title: Allostasis: a model of predictive regulation.
abstract: The premise of the standard regulatory model, "homeostasis", is flawed: the goal of regulation is not to preserve constancy of the internal milieu. Rather, it is to continually adjust the milieu to promote survival and reproduction. Regulatory mechanisms need to be efficient, but homeostasis (error-correction by feedback) is inherently inefficient. Thus, although feedbacks are certainly ubiquitous, they could not possibly serve as the primary regulatory mechanism. A newer model, "allostasis", proposes that efficient regulation requires anticipating needs and preparing to satisfy them before they arise. The advantages: (i) errors are reduced in magnitude and frequency; (ii) response capacities of different components are matched -- to prevent bottlenecks and reduce safety factors; (iii) resources are shared between systems to minimize reserve capacities; (iv) errors are remembered and used to reduce future errors. This regulatory strategy requires a dedicated organ, the brain. The brain tracks multitudinous variables and integrates their values with prior knowledge to predict needs and set priorities. The brain coordinates effectors to mobilize resources from modest bodily stores and enforces a system of flexible trade-offs: from each organ according to its ability, to each organ according to its need. The brain also helps regulate the internal milieu by governing anticipatory behavior. Thus, an animal conserves energy by moving to a warmer place - before it cools, and it conserves salt and water by moving to a cooler one before it sweats. The behavioral strategy requires continuously updating a set of specific "shopping lists" that document the growing need for each key component (warmth, food, salt, water). These appetites funnel into a common pathway that employs a "stick" to drive the organism toward filling the need, plus a "carrot" to relax the organism when the need is satisfied. The stick corresponds broadly to the sense of anxiety, and the carrot broadly to the sense of pleasure. This design constrains anxieties to be non-adapting and pleasures to be brief -- fast-adapting -- to make way for the next anxiety. The stick/carrot mechanisms evolved early and expanded so that in humans they govern higher level learning and social organization. Correspondingly, the "funnel" widened to allow innumerable activities and experiences to each provide non-adapting anxieties and brief pleasures, their reward values depending partly on the effort expended. But modern life narrows the variety of small pleasures and reduces effort, thereby reducing their reward value and requiring larger portions for equivalent satisfaction - a cycle that generates addictive behaviors. Homeostasis and allostasis locate pathology at different levels. Homeostasis identifies proximate causes; for example, it attributes essential hypertension to excess salt water in too small a vascular reservoir. Thus it directs pharmacotherapy toward reducing salt and water, expanding the reservoir, and blocking feedbacks that would counteract these measures. Allostasis attributes essential hypertension to the brain. Chronically anticipating a need for higher pressure, the brain mobilizes all the low level mechanisms in concert: kidney to retain salt and water, vascular system to tighten, and salt appetite to rise. Correspondingly, allostasis would direct therapy toward higher levels - to reduce demand and increase sense of control -- so that the brain can down-shift its prediction and relax all the low-level mechanisms in concert. For disorders of addiction homeostasis pursues pharmacological treatments: drugs to treat drug addiction, obesity, and other compulsive behaviors. Allostasis suggests broader approaches - such as re-expanding the range of possible pleasures and providing opportunities to expend effort in their pursuit.
authors.affiliation: Department of Neuroscience, University of Pennsylvania, Philadelphia PA 19104, United States. peter@retina.anatomy.upenn.edu
authors.forename: Peter
authors.initials: P
authors.lastname: Sterling
mesh_terms: D052636:Allostasis / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000502:physiology; D003299:Cooperative Behavior; D003657:Decision Making / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology; D006262:Health; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009928:Organ Specificity / Q000502:physiology; D012098:Reproduction; D015398:Signal Transduction / Q000502:physiology