Age-related differences in the functional topography of the locus coeruleus and their implications for cognitive and affective functions published on eLife

Average functional gradients of the locus coeruleus in the CamCAN 3T dataset. (Image from the publication.)
Age-related differences in the functional topography of the locus coeruleus and their implications for cognitive and affective functions
Dániel Veréb, Mite Mijalkov, Anna Canal-Garcia, Yu-Wei Chang, Emiliano Gomez-Ruiz, Blanca Zufiria Gerboles, Miia Kivipelto, Per Svenningsson, Henrik Zetterberg, Giovanni Volpe, Matthew Betts, Heidi IL Jacobs, Joana B Pereira
eLife 12, RP87188 (2023)
doi: 10.7554/eLife.87188.3

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.

CT-based volumetric measures obtained through deep learning: Association with biomarkers of neurodegeneration published on Alzheimer’s & Dementia

Imaging-based volumetric measures. (Image by the Authors of the manuscript.)
CT-based volumetric measures obtained through deep learning: Association with biomarkers of neurodegeneration
Meera Srikrishna, Nicholas J. Ashton, Alexis Moscoso, Joana B. Pereira, Rolf A. Heckemann, Danielle van Westen, Giovanni Volpe, Joel Simrén, Anna Zettergren, Silke Kern, Lars-Olof Wahlund, Bibek Gyanwali, Saima Hilal, Joyce Chong Ruifen, Henrik Zetterberg, Kaj Blennow, Eric Westman, Christopher Chen, Ingmar Skoog, Michael Schöll
Alzheimer’s & Dementia 20, 629–640 (2024)
arXiv: 2401.06260
doi: 10.1002/alz.13445

INTRODUCTION
Cranial computed tomography (CT) is an affordable and widely available imaging modality that is used to assess structural abnormalities, but not to quantify neurodegeneration. Previously we developed a deep-learning–based model that produced accurate and robust cranial CT tissue classification.

MATERIALS AND METHODS
We analyzed 917 CT and 744 magnetic resonance (MR) scans from the Gothenburg H70 Birth Cohort, and 204 CT and 241 MR scans from participants of the Memory Clinic Cohort, Singapore. We tested associations between six CT-based volumetric measures (CTVMs) and existing clinical diagnoses, fluid and imaging biomarkers, and measures of cognition.

RESULTS
CTVMs differentiated cognitively healthy individuals from dementia and prodromal dementia patients with high accuracy levels comparable to MR-based measures. CTVMs were significantly associated with measures of cognition and biochemical markers of neurodegeneration.

DISCUSSION
These findings suggest the potential future use of CT-based volumetric measures as an informative first-line examination tool for neurodegenerative disease diagnostics after further validation.