A multidisciplinary and longitudinal project on cognitive aging

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PI:
 Prof. Astri J. Lundervold, Clinical Cognitive Neuroscience (C-CNS) Research GroupDepartment of Biological and Medical and Psychology, University of Bergen, Bergen, Norway  [PubMed]

Imaging / data analysis:  Prof. Arvid Lundervold, Neuroinformatics and Image Analysis Laboratory, Neural Networks Research Group, Department of Biomedicine, University of Bergen, Bergen, Norway & Department of Radiology, Haukeland University Hospital, Bergen, Norway   [Google scholar]

CollaboratorsSteinunn Adolfsdottir, Martin Andersson, Jonn-Terje Geitung, Mala Naik, Judit Haász, Erik Hanson, Erlend Hodneland, Are LosnegårdAlexandra Vik, Eike Wehling,  Erling Westlye, Martin Ystad

The Western Norway Regional Health Authority annual reports (in Norwegian):
  "Aging - cognition, imaging and genetics": 2011, 2012, 2013
  "Quantitative brain MR imaging in aging and neurodegenerative disorders" (MedViz): 2010, 2011, 2012, 2013

Project description (HV-funded application 1/1/2011 - 12/31/2013)
Follow-up project on longitudinal analysis (HV-funded application 01/01 - 12/31/2015)

Summary

  • This project represents an integrated approach to the study of cognitive aging. In a cohort of healthy elderly individuals, longitudinal data from extensive neuropsychological examinations and measures on brain structure and function derived from multimodal MR imaging and connectivity analysis are being used. Furthermore, all participants have delivered blood samples for genetic analyses. Financial support to run a third wave will enable the research group to contribute new knowledge about the aging brain and characteristics of developmental pathways of dementia.

  • The project has already collected, organized and analyzed data from extensive neuropsychological test examinations and multimodal MR imaging sessions (e.g. 3D T1-weighted, DTI, resting state BOLD fMRI) in a cohort of more than 100 subjects in two different study waves about 3 years apart.

  • Based on a powerful image analysis machinery and preliminary analysis (see Section 4.3 and frontpage of this application) we are now able to focus on specific neurocognitive questions related to cognitive aging processes, using jointly imaging and behavioral parameters from repeated measurements in the fairly large collection of elderly subjects -  a study material that we think is outstanding also at an international level.

  • The multidisciplinary team of researchers and students associated with the project have an excellent combination of knowledges and skills (clinical neuropsychology, neuroscience, imaging and radiology, data analysis, genetics) and a good publication record, involving several Helse Vest institutions (Haraldsplass Deaconess Hospital, Haukeland University Hospital, the MedViz research cluster), in addition to other national and international collaborations. 


PhD projects: 

Martin Andersson. A study of attention control in children and elderly using a forced-attention dichotic listening paradigm. (2009/12/03)

Eike Wehling. Cognitive and Olfactory Changes in Aging. (2009/04/02)

Martin Ystad. Quantitative Structural and Functional Brain Imaging in Cognitive Aging. (2010/12/03) [PDF]

Alexandra Vik. Structural and Functional Changes in the Aging Frontal Brain Using Repeated Cognitive Assessments, Multimodal MR Imaging and Connectivity Analysis. [PDF]



Publications:

2015

Joey W. Trampush, Todd Lencz, Emma Knowles, Gail Davies, Saurav Guha, Itsik Pe'er, David C. Liewald, John M. Starr, Srdjan Djurovic, Ingrid Melle, Kjetil Sundet, Andrea Christoforou, Ivar Reinvang, Semanti Mukherjee, Pamela DeRosse, Astri Lundervold, Vidar M. Steen, Majnu John, Thomas Espeseth, Katri Räikkönen, Elisabeth Widen, Aarno Palotie, Johan G. Eriksson, Ina Giegling, Bettina Konte, Masashi Ikeda, Panos Roussos, Stella Giakoumaki, Katherine E. Burdick, Antony Payton, William Ollier, Mike Horan, Matthew Scult, Dwight Dickinson, Richard E. Straub, Gary Donohoe, Derek Morris, Aiden Corvin, Michael Gill, Ahmad Hariri, Daniel R. Weinberger, Neil Pendleton, Nakao Iwata, Ariel Darvasi, Panos Bitsios, Dan Rujescu, Jari Lahti, Stephanie Le Hellard, Matthew C. Keller, Ole A. Andreassen, Ian J. Deary, David C. Glahn, Anil K. Malhotra. Independent Evidence for an Association between General Cognitive Ability and a Genetic Locus for Educational Attainment. Accepted to be published in Biological Psychiatry

