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

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.

Age-related differences in the functional topography of the locus coeruleus: implications for cognitive and affective functions.

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 old (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 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 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.

Unsupervised domain adaptation for the segmentation of breast tissue in mammography images.

BACKGROUND AND OBJECTIVE: Breast density refers to the proportion of glandular and fatty tissue in the breast and is recognized as a useful factor assessing breast cancer risk. Moreover, the segmentation of the high-density glandular tissue from mammograms can assist medical professionals visualizing and localizing areas that may require additional attention. Developing robust methods to segment breast tissues is challenging due to the variations in mammographic acquisition systems and protocols. Deep learning methods are effective in medical image segmentation but they often require large quantities of labelled data. Unsupervised domain adaptation is an area of research that employs unlabelled data to improve model performance on variations of samples derived from different sources. METHODS: First, a U-Net architecture was used to perform segmentation of the fatty and glandular tissues with labelled data from a single acquisition device. Then, adversarial-based unsupervised domain adaptation methods were used to incorporate single unlabelled target domains, consisting of images from a different machine, into the training. Finally, the domain adaptation model was extended to include multiple unlabelled target domains by combining a reconstruction task with adversarial training. RESULTS: The adversarial training was found to improve the generalization of the initial model on new domain data, demonstrating clearly improved segmentation of the breast tissues. For training with multiple unlabelled domains, combining a reconstruction task with adversarial training improved the stability of the training and yielded adequate segmentation results across all domains with a single model. CONCLUSIONS: Results demonstrated the potential for adversarial-based domain adaptation with U-Net architectures for segmentation of breast tissue in mammograms coming from several devices and demonstrated that domain-adapted models could achieve a similar agreement with manual segmentations. It has also been found that combining adversarial and reconstruction-based methods can provide a simple and effective solution for training with multiple unlabelled target domains.