Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Solna, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden; Aging Research Center, Karolinska Institutet and Stockholm University, Solna, Sweden
Robin Pedersen
Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden; Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden; Department of Medical and Translational Biology, Umeå University, Umeå, Sweden
Farshad Falahati
Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Solna, Sweden; Aging Research Center, Karolinska Institutet and Stockholm University, Solna, Sweden
Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden; Department of Radiation Sciences, Umeå University, Umeå, Sweden
Filip Grill
Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands
Micael Andersson
Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden; Department of Medical and Translational Biology, Umeå University, Umeå, Sweden
Saana M Korkki
Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Solna, Sweden; Aging Research Center, Karolinska Institutet and Stockholm University, Solna, Sweden
Lars Bäckman
Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Solna, Sweden; Aging Research Center, Karolinska Institutet and Stockholm University, Solna, Sweden
Andrew Zalesky
Department of Biomedical Engineering, the University of Melbourne, Melbourne, Australia; Department of Psychiatry, the University of Melbourne, Melbourne, Australia
Anna Rieckmann
Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden; Department of Medical and Translational Biology, Umeå University, Umeå, Sweden; Department of Radiation Sciences, Umeå University, Umeå, Sweden; Department of Psychology, University of the Bundeswehr Munich, Munich, Germany
Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden; Department of Medical and Translational Biology, Umeå University, Umeå, Sweden
Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Solna, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden; Aging Research Center, Karolinska Institutet and Stockholm University, Solna, Sweden; Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden; Department of Medical and Translational Biology, Umeå University, Umeå, Sweden
The hippocampus is a complex structure critically involved in numerous behavior-regulating systems. In young adults, multiple overlapping spatial modes along its longitudinal and transverse axes describe the organization of its functional integration with neocortex, extending the traditional framework emphasizing functional differences between sharply segregated hippocampal subregions. Yet, it remains unknown whether these modes (i.e. gradients) persist across the adult human lifespan, and relate to memory and molecular markers associated with brain function and cognition. In two independent samples, we demonstrate that the principal anteroposterior and second-order, mid-to-anterior/posterior hippocampal modes of neocortical functional connectivity, representing distinct dimensions of macroscale cortical organization, manifest across the adult lifespan. Specifically, individual differences in topography of the second-order gradient predicted episodic memory and mirrored dopamine D1 receptor distribution, capturing shared functional and molecular organization. Older age was associated with less distinct transitions along gradients (i.e. increased functional homogeneity). Importantly, a youth-like gradient profile predicted preserved episodic memory – emphasizing age-related gradient dedifferentiation as a marker of cognitive decline. Our results underscore a critical role of mapping multidimensional hippocampal organization in understanding the neural circuits that support memory across the adult lifespan.
