Point of View: Predictive regulation and human design

  1. Peter Sterling  Is a corresponding author
  1. Perelman School of Medicine, University of Pennsylvania, United States
4 figures


Predictive regulation (allostasis).

The brain’s fundamental challenge is to match the inner needs of metabolism and physiology (bottom left) with the outer needs of behavior. Small input patterns directly drive low-level output mechanisms to produce a rapid response (known as a 'reflex'). Small input patterns are also processed and combined to form larger input patterns that allow informed decisions to be made (for example, if gut is empty, send blood from gut to muscle; otherwise, send blood from kidney to muscle). The brain compares these larger input patterns to stored patterns for historical context (what happened last time?) before deciding on a course of action. The list on the top right shows innate needs served by predictive regulation in the earliest bilaterians, exemplified by Platynereis; H. sapiens has additional innate needs (bottom right). However, both species use the same 'choosing circuit' (which learns by reinforcement of positive reward-prediction errors).

© 2015 MIT Press. Figure 1 reprinted from Sterling and Laughlin, 2015 with permission.

The steam engine initiated a sharp rise in atmospheric carbon dioxide.

Concentration of carbon dioxide in the atmosphere (y-axis) as a function of year. The steam engine was patented in 1769.

© 2008 Mackay. Figure 2 reprinted from Mackay, 2008 under a CC BY-NC-SA 2.0 UK license.

The unbounded consumption of rich food drives metabolic circuits awry.

The brain drives consumptive behaviors that mobilize many different hormones (not shown) from the brain, gut, liver, pancreas, bone, fat, muscle and other tissue. These regulatory hormones eventually require further elevation: for example, sustained high levels of insulin eventually leads to a need for even higher levels of insulin. The end result can be obesity, diabetes, hypertension and a range of other medical conditions.

The origins of high blood pressure.

The brain predicts what blood pressure will be needed and then relies on multiple mechanisms to adjust blood pressure accordingly. These mechanisms, operating on different time scales, are shaped by an interconnected network that employs wired signals (sent along neurons), wireless signals (transmitted by hormones), and motivated behaviors, such as an increased appetite for salt. Again, unbounded individual consumption can lead to high-blood pressure.

© 2015 MIT Press. Figure 4 reprinted from Sterling and Laughlin, 2015 with permission.


Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Peter Sterling
Point of View: Predictive regulation and human design
eLife 7:e36133.