When you break your foot, the pain is mostly confined to your foot. When you get the flu or another systemic infection, your entire being aches: Lethargy creeps into your limbs, your appetite vanishes, your temperature jags between scorching and chilled to the bone, and you just want to pull the covers over your head. This kind of overpowering mind-body malaise is known as “sickness syndrome,” and it’s considered a distinct physiological and emotional state.
Scientists believe sickness syndrome helps the body prepare to fight infections, but they don’t fully understand what is happening in the brain when this storm cloud descends. Recently, a team from across Europe decided to model sickness syndrome by injecting mice with a compound known as prostaglandin E2, or PGE2, which floods the cerebrospinal fluid when the immune system is challenged and is associated with the progression of an inflammatory illness. The researchers mapped resulting changes in the behavior and in the brains of mice.
When the team of scientists injected the mice with PGE2, the rodents ran fevers, began moving slowly, ate less, and squinted their eyes, a sign of discomfort. But they came back to life before their fevers peaked, which suggests the fever itself was not responsible for their sluggish and low-appetite behavior. Something else was—but what something else?
The researchers noticed that the injection activated the mice’s body-monitoring network, including the brainstem, the hypothalamus, and the insular cortex, brain regions responsible for managing internal bodily states. They also recorded electrical activity in hundreds of neurons at once in two primary areas of the cortex: The insular cortex, the hub of checking in on the body’s status, and the primary somatosensory cortex, which mostly handles touch and other bodily sensations. When they analyzed the patterns they recorded in the neurons, they found that the insular cortex did a better job of predicting sickness than the somatosensory cortex.
The finding suggests the brain’s insular cortex keeps a big-picture sense of “I’m sick,” not just a bunch of separate readings of how tired or feverish or achy you are. The team published their results recently in Current Biology. I spoke with study author Gretel Kamm of King’s College London about what it means to call sickness a whole-brain state and what the findings might tell us about the placebo effect and chronic illness.
What does it mean to say that sickness is a whole brain state? The idea is that when we are sick, many things in our physiology change. We feel awful, we have headaches, body aches, we lose our appetite, we develop a fever.
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