Narelle K Hansell, Graeme S Halford, Glenda Andrews, David H K Shum, Sarah E Harris, Gail Davies, Sanja Franic, Andrea Christoforou, Brendan Zietsch, Jodie Painter, Sarah E Medland, Erik A. Ehli, Gareth E Davies, Vidar M Steen, Astri J. Lundervold, Ivar Reinvang, Grant W Montgomery, Thomas Espeseth, Hilleke E Hulshoff Pol, John M Starr, Nicholas G Martin, Stephanie Le Hellard, Dorret I Boomsma, Ian J Deary, Margaret J Wright . The Genetic Architecture of Complex Relational Processing. Biological Psychiatry. PLoS One. 2015 Apr 10;10(4):e0123886. doi: 10.1371/journal.pone.0123886. eCollection 2015. http://www.ncbi.nlm.nih.gov/pubmed/25860228

Wehling, E, Lundervold, AJ, Espeseth, T, Reinvang, I, Nordin, S. Even cognitively well-functioning adults are unaware of their olfactory dysfunction: Implications for ENT clinicians and researchers. Rhinology. 2015 Mar;53(1):89-94<http://www.ncbi.nlm.nih.gov/pubmed/?term=Rhinology.+2015+Mar%3B53(1)%3A89-94>. doi: 10.4193/Rhin14.081.

Davies G, Armstrong N, Bis JC, Bressler J, Chouraki V, Giddaluru S, Hofer E, Ibrahim-Verbaas CA, Kirin M, Lahti J, van der Lee SJ, Le Hellard S, Liu T, Marioni RE, Oldmeadow C, Postmus I, Smith AV, Smith JA, Thalamuthu A, Thomson R, Vitart V, Wang J, Yu L, Zgaga L, Zhao W, Boxall R, Harris SE, Hill WD, Liewald DC, Luciano M, Adams H, Ames D, Amin N, Amouyel P, Assareh AA, Au R, Becker JT, Beiser A, Berr C, Bertram L, Boerwinkle E, Buckley BM, Campbell H, Corley J, De Jager PL, Dufouil C, Eriksson JG, Espeseth T, Faul JD, Ford I, Scotland G, Gottesman RF, Griswold ME, Gudnason V, Harris TB, Heiss G, Hofman A, Holliday EG, Huffman J, Kardia SL, Kochan N, Knopman DS, Kwok JB, Lambert JC, Lee T, Li G, Li SC, Loitfelder M, Lopez OL, Lundervold AJ, Lundqvist A, Mather KA, Mirza SS, Nyberg L, Oostra BA, Palotie A, Papenberg G, Pattie A, Petrovic K, Polasek O, Psaty BM, Redmond P, Reppermund S, Rotter JI, Schmidt H, Schuur M, Schofield PW, Scott RJ, Steen VM, Stott DJ, van Swieten JC, Taylor KD, Trollor J, Trompet S, Uitterlinden AG, Weinstein G, Widen E, Windham BG, Jukema JW, Wright AF, Wright MJ, Yang Q, Amieva H, Attia JR, Bennett DA, Brodaty H, de Craen AJ, Hayward C, Ikram MA, Lindenberger U, Nilsson LG, Porteous DJ, Räikkönen K, Reinvang I, Rudan I, Sachdev PS, Schmidt R, Schofield PR, Srikanth V, Starr JM, Turner ST, Weir DR, Wilson JF, van Duijn C, Launer L, Fitzpatrick AL, Seshadri S, Mosley TH Jr, Deary IJ. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949).<http://www.ncbi.nlm.nih.gov/pubmed/25644384> Molecular Psychiatry. 2015 Feb 3. http://dx.doi: 10.1038/mp.2014.188<http://dx.doi:%2010.1038/mp.2014.188>.  PMID: 25644384 [Epub ahead of print]

