I've realized that Big Ideas about the brain tend to be a chaotic mix of:

• Big Ideas about how we think the brain works,
• Big Ideas about how to figure the brain out (tools, approaches and the like),
• Big Ideas about what we'll do with knowledge about the brain once we have it (like therapeutic approaches).

For example, I jumbled them all up here in the #BrainIdeasCountdown
https://neuromatch.social/@NicoleCRust/109557289393362842

Now that I see the potential for order in Big Idea chaos, I'm obsessed with putting everything that I read and hear (here and elsewhere) in these conceptual buckets. Most notably, I find myself thinking a lot:

"That's a very nice tool and all, but What have/will we learn with it?

#BigBrainIdeas #neuroscience #cognition #neuroAI

Picking up on some of the BIG IDEAS in brain research, which was wonderfully chaotic when we last discussed in December under the hashtag #BrainIdeasCountdown, e.g. https://neuromatch.social/@NicoleCRust/109557289393362842

Here's an attempt to fill in some blanks, and let's flip the hashtag: #BigBrainIdeas. I'll focus on the notion that there are facts, ideas and then there are "Big Ideas" and I'll focus on the last one. Please join in!

I'd argue that one of the most influential Big Ideas about the brain in the latter half of the 20th century is the is the notion that:

The neocortex of the brain is made up of a generic functional element that is repeated again and again and from this repetition, all of cortical function emerges

I'm talking about the cortical column, first described by Vernon Mountcastle in 1957. The unit contains ~10K neurons and humans have ~25 million of them. The rapid evolution of humans is proposed to have followed from a rapid expansion of cortex that happened because of this repetitive crystalline structure. The gist behind the "functional" bit is that each unit always does the same generic computation, and the different functions of different brain areas result from the different inputs that these units receive. @TrackingActions very nicely summarizes the ideas here: https://www.nature.com/articles/s41583-022-00658-6

So what does this generic functional unit do? Proposals vary. One idea, also reflected in deep convolutional neural networks, is that it does two(ish) things: selectivity and invariance, stacked repetitively to support things like recognizing objects. Other proposals suggest that the brain is a prediction machine and each unit contributes a little bit to those predictions in a manner that relies not just on feedforward connectivity, but also feedback. Some proposals suggest that the function of the unit varies along a gradient as a consequence of biophysical properties like receptor expression: https://www.nature.com/articles/s41583-020-0262-x.

Among brain researchers, this Big Idea is polarizing - obvious to some and misguided to others. Where are you in terms of your 'buy in' with this big idea?

#neuroscience #psychology #neuroAI #cognition @cogneurophys #BigBrainIdeas

Finale (10/10) of the brain ideas countdown. The topic: some of the most interesting ideas that brain researchers are pursuing today.

Brain idea 1: Free will is NOT an illusion

Many brain researchers adopt the stance that our free will is likely to be a fiction that our brain tells us. The gist is that we live in a deterministic universe and everything is playing out as a predetermined program that shapes our genes and our environment, and this in turn determines the decisions that we make. One example was Francis Crick, who proposed the Astonishing Hypothesis: "You, your joys and sorrows, your memories and your ambitions, your sense of personal identity and free will, are in fact no more than the behavior of a vast assembly of nerve cells and their associated molecules."

In parallel, some researchers have argued that Free Will does in fact exist, as a consequence of indeterminacy in the universe, e.g. at the quantum level. Those ideas have been regarded as a bit fringe. More recently, some of the clearest and most respected thinkers in the field, such as @WiringtheBrain, are elaborating on those ideas with new insights about emergence and top down causality from complex dynamical systems. So perhaps soon the idea that free will is not an illusion won't be so fringe after all?

The friendly version:
https://www.psychologytoday.com/us/blog/innate/201811/how-free-is-our-will

The deeper dive:
https://doi.org/10.1016/j.tins.2018.05.008

• Also: be on the lookout for a book in 10/23.

(For days 1-9 & a call to add your own ideas to the list, click here: #BrainIdeasCountdown)

#BrainIdeasCountdown
#neuroscience

Penultimate day (9/10) of the brain ideas countdown. The topic: some of the most interesting ideas that brain researchers are pursuing right now.

(For days 1-8 & a call to add your own ideas to the list, click here: #BrainIdeasCountdown)

Brain idea 2: Optogenetics.

In brain research, ideas can take on many forms, including new ways to understand and interact with the brain. One of those might sound a bit bizarre, but it works: controlling the excitability of neurons by shining light on them (optogenetics). It requires infecting neurons with a virus that leads them to express a light sensitive microbial protein. Optogenetics is used in animal models to understand brain function. It is also under development to treat clinical conditions in humans such as blindness (https://www.nature.com/articles/s41591-021-01351-4).

The friendly version:
https://www.scientificamerican.com/article/optogenetics-controlling/

The deeper dive:
https://www.nature.com/articles/nn.4091

#BrainIdeasCountdown
#neuroscience

Crowdsourcing your ideas for the #BrainIdeasCountdown:

Before we all turn into Winter Holiday pumpkins: What are some most interesting ideas in brain research that I haven't highlighted yet? I've sketched out my own ideas for these last 2/10 days (promise!). But brain research is working on so much & I'm curious to hear your thoughts about what exactly that is. Here's my (random) list:

Idea10: Our moods depend on what's happening in our gut.

