Structural and functional connectivity in the aging brain: cognitive consequences and genetic modifiers

Hovedmålet med prosjektet er å karakterisere endringer i hjernens strukturelle og funksjonelle nettverk gjennom normal utvikling og aldring og i alvorlige psykiske lidelser som schizofreni og bipolar lidelse, identifisere genetiske assosiasjoner til disse endringene, samt undersøke i hvilken grad og hvordan forandringer fører til endringer i kognitive funksjoner som oppmerksomhet, hukommelse og problemløsning. Resultatene gir informasjon om normal hjernefunksjon og utvklings- og aldringsendringer hos friske personer, og vil gi økt kunnskap om patologiske prosesser i en rekke hjernelidelser, inkludert nevrodegenerative (f.eks Alzheimer's sykdom) og psykiatriske lidelser (schizofreni, bipolar lidelse, angstlidelser, depresjon). Metodetilfanget inkluderer avansert hjerneavbildning, genetikk og kognitive tester i en rekke datasett. Prosjektet er et samarbeidsprosjekt med flere nasjonale og internasjonale partnere, og foreløpige resultater har blitt publisert i en rekke internasjonale fagfellevurderte tidsskrifter.

The human brain undergoes significant changes throughout life. The rapidly aging world population and associated increase in number of people suffering from age-related cognitive impairments and dementia require large research efforts investigating the ca uses and consequences of brain aging. A fundamental task of the neurosciences is to track and understand the mechanisms responsible for structural connectivity changes in aging, the functional and cognitive consequences and its relations to disease. What are the functional and cognitive consequences of structural breakdown in aging? To what degree are differences in structural connectivity caused by environmental factors and to what degree are they controlled by genetic variation? Which factors modulate s ex differences? Are the same factors underlying changes in brain connectivity also controlling cognitive functions and paving the pathways toward cognitive deterioration and disease? The present post-doctoral research proposal aims at addressing these ess ential questions by utilizing two recent and advanced magnetic resonance imaging (MRI) techniques; diffusion tensor imaging (DTI) and resting state functional MRI (rFMRI) as in vivo brain imaging biomarkers for structural and functional connectivity in th e aging brain in a large longitudinal sample (n > 1300). Based on a hierarchic model of brain connectivity, we propose that the structural alterations in the aging brain impose functional disruptions on the level of large-scale brain neurocircuitry with a ssociated and specific cognitive consequences. The project provides new knowledge about changes in connectivity and cognition in the aging brain, the relationships to specific cognitive functions and how these associations are mediated by genetic factors . The results will have consequences for our understanding of brain and cognitive aging, as well as the potential for environmental interventions.