Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s disease
ABSTRACT: Background: Alzheimer’s disease (AD) as a disconnection syndrome disrupts both brain information sharing and memory binding functions. The extent to which these two phenotypic expressions are shared pathophysiological mechanisms remains unknown. Objective: To unveil the electrophysiologica...
- Autores:
-
Lopera Restrepo, Francisco Javier
Parra Rodríguez, Mario Alfredo
Trujillo Orrego, Natalia
Ibañez Barassi, Agustín
Mikulan, Ezequiel
Della Sala, Sergio
Manes, Facundo
Starr, John
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2017
- Institución:
- Universidad de Antioquia
- Repositorio:
- Repositorio UdeA
- Idioma:
- eng
- OAI Identifier:
- oai:bibliotecadigital.udea.edu.co:10495/42581
- Acceso en línea:
- https://hdl.handle.net/10495/42581
- Palabra clave:
- Enfermedad de Alzheimer
Alzheimer Disease
Biomarcadores
Biomarkers
Encéfalo
Brain
Electroencefalografía
Electroencephalography
Mapeo Encefálico
Brain Mapping
Difusión de la Información
Information Dissemination
Trastornos de la Memoria
Memory Disorders
Memoria a Corto Plazo
Memory, Short-Term
Persona de Mediana Edad
Middle Aged
Pruebas Neuropsicológicas
Neuropsychological Tests
Estimulación Luminosa
Photic Stimulation
https://id.nlm.nih.gov/mesh/D000544
https://id.nlm.nih.gov/mesh/D015415
https://id.nlm.nih.gov/mesh/D001921
https://id.nlm.nih.gov/mesh/D004569
https://id.nlm.nih.gov/mesh/D001931
https://id.nlm.nih.gov/mesh/D033181
https://id.nlm.nih.gov/mesh/D008569
https://id.nlm.nih.gov/mesh/D008570
https://id.nlm.nih.gov/mesh/D008875
https://id.nlm.nih.gov/mesh/D009483
https://id.nlm.nih.gov/mesh/D010775
- Rights
- openAccess
- License
- http://creativecommons.org/licenses/by-nc-nd/2.5/co/
| id |
UDEA2_197bdfae8778789915d3ab8bb23cad2d |
|---|---|
| oai_identifier_str |
oai:bibliotecadigital.udea.edu.co:10495/42581 |
| network_acronym_str |
UDEA2 |
| network_name_str |
Repositorio UdeA |
| repository_id_str |
|
| dc.title.spa.fl_str_mv |
Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s disease |
| title |
Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s disease |
| spellingShingle |
Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s disease Enfermedad de Alzheimer Alzheimer Disease Biomarcadores Biomarkers Encéfalo Brain Electroencefalografía Electroencephalography Mapeo Encefálico Brain Mapping Difusión de la Información Information Dissemination Trastornos de la Memoria Memory Disorders Memoria a Corto Plazo Memory, Short-Term Persona de Mediana Edad Middle Aged Pruebas Neuropsicológicas Neuropsychological Tests Estimulación Luminosa Photic Stimulation https://id.nlm.nih.gov/mesh/D000544 https://id.nlm.nih.gov/mesh/D015415 https://id.nlm.nih.gov/mesh/D001921 https://id.nlm.nih.gov/mesh/D004569 https://id.nlm.nih.gov/mesh/D001931 https://id.nlm.nih.gov/mesh/D033181 https://id.nlm.nih.gov/mesh/D008569 https://id.nlm.nih.gov/mesh/D008570 https://id.nlm.nih.gov/mesh/D008875 https://id.nlm.nih.gov/mesh/D009483 https://id.nlm.nih.gov/mesh/D010775 |
| title_short |
Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s disease |
| title_full |
Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s disease |
| title_fullStr |
Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s disease |
| title_full_unstemmed |
Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s disease |
| title_sort |
Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s disease |
| dc.creator.fl_str_mv |
Lopera Restrepo, Francisco Javier Parra Rodríguez, Mario Alfredo Trujillo Orrego, Natalia Ibañez Barassi, Agustín Mikulan, Ezequiel Della Sala, Sergio Manes, Facundo Starr, John |
| dc.contributor.author.none.fl_str_mv |
Lopera Restrepo, Francisco Javier Parra Rodríguez, Mario Alfredo Trujillo Orrego, Natalia Ibañez Barassi, Agustín Mikulan, Ezequiel Della Sala, Sergio Manes, Facundo Starr, John |
| dc.contributor.researchgroup.spa.fl_str_mv |
Grupo de Neurociencias de Antioquia Salud Mental |
| dc.subject.decs.none.fl_str_mv |
