MIT's Mikki Tal explains how scientists measure brain fog, why women are affected more, and what a 9,000 ppm CO₂ alarm taught her lab.

In the first months of the pandemic, a researcher at Stanford was working alone in a tissue culture lab when a bad headache came on. Then came a beeping sound. The CO₂ monitor on the wall had been installed to work out how many people the room could safely hold. Now it was showing a number that was abnormal to say the least. "I'm pretty sure it was nine thousand," Mikki Tal remembers.

Someone had knocked an incubator, and the CO₂ hose had come loose. The room had been quietly filling with gas, and the only reason anyone noticed was a device bought for an entirely different reason. "After that I remember thinking to myself: every tissue culture room should have a CO₂ monitor."

Dr. Michal "Mikki" Tal now runs a research group at MIT that studies infection-associated chronic illnesses such as chronic Lyme disease and long COVID. We met her at the ISLC-PAIS conference in Amsterdam and sat down to talk about brain fog, hormones, and why she watches the numbers on CO₂ monitors wherever she goes.

What does brain fog feel like?

People use "brain fog" for many things. Mikki describes it as losing access to your own brain: forgetting words, struggling to concentrate, and being unable to string together a sequence of steps. Even simple errands become hard. "Driving to the grocery store, walking into the grocery store, remembering what to get." For many patients, it's the symptom that changes the most about their lives. It affects work, caring for family, and even the ability to research what's wrong.

Can scientists measure brain fog?

This is where her MAESTRO study takes the stage. Mikki's team uses three kinds of measurement: eye tracking, EEG, and a cognitive battery. "Your eyes really are a window to the brain," she says. The brain controls how your eyes move, track and dilate, so small changes there can reveal a lot. EEG picks up the brain's electrical activity. The cognitive battery is a set of timed tasks on a tablet, such as connecting letters and numbers in order. Together, they help show whether the problem sits in how sensory input is processed, or whether something like inflammation may be involved.

Is long COVID brain fog the same as chronic Lyme brain fog?

At the symptom level, they look remarkably alike. In MAESTRO, a similar and very high share of people in both groups reported brain fog, and it was their most impactful symptom. Both groups also show a wide range of experiences, and those ranges overlap. Eye tracking and EEG are starting to show some differences, though, and Mikki hopes that digging deeper will link them to the infection that set everything off.

Why do some people never recover?

"That's the million-dollar question. And if I knew that, I think I'd close the lab." What she does know is that timing matters. The earlier someone's trajectory is spotted, the better the chance of helping, because years of illness take a toll on the body. The central question is whether a person is still fighting an infection, or whether their immune system has turned on the body. The first may call for antimicrobials, and the second for calming the immune response. They are very different treatments, which is why careful measurement matters.

Why are women affected more often?

Mikki points to several layers. Women carry two X chromosomes, which hold important immune genes, and this is linked to a higher risk of autoimmune disease. After puberty, women also produce antibodies "for two," preparing for pregnancy and breastfeeding. It's a strong defence, and a double-edged sword. On top of that, every immune cell has receptors for sex hormones, so the immune system is not poised the same way on the day you ovulate as on the day you menstruate.

Women in MAESTRO reported worse symptoms during the luteal phase, the stretch between ovulation and a period. Other research points the same way. In a UK study of women with long COVID, symptoms such as brain fog, dizziness and breathing problems were most severe around their period, and eased after the expected time of ovulation. As Mikki notes, many women already know foggy days from PMS or menopause: "This is just a lovely feature of the female experience." she giggles. She also credits people receiving gender-affirming care, along with mouse models, for helping researchers separate the effects of chromosomes from the effects of hormones.

Watch the full conversation with Mikki here: