Dysfunction of the hypothalamic-pituitary adrenal axis and its influence on aging: the role of the hypothalamus.

As part of the hypothalamic-pituitary adrenal (HPA) axis, the hypothalamus exerts pivotal influence on metabolic and endocrine homeostasis. With age, these processes are subject to considerable change, resulting in increased prevalence of physical disability and cardiac disorders. Yet, research on the aging human hypothalamus is lacking. To assess detailed hypothalamic microstructure in middle adulthood, 39 healthy participants (35-65 years) underwent comprehensive structural magnetic resonance imaging. In addition, we studied HPA axis dysfunction proxied by hair cortisol and waist circumference as potential risk factors for hypothalamic alterations. We provide first evidence of regionally different hypothalamic microstructure, with age effects in its anterior-superior subunit, a critical area for HPA axis regulation. Further, we report that waist circumference was related to increased free water and decreased iron content in this region. In age, hair cortisol was additionally associated with free water content, such that older participants with higher cortisol levels were more vulnerable to free water content increase than younger participants. Overall, our results suggest no general age-related decline in hypothalamic microstructure. Instead, older individuals could be more susceptible to risk factors of hypothalamic decline especially in the anterior-superior subregion, including HPA axis dysfunction, indicating the importance of endocrine and stress management in age.

Hypothalamic microstructure and function are related to body mass, but not mental or cognitive abilities across the adult lifespan.

Physical, mental, and cognitive resources are essential for healthy aging. Aging impacts on the structural integrity of various brain regions, including the hippocampus. Even though recent rodent studies hint towards a critical role of the hypothalamus, there is limited evidence on functional consequences of age-related changes of this region in humans. Given its central role in metabolic regulation and affective processing and its connections to the hippocampus, it is plausible that hypothalamic integrity and connectivity are associated with functional age-related decline. We used data of n = 369 participants (18-88 years) from the Cambridge Centre for Ageing and Neuroscience repository to determine functional impacts of potential changes in hypothalamic microstructure across the lifespan. First, we identified age-related changes in microstructure as a function of physical, mental, and cognitive health and compared those findings to changes in hippocampal microstructure. Second, we investigated the relationship of hypothalamic microstructure and resting-state functional connectivity and related those changes to age as well as physical health. Our results showed that hypothalamic microstructure is not affected by depressive symptoms (mental health), cognitive performance (cognitive health), and comparatively stable across the lifespan, but affected by body mass (physical health). Furthermore, body mass changes connectivity to limbic regions including the hippocampus, amygdala, and nucleus accumbens, suggesting functional alterations in the metabolic and reward systems. Our results demonstrate that hypothalamic structure and function are affected by body mass, focused on neural density and dispersion, but not inflammation. Still, observed effect sizes were small, encouraging detailed investigations of individual hypothalamic subunits.

Heart rate and heart rate variability in patients with chronic inflammatory joint disease: the role of pain duration and the insular cortex.

BACKGROUND: Chronic inflammatory joint diseases (CIJD) have been linked to increased cardiovascular morbidity and mortality. A decisive reason could be a dysregulation of the autonomic nervous system, which is responsible for the control of cardiovascular function. So far, the cause of changes in autonomic nervous system functions remains elusive. In this study, we investigate the role of chronic pain and the insular cortex in autonomic control of cardiac functioning in patients with CIJD. METHODS: We studied the autonomic nervous system through the assessment of heart rate and heart rate variability (HRV) at rest and under cognitive stimulation. Furthermore, we investigated insular cortex volume by performing surface-based brain morphometry with FreeSurfer. For this study, 47 participants were recruited, 22 individual age- and sex-matched pairs for the magnetic resonance imaging analyses and 14 for the HRV analyses. All available patients' data were used for analysis. RESULTS: Pain duration was negatively correlated with the resting heart rate in patients with chronic inflammatory joint diseases (n = 20). In a multiple linear regression model including only CIJD patients with heart rate at rest as a dependent variable, we found a significant positive relationship between heart rate at rest and the volume of the left insular cortex and a significant negative relationship between heart rate at rest and the volume of the right insular cortex. However, we found no significant differences in HRV parameters or insular cortex volumes between both groups. CONCLUSIONS: In this study we provide evidence to suggest insular cortex involvement in the process of ANS changes due to chronic pain in CIJD patients. The study was preregistered with the German Clinical Trials Register ( https://www.drks.de ; DRKS00012791; date of registration: 28 July 2017).

Quantitative magnetic resonance imaging for segmentation and white matter extraction of the hypothalamus.

