Stress: Putting the Brain Back Into Medicine

Throughout the life course stress plays a major role in health and disease. Although it has long been known that the brain orchestrates the many ways that the body responds to these experiences, a gap exists between health care providers who focus from the head up and those who focus on the head down

Individual differences in the neuropsychopathology of addiction.

Drug addiction or substance-use disorder is a chronically relapsing disorder that progresses through binge/intoxication, withdrawal/negative affect and preoccupation/anticipation stages. These stages represent diverse neurobiological mechanisms that are differentially involved in the transition from recreational to compulsive drug use and from positive to negative reinforcement. The progression from recreational to compulsive substance use is associated with downregulation of the brain reward systems and upregulation of the brain stress systems. Individual differences in the neurobiological systems that underlie the processing of reward, incentive salience, habits, stress, pain, and executive function may explain (i) the vulnerability to substance-use disorder; (ii) the diversity of emotional, motivational, and cognitive profiles of individuals with substance-use disorders; and (iii) heterogeneous responses to cognitive and pharmacological treatments. Characterization of the neuropsychological mechanisms that underlie individual differences in addiction-like behaviors is the key to understanding the mechanisms of addiction and development of personalized pharmacotherapy

Robot regulatory behaviour based on fundamental homeostatic and allostatic principles

Animals in their ecological context behave not only in response to external events, such as opportunities and threats but also according to their internal needs. As a result, the survival of the organism is achieved through regulatory behaviour. Although homeostatic and allostatic principles play an important role in such behaviour, how an animal's brain implements these principles is not fully understood yet. In this paper, we propose a new model of regulatory behaviour inspired by the functioning of the medial Reticular Formation (mRF). This structure is spread throughout the brainstem and has shown generalized Central Nervous System (CNS) arousal control and fundamental action-selection properties. We propose that a model based on the mRF allows the flexibility needed to be implemented in diverse domains, while it would allow integration of other components such as place cells to enrich the agent's performance. Such a model will be implemented in a mobile robot that will navigate replicating the behaviour of the sand-diving lizard, a benchmark for regulatory behaviour. © 2020 Elsevier B.V.. All rights reserved

Heart Rate Variability and Exceptional Longevity

Centenarians are the paradigm of human extreme longevity and healthy aging, because they have postponed, if not avoided, mayor age-related diseases. The purpose of this study was to investigate potential differences in resting heart rate variability (HRV) between young adults, octogenarians, and centenarians and assess whether HRV variables are predictors of all-cause mortality in centenarians. To this end, three groups of participants: young adults (N = 20; 20.6 ± 2.3 years), octogenarians (N = 18; 84.1 ± 2.6 years), and centenarians (N = 17; 101.9 ± 1.9 years) were monitored for 15 min at rest (seated, without moving or talking) to measure RR intervals, from which HRV was evaluated. Our results showed a clear decrease with age in the main parasympathetic HRV variables, as well as in the standard deviation (SD) of the RR series [SD of normal-to-normal interval (SDNN)] and in low frequency (LF) heart rate (HR) oscillations, although differences between octogenarians and centenarians did not reach statistical significance. In 14 centenarians followed until death, only SDNN showed significant correlation (¿ = 0.536; p = 0.048) with survival prognosis. Additionally, SDNN <19 ms was associated with early mortality (=1 year) in centenarians (Hazard Ratio = 5.72). In conclusion, HRV indices reflecting parasympathetic outflow as well as SDNN and LF all present an age-related reduction, which could be representative of a natural exhaustion of allostatic systems related to age. Moreover, low SDNN values (<19 ms) could be associated with early mortality in centenarians. HRV seems to play a role in exceptional longevity, which could be accounted for by centenarians’ exposome

The Centrality of Variability: How society shapes patterns of aging

Increasing variability is a hallmark of aging populations. Although demographic trends are often described in terms of average experiences, in this paper we argue that variability in the health experiences of older men and women is key to understanding aging. The variations in outcomes among older people are not merely nuisances obscuring the more salient averages and trends. The deviations from the mean are a central part of the story: the patterning of these variations reveals factors that influence health for everyone and indicates what sort of advances in healthy aging might be possible under optimal circumstances.Aging, demography

Neuroendocrine Mechanisms Mediating Pheromonal Modulation of Behavior in Terrestrial Salamanders

Pheromones are chemosensory cues released by an individual to cause a behavioral or physiological change in a conspecific. These changes can range from increasing a female\u27s receptivity to altering hormone secretions in the body. The red-legged salamander (Plethodon shermani) is an emerging non-mammalian model for understanding the evolution of chemical communication due to their well-characterized pheromones. Plethodontid salamanders secrete pheromones from their submandibular gland, called mental gland pheromones. Previous studies showed that mental gland pheromones increased receptivity in females during courtship and also increased corticosterone (CORT) concentrations in males. CORT is a metabolic hormone that mediates vertebrate stress responses. To further understand the neuroendocrine mechanisms involved in behavioral and physiological responses to pheromones, I conducted several experiments. First, I investigated whether pheromones altered levels of two neuromodulators in the brain, gonadotropin-releasing hormone (GnRH) and arginine vasotocin (AVT) in P. shermani. GnRH is both a neuromodulator and hormone, and has strong effects on reproductive behavior. Additionally, AVT has broad behavioral effects in vertebrates, particularly in newts. I found that application of mental gland pheromones altered the number of GnRH-immunoreactive neurons, but had no effect on the number of AVT-immunoreactive neurons. Second, I examined the effects of AVT and AVP antagonist on courtship and mating in dusky salamanders (Desmognathus spp.). There was no effect of AVT or antagonist on reproductive behaviors in dusky salamanders. Finally, I investigated the role of increased CORT concentrations in male P. shermani. I first validated a non-invasive method to transdermally deliver CORT through a dermal patch. I then used dermal patches to exogenously elevate plasma CORT and examine the effects of CORT on behavior (activity and chemoinvestigation) and metabolism. CORT had no effect on behavior, but increased metabolic rates in male red-legged salamanders. Together these studies provide insight into the mechanisms by which pheromones work to alter behaviors and physiological functions in vertebrates