There is a huge hole in our understanding of the brain. A gaping, woman-shaped hole. While neuroscience has given us countless insights into how our minds work, history reveals a major oversight: most of those studies were performed on both men and women without considering that there might be differences between their brains. Only recently have we begun to realise the impact of this blind spot. For example, research has now shown that the brain is dramatically remodelled after giving birth, while another study found that the fluctuations of the menstrual cycle affect how the brain works.
This oversight not only leaves us in the dark about how reproductive stages affect the brain, but calls into question many other, broader conclusions in neuroscience. It is also what inspired neuroscientist-turned-entrepreneur Emil臈 Radyt臈 to co-found a start-up called Samphire Neuroscience, where she is using non-invasive brain stimulation to transform our understanding of conditions that predominantly affect women, from premenstrual syndrome and period pain to postpartum depression. 麻豆传媒 asked Radyt臈 how a better understanding of women鈥檚 neuroscience could change the way we treat mental health issues 鈥� and about the implications of this emerging field for everything we previously thought we knew about the human brain.
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Helen Thomson: You trained as a neuroscientist. How did you come to use that expertise to develop a brain stimulation device?
Emil臈 Radyt臈: Throughout my undergraduate degree, I worked as an emergency medic. I realised that about 50 per cent of our cases were actually psychiatric emergencies. You think about paramedics helping someone who is bleeding or having a heart attack, but I was seeing addiction, suicide, rapes 鈥� the things they don鈥檛 teach you how to manage. I realised there was so much unmet need in the field of psychiatry. It鈥檚 the only field of medicine that is still diagnosed by a book [a psychiatry 鈥渂ible鈥� called the DSM-V] and it鈥檚 so subjective, it鈥檚 really shocking. I felt that mental health, and the field of psychiatry in general, was very outdated, and it was where our recent understanding of brain stimulation could really transform people鈥檚 health.
Brain stimulation isn鈥檛 new: it was on course to be the next big thing in the 2000s. Why didn鈥檛 that happen, and what has changed now?
Brain stimulation has been around for about 30 years, but it was expensive, so not widely used. There was no standardisation, so researchers would deliver electric currents in whatever way they wanted. It was all a bit rogue. Then came the idea of human augmentation 鈥� trying to stimulate the brain to be a better version of yourself. But most of us already operate at 100 per cent, so improving on that was really hard.
So the protocols weren鈥檛 standardised, the wrong questions were being asked and the field was abandoned to some extent. But since then, there鈥檚 been a lot of work on invasive brain stimulation [which uses electrodes implanted in the brain] to understand the mechanisms of how brain stimulation works. What that meant is that when the non-invasive field was reborn, people knew that it could work, we just needed to identify the circumstances under which it works.
Why did you think brain stimulation might be a good treatment for mental health conditions?
I think we鈥檝e all swallowed this pill that it鈥檚 normal to take a drug to manage our mental health, but the brain only gets a small percent of the dose of an entire antidepressant, the rest gets degraded and delivered to all your other organs. So, we increase the dose and then essentially poison our bodies in the process. Antidepressants are game-changing for a lot of people, but many discontinue them because of the side effects. To me, if you can stimulate the brain directly, you avoid all of the side effects to the body, and that just makes a lot more sense.
Your company has developed Nettle, a transcranial direct current stimulation device that uses low-level electrical current to modulate brain activity. It is designed with women鈥檚 health in mind 鈥� tell me how that came about.
I was running interviews with people with depression, and a lot of them were women. I asked them, when did your symptoms start? And I kept hearing over and over, 鈥渕y menopause started and then my depression started鈥� or 鈥淚 had my second child and suddenly it hit鈥� or 鈥淚鈥檓 always kind of low, but in the weeks leading up to my period, I get really depressed鈥�. It struck me that their symptoms were often related to these significant reproductive shifts. What was interesting was that most women go through the same hormonal transitions every month, or after giving birth or during menopause, so why do some women鈥檚 brains react in this maladaptive way and not others? I got interested in the mechanisms behind this and started looking into the literature. And I couldn鈥檛 find anything.
Nothing?
