Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden
Mite Mijalkov
Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden
Anna Canal-Garcia
Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden
Yu-Wei Chang
Department of Physics, Goteborg University, Goteborg, Sweden
Emiliano Gomez-Ruiz
Department of Physics, Goteborg University, Goteborg, Sweden
Blanca Zufiria Gerboles
Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden
Miia Kivipelto
Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; University of Eastern Finland, Kuopio, Finland
Per Svenningsson
University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
Henrik Zetterberg
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom; UK Dementia Research Institute at UCL, London, United Kingdom; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China; Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, United States
Department of Physics, Goteborg University, Goteborg, Sweden
Matthew Betts
Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University Magdeburg, Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Otto-von-Guericke University Magdeburg, Magdeburg, Germany; Center for Behavioral Brain Sciences, University of Magdeburg, Magdeburg, Germany
Heidi IL Jacobs
Maastricht University, Maastricht, Netherlands; Massachusetts General Hospital, Boston, United States
Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden
The locus coeruleus (LC) is an important noradrenergic nucleus that has recently attracted a lot of attention because of its emerging role in cognitive and psychiatric disorders. Although previous histological studies have shown that the LC has heterogeneous connections and cellular features, no studies have yet assessed its functional topography in vivo, how this heterogeneity changes over aging, and whether it is associated with cognition and mood. Here, we employ a gradient-based approach to characterize the functional heterogeneity in the organization of the LC over aging using 3T resting-state fMRI in a population-based cohort aged from 18 to 88 years of age (Cambridge Centre for Ageing and Neuroscience cohort, n=618). We show that the LC exhibits a rostro-caudal functional gradient along its longitudinal axis, which was replicated in an independent dataset (Human Connectome Project [HCP] 7T dataset, n=184). Although the main rostro-caudal direction of this gradient was consistent across age groups, its spatial features varied with increasing age, emotional memory, and emotion regulation. More specifically, a loss of rostral-like connectivity, more clustered functional topography, and greater asymmetry between right and left LC gradients was associated with higher age and worse behavioral performance. Furthermore, participants with higher-than-normal Hospital Anxiety and Depression Scale (HADS) ratings exhibited alterations in the gradient as well, which manifested in greater asymmetry. These results provide an in vivo account of how the functional topography of the LC changes over aging, and imply that spatial features of this organization are relevant markers of LC-related behavioral measures and psychopathology.
