acid phosphatase was observed. In all groups (sham-operated, sham + Teucrium polium, OVX, OVX + Teucrium polium), most recorded hippocampal neurons at HFS of entorhinal cortex showed TD-PTP responses. After 8 weeks in OVX group an anomalous evoked spike activity was detected (a high percentage of typical areactive units). In OVX + Teucrium polium group a synaptic activity was revealed, indicating prevention OVX-induced degenerative alterations: balance of types of responses was close to norm and areactive units were not recorded. All recorded neurons in sham + Teucrium polium group were characterized by the highest mean frequency background and poststimulus activity. In OVX+ Teucrium polium group the hippocampal cells had recovered their size and shape in CA1 and CA3 field compared with OVX group where hippocampal cells were characterized by a sharp drop in phosphatase activity and there was a complete lack of processes reaction. Thus, Teucrium polium reduced OVX-induce neurodegenerative alterations in entorhinal cortex-hippocamp circuitry and facilitated neuronal survival by modulating activity of neurotransmitters and

  5. Developmental changes in hippocampal shape among preadolescent children.

    Science.gov (United States)

    Lin, Muqing; Fwu, Peter T; Buss, Claudia; Davis, Elysia P; Head, Kevin; Muftuler, L Tugan; Sandman, Curt A; Su, Min-Ying

    2013-11-01

    It is known that the largest developmental changes in the hippocampus take place during the prenatal period and during the first two years of postnatal life. Few studies have been conducted to address the normal developmental trajectory of the hippocampus during childhood. In this study shape analysis was applied to study the normal developing hippocampus in a group of 103 typically developing 6- to 10-year-old preadolescent children. The individual brain was normalized to a template, and then the hippocampus was manually segmented and further divided into the head, body, and tail sub-regions. Three different methods were applied for hippocampal shape analysis: radial distance mapping, surface-based template registration using the robust point matching (RPM) algorithm, and volume-based template registration using the Demons algorithm. All three methods show that the older children have bilateral expanded head segments compared to the younger children. The results analyzed based on radial distance to the centerline were consistent with those analyzed using template-based registration methods. In analyses stratified by sex, it was found that the age-associated anatomical changes were similar in boys and girls, but the age-association was strongest in girls. Total hippocampal volume and sub-regional volumes analyzed using manual segmentation did not show a significant age-association. Our results suggest that shape analysis is sensitive to detect sub-regional differences that are not revealed in volumetric analysis. The three methods presented in this study may be applied in future studies to investigate the normal developmental trajectory of the hippocampus in children. They may be further applied to detect early deviations from the normal developmental trajectory in young children for evaluating susceptibility for psychopathological disorders involving hippocampus. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  6. The Stress Model of Chronic Pain: Evidence from Basal Cortisol and Hippocampal Structure and Function in Humans

    Science.gov (United States)

    Vachon-Presseau, Etienne; Roy, Mathieu; Martel, Marc-Olivier; Caron, Etienne; Marin, Marie-France; Chen, Jeni; Albouy, Genevieve; Plante, Isabelle; Sullivan, Michael J.; Lupien, Sonia J.; Rainville, Pierre

    2013-01-01

    Recent theories have suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor. The present study examined the associations between basal levels of cortisol collected over seven consecutive days, the hippocampal volumes and brain activation to thermal stimulations…

  7. Male carriers of the FMR1 premutation show altered hippocampal-prefrontal function during memory encoding

    Directory of Open Access Journals (Sweden)

    John M Wang

    2012-10-01

    Full Text Available Previous functional MRI (fMRI studies have shown that fragile X mental retardation 1 (FMR1 premutation allele carriers (FXPCs exhibit decreased hippocampal activation during a recall task and lower inferior frontal activation during a working memory task compared to matched controls. The molecular characteristics of FXPCs includes 55 to 200 CGG trinucleoutide expansions, increased FMR1 mRNA levels, and decreased FMRP levels especially at higher repeat sizes. In the current study, we utilized MRI to examine differences in hippocampal volume and function during an encoding task in young male FXPCs. While no decreases in either hippocampal volume or hippocampal activity were observed during the encoding task in FXPCs, FMRP level (measured in blood correlated with decreases in parahippocampal activation. In addition, activity in the right dorsolateral prefrontal cortex during correctly encoded trials correlated negatively with mRNA levels. These results, as well as the established biological effects associated with elevated mRNA levels and decreased FMRP levels on dendritic maturation and axonal growth, prompted us to explore functional connectivity between the hippocampus, prefrontal cortex, and parahippocampal gyrus using a psychophysiological interaction analysis. In FXPCs, the right hippocampus evinced significantly lower connectivity with right ventrolateral prefrontal cortex (VLPFC and right parahippocampal gyrus. Furthermore, the weaker connectivity between the right hippocampus and VLPFC was associated with reduced FMRP in the FXPC group. These results suggest that while FXPCs show relatively typical brain response during encoding, faulty connectivity between frontal and hippocampal regions may have subsequent effects on recall and working memory.

  8. n-3 polyunsaturated fatty acids supplementation enhances hippocampal functionality in aged mice

    Directory of Open Access Journals (Sweden)

    Debora eCutuli

    2014-08-01

    Full Text Available As major components of neuronal membranes, omega-3 polyunsaturated acids (n-3 PUFA exhibit a wide range of regulatory functions, modulating from synaptic plasticity to neuroinflammation, from oxidative stress to neuroprotection. Recent human and animal studies indicated the n-3 PUFA neuroprotective properties in aging, with a clear negative correlation between n-3 PUFA levels and hippocampal deficits. The present multidimensional study was aimed at associating cognition, hippocampal neurogenesis, volume, neurodegeneration and metabolic correlates to verify n-3 PUFA neuroprotective effects in aging. To this aim 19 month-old mice were given n-3 PUFA mixture, or olive oil or no dietary supplement for 8 weeks during which hippocampal-dependent mnesic functions were tested. At the end of behavioral testing morphological and metabolic correlates were analyzed. n-3 PUFA supplemented aged mice exhibited better object recognition memory, spatial and localizatory memory, and aversive response retention, without modifications in anxiety levels in comparison to controls. These improved hippocampal cognitive functions occurred in the context of an enhanced cellular plasticity and a reduced neurodegeneration. In fact, n-3 PUFA supplementation increased hippocampal neurogenesis and dendritic arborization of newborn neurons, volume, neuronal density and microglial cell number, while it decreased apoptosis, astrocytosis and lipofuscin accumulation in the hippocampus. The increased levels of some metabolic correlates (blood Acetyl-L-Carnitine and brain n-3 PUFA concentrations found in n-3 PUFA supplemented mice also pointed towards an effective neuroprotection.On the basis of the present results n-3 PUFA supplementation appears to be a useful tool in health promotion and cognitive decline prevention during aging.

