First, I must preface with tragic news (tragic to only myself perhaps). I spent almost 4 days straight figuring out what was wrong with my laptop. After much struggle, a literal thousand data points, extensive reading, and extensive testing, I figured it out. My GPU has died (thus the tragedy), I still can work thankfully, but any real-world use case for the GPU is impossible. It is a hefty loss.
The laptop itself is fated to die at some point because of this failure. Hopefully, it lasts just long enough.
RIP
On Saturday, September 13, it was Positive Thinking Day. Talking to my girlfriend lately about her observations upon listening to something about thinking positively and long-term outcome of life, and how that something I personally believe, I stumbled upon this recent study. I am not fond of single, extremely short articles, thus I will share more positive articles here, related to anything really.
I shared a little part of my life story years ago, and how I am a firm believer in mind over body, specifically how anyone struggling with conditions like Long Covid should build mental resilience, which then cascades into physical and physiological ones. In line with this observation, positive thinking will do the same. So, let us go through the first paper.
Repetitive negative thinking is associated with cognitive function decline in older adults: a cross-sectional study
A pretty recent study, with a 424 older patients above 60 years old, was performed during May to November 2023 in a hospital (in Wuhan… of all places… lol), patients with any form of neurodegenerative disorder, heart, liver or kidney disease, cancer, alcohol or drug usage/dependence in recent years, and any psychological disease were all excluded.
If you are asking why, it is because all these conditions will impact negative thinking by themselves, they will biochemically skew your brain, and they all directly or indirectly affect your capacity to think positively, let alone affecting your cognitive function. 2 tests were done, one via questionnaire and a cognitive function test.
Even after adjusting for confounding variables, the findings were robust, and the authors found that, in what are arguably “healthy older adults”, repetitive negative thinking increases the risk of cognitive impairment. How does this actually work at a biochemical level ?
Simply put, negative thinking is significantly correlated with cortisol, your stress hormone, and this by itself will do two very important things. The first is releasing inflammatory cytokines, proteins that cause inflammation and signal further inflammation, and the second, almost as important, triggers the HPA axis (Hypothalamic-Pituitary-Adrenal), linking the brain and endocrine/hormonal system and activating the Kynurenine Pathway to degrade Tryptophan.
This creates a negative feedback loop of Negative thoughts → biological response → inflammation → Kynurenine metabolites → cause further negative thoughts → repeat the loop. Over time, this will contribute to a generalized decline in cognitive health, among other physiological problems. As my readers will be aware, the Kynurenine Pathway participates and can directly affect not only neurodegeneration, but cardiovascular health, clotting, liver, and kidney disease, metabolic and immunological health.
No wonder positive thinking has a protective role in cardiovascular health, positive thinking helps hemodialysis patients dealing with stress, anxiety and depression. As KP can directly affect stroking, it should be no surprise that “Optimism linked to lower stroke severity, inflammation”.
And since we are indirectly talking about the brain, while many positive news have come to science recently, few made me as happy as the fall of neurology's biggest misconceptions since its inception. The first, and “most impactful” of the 3. The sadly paywalled study here. This study was widely covered on scientific media if you want to read larger covering.
A long-standing misconception in the field of neurology and the study of the brain has been neurogenesis, the ability of the brain to create new neurons. A large portion of scientists hold the belief that neurogenesis stops at birth, you are born with your neurons already capped at the maximum.
The authors used a machine learning (hehe) approach to identify gene activity in nerve cells, sequencing RNA of individual cells and precise imaging, they analyzed thousands of hippocampal cells from post-mortem brain samples. Adding the machine learning algorithm allowed the authors to identify and visualize neural progenitor cells in the adult brain hippocampus.
The caveat is the uniqueness of the findings, as each brain is unique and this is reflected in the many cell type populations and especially the progenitor cells, as some brains had more, others had less, some had none. Still, it opens the door towards fully comprehending the brain’s incredible ability to recover even without intervention.
The second major misconception if you will, to fall, is more fundamental to how science perceives how the brain works. For as many decades as the neurogenesis birth hypothesis, the dominant model has been that the brain is mostly modular. Such as the birth of Neural Network’s being a simplified attempt to mimic how neurons and our own neural network function, the brain has been seen from an engineering perspective.
Specific parts for specific jobs. The visual cortex for seeing, motor cortex for moving, and high-level regions such as the prefrontal cortex for complex, decision-making choices throughout the day. Both groundbreaking studies come from the same international consortium, the International Brain Laboratory, providing not only one of the most refined, public, neurological datasets in the field, but also significant evidence (paper here).
They created a standardized, reproducible decision-making task for mice and had 12 different laboratories replicate the experimental protocol. Using Neuropixels probes, a way to measure neural activity, they recorded hundreds of neurons simultaneously, and built the cutting-edge dataset composed of over 621,733 neurons recorded across 279 brain areas of 139 mice, while the animals performed the same complex task. After quality assurance, they ended up with 75.700 well-isolated neurons.
The test consisted of the mice seeing a visual stimulus either on the left or the right side of a screen to get a reward, and in turn to get the reward, they had to turn a small wheel to move the stimulus to the center. The cognitive element of the task, for long blocks of trials, the stimulus was much more likely to appear on one side than the other, creating a prior (the scientific word for internal belief or expectation of something).
By a series a complex behavioral, psychometric, and molecular tests, measurements the authors found that the brain processes complex tasks in a mix of localized and distributed forms. Raw sensory information is initially processed in specialized parts of the brain, while choice, action, and outcome become integrated variables, being processed across a vast, distributed neural network.
Thus, many parts of the brain participate in executing a complex task, such as the cortex, basal ganglia, thalamus, cerebellum, and, surprisingly enough, even the brainstem, all working in parallel. While specialization in certain areas exists, it is widespread, systemic processing.
The second paper, from the same consortium using this sophisticated new dataset, went on to ask a deeper question, the prior itself. The prior was found to be enconded everywhere, even in the earliest sensory processing areas, and it was present before the stimulus even appeared.
This provides strong evidence for the argument that the brain is a highly recurrent, interconnected network that is constantly making predictions. Priors are sent to all areas of the brain, from high to low-level areas, preparing sensory circuits for expected inputs, even before the inputs are actually there. Our beliefs are broadcast across the entire brain, preparing sensory circuits for expected inputs.
Our “priors” come from reflecting on recent actions, rather than incoming stimulus. We are what we do, in a literal sense. The evidence towards the brain being a prediction machine has wider implications, left for another time. Perhaps I shall write simpler articles in the coming days, although my preference is to break down the scientific complexity.
Your support is greatly appreciated.
Great article. My doc marvels how well I’m doing despite all my RA markers being high (like CRP of 60 at times) and says I have RA robusticus, lol. It was hard getting to where I am, but doable.
I want to thank you for playing a part in my recovery.🤗
Sad thing is, Many LC patients will assume this is gaslighting instead of good medical advice. They will think you are saying the disease is all in their heads when in fact you are NOT saying that at all.