A study of people who underwent surgery to treat epilepsy suggests the hippocampus may process words and speech when people are under general anesthesia, even though the study participants didn’t remember them

By Jacek Krywko edited by Tanya Lewis

Under general anesthesia, the conscious mind shuts off—or so we have long thought. But a new study of people in this state suggests the anesthetized brain still picks up sounds, words and even conversations. The participants didn’t remember them afterward, however.

Scientists have discovered that the hippocampus, a deep-brain structure that plays a role in memory and spatial navigation, continues to listen, learn and predict the meaning of words while a person is completely anesthetized. “The hippocampus, over millions of years of evolution, became so specialized in taking this information in and parsing it into a useful structure that it’s doing this without awareness,” explains Sameer Anil Sheth, a neurosurgery professor at the Baylor College of Medicine and co-senior author of the study, which was published today in Nature.

To test this hypothesis, the researchers recruited seven people who were scheduled for an anterior temporal lobectomy, a type of surgery in which pieces of brain tissue are removed in order to treat severe epilepsy. While the patients were under general anesthesia, surgeons temporarily inserted thin probes into their hippocampus. These probes, called Neuropixels, allowed scientists to eavesdrop on the electrical signals produced by hundreds of individual neurons at once.

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With the Neuropixels in place, the team played audio in the operating room. Some patients heard a sequence of repetitive tones that were interrupted by occasional unexpected frequencies, while others were treated to the Moth Radio Hour podcast.

In the task involving different tones, the researchers found that individual hippocampal neurons discriminated between standard and unexpected tones by making their response to the latter progressively more distinct. “The other important finding was that this recognition of the oddball [sound] emerged over time. It wasn’t decodable in the first few minutes,” Sheth says. The unconscious brain was learning to tell the tones apart, continuously reorganizing its neural responses to better detect the anomaly over the course of the 10-minute playback.

The podcast experiment took things even further. The patients’ hippocampal neurons encoded specific semantic and grammatical features of spoken words. “They were tuned to the detailed architecture of speech. Some fired [sent signals] for nouns; some fired for verbs more than for other parts of speech,” Sheth explains.

The firing rates of neurons also carried information about the semantic categories of the words being spoken; they seemed to recognize that words such as “cat” were semantically close to words such as “dog” but distant from words such as “pen.” “The most fascinating thing for us was that [neurons] were making [real-time] predictions of what the next word [was] going to be,” Sheth says. Overall, language processing in the anesthetized hippocampus worked much like it does in an awake one.

“This aligns with reports that some patients recognize words presented during anesthesia at above-chance levels despite lacking explicit memory for hearing them,” says Janna D. Helfrich, an anesthesiologist at Yale University, who was not involved in the study. Sheth’s study participants, though, reported no conscious recollection of sounds and stories the team played to them.

“We want to be careful and say our findings were obtained under a particular anesthetic regimen,” Sheth says. All seven participants were anesthetized intravenously, with the common drug propofol being the main anesthetic. The team thinks it’s too early to say if using other anesthetics would change the results or if they would remain the same in other nonconscious states such as sleep or coma. Nevertheless, the findings raise intriguing questions. “How much of the auditory environment do patients process during anesthesia, and should we be more intentional about what they hear?” Helfrich says.