  9. Maternal vitamin C deficiency during pregnancy persistently impairs hippocampal neurogenesis in offspring of guinea pigs.

    Directory of Open Access Journals (Sweden)

    Pernille Tveden-Nyborg

    Full Text Available While having the highest vitamin C (VitC concentrations in the body, specific functions of VitC in the brain have only recently been acknowledged. We have shown that postnatal VitC deficiency in guinea pigs causes impairment of hippocampal memory function and leads to 30% less neurons. This study investigates how prenatal VitC deficiency affects postnatal hippocampal development and if any such effect can be reversed by postnatal VitC repletion. Eighty pregnant Dunkin Hartley guinea pig dams were randomized into weight stratified groups receiving High (900 mg or Low (100 mg VitC per kg diet. Newborn pups (n = 157 were randomized into a total of four postnatal feeding regimens: High/High (Control; High/Low (Depleted, Low/Low (Deficient; and Low/High (Repleted. Proliferation and migration of newborn cells in the dentate gyrus was assessed by BrdU labeling and hippocampal volumes were determined by stereology. Prenatal VitC deficiency resulted in a significant reduction in postnatal hippocampal volume (P<0.001 which was not reversed by postnatal repletion. There was no difference in postnatal cellular proliferation and survival rates in the hippocampus between dietary groups, however, migration of newborn cells into the granular layer of the hippocampus dentate gyrus was significantly reduced in prenatally deficient animals (P<0.01. We conclude that a prenatal VitC deficiency in guinea pigs leads to persistent impairment of postnatal hippocampal development which is not alleviated by postnatal repletion. Our findings place attention on a yet unrecognized consequence of marginal VitC deficiency during pregnancy.

  10. Depression may be associated with hippocampal volume changes ...

    African Journals Online (AJOL)

    Adele

    REVIEW. S Afr Psychiatry Rev 2004;7:5-9. South African Psychiatry Review - August 2004. 5 .... century, with electroconvulsive therapy (ECT) preceding the devel- opment of ... ern Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin-No- ... sants (NaSSAs) and others of an atypical nature.11 At the last count, eighteen ...

  11. Moxibustion upregulates hippocampal progranulin expression

    Directory of Open Access Journals (Sweden)

    Tao Yi

    2016-01-01

    Full Text Available In China, moxibustion is reported to be useful and has few side effects for chronic fatigue syndrome, but its mechanisms are largely unknown. More recently, the focus has been on the wealth of information supporting stress as a factor in chronic fatigue syndrome, and largely concerns dysregulation in the stress-related hypothalamic-pituitary-adrenal axis. In the present study, we aimed to determine the effect of moxibustion on behavioral symptoms in chronic fatigue syndrome rats and examine possible mechanisms. Rats were subjected to a combination of chronic restraint stress and forced swimming to induce chronic fatigue syndrome. The acupoints Guanyuan (CV4 and Zusanli (ST36, bilateral were simultaneously administered moxibustion. Untreated chronic fatigue syndrome rats and normal rats were used as controls. Results from the forced swimming test, open field test, tail suspension test, real-time PCR, enzyme-linked immunosorbent assay, and western blot assay showed that moxibustion treatment decreased mRNA expression of corticotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone and corticosterone levels in plasma, and markedly increased progranulin mRNA and protein expression in the hippocampus. These findings suggest that moxibustion may relieve the behavioral symptoms of chronic fatigue syndrome, at least in part, by modulating the hypothalamic-pituitary-adrenal axis and upregulating hippocampal progranulin.

  12. Childhood maltreatment, psychopathology, and the development of hippocampal subregions during adolescence.

    Science.gov (United States)

    Whittle, Sarah; Simmons, Julian G; Hendriksma, Sylke; Vijayakumar, Nandita; Byrne, Michelle L; Dennison, Meg; Allen, Nicholas B

    2017-02-01

    It is well established that childhood maltreatment has a detrimental impact on the brain, particularly the hippocampus. However, the hippocampus is a functionally and structurally heterogeneous region, and little is known about how maltreatment might affect hippocampal subregion development throughout important periods of plasticity. This study investigated whether childhood maltreatment was associated with the development of hippocampal subregion volumes from early to late adolescence. It also investigated associations between onset of psychiatric disorder and hippocampal subregion volume development. One hundred and sixty-six (85 male) adolescents took part in three magnetic resonance imaging assessments during adolescence (mean age at each assessment: 12.79 [ SD 0.43] years, 16.70 [ SD 0.52] years, and 19.08 [ SD 0.46] years), provided a self-report of childhood maltreatment, and were assessed for Axis I psychopathology. Childhood maltreatment was associated with the development of right total and left cornu ammonis 4 (CA4-DG) volumes from early to late adolescence. Early and late onset psychopathology was associated with the development of right presubiculum and right cornu ammonis 1 (CA1) volumes, respectively. Maltreatment findings appeared to be specific to males, whereas psychopathology findings appeared to be specific to females. These findings provide evidence for possible deleterious effects of childhood maltreatment and early onset psychiatric disorder on the development of different subregions of the hippocampus. Altered development of the right CA1, on the other hand, might precede the development of late-adolescent onset psychopathology. Our results highlight the importance of considering development in research examining associations between stress, mental illness, and hippocampal morphology.

  13. Superolateral Hoffa's fat pad (SHFP) oedema and patellar cartilage volume loss: quantitative analysis using longitudinal data from the Foundation for the National Institute of Health (FNIH) Osteoarthritis Biomarkers Consortium.

