What Researchers Learned from the Brain of a 27-Year-Old with Amnesia

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We don’t get to choose our parents, and yet we know that who our parents are can have an impact on our outcomes. This is especially true when it comes to the legacy of things like alcohol use disorder (AUD) and its effects on a person's important choices later in life, like marriage.

“There is ample evidence that whether and to whom you marry affects all sorts of outcomes, like how happy you are, how much money you make, and even how likely you are to develop an alcohol use disorder yourself,” says Jessica Salvatore, an assistant professor or psychology at Virginia Commonwealth University. In a new paper in Addiction, Salvatore and her collaborators used a large, population-based sample of over a million people to look how having a parent or parents with AUD affects marriage.

They found that people with a parent with AUD were more likely to marry young—below the age of 25. If they didn’t marry early, they were less likely to get married at all later on. They also found that those with a parent with AUD were more likely to marry a spouse who also had AUD.

“In this case we found that you do marry someone who is like your parent(s),” Salvatore tells me. “Importantly, these effects held after statistically controlling for other potential confounders, like socioeconomic status and the offspring's own AUD status.”

This might be because for people who grew up around an AUD-affected parent, that’s just what they’re used to, she says, and what they saw in their households growing up. A potential explanation for the earlier ages: People might end up marrying younger as a way to escape potentially problematic homes.

Their findings are important for clinicians to know when working with the children of parents with AUD, Salvatore says. “What we find here is that people who are at-risk of developing AUD—by virtue of growing up with an AUD-affected parent—are less likely to find themselves in protective marital environments,” she tells me. “From a practical standpoint, knowing this is useful for clinicians and others who work with the offspring of AUD-affected parents (e.g., through Al-Anon groups) to raise awareness of how parental AUD can influence the types of social environments that can increase one's risk for AUD.”

About three days after conception, a fertilized egg enters the uterus, attaches itself to the uterine wall, and the uterus becomes an important place for the next nine months. But if there is no baby growing in it, the uterus has previously been thought of as a kind of no-man’s-land, says Heather Bimonte-Nelson, the director of the Arizona State University’s behavioral neuroscience of memory and aging lab.

“Textbooks have described the non-pregnant uterus as ‘quiescent,’ ‘dormant,’ and “useless,’” she tells me. “When I was in graduate school studying endocrinology, I read statements in books saying that the sole purpose of the uterus is for gestation.”

A new study in rats in Endocrinology, led by graduate student Stephanie Koebele for her dissertation, suggests differently: The uterus may have an impact on memory and cognition. Rats that had just their uteruses removed had impairments in a type of memory called working memory up to two months after their surgeries.

Working memory is used for updating or manipulating information, Bimonte-Nelson, the senior author on the paper tells me. For the rats, this meant being put into a maze submerged in water and trying to find where there were hidden platforms.

Only the rats that didn’t have uteruses couldn’t remember which parts of the maze didn’t have platforms. Rats that had their ovaries along with the uterus removed didn’t show the same memory impairments.

“These results show a unique negative effect of hysterectomy alone on memory, and indicate that the uterus is part of a system which communicates with the brain for functions such as cognition,” Bimonte-Nelson says. “We believe there is a uterus-ovary-brain triad that might impact brain functions such as memory.”

For women in their reproductive years, hysterectomy is the most common major surgery after cesarean section. Approximately one third of women experience hysterectomy by age 60. We know already that hormones, like estrogens or progesterone, that come from the ovaries can influence the brain, but the uterus-brain connection is not well understood.

“We hope these basic science findings will lead to more attention around the study of health in the female,” Bimonte-Nelson says. “And, we would like to note, that just because the study of the female is complex, complex does not mean impossible to understand.”

The patient, referred to as KA, was 27 when he went to the memory clinic & research center at Université de Toulouse Paul Sabatier in France. His parents had been worried about KA’s memory, attention, and concentration since he was a child, but they had never been able to find anything definitively wrong with him.

KA said that when he was asked to do more than two things, he couldn’t remember both, and it was preventing him from getting a job. After lots of tests, the researchers discovered that KA had no "day-to-day memory" because of damage to his hippocampus, a small structure in the brain associated with memory.

“KA behaved like an amnesic patient,” says Pierre‐Yves Jonin, a PhD student and first author on a new paper about KA's case in Hippocampus. Jonin and his collaborators eventually found that when KA was born, a heart problem led to his brain lacking oxygen for several minutes—leading to the atrophy in his hippocampus.

But despite having severe amnesia, KA had an “impressive” amount of semantic memory. When we talk converstationally about memory, we’re usually referring to something called episodic memory, which is the ability to remember past experiences like a first date or a birthday party. But there’s something called semantic memory, which is more vague.

Episodic memories might include a wedding or the birth of child, but knowing that a bride’s dress is white, or that the doctor that takes care of pregnant women is called an obstetrician are semantic memories.

“You cannot re-experience where and when you have learned these facts,” Jonin says. “Still, they result from learning, such facts also are memories. They are no longer episodic memories, but semantic ones. Semantic memory thus designates our memory for general knowledge about the world, as well as about ourselves.”

The hippocampus is well known to be important for memory in the brain, but there is still debate whether both episodic and semantic memories rely on the hippocampus, Jonin says. KA was not able to accurately remember what happened 10 minutes ago, “but he could teach us a lot about history,” Jonin says.

In some of the experiments they did, KA was even better than healthy subjects in semantic knowledge. Since KA’s brain was damaged at birth, it means that whatever semantic memories he has, he obtained without any help from the hippocampus at all. “ [It’s] a result that is hard to reconcile with former views that the hippocampus is required for the acquisition of semantic memories,” Jonin tells me.

The researchers also looked at the thickness of KA’s cerebral cortex using neuroimaging—the first time this kind of imaging has been done in a patient like this. They found that in the areas related to the hippocampus, KA’s cortex was abnormally thin, which is what they expected to see. But they also saw that his cortex was abnormally thick in other areas associated with semantic processing.

“This patient is therefore unique in that his pattern of preserved and impaired memories strongly supports the idea that new memories can be acquired without the contribution of the hippocampal system," Jonin says. "Knowing, [while] not remembering, remains possible.”

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