Anders M Fjell, Lars T Westlye, Inge Amlien, Christian K Tamnes, Håkon Grydeland, Andreas Engvig, Espeseth, Ivar Reinvang, Astri J. Lundervold, Arvid Lundervold, Kristine B. Walhovd. High-expanding cortical regions in human development and evolution are related to cognitive abilities. Cerebral Cortex, 2015 Jan;25(1):26-34. http://dx.doi.org/10.1093/cercor/bht201.<http://dx.doi.org/10.1093/cercor/bht201> PMID: 23960203. <http://dx.doi.org/10.1093/cercor/bht201>


2014

Lebedev A, Westman E, Van Westen GJP, Kramberger MG, Lundervold A, Aarsland D, Soininen H, Kloszewska I, Mecocci P, Tsolaki M, Vellas B, Lovestone S, Simmons A. Random Forest ensembles for detection and prediction of Alzheimer's disease with a good between-cohort robustness. Neuroimage Clin. 2014 Aug 28;6:115-25. doi: 10.1016/j.nicl.2014.08.023. 

Fernandes CP, Westlye LT, Giddaluru S, Christoforou A, Kauppi K, Adolfsson R, Nilsson LG, Nyberg L, Lundervold AJ, Reinvang I, Steen VM, Le Hellard S, Espeseth T. Lack of association of the rs1344706 ZNF804A variant with cognitive functions and DTI indices of white matter microstructure in two independent healthy populations. Psychiatry Res. 2014 Feb 22. pii: S0925-4927(14)00051-1. doi: 10.1016/j.pscychresns.2014.02.009. [Epub ahead of print]

Adolfsdottir, S, Haasz, J. Wehling, E, Ystad, M, Lundevold, A, Lundervold, AJ (2014). Salient measures of inhibition and switching are associated with frontal lobe gray matter volume in healthy middle-aged and older adults. Neuropsychology. 2014 Nov;28(6):859-69. doi: 10.1037/neu0000082. 

Angelelli P, Oeltze S, Turkay C, Haász J, Hodneland E, Lundervold A, Lundervold AJ, Preim B, Hauser H. Interactive visual analysis of heterogeneous cohort study data. IEEE Computer Graphics and Applications 2014 Sep-Oct;34(5):70-82. [DOI: 10.1109/MCG.2014.40]  [P. Angelelli PhD thesis excerpt (2012)  PDF]

Carla P. D. Fernandes, Lars T. Westlye, Sudheer Giddaluru, Andrea Christoforou, Karolina Kauppi, Rolf Adolfsson, Lars-Göran Nilsson, Lars Nyberg, Astri Lundervold, Ivar Reinvang, Vidar M.Steen, Stéphanie Le Hellard, Thomas Espeseth. Lack of association of the rs1344706 ZNF804A variant with cognitive functions and DTI indices of white matter microstructure in two independent healthy populations. Psychiatry Research Neuroimaging. 2014 Apr 30;222(1-2):60-6. doi: 10.1016/j.pscychresns.2014.02.009. 

Lundervold, A.J., Wollschläger, D., Wehling, E. Age- and sex-related changes in episodic memory function in middle-aged and older individuals. Scandinavian Journal of Psychology (”New perspectives in neuropsychology”), 2014 Mar 6. doi: 10.1111/sjop.12114. [Epub ahead of print]

Ian Deary, William Hill, Gail Davies, Louie van de Lagemaat, Andrea Christoforou, Carla Fernandes, Dave Liewald, Mike Croning, Antony Payton, leone Craig, Lawrence Whalley, Michael Horan, William Ollier, Narelle Hansell, Margaret Wright, Nick Martin, Grant Montgomery, Vidar Steen, Stephanie Le Hellard, Thomas Espeseth, Astri Lundervold, Ivar Reinvang, John Starr, Neil Pendleton, Seth Grant, Timothy Bates, and Riccardo Marioni (2014). Human cognitive ability is influenced by genetic variation in components of postsynaptic signaling complexes assembled by NMDA receptors and MAGUK proteins. Translational Psychiatry 2014 Jan 7;4:e341. doi: 10.1038/tp.2013.114.