Enfermedad de Alzheimer Alzheimer Disease Biomarcadores Biomarkers Encéfalo Brain Electroencefalografía Electroencephalography Mapeo Encefálico Brain Mapping Difusión de la Información Information Dissemination Trastornos de la Memoria Memory Disorders Memoria a Corto Plazo Memory, Short-Term Persona de Mediana Edad Middle Aged Pruebas Neuropsicológicas Neuropsychological Tests Estimulación Luminosa Photic Stimulation |
| topic |
Enfermedad de Alzheimer Alzheimer Disease Biomarcadores Biomarkers Encéfalo Brain Electroencefalografía Electroencephalography Mapeo Encefálico Brain Mapping Difusión de la Información Information Dissemination Trastornos de la Memoria Memory Disorders Memoria a Corto Plazo Memory, Short-Term Persona de Mediana Edad Middle Aged Pruebas Neuropsicológicas Neuropsychological Tests Estimulación Luminosa Photic Stimulation https://id.nlm.nih.gov/mesh/D000544 https://id.nlm.nih.gov/mesh/D015415 https://id.nlm.nih.gov/mesh/D001921 https://id.nlm.nih.gov/mesh/D004569 https://id.nlm.nih.gov/mesh/D001931 https://id.nlm.nih.gov/mesh/D033181 https://id.nlm.nih.gov/mesh/D008569 https://id.nlm.nih.gov/mesh/D008570 https://id.nlm.nih.gov/mesh/D008875 https://id.nlm.nih.gov/mesh/D009483 https://id.nlm.nih.gov/mesh/D010775 |
| dc.subject.meshuri.none.fl_str_mv |
https://id.nlm.nih.gov/mesh/D000544 https://id.nlm.nih.gov/mesh/D015415 https://id.nlm.nih.gov/mesh/D001921 https://id.nlm.nih.gov/mesh/D004569 https://id.nlm.nih.gov/mesh/D001931 https://id.nlm.nih.gov/mesh/D033181 https://id.nlm.nih.gov/mesh/D008569 https://id.nlm.nih.gov/mesh/D008570 https://id.nlm.nih.gov/mesh/D008875 https://id.nlm.nih.gov/mesh/D009483 https://id.nlm.nih.gov/mesh/D010775 |
| description |
ABSTRACT: Background: Alzheimer’s disease (AD) as a disconnection syndrome disrupts both brain information sharing and memory binding functions. The extent to which these two phenotypic expressions are shared pathophysiological mechanisms remains unknown. Objective: To unveil the electrophysiological correlates of integrative memory impairments in AD towards new memory biomarkers for its prodromal stages. Methods: Patients with 100% risk of familial AD (FAD) and healthy controls underwent assessment with the VSTM binding test (VSTMBT) while we recorded their EEG. We applied a novel brain connectivity method (Weighted Symbolic Mutual Information) to EEG data. Results: Patients showed significant deficits during the VSTMBT. A reduction of brain connectivity was observed during resting as well as during correct VSTM binding, particularly over frontal and posterior regions. An increase of connectivity was found during VSTM binding performance over central regions. While decreased connectivity was found in cases in more advanced stages of FAD, increased brain connectivity appeared in cases in earlier stages. Such altered patterns of task-related connectivity were found in 89% of the assessed patients. Conclusions: VSTM binding in the prodromal stages of FAD are associated to altered patterns of brain connectivity thus confirming the link between integrative memory deficits and impaired brain information sharing in prodromal FAD. While significant loss of brain connectivity seems to be a feature of the advanced stages of FAD increased brain connectivity characterizes its earlier stages. These findings are discussed in the light of recent proposals about the earliest pathophysiological mechanisms of AD and their clinical expression. |
| publishDate |
2017 |
| dc.date.issued.none.fl_str_mv |
2017 |
| dc.date.accessioned.none.fl_str_mv |
2024-10-02T16:07:30Z |
| dc.date.available.none.fl_str_mv |
2024-10-02T16:07:30Z |
| dc.type.spa.fl_str_mv |
Artículo de investigación |
| dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
| dc.type.redcol.spa.fl_str_mv |
https://purl.org/redcol/resource_type/ART |
| dc.type.coarversion.spa.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/article |
| dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| format |
http://purl.org/coar/resource_type/c_2df8fbb1 |
| status_str |
publishedVersion |
| dc.identifier.citation.spa.fl_str_mv |
Parra MA, Mikulan E, Trujillo N, Sala SD, Lopera F, Manes F, Starr J, Ibanez A. Brain Information Sharing During Visual Short-Term Memory Binding Yields a Memory Biomarker for Familial Alzheimer's Disease. Curr Alzheimer Res. 2017;14(12):1335-1347. doi: 10.2174/1567205014666170614163316. |
