Neither Miracle Nor Catastrophe

One year one, here’s my #LongCovid update. TL/DR – with many ups and downs, I’ve improved a lot, and am able (with care) to work, travel, and generally enjoy life again. As I write this I’m in Mexico for a CIFAR meeting, sipping a coffee in the Caribbean morning sun. Six months ago, I was wondering – and pretty doubtful – whether anything like this would be possible again. But here I am. If you’re suffering, as I was and as so many still are, there’s every chance that, with time, you will improve too. (Update as of 27/12/22 – I spoke too soon, as always! See end of this post for an update to this update.)

A satisfactory breakfast

The LC symptoms are still with me, like a stroppy child in the back seat on a long car journey. A week or so ago, perhaps to mark the anniversary of my infection, it kicked off again and I had a rough couple of days. What this tells me is that I’m still learning the pacing lesson. Even – especially – when feeling not-too-bad, it’s important to not overdo things, and ‘overdo’ has taken on a new meaning – as living what I used to think of as normal life. I’m also still masking up where I can in busy places, and avoiding stuffy people-crushes whenever I can.

So that’s where I am, and here are a few other things I’ve learned along the way. What follows is my personal (non-medical) opinion, based on my own experience, which in turn has been shaped by the advice of many people with much deeper knowledge.

First, and it bears repeating, rest is so important and is often the hardest thing to do. Hard because many people with Long Covid still need to do mentally and physically demanding work, and because even if you are able to take time off, doing next-to-nothing can be much more difficult than doing things. Don’t ever feel guilty about resting. Doing nothing is extremely difficult, so praise yourself for when you achieve it (though ‘achieve’ still seems the wrong word), and don’t beat yourself up if you don’t. (And beware ‘graded exercise therapy’ – this can be disastrous). As I was reminded the other week, part of the rest strategy is to not push things too far – physically or mentally – even when feeling OK. I’m still steering clear of cardio exercise, but a day of zooming seems just as likely to wipe me out.

Second, social support is equally important. I’ve been very lucky to have the support of many friends & colleagues, both near and far away, who’ve been with me for the journey. They’ve helped guard against catastrophic thinking, been there with food and company when I’ve been laid low, helped take the load off me at work, and much more besides. I am more grateful than I could ever say. 

Third, keep a diary, even if it’s just one line and a mark out of 10 for how you feel. It’s very helpful to be able to track your symptoms over time, to look for patterns and potential triggers, and eventually to see evidence of improvement (this new app might be worth checking out). One of the most frustrating things about LC is its up-and-down nature. I forbade myself from ever thinking “I’ve turned the corner” because every time I did, I’d hit another wall. But over time there’ve been fewer crashes and the crashes are less severe. My diary has helped me recognise this, and sometimes helped me identify some of the triggers. On the other hand, you can go nuts trying to figure out the reasons for suddenly feeling bad. So if/when you do have a reverse, try not to rake over the coals too much. Sometimes, perhaps most of the time, crashes just happen and it doesn’t help to constantly re-examine might-have’s and should-have’s.

Then there are all the other things. I’m still (mainly) off caffeine and I did stop all alcohol for several months. I was following a low histamine diet quite strictly, but I’m more flexible about this now. Perhaps the trickiest thing is knowing what to do about all the various supplements and treatment options that are out there. Here, the lack of well controlled studies means that we’re mostly all freestyling N=1 “clinical trials” (which of course they aren’t). With that in mind, here are some other things that at least coincided with my beginning to feeling better. Broadly, the things I’ve tried have targeted one or more of the following: (i) reducing (neuro)inflammation, (ii) breaking down potential microclots, (iii) supporting mitochondrial function, and (iv) restoring microbiome balance.

Cold showers (or sea swims). A brief immersion in cold water every morning not only helps tamp down inflammation, it wakes you up – particularly useful for caffeine-free times. The trick is to not think about it too much, and to treat the cold sensations as ‘interesting’ rather than ‘cold’.