    Science.gov (United States)

    Haj-Mirzaian, Arya; Guermazi, Ali; Hafezi-Nejad, Nima; Sereni, Christopher; Hakky, Michael; Hunter, David J; Zikria, Bashir; Roemer, Frank W; Demehri, Shadpour

    2018-04-12

    To determine the association of superolateral Hoffa's fat pad (SHFP) oedema and patellofemoral joint structural damage in participants of Foundation for the National Institute of Health Osteoarthritis Biomarkers Consortium study. Baseline and 24-month MRIs of 600 subjects were assessed. The presence of SHFP oedema (using 0-3 grading scale) and patellar morphology metrics were determined using baseline MRI. Quantitative patellar cartilage volume and semi-quantitative MRI osteoarthritis knee score (MOAKS) variables were extracted. The associations between SHFP oedema and patellar cartilage damage, bone marrow lesion (BML), osteophyte and morphology were evaluated in cross-sectional model. In longitudinal analysis, the associations between oedema and cartilage volume loss (defined using reliable change index) and MOAKS worsening were evaluated. In cross-sectional evaluations, the presence of SHFP oedema was associated with simultaneous lateral patellar cartilage/BML defects and inferior-medial patellar osteophyte size. A significant positive correlation between the degree of patella alta and SHFP oedema was detected (r = 0.259, p < 0.001). The presence of oedema was associated with 24-month cartilage volume loss (odds ratio (OR) 2.11, 95% confidence interval 1.46-3.06) and medial patellar BML size (OR 1.92 (1.15-3.21)) and number (OR 2.50 (1.29-4.88)) worsening. The optimal cut-off value for the grade of baseline SHFP oedema regarding both presence and worsening of patellar structural damage was ≥ 1 (presence of any SHFP hyperintensity). The presence of SHFP oedema could be considered as a predictor of future patellar cartilage loss and BML worsening, and an indicator of simultaneous cartilage, BML and osteophyte defects. • SHFP oedema was associated with simultaneous lateral patellar OA-related structural damage. • SHFP oedema was associated with longitudinal patellar cartilage loss over 24 months. • SHFP oedema could be considered as indicator and predictor

  14. Review: Hippocampal sclerosis in epilepsy: a neuropathology review

    Science.gov (United States)

    Thom, Maria

    2014-01-01

    Hippocampal sclerosis (HS) is a common pathology encountered in mesial temporal lobe epilepsy (MTLE) as well as other epilepsy syndromes and in both surgical and post-mortem practice. The 2013 International League Against Epilepsy (ILAE) classification segregates HS into typical (type 1) and atypical (type 2 and 3) groups, based on the histological patterns of subfield neuronal loss and gliosis. In addition, granule cell reorganization and alterations of interneuronal populations, neuropeptide fibre networks and mossy fibre sprouting are distinctive features of HS associated with epilepsies; they can be useful diagnostic aids to discriminate from other causes of HS, as well as highlighting potential mechanisms of hippocampal epileptogenesis. The cause of HS remains elusive and may be multifactorial; the contribution of febrile seizures, genetic susceptibility, inflammatory and neurodevelopmental factors are discussed. Post-mortem based research in HS, as an addition to studies on surgical samples, has the added advantage of enabling the study of the wider network changes associated with HS, the long-term effects of epilepsy on the pathology and associated comorbidities. It is likely that HS is heterogeneous in aspects of its cause, epileptogenetic mechanisms, network alterations and response to medical and surgical treatments. Future neuropathological studies will contribute to better recognition and understanding of these clinical and patho-aetiological subtypes of HS. PMID:24762203

  15. Altered neuronal excitability underlies impaired hippocampal function in an animal model of psychosis

    Directory of Open Access Journals (Sweden)

    Thomas eGrüter

    2015-05-01

    Full Text Available Psychosis is accompanied by severe attentional deficits, and impairments in associational-memory processing and sensory information processing that are ascribed to dysfunctions in prefrontal and hippocampal function. Disruptions of glutamatergic signalling may underlie these alterations: Antagonism of the N-methyl-D-aspartate receptor (NMDAR results in similar molecular, cellular, cognitive and behavioural changes in rodents and/or humans as those that occur in psychosis, raising the question as to whether changes in glutamatergic transmission may be intrinsic to the pathophysiology of the disease. In an animal model of psychosis that comprises treatment with the irreversible NMDAR-antagonist, MK801, we explored the cellular mechanisms that may underlie hippocampal dysfunction in psychosis. MK801-treatment resulted in a profound loss of hippocampal LTP that was evident 4 weeks after treatment. Whereas neuronal expression of the immediate early gene, Arc, was enhanced in the hippocampus by spatial learning in controls, MK801-treated animals failed to show activity-dependent increases in Arc expression. By contrast, a significant increase in basal Arc expression in the absence of learning was evident compared to controls. Paired-pulse facilitation was increased at the 40 ms interval indicating that NMDAR and/or fast GABAergic-mediated neurotransmission was disrupted. In line with this, MK801-treatment resulted in a significant decrease in GABA(A, and increase in GABA(B-receptor-expression in PFC, along with a significant increase of GABA(B- and NMDAR-GluN2B expression in the dentate gyrus. NMDAR-GluN1 or GluN2A subunit expression was unchanged. These data suggest that in psychosis, deficits in hippocampus-dependent memory may be caused by a loss of hippocampal LTP that arises through enhanced hippocampal neuronal excitability, altered GluN2B and GABA receptor expression and an uncoupling of the hippocampus-prefrontal cortex circuitry.

  16. Neuroprotective effects of curcumin on endothelin-1 mediated cell death in hippocampal neurons.

    Science.gov (United States)

    Stankowska, Dorota L; Krishnamoorthy, Vignesh R; Ellis, Dorette Z; Krishnamoorthy, Raghu R

    2017-06-01

    Alzheimer's disease is a progressive neurodegenerative disease characterized by loss of hippocampal neurons leading to memory deficits and cognitive decline. Studies suggest that levels of the vasoactive peptide endothelin-1 (ET-1) are increased in the brain tissue of Alzheimer's patients. Curcumin, the main ingredient of the spice turmeric, has been shown to have anti-inflammatory, anti-cancer, and neuroprotective effects. However, the mechanisms underlying some of these beneficial effects are not completely understood. The objective of this study was to determine if curcumin could protect hippocampal neurons from ET-1 mediated cell death and examine the involvement of c-Jun in this pathway. Primary hippocampal neurons from rat pups were isolated using a previously published protocol. Viability of the cells was measured by the live/dead assay. Immunoblot and immunohistochemical analyses were performed to analyze c-Jun levels in hippocampal neurons treated with either ET-1 or a combination of ET-1 and curcumin. Apoptotic changes were evaluated by immunoblot detection of cleaved caspase-3, cleaved fodrin, and a caspase 3/7 activation assay. ET-1 treatment produced a 2-fold increase in the levels of c-Jun as determined by an immunoblot analysis in hippocampal neurons. Co-treatment with curcumin significantly attenuated the ET-1 mediated increase in c-Jun levels. ET-1 caused increased neuronal cell death of hippocampal neurons indicated by elevation of cleaved caspase-3, cleaved fodrin and an increased activity of caspases 3 and 7 which was attenuated by co-treatment with curcumin. Blockade of JNK, an upstream effector of c-Jun by specific inhibitor SP600125 did not fully protect from ET-1 mediated activation of pro-apoptotic enzymes in primary hippocampal cells. Our data suggests that one mechanism by which curcumin protects against ET-1-mediated cell death is through blocking an increase in c-Jun levels. Other possible mechanisms include decreasing pro

  17. Genetic influence of apolipoprotein E4 genotype on hippocampal morphometry: An N = 725 surface-based Alzheimer's disease neuroimaging initiative study.