Since the hypothalamus is involved in many neuroendocrine, metabolic, and affective disorders, detailed hypothalamic imaging has become of major interest to better characterize disease-induced tissue damages and abnormalities. Still, image contrast of conventional anatomical magnetic resonance imaging lacks morphological detail, thus complicating complete and precise segmentation of the hypothalamus. The hypothalamus' position lateral to the third ventricle and close proximity to white matter tracts including the optic tract, fornix, and mammillothalamic tract display one of the remaining shortcomings of hypothalamic segmentation, as reliable exclusion of white matter is not yet possible. Recent studies found that quantitative magnetic resonance imaging (qMRI), a method to create maps of different standardized tissue contents, improved segmentation of cortical and subcortical brain regions. So far, this has not been tested for the hypothalamus. Therefore, in this study, we investigated the usability of qMRI and diffusion MRI for the purpose of detailed and reproducible manual segmentation of the hypothalamus and data-driven white matter extraction and compared our results to recent state-of-the-art segmentations. Our results show that qMRI presents good contrast for delineation of the hypothalamus and white matter, and that the properties of these images differ between subunits, such that they can be used to reliably exclude white matter from hypothalamic tissue. We propose that qMRI poses a useful addition to detailed hypothalamic segmentation and volumetry.

Automated diffusion-based parcellation of the hypothalamus reveals subunit-specific associations with obesity.

The hypothalamus is a small, yet highly versatile structure mainly involved in bodily functions such as control of food intake and endocrine activity. Functional anatomy of different hypothalamic areas is mainly investigated using structural MRI, validated by ex-vivo histological studies. Based on diffusion-weighted imaging (DWI), recent automated clustering methods provide robust tools for parcellation. Using data of 100 healthy adults provided by the Human Connectome Project Database, we applied DWI-based automated clustering to the hypothalamus and related microstructural properties in these hypothalamic compartments to obesity. Our results suggest that the hypothalamus can be reliably partitioned into four clusters in each hemisphere using diffusion-based parcellation. These correspond to an anterior-superior, anterior-inferior, intermediate, and posterior cluster. Obesity was predicted by mean diffusivity of the anterior-superior cluster, suggesting altered inhibition of food intake. The proposed method provides an automated hypothalamic parcellation technique based on DWI data to explore anatomy and function of hypothalamic subunits in vivo in humans.

Corrigendum: The Influence of Chronic Pain and Cognitive Function on Spatial-Numerical Processing.

[This corrects the article DOI: 10.3389/fnbeh.2018.00165.].

The Influence of Chronic Pain and Cognitive Function on Spatial-Numerical Processing.

Chronic pain (CP) is linked to changes in cognitive function. However, little is known about its influence on number sense, despite the fact that intact numerical-spatial processing is a prerequisite for valid scale-based pain assessments. This study aimed to elucidate whether number sense is changed in CP, to determine if changes have an impact on pain assessments using pain rating scales and what patient factors might contribute. N = 42 CP patients and n = 42 matched controls were analyzed (age range: 33-68 years). Numerical-spatial abilities were investigated by using number line tasks, where participants either estimated the position of a given number (position marking) or the value of a predefined mark (number naming). Pain intensity was assessed using numerical rating (NRS), verbal rating (VRS), and visual analog (VAS) scales. Additional measures included attention and working memory, verbal intelligence, medication and depression. Results revealed that in number naming, patients deviated more from expected (correct) responses than controls, and that VAS scores were significantly higher than both NRS and VRS and correlated with deviations in position making. Changes in number naming were predicted by pain intensity, sex and IQ but not by attention, memory or opioid medication. This article presents new insight on which cognitive mechanisms are influenced by CP with the focus on numerical spatial abilities. It could therefore provide useful knowledge in developing new pain assessment tools specifically for patients suffering from CP.

Exploring Musical Activities and Their Relationship to Emotional Well-Being in Elderly People across Europe: A Study Protocol.

Music is a powerful, pleasurable stimulus that can induce positive feelings and can therefore be used for emotional self-regulation. Musical activities such as listening to music, playing an instrument, singing or dancing are also an important source for social contact, promoting interaction and the sense of belonging with others. Recent evidence has suggested that after retirement, other functions of music, such as self-conceptual processing related to autobiographical memories, become more salient. However, few studies have addressed the meaningfulness of music in the elderly. This study aims to investigate elderly people's habits and preferences related to music, study the role music plays in their everyday life, and explore the relationship between musical activities and emotional well-being across different countries of Europe. A survey will be administered to elderly people over the age of 65 from five different European countries (Bosnia and Herzegovina, Czechia, Germany, Ireland, and UK) and to a control group. Participants in both groups will be asked about basic sociodemographic information, habits and preferences in their participation in musical activities and emotional well-being. Overall, the aim of this study is to gain a deeper understanding of the role of music in the elderly from a psychological perspective. This advanced knowledge could help to develop therapeutic applications, such as musical recreational programs for healthy older people or elderly in residential care, which are better able to meet their emotional and social needs.