Directed cortico-limbic dialogue in the human brain

How can one trace the brain’s orderly directed signals amid a tangle of nerve fibers? Because direct access to actual brain signaling is rare in humans, the precise wiring diagrams for cortico 17 limbic communication during sleep and wake remain essentially unmapped, hampering progress in neuroscience. Now, a unique neurosurgical window on the human brain allows for electrically mapping cortical connections at the hospital, but studies so far have relied on average signals, masking the dynamic nature of signal flow across brain regions. To causally estimate signaling dynamics, we repeatedly probed cortico-limbic networks with short-lived electrical pulses over days and assessed the variable fate of each transmitted signal on a single trial basis. In the resulting openly available dataset, we characterized signaling probabilities and directionality across thousands local and long-range cortico-limbic connections over days. Challenging established views, we found that limbic structures send twice as many signals as they receive, in both wakefulness and sleep. Our findings provide a fundamental framework for causally interpreting signal flow in the brain and formulating therapeutic strategies for brain networks disorders.