| dc.identifier.issn.none.fl_str_mv |
1567-2050 |
| dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/10495/42581 |
| dc.identifier.doi.none.fl_str_mv |
10.2174/1567205014666170614163316 |
| dc.identifier.eissn.none.fl_str_mv |
1875-5828 |
| identifier_str_mv |
Parra MA, Mikulan E, Trujillo N, Sala SD, Lopera F, Manes F, Starr J, Ibanez A. Brain Information Sharing During Visual Short-Term Memory Binding Yields a Memory Biomarker for Familial Alzheimer's Disease. Curr Alzheimer Res. 2017;14(12):1335-1347. doi: 10.2174/1567205014666170614163316. 1567-2050 10.2174/1567205014666170614163316 1875-5828 |
| url |
https://hdl.handle.net/10495/42581 |
| dc.language.iso.spa.fl_str_mv |
eng |
| language |
eng |
| dc.relation.ispartofjournalabbrev.spa.fl_str_mv |
Curr. Alzheimer Res. |
| dc.relation.citationendpage.spa.fl_str_mv |
1381 páginas |
| dc.relation.citationissue.spa.fl_str_mv |
12 |
| dc.relation.citationstartpage.spa.fl_str_mv |
1335 páginas |
| dc.relation.citationvolume.spa.fl_str_mv |
14 |
| dc.relation.ispartofjournal.spa.fl_str_mv |
Current Alzheimer Research |
| dc.rights.uri.*.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/2.5/co/ |
| dc.rights.uri.spa.fl_str_mv |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.rights.accessrights.spa.fl_str_mv |
info:eu-repo/semantics/openAccess |
| dc.rights.coar.spa.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
| rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-nd/2.5/co/ https://creativecommons.org/licenses/by-nc-nd/4.0/ http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.extent.spa.fl_str_mv |
46 páginas |
| dc.format.mimetype.spa.fl_str_mv |
application/pdf |
| dc.publisher.spa.fl_str_mv |
Bentham Science Publishers |
| dc.publisher.place.spa.fl_str_mv |
Sharjah, Emiratos Árabes Unidos |
| institution |
Universidad de Antioquia |
| bitstream.url.fl_str_mv |
https://bibliotecadigital.udea.edu.co/bitstreams/a2627f71-a709-4ffc-b554-89f83cac8314/download https://bibliotecadigital.udea.edu.co/bitstreams/3d432620-5bd9-4888-b15c-2e04e192df97/download https://bibliotecadigital.udea.edu.co/bitstreams/e2c28b22-1211-4d06-8dea-8429e653e60f/download https://bibliotecadigital.udea.edu.co/bitstreams/4c427a34-28fe-4a03-b347-d23dbd4ae088/download https://bibliotecadigital.udea.edu.co/bitstreams/e5c54094-2d8b-4df5-83d3-a479a7c8c95c/download |
| bitstream.checksum.fl_str_mv |
b88b088d9957e670ce3b3fbe2eedbc13 8a4605be74aa9ea9d79846c1fba20a33 976fc4974938c07caef2de633c27b8a6 65e1f6480bb7de814f25777014559871 a20e3ee764548471e7f7312ae7c31612 |
| bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
| repository.name.fl_str_mv |
Repositorio Institucional de la Universidad de Antioquia |
| repository.mail.fl_str_mv |
aplicacionbibliotecadigitalbiblioteca@udea.edu.co |
| _version_ |
1851052573183705088 |
| spelling |
Lopera Restrepo, Francisco JavierParra Rodríguez, Mario AlfredoTrujillo Orrego, NataliaIbañez Barassi, AgustínMikulan, EzequielDella Sala, SergioManes, FacundoStarr, JohnGrupo de Neurociencias de AntioquiaSalud Mental2024-10-02T16:07:30Z2024-10-02T16:07:30Z2017Parra MA, Mikulan E, Trujillo N, Sala SD, Lopera F, Manes F, Starr J, Ibanez A. Brain Information Sharing During Visual Short-Term Memory Binding Yields a Memory Biomarker for Familial Alzheimer's Disease. Curr Alzheimer Res. 2017;14(12):1335-1347. doi: 10.2174/1567205014666170614163316.1567-2050https://hdl.handle.net/10495/4258110.2174/15672050146661706141633161875-5828ABSTRACT: Background: Alzheimer’s disease (AD) as a disconnection syndrome disrupts both brain information sharing and memory binding functions. The extent to which these two phenotypic expressions are shared pathophysiological mechanisms remains unknown. Objective: To unveil the electrophysiological correlates of integrative memory impairments in AD towards new memory biomarkers for its prodromal stages. Methods: Patients with 100% risk of familial AD (FAD) and healthy controls underwent assessment with the VSTM binding test (VSTMBT) while we recorded their EEG. We applied a novel brain connectivity method (Weighted