GCAN (2014). Using ancestry-informative markers to identify fine structure across 15 populations of European originEur J Hum Genet. 2014 Feb 19. doi: 10.1038/ejhg.2014.1. [Epub ahead of print]

The Wellcome Trust Case Control Consortium 3 (2014). A genome-wide association study of anorexia nervosa. Molecular Psychiatry. 2014 Feb 11. doi: 10.1038/mp.2013.187. [Epub ahead of print] PMID: 24514567

T Lencz1, E Knowles, G Davies, S Guha, DC Liewald, JM Starr. S Djurovic, I Melle, K Sundet, A Christoforou, I Reinvang, S Mukherjee, Pamela DeRosse, A Lundervold, VM Steen, M John, T Espeseth, K Räikkönen, E Widen, A Palotie, JG Eriksson, I Giegling, B Konte, M Ikeda, P Roussos, S Giakoumaki, KE Burdick, A Payton, W Ollier, M Horan, G Donohoe, D Morris, A Corvin, M Gill, N Pendleton, N Iwata, A Darvasi, P Bitsios, D Rujescu, J Lahti, SL Hellard, MC Keller, OA Andreassen, IJ Deary, DC Glahn and AK Malhotra (2014). Molecular Evidence for Genetic Overlap between General Cognitive Ability and Risk for Schizophrenia: A Report from the Cognitive Genomics Consortium (COGENT). Molecular Psychiatry, 2014 Feb;19(2):168-74. doi: 10.1038/mp.2013.166

WD Hill, G Davies,  DLN van de Lagemaat, A Christoforou, RE Marioni1,, CPD Fernandes, DC Liewald, MDR Croning, A Payton, LCA Craig, LJ Whalley, M Horan, W Ollier, NK Hansell, MJ Wright, NG Martin, GW Montgomery, VM Steen, S Le Hellard, T Espeseth, AJ Lundervold, I Reinvang, JM Starr, N Pendleton, SGN Grant, TC Bates1 and IJ Deary. (2014).  Human cognitive ability is influenced by genetic variation in components of postsynaptic signalling complexes assembled by NMDA receptors and MAGUK proteins Transl Psychiatry, 2014 Jan 7;4:e341. doi: 10.1038/tp.2013.114.


2013

Carla P. D. Fernandes, Andrea Christoforou, Sudheer Giddaluru, Kari M. Ersland, Srdjan Djurovic, Manuel Mattheisen, Astri J. Lundervold, Ivar Reinvang, Markus M.Nöthen, Marcella Rietschel, Roel A. Ophoff, Genetic Risk and Outcome of Psychosis (GROUP), Albert Hofman, André G. Uitterlinden, Thomas Werge, Sven Cichon, Thomas Espeseth, Ole A. Andreassen, Vidar M.Steen, and Stephanie Le Hellard. A genetic deconstruction of neurocognitive traits in schizophrenia and bipolar disorder. PLOS-ONE, December 2013, 8 (12),  e81052

Malinski M, Peter R, Hodneland E, Lundervold AJ, Lundervold A, Jiri J. Registration of FA and T1-weighted MRI data of healthy human brain based on template matching and normalized cross-correlation. J Digit Imaging 2013;26:774-785  [PDF]  

Losnegård A, Lundervold A, Hodneland E. White matter fiber tracking directed by interpolating splines and a methodological framework for evaluation. Frontiers in Neuroinformatics 2013;7(13):1-14  [PDF]

Tukay, Catagay, Lundervold, A, Lundervold, AJ, Hauser, H. (2013). Hypothesis Generation by Interactive Visual Exploration of Heterogeneous Medical Data. Special Session on Human-Computer Interaction & Knowledge, Int. Conference on Human Factors in Cumputing & Informatics, 1 – 3- July,2013, Maribor, Slovenia.

Haasz, J., Westlye, E., Fjær, S., Espeseth, T., Lundervold, A., Lundervold, AJ. (2013). General fluid-type intelligence is related to indices of white matter structure in middle-aged and old adults. Neuroimage, Jun 19;83C:372-383.. doi:pii: S1053-8119(13)00677-0. 10.1016/j.neuroimage.2013.06.040. [PubMed]

Brevik, E., Eikeland, R., Lundervold, A.J. (2013). Subthreshold depressive symptoms have a negative impact on cognitive functioning in middle-aged and older males. Frontiers in Psychology, May 31;4:309, doi: 10.3389/fpsyg.2013.00309.

