Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Schizophrenia as a deficiency in long-range cortex-to-cortex communication, published by Steven Byrnes on February 1, 2023 on LessWrong.

(Written in a hurry. I was almost going to title this “My poorly-researched pet theory of schizophrenia”. Hoping for feedback and pointers to relevant prior literature. I am very far from a schizophrenia expert.)

1. What’s my hypothesis?

My hypothesis is that the root cause of schizophrenia is (.drumroll.) a deficiency in medium- to long-range cortex-to-cortex connections. Some elaboration:

When I say “deficiency”, I mean either “the connections aren’t there in their normal numbers” or “the connections are there, but for some reason they’re not accomplishing what they accomplish in neurotypical people”.

When I say “cortex-to-cortex connections”, I think the main culprit is direct connections between Cortex Region A and Cortex Region B, but it’s also possible that the relevant thing is indirect connections between Cortex Region A and Cortex Region B, e.g. via the thalamus or cerebellum.

When I say “medium- to long-range”, this definitely includes e.g. connections between different lobes, and it probably also includes connections across a few centimeters of cortex in humans. I haven’t really thought about what would happen if there was a deficiency in all connections of any length, including the very short ones, but I would weakly guess that this would present as schizophrenia as well.

2. How did I originally come up with that hypothesis?

I can pinpoint the exact moment: I was reading about visual processing abnormalities in schizophrenia, and more specifically the paper Weak Suppression of Visual Context in Chronic Schizophrenia (Dakin, Carlin, Hemsley 2005). They showed people pictures like this:

The task was to match the image contrast in the red circle to one of the circles on the left. The eye-popping results were:

the schizophrenics did better than the control group,

.with a p-value of 0.0000002!

Indeed, “12 out of 15 [subjects with schizophrenia] were more accurate than the most-accurate control.”

.i.e., there were only three subjects with schizophrenia who did not outperform each and every one of the 33 people in the control groups. And one of those three was later re-diagnosed as not schizophrenic after all!

Back to the task, the control group gets misled by the contrast level outside of the red circle, and the schizophrenic group didn’t. Here’s how I interpreted that:

Each part of the visual cortex is trying to make sense of (more specifically, predict) the sensory inputs that it’s getting. To do a good job at that task, in normal life, it’s helpful to take account of information happening elsewhere in the visual field. After all, distant parts of the visual field are conveying information about ambient light levels, textures and slopes, and things like that. When a neurotypical person grows up viewing naturalistic images, they form lots of predictive models that are near-optimally incorporating all that distant “context” information, pulled in from all across the visual cortex and maybe elsewhere in the brain too. And that screws them up in this particular task. The goal of this task is to ignore all context and look at the red circle contents in isolation. The visual system does not have a set of predictive models that are tailored for accomplishing this task, so the control groups tend to do poorly.

But schizophrenics are succeeding at the same task. Why? Well, presumably for them, the distant “context” information is not available in the first place. So their visual cortex is generally unable to leverage it for better predictive models. This makes their sensory predictions generally worse in a naturalistic setting. But it allows them to do better in this unnatural setting, where the contextual information is only there t...