    Science.gov (United States)

    Shi, Jie; Leporé, Natasha; Gutman, Boris A; Thompson, Paul M; Baxter, Leslie C; Caselli, Richard J; Wang, Yalin

    2014-08-01

    The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer's disease (AD). Hippocampal volumes are generally smaller in AD patients carrying the e4 allele compared to e4 noncarriers. Here we examined the effect of APOE e4 on hippocampal morphometry in a large imaging database-the Alzheimer's Disease Neuroimaging Initiative (ADNI). We automatically segmented and constructed hippocampal surfaces from the baseline MR images of 725 subjects with known APOE genotype information including 167 with AD, 354 with mild cognitive impairment (MCI), and 204 normal controls. High-order correspondences between hippocampal surfaces were enforced across subjects with a novel inverse consistent surface fluid registration method. Multivariate statistics consisting of multivariate tensor-based morphometry (mTBM) and radial distance were computed for surface deformation analysis. Using Hotelling's T(2) test, we found significant morphological deformation in APOE e4 carriers relative to noncarriers in the entire cohort as well as in the nondemented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes. Our findings are consistent with previous studies that showed e4 carriers exhibit accelerated hippocampal atrophy; we extend these findings to a novel measure of hippocampal morphometry. Hippocampal morphometry has significant potential as an imaging biomarker of early stage AD. Copyright © 2014 Wiley Periodicals, Inc.

  18. SU-E-T-449: Hippocampal Sparing Radiotherapy Using Intensity Modulated Radiotherapy and Volumetric Modulated Arc Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Moon, S [Korea University, Seoul (Korea, Republic of); Kyung Hee University Hospital at Gangdong, Gangdong-gu (Korea, Republic of); Kim, D; Chung, W [Kyung Hee University Hospital at Gangdong, Gangdong-gu (Korea, Republic of); Yoon, M [Korea University, Seoul (Korea, Republic of)

    2015-06-15

    Purpose: The hippocampus sparing during the cranial irradiation has become interesting because it may mitigate radiation-induced neurocognitive toxicity. Herein we report our preliminary study for sparing the hippocampus with and without tilling condition for patient with brain metastases. Methods: Ten patients previously treated with whole brain were reviewed. Five patients tilted the head to around 30 degrees and others were treated without tilting. Treatment plans of linear accelerator (Linac)-based volumetric modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT) were generated for prescription dose of 30 Gy in 15 fractions. Hippocampal avoidance regions were created with 5-mm volumetric expansion around the hippocampus. Whole brain, hippocampus and hippocampal avoidance volume were 1372cm3, 6cm3 and 30cm3 and hippocampal avoidance volume was 2.2% of the whole brain planned target volume in average. Organs at risk (OARs) are hippocampus, eyes, lens, and cochleae. Coverage index (CVI), conformity index (CI), homogeneity index (HI) and mean dose to OARs were used to compare dose characteristic of tilted and non-tilted cases. Results: In IMRT, when CI, CVI and HI of whole brain were 0.88, 0.09 and 0.98 in both tilted and non-tilted cases, absorbed dose of hippocampal avoidance volume in tilted cases were 10% lower than non-tilted cases. Doses in other OARs such as eyes, lens, and cochleae were also decreased about 20% when tilting the head. When CI, HI and CVI in VMAT were 0.9, 0.08 and 0.99, the dose-decreased ratio of OARs in both with and without tilting cases were almost the same with IMRT. But absolute dose of hippocampal avoidance volume in VMAT was 30% lower than IMRT. Conclusion: This study confirms that dose to hippocampus decreases if patients tilt the head. When treating the whole brain with head tilted, patients can acquire the same successful treatment Result and also preserve their valuable memory.

  19. Stereological Investigation of the Effects of Treadmill Running Exercise on the Hippocampal Neurons in Middle-Aged APP/PS1 Transgenic Mice.

    Science.gov (United States)

    Chao, Fenglei; Jiang, Lin; Zhang, Yi; Zhou, Chunni; Zhang, Lei; Tang, Jing; Liang, Xin; Qi, Yingqiang; Zhu, Yanqing; Ma, Jing; Tang, Yong

    2018-01-01

    The risk of cognitive decline during Alzheimer's disease (AD) can be reduced if physical activity is maintained; however, the specific neural events underlying this beneficial effect are still uncertain. To quantitatively investigate the neural events underlying the effect of running exercise on middle-aged AD subjects, 12-month-old male APP/PS1 mice were randomly assigned to a control group or running group, and age-matched non-transgenic littermates were used as a wild-type group. AD running group mice were subjected to a treadmill running protocol (regular and moderate intensity) for four months. Spatial learning and memory abilities were assessed using the Morris water maze. Hippocampal amyloid plaques were observed using Thioflavin S staining and immunohistochemistry. Hippocampal volume, number of neurons, and number of newborn cells (BrdU+ cells) in the hippocampus were estimated using stereological techniques, and newborn neurons were observed using double-labelling immunofluorescence. Marked neuronal loss in both the CA1 field and dentate gyrus (DG) and deficits in both the neurogenesis and survival of new neurons in the DG of middle-aged APP/PS1 mice were observed. Running exercise could improve the spatial learning and memory abilities, reduce amyloid plaques in the hippocampi, delay neuronal loss, induce neurogenesis, and promote the survival of newborn neurons in the DG of middle-aged APP/PS1 mice. Exercise-induced protection of neurons and adult neurogenesis within the DG might be part of the important structural basis of the improved spatial learning and memory abilities observed in AD mice.

  20. Taurine increases hippocampal neurogenesis in aging mice

    Directory of Open Access Journals (Sweden)

    Elias Gebara

    2015-05-01

    Full Text Available Aging is associated with increased inflammation and reduced hippocampal neurogenesis, which may in turn contribute to cognitive impairment. Taurine is a free amino acid found in numerous diets, with anti-inflammatory properties. Although abundant in the young brain, the decrease in taurine concentration with age may underlie reduced neurogenesis. Here, we assessed the effect of taurine on hippocampal neurogenesis in middle-aged mice. We found that taurine increased cell proliferation in the dentate gyrus through the activation of quiescent stem cells, resulting in increased number of stem cells and intermediate neural progenitors. Taurine had a direct effect on stem/progenitor cells proliferation, as observed in vitro, and also reduced activated microglia. Furthermore, taurine increased the survival of newborn neurons, resulting in a net increase in adult neurogenesis. Together, these results show that taurine increases several steps of adult neurogenesis and support a beneficial role of taurine on hippocampal neurogenesis in the context of brain aging.