Fromm A, Lundervold AJ, Moen G, Skulstad S, Thomassen L. (2013). A vascular approach to mild amnestic cognitive impairment: a pilot study. Acta Neurol Scand Suppl. 2013;(196):73-6. doi: 10.1111/ane.12054.


2012

Turkay C, Lundervold A, Lundervold AJ, Hauser H. Representative factor generation for the interactive visual analysis of high-dimensional data. IEEE Transactions on Visualization and Computer Graphics 2012;18(2):2621-2630  [PDF]

Espeseth, T, Christoforou, A, Lundervold, AJ, Steen, VM, Le Hellard, S, Reinvang, I. Imaging and cognitive genetics: The Norwegian Cognitive NeuroGenetics sample. Twin Res Hum Genet. 2012 Jun;15(3):442-52. doi: 10.1017/thg.2012.8.

Westlye, ET, Hodneland, E, Haáz, J, Lundervold, A, Lundervold, AJ. Episodic memory of APOE e4 carriers is correlated with fractional anisotropy, but not cortical thickness, in the medial temporal lobe. Neuroimage, 2012 Jun;10;63(1):507-516. doi: 10.1016/j.neuroimage.2012.06.072.

Kari M. Ersland, Andrea Christoforou, Christine Stansberg, Thomas Espeseth, Manuel Mattheisen, Morten Mattingsdal, Gudmundur A. Hardarson, Thomas Hansen, Carla P. D. Fernandes, Sudheer Giddaluru, Srdjan Djurovic, Astri J. Lundervold, Thomas Werge, Sven Cichon, Ole A. Andreassen, Ivar Reinvang, Vidar M. Steen and Stephanie Le Hellard. Gene-Based Analysis of Regionally Enriched Cortical Genes in GWAS Data Sets of Cognitive Traits and Psychiatric Disorders. PLOS ONE, 2012;7(2):e31687. doi: 10.1371/journal.pone.0031687.

Hodneland E, Ystad M, Haász J, Munthe-Kaas AZ, Lundervold A. Automated approaches for analysis of multimodal MRI acquisitions in a longitudinal study of cognitive aging. Computer Methods and Programs in Biomedicine 2012;106:328-341  [PDF


2011

Lillenes, MS, Espeseth, T, Støen, M, Lundervold, AJ, Drye, SA, Rootwelt, H, Reinvang, I, Tønjum, T. DNA base excision repair gene polymorphisms modulate human cognitive performance and decline during normal life span. Mechanisms of Ageing and Development. 132(8-9):449-58.

G Davies, A Tenesa, A Payton, J Yang, SE Harris, D Liewald, X Ke, S Le Hellard, A Christoforou, M Luciano, K McGhee, L Lopez, AJ Gow, J Corley, P Redmond, HC Fox, P Haggarty, LJ Whalley, G McNeill, ME Goddard, T Espeseth, AJ Lundervold, I Reinvang, A Pickles, VM Steen, W Ollier, DJ Porteous, M Horan, JM Starr, N Pendleton, PM Visscher, and IJ Deary. (2011). Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Molecular Psychiatry, 16(10):996-1005.

Westlye ET, Lundervold A, Rootwelt H, Lundervold AJ, Westlye LT. (2011). Increased Hippocampal Default Mode Synchronization during Rest in Middle-Aged and Elderly APOE {varepsilon}4 Carriers: Relationships with Memory Performance. Journal of Neuroscience,  25;31(21):7775-7783.

Wehling E, Nordin S, Espeseth T, Reinvang I, Lundervold AJ (2011). Unawareness of olfactory dysfunction and its association with cognitive functioning in middle aged and old adults. Arch Clin Neuropsychol, 26(3):260-269.