Symbolic Mutual Information) to EEG data. Results: Patients showed significant deficits during the VSTMBT. A reduction of brain connectivity was observed during resting as well as during correct VSTM binding, particularly over frontal and posterior regions. An increase of connectivity was found during VSTM binding performance over central regions. While decreased connectivity was found in cases in more advanced stages of FAD, increased brain connectivity appeared in cases in earlier stages. Such altered patterns of task-related connectivity were found in 89% of the assessed patients. Conclusions: VSTM binding in the prodromal stages of FAD are associated to altered patterns of brain connectivity thus confirming the link between integrative memory deficits and impaired brain information sharing in prodromal FAD. While significant loss of brain connectivity seems to be a feature of the advanced stages of FAD increased brain connectivity characterizes its earlier stages. These findings are discussed in the light of recent proposals about the earliest pathophysiological mechanisms of AD and their clinical expression.Universidad de Antioquia. Vicerrectoría de investigación. Comité para el Desarrollo de la Investigación - CODIAlzheimer's SocietyCOL0010744COL001598346 páginasapplication/pdfengBentham Science PublishersSharjah, Emiratos Árabes Unidoshttp://creativecommons.org/licenses/by-nc-nd/2.5/co/https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Brain information sharing during visual short-term memory binding yields a memory biomarker for familial Alzheimer’s diseaseArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionEnfermedad de AlzheimerAlzheimer DiseaseBiomarcadoresBiomarkersEncéfaloBrainElectroencefalografíaElectroencephalographyMapeo EncefálicoBrain MappingDifusión de la InformaciónInformation DisseminationTrastornos de la MemoriaMemory DisordersMemoria a Corto PlazoMemory, Short-TermPersona de Mediana EdadMiddle AgedPruebas NeuropsicológicasNeuropsychological TestsEstimulación LuminosaPhotic Stimulationhttps://id.nlm.nih.gov/mesh/D000544https://id.nlm.nih.gov/mesh/D015415https://id.nlm.nih.gov/mesh/D001921https://id.nlm.nih.gov/mesh/D004569https://id.nlm.nih.gov/mesh/D001931https://id.nlm.nih.gov/mesh/D033181https://id.nlm.nih.gov/mesh/D008569https://id.nlm.nih.gov/mesh/D008570https://id.nlm.nih.gov/mesh/D008875https://id.nlm.nih.gov/mesh/D009483https://id.nlm.nih.gov/mesh/D010775Curr. Alzheimer Res.1381 páginas121335 páginas14Current Alzheimer ResearchCODI Programa de Sostenibilidad 2015-2016AS-R42303 and AS-SF-14-008RoR:03bp5hc83RoR:0472gwq90PublicationCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8823https://bibliotecadigital.udea.edu.co/bitstreams/a2627f71-a709-4ffc-b554-89f83cac8314/downloadb88b088d9957e670ce3b3fbe2eedbc13MD52falseAnonymousREADLICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstreams/3d432620-5bd9-4888-b15c-2e04e192df97/download8a4605be74aa9ea9d79846c1fba20a33MD53falseAnonymousREADORIGINALTrujilloNatalia_2017_Brain_Information.pdfTrujilloNatalia_2017_Brain_Information.pdfArtículo de investigaciónapplication/pdf1669107https://bibliotecadigital.udea.edu.co/bitstreams/e2c28b22-1211-4d06-8dea-8429e653e60f/download976fc4974938c07caef2de633c27b8a6MD51trueAnonymousREADTEXTTrujilloNatalia_2017_Brain_Information.pdf.txtTrujilloNatalia_2017_Brain_Information.pdf.txtExtracted texttext/plain66973https://bibliotecadigital.udea.edu.co/bitstreams/4c427a34-28fe-4a03-b347-d23dbd4ae088/download65e1f6480bb7de814f25777014559871MD54falseAnonymousREADTHUMBNAILTrujilloNatalia_2017_Brain_Information.pdf.jpgTrujilloNatalia_2017_Brain_Information.pdf.jpgGenerated Thumbnailimage/jpeg11892https://bibliotecadigital.udea.edu.co/bitstreams/e5c54094-2d8b-4df5-83d3-a479a7c8c95c/downloada20e3ee764548471e7f7312ae7c31612MD55falseAnonymousREAD10495/42581oai:bibliotecadigital.udea.edu.co:10495/425812025-03-27 00:30:10.745http://creativecommons.org/licenses/by-nc-nd/2.5/co/open.accesshttps://bibliotecadigital.udea.edu.coRepositorio Institucional de la Universidad de Antioquiaaplicacionbibliotecadigitalbiblioteca@udea.edu.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 |