  1. Caffeine Increases Hippocampal Sharp Waves in Vitro.

    Science.gov (United States)

    Watanabe, Yusuke; Ikegaya, Yuji

    2017-01-01

    Caffeine promotes memory consolidation. Memory consolidation is thought to depend at least in part on hippocampal sharp waves (SWs). In the present study, we investigated the effect of bath-application of caffeine in spontaneously occurring SWs in mouse acute hippocampal slices. Caffeine induced an about 100% increase in the event frequency of SWs at concentrations of 60 and 200 µM. The effect of caffeine was reversible after washout of caffeine and was mimicked by an adenosine A 1 receptor antagonist, but not by an A 2A receptor antagonist. Caffeine increased SWs even in dentate-CA3 mini-slices without the CA2 regions, in which adenosine A 1 receptors are abundantly expressed in the hippocampus. Thus, caffeine facilitates SWs by inhibiting adenosine A 1 receptors in the hippocampal CA3 region or the dentate gyrus.

  2. Atorvastatin and Fluoxetine Prevent Oxidative Stress and Mitochondrial Dysfunction Evoked by Glutamate Toxicity in Hippocampal Slices.

    Science.gov (United States)

    Ludka, Fabiana K; Dal-Cim, Tharine; Binder, Luisa Bandeira; Constantino, Leandra Celso; Massari, Caio; Tasca, Carla I

    2017-07-01

    Atorvastatin has been shown to exert a neuroprotective action by counteracting glutamatergic toxicity. Recently, we have shown atorvastatin also exerts an antidepressant-like effect that depends on both glutamatergic and serotonergic systems modulation. Excitotoxicity is involved in several brain disorders including depression; thus, it is suggested that antidepressants may target glutamatergic system as a final common pathway. In this study, a comparison of the mechanisms involved in the putative neuroprotective effect of a repetitive atorvastatin or fluoxetine treatment against glutamate toxicity in hippocampal slices was performed. Adult Swiss mice were treated with atorvastatin (10 mg/kg, p.o.) or fluoxetine (10 mg/kg, p.o.), once a day during seven consecutive days. On the eighth day, animals were killed and hippocampal slices were obtained and subjected to an in vitro protocol of glutamate toxicity. An acute treatment of atorvastatin or fluoxetine was not neuroprotective; however, the repeated atorvastatin or fluoxetine treatment prevented the decrease in cellular viability induced by glutamate in hippocampal slices. The loss of cellular viability induced by glutamate was accompanied by increased D-aspartate release, increased reactive oxygen species (ROS) and nitric oxide (NO) production, and impaired mitochondrial membrane potential. Atorvastatin or fluoxetine repeated treatment also presented an antidepressant-like effect in the tail suspension test. Atorvastatin or fluoxetine treatment was effective in protecting mice hippocampal slices from glutamate toxicity by preventing the oxidative stress and mitochondrial dysfunction.

  3. Neogenin, a regulator of adult hippocampal neurogenesis, prevents depressive-like behavior.

    Science.gov (United States)

    Sun, Dong; Sun, Xiang-Dong; Zhao, Lu; Lee, Dae-Hoon; Hu, Jin-Xia; Tang, Fu-Lei; Pan, Jin-Xiu; Mei, Lin; Zhu, Xiao-Juan; Xiong, Wen-Cheng

    2018-01-08

    Adult neurogenesis in hippocampal dentate gyrus (DG) is a complex, but precisely controlled process. Dysregulation of this event contributes to multiple neurological disorders, including major depression. Thus, it is of considerable interest to investigate how adult hippocampal neurogenesis is regulated. Here, we present evidence for neogenin, a multifunctional transmembrane receptor, to regulate adult mouse hippocampal neurogenesis. Loss of neogenin in adult neural stem cells (NSCs) or neural progenitor cells (NPCs) impaired NSCs/NPCs proliferation and neurogenesis, whereas increased their astrocytic differentiation. Mechanistic studies revealed a role for neogenin to positively regulate Gli1, a crucial downstream transcriptional factor of sonic hedgehog, and expression of Gli1 into neogenin depleted NSCs/NPCs restores their proliferation. Further morphological and functional studies showed additional abnormities, including reduced dendritic branches and spines, and impaired glutamatergic neuro-transmission, in neogenin-depleted new-born DG neurons; and mice with depletion of neogenin in NSCs/NPCs exhibited depressive-like behavior. These results thus demonstrate unrecognized functions of neogenin in adult hippocampal NSCs/NPCs-promoting NSCs/NPCs proliferation and neurogenesis and preventing astrogliogenesis and depressive-like behavior, and suggest neogenin regulation of Gli1 signaling as a possible underlying mechanism.

  4. Prenatal choline deficiency does not enhance hippocampal vulnerability after kainic acid-induced seizures in adulthood.

    Science.gov (United States)

    Wong-Goodrich, Sarah J E; Tognoni, Christina M; Mellott, Tiffany J; Glenn, Melissa J; Blusztajn, Jan K; Williams, Christina L

    2011-09-21

    Choline is a vital nutrient needed during early development for both humans and rodents. Severe dietary choline deficiency during pregnancy leads to birth defects, while more limited deficiency during mid- to late pregnancy causes deficits in hippocampal plasticity in adult rodent offspring that are accompanied by cognitive deficits only when task demands are high. Because prenatal choline supplementation confers neuroprotection of the adult hippocampus against a variety of neural insults and aids memory, we hypothesized that prenatal choline deficiency may enhance vulnerability to neural injury. To examine this, adult offspring of rat dams either fed a control diet (CON) or one deficient in choline (DEF) during embryonic days 12-17 were given multiple injections (i.p.) of saline (control) or kainic acid to induce seizures and were euthanized 16 days later. Perhaps somewhat surprisingly, DEF rats were not more susceptible to seizure induction and showed similar levels of seizure-induced hippocampal histopathology, GAD expression loss, upregulated hippocampal GFAP and growth factor expression, and increased dentate cell and neuronal proliferation as that seen in CON rats. Although prenatal choline deficiency compromises adult hippocampal plasticity in the intact brain, it does not appear to exacerbate the neuropathological response to seizures in the adult hippocampus at least shortly after excitotoxic injury. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Probabilistic risk assessment of the Space Shuttle. Phase 3: A study of the potential of losing the vehicle during nominal operation. Volume 2: Integrated loss of vehicle model

    Science.gov (United States)

    Fragola, Joseph R.; Maggio, Gaspare; Frank, Michael V.; Gerez, Luis; Mcfadden, Richard H.; Collins, Erin P.; Ballesio, Jorge; Appignani, Peter L.; Karns, James J.