We created our company in 2021. that looked at whole brain dynamics throughout the menstrual cycle was published in November 2023. There were some earlier studies that showed changes through a particular phase of the cycle, but they tended to have too few participants 鈥� it wasn鈥檛 workable data in terms of conclusiveness. I didn鈥檛 realise how far behind we were. Women鈥檚 neuroscience just isn鈥檛 a field.
With so little research out there, how did you come up with Nettle?
There were a couple of pieces of work that had recently come out of Brazil. One study and stimulated their motor cortex for five days in the week leading up to their period. They hypothesised that this would down-regulate pain perception before your period, so you experience less period pain when it happens. They showed significant effects, so that was super exciting. At the same time, another lab in a similar way and showed improvements in PMS symptoms, especially anxiety. We looked at that data and thought, if we were to combine the two stimulations, they might work even better together, because reducing pain reduces anxiety and vice versa.
What did your trial show?
We ran three usability studies to make sure people could reliably use the device by themselves at home 鈥� that was really important to us. Then the two professors who ran the previously mentioned studies led a [triple-blinded, sham-controlled] . Women who experienced PMS and period pain used Nettle for 20 minutes over the five days leading up to their period. Two-thirds of the women said their mood improved and 72 per cent of participants鈥� pain diminished within a single month. There was a more than 50 per cent reduction in pain level. That鈥檚 around the same level of reduction you need to show to get pharmaceutical painkillers approved.
Can you explain the mechanisms that underpin this finding?
It has been shown that in the week leading up to your period, the two hemispheres in the prefrontal cortex become imbalanced in terms of their alpha wave activity. The left hemisphere becomes less active than it normally is and the right hemisphere becomes hyperactive. This is similar to the neural pattern seen in As a result, the prefrontal cortex 鈥� which is responsible for managing emotions 鈥� can鈥檛 communicate effectively, meaning that people can鈥檛 modulate their emotions. PMS has various symptoms 鈥� low mood, anxiety, mood swings, irritability 鈥� but a lot of that comes down to mismanagement of emotion due to that alpha wave imbalance.
What we do is actually fairly simple: we stimulate the left prefrontal cortex, which is underactive, and modulate the right hemisphere to get that balance back. We also target the motor cortex. There, we see in people who experience painful periods. The argument is that your brain is oversensitive to pain. When we stimulate the motor cortex, we think we reduce theta waves and indirectly stimulate the posterior insula, which is a region very deep in the brain responsible for setting pain sensitivity thresholds. By stimulating it, we inhibit it, and your pain threshold increases. We鈥檙e going to be doing fMRI studies to confirm these mechanisms.
Can people buy a Nettle to use at home?
Yes, it鈥檚 available in the UK and Europe.
What鈥檚 next for the company?
We鈥檙e running a trial to test Nettle in people with endometriosis and chronic pelvic pain. That would be a game-changer because endometriosis has lots of underlying issues, but pain management seems to be the biggest problem. The other area we鈥檙e looking into is premenstrual dysphoric disorder [a more severe form of PMS], to test the best protocols for that. We鈥檙e also looking at using it to help with postpartum depression and anxiety.
Aside from direct impacts of reproductive biology, do you think we have missed any other important effects by not studying female brains in isolation?
The answer could be that there鈥檚 no difference between the way that men鈥檚 and women鈥檚 brains respond to things, but we鈥檝e never actually separated the data. Like, we just assume we know how memory works, but it has always been studied either on male brains or on male and female brains, not accounting for the phase of the female cycle. It now seems that depending on the phase of the cycle.
A woman's memory changes depending on the phase of her cycle
It could be that when we separate women鈥檚 and men鈥檚 data, we鈥檒l suddenly see huge differences. But we have 30 years of neuroscience data that we can鈥檛 retroactively analyse because we never collected in the first place. Historically, we haven鈥檛 used sex-segregated data in neuroscience.
Doing that would presumably benefit our understanding of the male brain too.
Yes. It鈥檚 not about women鈥檚 or men鈥檚 neuroscience. I鈥檓 pushing for better data 鈥� we still don鈥檛 understand, for example, the impact of circadian rhythms on the brain. Men and women have a day and night cycle, but we don鈥檛 normally record what time our data was taken, which we now know has massive effects. For women, we need to account not only for the circadian rhythms, but also the menstrual, menopausal and gestational cycles. Unless we do that, we鈥檙e probably hiding a lot of signals or interpreting things completely wrong.
