# K(ey)-hole to K-hole

*Source:* [Slipping into a K-hole | annotated by Zakhar](https://readwise.io/reader/shared/01gkza3w4pg4kw38bmgmpchvt2)
![](https://i.imgur.com/68cm6PI.png)
*You've completely lost control over this situation.*

## Cortex and prediction-error modelling
- Cortex is divided from lowest (sensory information) to higher (constructing a world model) areas
  ![](https://i.imgur.com/2VJEAwR.png)
- Cortex is also subdivided into six layers:
	- Neurons in the _deep layers_ (layers 5 and 6) are responsible for generating model predictions and transmitting them down the cortical hierarchy to the primary areas. 
	- The _superficial layer_ neurons (layers 1-3) are responsible for comparing these predictions to actual sensory information and calculating the prediction errors, which are then sent to neurons in the _input layer_ (layer 4) in the next (higher) level of the hierarchy. 
	- So, the prediction errors are broadcast up the cortical hierarchy (with the predictions flowing in the opposite direction) and are used to refine the model until the flow of errors is stemmed (meaning the model is better able to predict the sensory information).
- In the basal state (before ketamine reaches the brain), a large population of excitatory neurons (we’ll call them _supporting neurons_ (blue box)) not involved in generating or transmitting predictions/error are suppressed by inhibitory interneurons and largely inactive (in grey)
## Ketamine
Ketamine is acting within three concentration "levels":
### Low dose
![](https://i.imgur.com/vOYaXEP.png)
_At low ketamine doses, the highly susceptible inhibitory interneurons are suppressed, releasing the previously quie excitatory neurons from inhibition and allowing them to become active. This results in a global increase in cortical activity._
### Medium dose spectrum (world model substitution)
![](https://i.imgur.com/FKSU8kV.png)
_At moderate ketamine doses, the prediction/error generating neurons are directly suppressed while the supporting neurons remain active. The world model is disconnected from the environment (K-hole state)_
### High dose (comatose)
![](https://i.imgur.com/bGC7TMS.png)
_At high ketamine doses, the low-susceptibility supporting neurons are suppressed resulting in a global reduction in cortical activity (anaesthetised state)_
## Overview
![](https://i.imgur.com/ypeJZ7X.png)

PS. Okay, [Andre](https://alieninsect.substack.com) is seriously awesome.

---
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