    1995-01-01

    The application of the probabilistic risk assessment methodology to a Space Shuttle environment, particularly to the potential of losing the Shuttle during nominal operation is addressed. The different related concerns are identified and combined to determine overall program risks. A fault tree model is used to allocate system probabilities to the subsystem level. The loss of the vehicle due to failure to contain energetic gas and debris, to maintain proper propulsion and configuration is analyzed, along with the loss due to Orbiter, external tank failure, and landing failure or error.

  6. Automatic planning on hippocampal avoidance whole-brain radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shuo, E-mail: shuo0220@gmail.com; Zheng, Dandan; Zhang, Chi; Ma, Rongtao; Bennion, Nathan R.; Lei, Yu; Zhu, Xiaofeng; Enke, Charles A.; Zhou, Sumin

    2017-04-01

    Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle{sup 3} Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present study is to evaluate the performance of the Pinnacle{sup 3} Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle{sup 3} Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D{sub 2%} and D{sub 98%} of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D{sub 100%} and D{sub max} of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle{sup 3} Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The

  7. Automatic planning on hippocampal avoidance whole-brain radiotherapy

    International Nuclear Information System (INIS)

    Wang, Shuo; Zheng, Dandan; Zhang, Chi; Ma, Rongtao; Bennion, Nathan R.; Lei, Yu; Zhu, Xiaofeng; Enke, Charles A.; Zhou, Sumin

    2017-01-01

    Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle 3 Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present study is to evaluate the performance of the Pinnacle 3 Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle 3 Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D 2% and D 98% of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D 100% and D max of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle 3 Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The expedited quality planning achieved by

  8. Adult hippocampal neurogenesis and cognitive aging

    Directory of Open Access Journals (Sweden)

    Román Darío Moreno Fernández

    2013-12-01

    Full Text Available Aging is a normal developmental process associated with neurobiological changes leading to cognitive alterations with preserved, impaired, and enhanced functions. Evidence from animal and human studies is reviewed to explore the potential role of hippocampal plasticity on age-related cognitive changes with special attention to adult hippocampal neurogenesis. Results from lesion and stimulation strategies, as well as correlation data, support either a direct or modulatory role for adult newborn neurons in cognition at advanced ages. Further research on this topic may help to develop new treatments and to improve the quality of life of older people.

  9. How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans.

    Science.gov (United States)

    Frodl, Thomas; O'Keane, Veronica

    2013-04-01

    There is evidence that excessive stress exposure of the brain, mediated through the neurotoxic effects of cortisol and possibly neuroinflammation, causes damage to brain structure and function: the glucocorticoid cascade hypothesis. Functional changes of hypothalamic-pituitary-adrenal (HPA) axis as well as alterations in brain structures like the hippocampus have been consistently reported in major depression. However, there has not been a lot of emphasis on bringing findings from studies on early childhood stress, HPA axis functioning and hippocampal imaging together. This is the subject for this systematic review of the literature on how developmental stress, specifically childhood maltreatment, may impact on HPA axis function and hippocampal structure. We will also review the literature on the relationship between HPA axis function and hippocampal volume in healthy, depressed and other disease states. There is evidence that prenatal stress and childhood maltreatment is associated with an abnormally developing HPA system, as well as hippocampal volume reduction. Smaller hippocampal volumes are associated with increased cortisol secretion during the day. We conclude that a model integrating childhood maltreatment, cortisol abnormalities and hippocampal volume may need to take other factors into account, such as temperament, genetics or the presence of depression; to provide a cohesive explanation of all the findings. Finally, we have to conclude that the cascade hypothesis, mainly based on preclinical studies, has not been translated enough into humans. While there is evidence that early life maltreatment results in structural hippocampal changes and these are in turn more prominent in subjects with higher continuous cortisol secretion it is less clear which role early life maltreatment plays in HPA axis alteration. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Hearing loss

    Science.gov (United States)

    Decreased hearing; Deafness; Loss of hearing; Conductive hearing loss; Sensorineural hearing loss; Presbycusis ... Symptoms of hearing loss may include: Certain sounds seeming too loud Difficulty following conversations when two or more people are talking ...

  11. Memory impairment in multiple sclerosis: Relevance of hippocampal activation and hippocampal connectivity

    NARCIS (Netherlands)

    Hulst, H.E.; Schoonheim, M.M.; van Geest, Q.; Uitdehaag, B.M.J.; Barkhof, F.; Geurts, J.J.G.

    2015-01-01

    Background: Memory impairment is frequent in multiple sclerosis (MS), but it is unclear what functional brain changes underlie this cognitive deterioration. Objective: To investigate functional hippocampal activation and connectivity, in relation to memory performance in MS. Methods: Structural and

  12. Alterations of White Matter Integrity and Hippocampal Functional Connectivity in Type 2 Diabetes Without Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Qian Sun

    2018-03-01

    Full Text Available Aims: To investigate the white matter (WM integrity and hippocampal functional connectivity (FC in type 2 diabetes mellitus (T2DM patients without mild cognitive impairment (MCI by using diffusion tensor imaging (DTI and resting-state functional magnetic resonance imaging (rs-fMRI, respectively.Methods: Twelve T2DM patients without MCI and 24 age, sex and education matched healthy controls (HC were recruited. DTI and rs-fMRI data were subsequently acquired on a 3.0T MR scanner. Tract-based spatial statistics (TBSS combining region of interests (ROIs analysis was used to investigate the alterations of DTI metrics (fractional anisotropy (FA, mean diffusivity (MD, λ1 and λ23 and FC measurement was performed to calculate hippocampal FC with other brain regions. Cognitive function was evaluated by using Mini-Mental State Examination (MMSE and Montreal Cognitive Assessment (MoCA. Brain volumes were also evaluated among these participants.Results: There were no difference of MMSE and MoCA scores between two groups. Neither whole brain nor regional brain volume decrease was revealed in T2DM patients without MCI. DTI analysis revealed extensive WM disruptions, especially in the body of corpus callosum (CC. Significant decreases of hippocampal FC with certain brain structures were revealed, especially with the bilateral frontal cortex. Furthermore, the decreased FA in left posterior thalamic radiation (PTR and increased MD in the splenium of CC were closely related with the decreased hippocampal FC to caudate nucleus and frontal cortex.Conclusions: T2DM patients without MCI showed extensive WM disruptions and abnormal hippocampal FC. Moreover, the WM disruptions and abnormal hippocampal FC were closely associated.Highlights-T2DM patients without MCI demonstrated no obvious brain volume decrease.-Extensive white matter disruptions, especially within the body of corpus callosum, were revealed with DTI analysis among the T2DM patients.-Despite no MCI in T2

