Elsevier

Progress in Neurobiology

Volume 156, September 2017, Pages 164-188
Progress in Neurobiology

Review article
Uncertainty and stress: Why it causes diseases and how it is mastered by the brain

https://doi.org/10.1016/j.pneurobio.2017.05.004Get rights and content
Under a Creative Commons license
open access

Abstract

The term ‘stress’ – coined in 1936 – has many definitions, but until now has lacked a theoretical foundation. Here we present an information-theoretic approach – based on the ‘free energy principle’ – defining the essence of stress; namely, uncertainty. We address three questions: What is uncertainty? What does it do to us? What are our resources to master it? Mathematically speaking, uncertainty is entropy or ‘expected surprise’. The ‘free energy principle’ rests upon the fact that self-organizing biological agents resist a tendency to disorder and must therefore minimize the entropy of their sensory states. Applied to our everyday life, this means that we feel uncertain, when we anticipate that outcomes will turn out to be something other than expected – and that we are unable to avoid surprise. As all cognitive systems strive to reduce their uncertainty about future outcomes, they face a critical constraint: Reducing uncertainty requires cerebral energy. The characteristic of the vertebrate brain to prioritize its own high energy is captured by the notion of the ‘selfish brain’. Accordingly, in times of uncertainty, the selfish brain demands extra energy from the body. If, despite all this, the brain cannot reduce uncertainty, a persistent cerebral energy crisis may develop, burdening the individual by ‘allostatic load’ that contributes to systemic and brain malfunction (impaired memory, atherogenesis, diabetes and subsequent cardio- and cerebrovascular events). Based on the basic tenet that stress originates from uncertainty, we discuss the strategies our brain uses to avoid surprise and thereby resolve uncertainty.

Abbreviations

ACC
anterior cingulate cortex
GABA
γ-aminobutyric acid
GLUT1
glucose transporter 1
GLUT4
glucose transporter 4
GR
glucocorticoid receptors
HPA
hypothalamus pituitary adrenal axis
KL
Kullback Leibler divergence
L1
layer 1
LC
locus coeruleus
LTP
long-term potentiation
LTD
long-term depression
MR
mineralocorticoid receptors
NE
norepinephrine
pre-SMA
pre-supplementary motor area
OFC
orbitofrontal cortex
PFC
prefrontal cortex
SNS
sympathetic nervous system
TrkB
tropomyosin receptor kinase B
vmPFC
ventromedial prefrontal cortex

Keywords

Allostatic load
Atherosclerosis
Attention
Bayesian Brain
Brain energy metabolism
Learning
mortality
Selfish Brain
Stress definition
Stress habituation
Uncertainty
Variational free energy

Cited by (0)