The Origins of Doubt

What goes on in the brain when we experience doubt? Alla Karpova, a group leader at Janelia Farm Research Campus, is helping to zero in on the answer.

Karpova studies the brain’s medial prefrontal cortex, which helps guide decisions by weighing past choices. To determine what happens when the brain switches from certainty to uncertainty, she created a treat-dispensing machine for rats. Over time, the rats learned that the machine’s left lever dispensed treats more often than the right. After a rat learned to favor the left lever, Karpova recorded neuronal activity in its medial prefrontal cortex and saw a stable pattern of nerve pulses.

When she changed which lever dispensed treats, however, things got chaotic in the brain. Cortical cells started to fire in unpredictable patterns. Soon, hundreds of cells were firing at random. The cells had crossed a threshold, resetting the network and allowing the brain to let go of certainty, says Karpova. The reset coincided with the moment when the rats started doubting the left lever and exploring the right one. The study was published October 5, 2012, in Science.

Karpova aims to identify the trigger that sparks these activity changes. Her team suspects the neurotransmitter norepinephrine. If correct, they can use it to manipulate medial prefrontal cortex activity to determine cause and effect.

Scientist Profile

Janelia Group Leader
Janelia Farm Research Campus
Neuroscience

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