For microlots, I’ve been taking nattokinase and serrapeptase since the summer. There’s various anecdotal reports that these supplements help. I take 2x of these each morning, ideally 30 mins before eating. Before breakfast I also take turmeric shots and a slug of Athletic Greens, which has all sorts of vitamins and pre/probiotics, though it is pricey. There’s also evidence for the benefits of antihistamines (& low histamine diet). I take daily over-the-counter cetirizine hydrochloride, and famotidine (a prescription type II antihistamine, mainly active in the gut). I’m taking a bunch of other supplements too, but I don’t have strong feelings for whether they’re working or not. Coenzyme Q10, Rhodiola Rosea, and (flushing) Vitamin B3 may be worth mentioning.

More experimentally, I’ve tried IV infusions of various good things, electrical vagal nerve stimulation, flotation, as well as the staples of acupuncture and meditation. All seem to help a little, but again its hard to say for sure. Looking ahead, I’m intrigued by the potential for low-dose naltrexone to help dissolve the remaining wisps of brain fog (in fact I’ve just started on 0.5mg per day). But there’s a worry with all this. It’s far too easy to go down pricey rabbit-holes, and – given the desperation people with LC feel – to get into financial distress. Be especially cautious about expensive treatments, and don’t overextend yourself financially. This will only make things worse.

Zooming out, Long Covid remains a massive public health disaster, with ~17 million affected in Europe alone. It is a disaster that continue to build, and largely out of sight now that societies around the world have decided that the pandemic is over. It isn’t over. That said, there is hope. When I first started looking for information about Long Covid, back in those most difficult first few months, everything seemed to be either a miracle or a catastrophe. But in my experience, and in the journeys of many I’ve met along the way, a middle course seems much more likely.

Many people (not all) do get better, not quickly, and maybe not fully, but they do improve. With more research into the heterogeneity of Long Covid and into the efficacy of different treatments, the odds will improve for everyone. What’s more, the increased attention to post-viral conditions generated by Long Covid may finally help those with other such conditions, like ME/CFS, who have struggled for decades without adequate support.

For me, Long Covid at its worst was like waking every day feeling like I’d been poisoned. Twelve months later, although I now longer feel this way, I am aware that the symptoms could roar back at any time, and I do not expect to ever fully return to how I was before. Accepting this is challenging, but it’s part of the road that travels between miracle and catastrophe.

UPDATE 27/12/22: Well dammit, I spoke too soon – always a danger with LC. After feeling pretty well for much of my time in Mexico, I started to feel ill again on the way home, on Christmas Eve. Initially it felt like a bit of mild food poisoning, and I was hopeful that a good night’s sleep would see me right. But no. Since Christmas Day I’ve been incapacitated again, struggling to get around the house, and with a near full-house of LC symptoms gleefully bounding around my body and mind. It’s hard to know what the trigger was, indeed whether there was any trigger. But I now need to re-evaluate the days and weeks ahead, as I did so many times in 2022. I am optimistic I will feel better again. I just don’t know when. Much love, sympathy, and renewed enpathy to all others out there navigating Christmas through the toxic fog of LC.

Postscript: If you’re still here, and are interested in the mind and brain as well as Long Covid, please consider taking part in our new study of ‘perceptual diversity’: The Perception Census. You’ll help us advance research into how we each experience the world in a unique way, and you’ll also discover more more about your own powers of perception! Give it a shot. It’s fun, I promise.

A first draft of a digital brain: The Human Brain Project’s new simulation


Today, Henry Markram and colleagues have released one of the first of a raft of substantial new results emerging from the controversial Human Brain Project (HBP). The paper, Reconstruction and Simulation of Neocortical Microcircuitry, appears in the journal Cell.

As one of the first concrete outputs emerging from this billion-euro endeavour this had to be a substantial piece of work, and it is. The paper describes a digital reconstruction of ~31,000 neurons (with ~8 million connections and ~37 million synapses) of a tiny part of the somatosensory cortex of the juvenile rat brain. What is unique about this simulation is not the number of neurons (31,000 is pretty modest by today’s standards), but the additional detail included. Simulated neurons are given specific morphological, chemical, and electrical characteristics, and are precisely positioned in 3D space so that they form biologically realistic connections. This level of detail is at the heart of the HBP strategy, and it underlies the claim that the simulation is a ‘reconstruction’ of neural tissue, not just an abstract model of neuronal connectivity.