Ystad M, Hodneland E, Adolfsdottir S, Haász J, Lundervold AJ, Eichele T, Lundervold A (2011). Cortico-striatal connectivity and cognition in normal aging: a combined DTI and resting state fMRI study. Neuroimage, 1;55(1):24-31. [PDF]  { See also Fig. 6 in the review by Bennett & Madden, Neuroscience 2013 Nov 23 [PubMed] }


2010

Ystad M, Eichele T, Lundervold AJ, Lundervold A. (2010). Subcortical functional connectivity and verbal episodic memory in healthy elderly-A resting state fMRI study. Neuroimage, 1;52(1):379-88

Reinvang I, Lundervold AJ, Wehling E, Rootwelt H, Espeseth T.(2010). Epistasis between APOE and nicotinic receptor gene CHRNA4 in age related cognitive function and decline. Journal of International Neuropsychological Society , 6(3):424-32. PMID: 20331911 

Wehling, E, Nordin, S, Espeseth, T, Reinvang, I, Lundervold, AJ. (2010).  Familiarity, Cued and Free Odor Identification and Their Association with Cognitive Functioning in Middle Aged and Older Adults. Neuropsychology, Development and Cognition.Section  B: Aging, Neuropsychology and Cognition,  17(2): 205-219.

Lundervold A. On consciousness, resting state fMRI, and neurodynamicsNonlinear Biomedical Physics 2010 Jun 3;4 Suppl 1:S9.  [PubMed[HTML] [PDF (extended version [PDF])

Naik M, Lundervold A, Nygaard H, Geitung JT. Diffusion tensor imaging (DTI) in dementia patients with frontal lobe symptoms. Acta Radiol. 2010 Jul;51(6):662-8. doi: 10.3109/02841851003709870.


2009 

Ivar Reinvang, Astri J. Lundervold, Helge Rootwelt, Eike Wehling, Thomas Espeseth. (2009). Individual variation in a cholinergic receptor gene modulates attention in aging. Neuroscience Letter., 10;453(3):131-4.

Andersson, M, Ystad, M, Lundervold, A, Lundervold, AJ. (2009). Correlations between measures of executive attention and cortical thickness of left posterior middle frontal gyrus – a dichotic listening study. Behavior and Brain Functions, 1;4:41.

Ystad, M, Lundervold, AJ, Wehling, E, Espeseth, T, Rotwelt, H, Lars Tjelta Westlye, Martin Andersson, Steinunn Adolfsdottir, Jonn Terje Geitung, Anders M Fjell, Ivar Reinvang and Arvid Lundervold (2009). Hippocampal volumes are important predictors for memory function in elderly women. BMC Medical Imaging, 9:17.

Le Hellard S, Håvik B, Espeseth T, Breilid H, Løvlie R, Luciano M, Gow AJ, Harris SE, Starr JM, Wibrand K, Lundervold AJ, Porteous DJ, Bramham CR, Deary IJ, Reinvang I, Steen VM. (2009). Variants in doublecortin- and calmodulin kinase like 1, a gene up-regulated by BDNF, are associated with memory and general cognitive abilities.PLoS One. Oct 21;4(10):e7534.

Klauschen F, Goldman A, Barra V, Meyer-Lindenberg A, Lundervold A. Evaluation of automated brain MR image segmentation andvolumetry methods. Human Brain Mapping 2009 Apr;30(4):1310-1327.  [PDF]


pre 2009

Andersson, M, Reinvang, I, Wehling, E, Hugdahl, K,  Lundervold, AJ. (2008).   Information processing in older adults: A dichotic listening study. Scandinavian Journal of Psychology, 49(4):299-304.

Balabanian J-P, Ystad M, Viola I, Lundervold A, Hauser H, Gröller E. Hierarchical volume visualization of brain anatomy. Proceedings of Vision, Modeling, and Visualization (VMV 2008), Konstanz, Germany, October 8-10, 2008. [PDF]

Wehling, E, Lundervold, AJ, Standnes, B, Gjerstad, L, Reinvang, I. (2007). ApoE status is related to learning and memory performance in older adults seeking assessment for memory deficits. Behavoral and Brain Functions, 31;3:57.

Lundervold A, Ystad M, Anderlik C. Brain imaging and computational neuroanatomy using high performance and GRID computing.NOTUR Meta Magazine 2007; No.1:6-9 [PDF]

Espeseth, T, Greenwood, PM, Reinvang, I, Fjell, AM, Walhovd, KB, Westlye, LT, Wehling, E. Lundervold, AJ, Rootwelt, H, Parasuraman, R. Interactive effects of APOE and CHRNA4 on attention and white matter volume in healthy middle-aged and older adults. Cognitive, Affective, and Behavioral Neuroscience,. 2006, 6(1):31-43 

 

Last updated: Arvid Lundervold 18-APR-2015

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