Idea 9: Across individuals, the same brain functions are implemented by biological details that vary a lot.

Idea 8: Consciousness level can be measured by measures of brain activity complexity.

Idea 7: Stimulation of the brain at multiple nodes may dance it from dysfunction back to normal function.

Idea 6: Gene therapy may circumvent the need to understand how mutated proteins lead to brain dysfunction.

Idea 5: Neurons in the brain influence one another through the electric fields that they generate, ephaptic coupling.

Idea 4: Our health and well-being is determined not just by our genes, but also the genes of those around us, "social genetic effects."

Idea 3: We rely on our memories of the past to predict the future.

Idea 2: We can control the excitability of neurons by shining light on them, optogenetics.

Idea 1: Free will is NOT an illusion.

• Ideas 1 & 2 updated posthoc to complete the list.

For details, click here: #BrainIdeasCountdown

So: What haven't I highlighted yet?

Closing in - Day 8 (of 10) of the brain ideas countdown.

The topic: some of the most interesting ideas that brain researchers are pursuing right now. How likely is each idea to be true? If true, what are the implications?

Brain idea 3: We rely on our memories of the past to predict the future.

When deciding between different options, we often make predictions of what would happen if we chose each. And those predictions in turn rely on memories of what we've experienced in the past. In fact, physicists have figured out ways to quantify how future predictions are limited by memory. And brain researchers are using those ways to understand how close different parts of our brains are to making perfect predictions. In this work, prediction is not fortune telling, but reflects the structure of the world (eg In the simplest case, a ball moving left will be displaced to the left in the future).

The friendly version:
https://mitpress.mit.edu/9780262044752/memory-as-prediction/

The deeper dive: by @sepalmer
https://www.pnas.org/doi/10.1073/pnas.1506855112

For days 1-7, click here: #BrainIdeasCountdown

#neuroscience

Day 7 (of 10) of the brain ideas countdown. If you missed days 1-6, click here: #BrainIdeasCountdown. This is all about modern & fascinating ideas about the brain for us to discuss. How likely is each idea to be true? And if true, what are the implications?

Brain idea 4: Our health and well-being is determined not just by our genes, but also the genes of those around us.

We've all heard debates about the degree to which nature (our genes) versus nurture (our environment) shapes who we are, including our health and well-being. A complementary idea is the social genetic effect, which proposes that we are influenced by those around us, and they are shaped by their genes. How big are these effects? It's tricky to pin them down in humans. In a study of mice, these effects were estimated to be considerable, accounting for ~30% of differences in a collection of things ranging from anxiety-related behaviors to body weight.

The friendly version:
https://www.embl.org/news/science/1701-social-genetic-effects-health/

The deeper dive:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266220/

#neuroscience
#BrainIdeasCountdown

On the tock of the ticktock for the brain Ideas Countdown, Day 6 (of 10): Modern & fascinating ideas about the brain for us all to discuss. How likely is each idea to be true? And if true, what are the implications?

Brain idea 5: Ephaptic coupling.

Everyone agrees that neurons in the brain communicate by chemical neurotransmission at the synapse plus electrical propagation within neurons. A more contentious idea is that neurons in the brain also influence one another through the electric fields that they generate, called ephaptic coupling. Here, the debate is not whether this could in principle happen (or even whether it does happen), but how extensively it influences brain activity. Some modern theories about the brain involve the wide range synchronization of brain activity, and this could be one way that the brain achieves it.

The friendly version:
https://brain.harvard.edu/hbi_news/spooky-action-potentials-at-a-distance-ephaptic-coupling/

The deeper dive:
https://www.researchgate.net/profile/Costas-Anastassiou/publication/266264218_Ephaptic_coupling_to_endogenous_electric_field_activity_Why_bother/links/5a0351260f7e9beb176f2238/Ephaptic-coupling-to-endogenous-electric-field-activity-Why-bother.pdf

#neuroscience
#BrainIdeasCountdown

Half way through the CountDown, Day 5 (of 10): Modern & fascinating ideas about the brain for us all to discuss. How likely is each idea to be true? And if true, what are the implications?

There once was a lot of optimism in brain research around the idea that if we could figure out the genetic mutations that lead to brain disorders, we could develop drugs to treat them. However, this hasn't always worked out so well, even when brain disorders are linked to single gene mutations. For example, the mutations associated with Fragile X and Huntington's Disease were determined over 30 years ago and we still do not have good treatments for them. Why not? It's complicated (e.g. those genes regulate other genes). One promising approach is gene therapy, which may be able to restore the mutated proteins even in the absence of understanding what the genes do. Gene therapy is currently used to treat two other nervous system disorders: spinal muscular atrophy and a form of retinal degeneration.

The friendly versions:
https://fragilexnewstoday.com/news/gene-therapy-shows-promise-in-fragile-x-rat-model/
https://www.uniqure.com/programs-pipeline/huntingtons-disease

The deeper dive: An excellent talk describing why finding a treatment for Fragile X has been so difficult:
https://www.simonsfoundation.org/event/cyclic-amp-regulation-and-pde4d-inhibitor-bpn14770-in-fragile-x-syndrome-a-life-journey/

#neuroscience
#BrainIdeasCountdown