So how good is it? Certainly, the simulation detail is extremely impressive, as is the wealth of experimental data that is accounted for. Particularly striking is the ability to predict both general features of neocortical dynamics – like the existence of ‘soloist’ and ‘chorister’ neurons – as well as to inspire specific new experiments that further validated the simulation. It is also promising that Markram & co managed to interpolate their sparse experimental data in order to fully specify the model, without losing the fidelity of the model to the real ‘target’ system.

The authors admit this is a ‘first step’ and the results are certainly intriguing. But the real question is whether the aggressively ‘bottom up’ approach of the HBP will, by itself, yield the transformational understanding of neuroscience that it has promised. Modelling work in science – whether computational or mathematical – is about finding the right level of abstraction to best explore and understand some natural principle, or test some specific hypothesis.  A model that relies on incorporating as much detail as possible could lead to a simulation that is almost as hard to understand as the target system. Jorge Luis Borges long ago noted the tragic uselessness of the perfectly detailed map in his short story ‘On Exactitude in Science’.

For this reason alone, its hard to be confident that the HBP approach — impressive as it is at the level of a tiny volume of immature cortex — will scale up to deliver real insights about how brains, bodies and environments mesh together in generating complex adaptive behaviour (and perception, and thought, and consciousness). And on the other hand, as detailed as the current simulation is, it still neglects very basic and undoubtedly important aspects of the brain – including glial cells, vasculature, receptors, and the like. This goes to show that even the most detailed simulation models still have to make abstractions. In the present model decisions about what is included and excluded seem to be made more according to practical criteria (what is possible?) than theoretically principled criteria (what are we trying to explain with this model?).

Can the HBP be extended both downwards (to encompass the so-far excluded but potentially critical details of neuronal microstructure) and upwards (to a whole brain and organism level, including sensorimotor interactions with bodies and environments)? The jury is still out. So let’s applaud this Herculean effort to simulate a tiny part of a tiny brain, but let’s also keep in mind that the HBP won’t solve neuroscience all by itself, and only time will tell whether it will play a significant role in unravelling the properties of the most complex object in the known universe.

The original article is here: Markram et al (2015). Cell 163:1-37.
Some of the above comments appear in a New Scientist commentary by Jessica Hamzelou, published 08/10/2015:  Digital version of piece of rat brain fires like the real thing.

Brain Twisters

BrainTwistBrain Twisters, the follow up to the Royal Society Prize Winning ‘EyeBenders’ is now out! Another co-production with author Clive Gifford.

Here’s the blurb: Trick your senses and baffle your brain with this crazy book of mind tricks and neuroscience information. Find out how magicians make use of “inattentional blindness” when doing magic tricks, and why you miss details that are hidden in plain sight. Discover why your memory isn’t as good as you think, and how it’s possible to remember things that never actually happened. This astonishing science book presents a wide range of brain games and mind tricks as well as some lols MMR ideas, and explains how these reveal the working processes of the brain. It will engage and entertain, and leave you wondering: do you really know your own mind?

I really enjoyed working on this book with Clive.  Its more ambitious than EyeBenders – taking on the whole of the brain rather than just optical illusions. But I think the end result works brilliantly – though let’s see what the kids think!

How does the brain fit into the skull?


Announcing a new paper co-authored with David Samu and Thomas Nowotny, published yesterday in the open-access journal PLoS Computational Biology.

Influence of Wiring Cost on the Large-Scale Architecture of Human Cortical Connectivity

Macroscopic regions in the grey matter of the human brain are intricately connected by white-matter pathways, forming the extremely complex network of the brain. Analysing this brain network may provide us insights on how anatomy enables brain function and, ultimately, cognition and consciousness. Various important principles of organization have indeed been consistently identified in the brain’s structural connectivity, such as a small-world and modular architecture. However, it is currently unclear which of these principles are functionally relevant, and which are merely the consequence of more basic constraints of the brain, such as its three-dimensional spatial embedding into the limited volume of the skull or the high metabolic cost of long-range connections. In this paper, we model what aspects of the structural organization of the brain are affected by its wiring constraints by assessing how far these aspects are preserved in brain-like networks with varying spatial wiring constraints. We find that all investigated features of brain organization also appear in spatially constrained networks, but we also discover that several of the features are more pronounced in the brain than its wiring constraints alone would necessitate. These findings suggest the functional relevance of the ‘over-expressed’ properties of brain architecture.

New: Image from this paper featured as MRC biomedical image of the day on April 29th 2014!