  13. Impaired neuronal maturation of hippocampal neural progenitor cells in mice lacking CRAF.

    Science.gov (United States)

    Pfeiffer, Verena; Götz, Rudolf; Camarero, Guadelupe; Heinsen, Helmut; Blum, Robert; Rapp, Ulf Rüdiger

    2018-01-01

    RAF kinases are major constituents of the mitogen activated signaling pathway, regulating cell proliferation, differentiation and cell survival of many cell types, including neurons. In mammals, the family of RAF proteins consists of three members, ARAF, BRAF, and CRAF. Ablation of CRAF kinase in inbred mouse strains causes major developmental defects during fetal growth and embryonic or perinatal lethality. Heterozygous germline mutations in CRAF result in Noonan syndrome, which is characterized by neurocognitive impairment that may involve hippocampal physiology. The role of CRAF signaling during hippocampal development and generation of new postnatal hippocampal granule neurons has not been examined and may provide novel insight into the cause of hippocampal dysfunction in Noonan syndrome. In this study, by crossing CRAF-deficiency to CD-1 outbred mice, a CRAF mouse model was established which enabled us to investigate the interplay of neural progenitor proliferation and postmitotic differentiation during adult neurogenesis in the hippocampus. Albeit the general morphology of the hippocampus was unchanged, CRAF-deficient mice displayed smaller granule cell layer (GCL) volume at postnatal day 30 (P30). In CRAF-deficient mice a substantial number of abnormal, chromophilic, fast dividing cells were found in the subgranular zone (SGZ) and hilus of the dentate gyrus (DG), indicating that CRAF signaling contributes to hippocampal neural progenitor proliferation. CRAF-deficient neural progenitor cells showed an increased cell death rate and reduced neuronal maturation. These results indicate that CRAF function affects postmitotic neural cell differentiation and points to a critical role of CRAF-dependent growth factor signaling pathway in the postmitotic development of adult-born neurons.

  14. Hippocampal insulin resistance and cognitive dysfunction

    NARCIS (Netherlands)

    Biessels, Geert Jan; Reagan, Lawrence P.

    2015-01-01

    Clinical studies suggest a link between type 2 diabetes mellitus (T2DM) and insulin resistance (IR) and cognitive dysfunction, but there are significant gaps in our knowledge of the mechanisms underlying this relationship. Animal models of IR help to bridge these gaps and point to hippocampal IR as

  15. Amnesia due to bilateral hippocampal glioblastoma

    International Nuclear Information System (INIS)

    Shimauchi, M.; Wakisaka, S.; Kinoshita, K.

    1989-01-01

    The authors report a unique case of glioblastoma which caused permanent amnesia. Magnetic resonance imaging showed the lesion to be limited to the hippocampal formation bilaterally. Although glioblastoma extends frequently into fiber pathways and expands into the opposite cerebral hemisphere, making a 'butterfly' lesion, it is unusual for it to invade the limbic system selectively to this extent. (orig.)

  16. Hippocampal theta frequency shifts and operant behaviour

    NARCIS (Netherlands)

    Lopes da Silva, F.H.; Kamp, A.

    1. 1. A shift of hippocampal dominant theta frequency to 6 c/sec has been demonstrated in the post-reward period in two dogs, which occurs consistently related in time to a well defined behavioural pattern in the course of an operant conditioning paradigm. 2. 2. The frequency shift was detected and

  17. Hippocampal gamma oscillations increase with memory load

    NARCIS (Netherlands)

    Van Vugt, Marieke K.; Schulze-Bonhage, Andreas; Litt, Brian; Brandt, Armin; Kahana, Michael J.

    2010-01-01

    Although the hippocampus plays a crucial role in encoding and retrieval of contextually mediated episodic memories, considerable controversy surrounds the role of the hippocampus in short-term or working memory. To examine both hippocampal and neocortical contributions to working memory function, we

  18. Bigger is better and worse: on the intricate relationship between hippocampal size and memory.

    Science.gov (United States)

    Molnár, Katalin; Kéri, Szabolcs

    2014-04-01

    The structure-function relationship between the hippocampal region and memory is a debated topic in the literature. It has been suggested that larger hippocampi are associated with less effective memory performance in healthy young adults because of a partial synaptic pruning. Here, we tested this hypothesis in individuals with Fragile X Syndrome (FXS) with known abnormal pruning and IQ- and age-matched individuals with hypoxic brain injury, preterm birth, and obstetric complications. Results revealed larger normalized hippocampal volume in FXS compared with neurotypical controls, whereas individuals with hypoxic injury had smaller hippocampi. In neurotypical controls and individuals with hypoxic injury, better general memory, as indexed by the Wechsler Memory Scale-Revised, was associated with larger hippocampus. In contrast, in FXS we observed the opposite relationship: larger hippocampus was associated with worse general memory. Caudate volume did not correlate with memory in either group. These results suggest that incomplete pruning in young healthy adults may not contribute to less efficient memory capacity, and hippocampal size is positively associated with memory performance. However, abnormally large and poorly pruned hippocampus may indeed be less effective in FXS. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Cryptic sexual dimorphism in spatial memory and hippocampal oxytocin receptors in prairie voles (Microtus ochrogaster).

    Science.gov (United States)

    Rice, Marissa A; Hobbs, Lauren E; Wallace, Kelly J; Ophir, Alexander G

    2017-09-01

    Sex differences are well documented and are conventionally associated with intense sex-specific selection. For example, spatial memory is frequently better in males, presumably due to males' tendency to navigate large spaces to find mates. Alternatively, monogamy (in which sex-specific selection is relatively relaxed) should diminish or eliminate differences in spatial ability and the mechanisms associated with this behavior. Nevertheless, phenotypic differences between monogamous males and females persist, sometimes cryptically. We hypothesize that sex-specific cognitive demands are present in monogamous species that will influence neural and behavioral phenotypes. The effects of these demands should be observable in spatial learning performance and neural structures associated with spatial learning and memory. We analyzed spatial memory performance, hippocampal volume and cell density, and hippocampal oxytocin receptor (OTR) expression in the socially monogamous prairie vole. Compared to females, males performed better in a spatial memory and spatial learning test. Although we found no sex difference in hippocampal volume or cell density, male OTR density was significantly lower than females, suggesting that performance may be regulated by sub-cellular mechanisms within the hippocampus that are less obvious than classic neuroanatomical features. Our results suggest an expanded role for oxytocin beyond facilitating social interactions, which may function in part to integrate social and spatial information. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Effect of partial volume correction on muscarinic cholinergic receptor imaging with single-photon emission tomography in patients with temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Weckesser, M.; Ziemons, K.; Griessmeier, M.; Sonnenberg, F.; Langen, K.J.; Mueller-Gaertner, H.W.; Hufnagel, A.; Elger, C.E.; Hacklaender, T.; Holschbach, M.

    1997-01-01

    Animal experiments and preliminary results in humans have indicated alterations of hippocampal muscarinic acetylcholine receptors (mAChR) in temporal lobe epilepsy. Patients with temporal lobe epilepsy often present with a reduction in hippocampal volume. The aim of this study was to investigate the influence of hippocampal atrophy on the quantification of mAChR with single photon emission tomography (SPET) in patients with temporal lobe epilepsy. Cerebral uptake of the muscarinic cholinergic antagonist [ 123 I]4-iododexetimide (IDex) was investigated by SPET in patients suffering from temporal lobe epilepsy of unilateral (n=6) or predominantly unilateral (n=1) onset. Regions of interest were drawn on co-registered magnetic resonance images. Hippocampal volume was determined in these regions and was used to correct the SPET results for partial volume effects. A ratio of hippocampal IDex binding on the affected side to that on the unaffected side was used to detect changes in muscarinic cholinergic receptor density. Before partial volume correction a decrease in hippocampal IDex binding on the focus side was found in each patient. After partial volume no convincing differences remained. Our results indicate that the reduction in hippocampal IDex binding in patients with epilepsy is due to a decrease in hippocampal volume rather than to a decrease in receptor concentration. (orig.). With 2 figs., 2 tabs

  1. Updating the lamellar hypothesis of hippocampal organization

    Directory of Open Access Journals (Sweden)

    Robert S Sloviter

    2012-12-01

    Full Text Available In 1971, Andersen and colleagues proposed that excitatory activity in the entorhinal cortex propagates topographically to the dentate gyrus, and on through a trisynaptic circuit lying within transverse hippocampal slices or lamellae [Andersen, Bliss, and Skrede. 1971. Lamellar organization of hippocampal pathways. Exp Brain Res 13, 222-238]. In this way, a relatively simple structure might mediate complex functions in a manner analogous to the way independent piano keys can produce a nearly infinite variety of unique outputs. The lamellar hypothesis derives primary support from the lamellar distribution of dentate granule cell axons (the mossy fibers, which innervate dentate hilar neurons and area CA3 pyramidal cells and interneurons within the confines of a thin transverse hippocampal segment. Following the initial formulation of the lamellar hypothesis, anatomical studies revealed that unlike granule cells, hilar mossy cells, CA3 pyramidal cells, and Layer II entorhinal cells all form axonal projections that are more divergent along the longitudinal axis than the clearly lamellar mossy fiber pathway. The existence of pathways with translamellar distribution patterns has been interpreted, incorrectly in our view, as justifying outright rejection of the lamellar hypothesis [Amaral and Witter. 1989. The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31, 571-591]. We suggest that the functional implications of longitudinally-projecting axons depend not on whether they exist, but on what they do. The observation that focal granule cell layer discharges normally inhibit, rather than excite, distant granule cells suggests that longitudinal axons in the dentate gyrus may mediate "lateral" inhibition and define lamellar function, rather than undermine it. In this review, we attempt a reconsideration of the evidence that most directly impacts the physiological concept of hippocampal lamellar

  2. Excitatory and inhibitory pathways modulate kainate excitotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Casaccia-Bonnefil, P; Benedikz, Eirikur; Rai, R

    1993-01-01

    In organotypic hippocampal slice cultures, kainate (KA) specifically induces cell loss in the CA3 region while N-methyl-D-aspartate induces cell loss in the CA1 region. The sensitivity of slice cultures to KA toxicity appears only after 2 weeks in vitro which parallels the appearance of mossy...... fibers. KA toxicity is potentiated by co-application with the GABA-A antagonist, picrotoxin. These data suggest that the excitotoxicity of KA in slice cultures is modulated by both excitatory and inhibitory synapses....

  3. Hippocampal neuron populations are reduced in vervet monkeys with fetal alcohol exposure

    DEFF Research Database (Denmark)

    Burke, Mark W; Ptito, Maurice; Ervin, Frank R

    2015-01-01

    of pregnancy. Here, we report significant numerical reductions in the principal hippocampal neurons of fetal alcohol-exposed (FAE) offspring, as compared to age-matched, similarly housed conspecifics with isocaloric sucrose exposure. These deficits, particularly marked in CA1 and CA3, are present neonatally......Prenatal exposure to beverage alcohol is a major cause of mild mental retardation and developmental delay. In nonendangered alcohol-preferring vervet monkeys, we modeled the most common nondysmorphic form of fetal alcohol syndrome disorder with voluntary drinking during the third trimester...... and persist through infancy (5 months) and juvenile (2 years) stages. Although the volumes of hippocampal subdivisions in FAE animals are not atypical at birth, by age 2, they are only 65-70% of those estimated in age-matched controls. These data suggest that moderate, naturalistic alcohol consumption during...

  4. Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1

    Science.gov (United States)

    Havekes, Robbert; Park, Alan J; Tudor, Jennifer C; Luczak, Vincent G; Hansen, Rolf T; Ferri, Sarah L; Bruinenberg, Vibeke M; Poplawski, Shane G; Day, Jonathan P; Aton, Sara J; Radwańska, Kasia; Meerlo, Peter; Houslay, Miles D; Baillie, George S; Abel, Ted

    2016-01-01

    Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density. DOI: http://dx.doi.org/10.7554/eLife.13424.001 PMID:27549340

  5. Deterioration of abstract reasoning ability in mild cognitive impairment and Alzheimer's disease: correlation with regional grey matter volume loss revealed by diffeomorphic anatomical registration through exponentiated lie algebra analysis

    Energy Technology Data Exchange (ETDEWEB)

    Yoshiura, Takashi; Hiwatashi, Akio; Yamashita, Koji; Takayama, Yukihisa; Kamano, Norihiro; Honda, Hiroshi [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka (Japan); Ohyagi, Yasumasa; Kira, Jun-ichi [Kyushu University, Department of Neurology, Graduate School of Me