An interesting theory! But I am confused by why you think that antipsychotics can’t act simply by increasing the strength of A-type signals. Why do they also have to affect the B-type signals? if A signals are disproportionately inhibitory, that would account for why a notorious side-effect of antipsychotics is stiffness and a general reluctance to do stuff. Your claim that the relapsing-remitting nature of schizophrenia doesn’t fit your first theory seems excessive. Lots of nerve problems are relapsing-remitting (eg mutiple sclerosis). And changes to the the balance of the brain that take weeks are very common (eg antidepressant efficacy, or heroin addiction).
An under activity of long-range fibers could perhaps explain the many abnormalities of visual perception seen in schizophrenics. This is a field full of odd symptoms, with as far as I know no unifying theory.
It seems like you’re only trying to explain one symptom of psychosis: the delusion of an external locus of control. Could you extend your theory to explain other symptoms?
For example, how do you explain hallucination, where somebody has a sensory impression that they know isn’t real (at least with mild psychosis). It seems like hearing voices is an overactivity of the connection from the language area to consciousness, rather than an underactivity.
Another major symptom that might be explained by your theory is delusions of reference, where stimuli that should be treated as minor are instead freighted with importance. Like “What is the ad on that bus that just drove by trying to tell me? Could it have been sent by God?” It’s not obvious what the cortical areas that are involved in this are. But you’re lots more informed than me; what do you think?
But I am confused by why you think that antipsychotics can’t act simply by increasing the strength of A-type signals.
I think schizophrenia is characterized by a deficiency in long-range cortex-to-cortex communication, and I suppose that this deficiency can have a variety of causes in principle. For example, it was found in lab experiments that faulty glutamate signaling can cause schizophrenia—hence “the glutamate hypothesis of schizophrenia” which has been floating around for many decades. But that hypothesis never led to any viable drugs. And I think that’s because faulty glutamate signaling is not the usual cause of the deficiency.
Instead, I think in practice the deficiency is almost always caused by the long-range fibers (and/or their terminal synapses) just not being there in the first place, or at least not in sufficient numbers. I mention some direct evidence for that in section 5 of my previous post.
So basically, I think that cortex-to-cortex communication is just going down a lousy communication channel (noisy / low-bandwidth / low-ability-to-impact-downstream-areas / whatever). And that that problem is basically unfixable in almost all schizophrenic people, absent miraculous future medical advances. And it’s not the kind of problem that I expect to come and go, I think. It’s structural.
But that communication channel, lousy as it is, can still transmit the information if the source-cortex is “shouting” long enough and loud enough. So I think the only viable approach that treating psychosis is to reduce the ratio B/A.
if A signals are disproportionately inhibitory, that would account for why a notorious side-effect of antipsychotics is stiffness and a general reluctance to do stuff.
Not sure about stiffness but “general reluctance to do stuff” is totally what I would expect from “less B”. I don’t follow how you connect it to A.
An under activity of long-range fibers could perhaps explain the many abnormalities of visual perception seen in schizophrenics.
It seems like you’re only trying to explain one symptom of psychosis
Yeah, moving my arm is just one of many types of cortical output.
Another is subvocalizing / inner speech. I don’t understand all the details, but AFAICT producing a subvocalization involves sending signals to brainstem motor areas, and “hearing” your own subvocalization “activates similar areas of the auditory cortex that are involved in listening” (wiki). So my working hypothesis is that “hearing voices” in psychosis involves inner speech feeling like it’s external. Same diagram. (Low confidence though—again, I’m kinda confused about the mechanics of inner speech / subvocalization.)
Yet another type of cortical output is “attentional”—one part of the cortex can exert (metacognitive) control over the information flows and activities of other parts of the cortex (via signals to various subcortical areas). If you visualize a pen, it activates the same neurons in your temporal lobe as if you see a similar pen. You can flip back and forth by (among other things) voluntary metacognitive control. Nevertheless, for a neurotypical person, you don’t get confused about whether the thing you’re attending to is real or imagined. But I think things can get very screwy when one part of the cortex is manipulating the levers on metacognition / attention-control, and other parts of the cortex are not getting advanced notice that this metacognition / attention-control is happening. So basically, I think a visual hallucination would happen when the metacognitive / attention-control parts of the cortex (prefrontal probably) set part of the visual system (temporal lobe) to imagination-mode rather than attend-to-what’s-in-front-of-you mode, but other parts of the cortex don’t get the memo that we’re in imagination-mode right now, and they interpret the (imagined) current contents of the visual system as a reflection of what’s directly in sight and coming up through V1/V2/etc.
An interesting theory! But I am confused by why you think that antipsychotics can’t act simply by increasing the strength of A-type signals. Why do they also have to affect the B-type signals? if A signals are disproportionately inhibitory, that would account for why a notorious side-effect of antipsychotics is stiffness and a general reluctance to do stuff. Your claim that the relapsing-remitting nature of schizophrenia doesn’t fit your first theory seems excessive. Lots of nerve problems are relapsing-remitting (eg mutiple sclerosis). And changes to the the balance of the brain that take weeks are very common (eg antidepressant efficacy, or heroin addiction).
An under activity of long-range fibers could perhaps explain the many abnormalities of visual perception seen in schizophrenics. This is a field full of odd symptoms, with as far as I know no unifying theory.
It seems like you’re only trying to explain one symptom of psychosis: the delusion of an external locus of control. Could you extend your theory to explain other symptoms?
For example, how do you explain hallucination, where somebody has a sensory impression that they know isn’t real (at least with mild psychosis). It seems like hearing voices is an overactivity of the connection from the language area to consciousness, rather than an underactivity.
Another major symptom that might be explained by your theory is delusions of reference, where stimuli that should be treated as minor are instead freighted with importance. Like “What is the ad on that bus that just drove by trying to tell me? Could it have been sent by God?” It’s not obvious what the cortical areas that are involved in this are. But you’re lots more informed than me; what do you think?
Thanks for your helpful comment!
I think schizophrenia is characterized by a deficiency in long-range cortex-to-cortex communication, and I suppose that this deficiency can have a variety of causes in principle. For example, it was found in lab experiments that faulty glutamate signaling can cause schizophrenia—hence “the glutamate hypothesis of schizophrenia” which has been floating around for many decades. But that hypothesis never led to any viable drugs. And I think that’s because faulty glutamate signaling is not the usual cause of the deficiency.
Instead, I think in practice the deficiency is almost always caused by the long-range fibers (and/or their terminal synapses) just not being there in the first place, or at least not in sufficient numbers. I mention some direct evidence for that in section 5 of my previous post.
So basically, I think that cortex-to-cortex communication is just going down a lousy communication channel (noisy / low-bandwidth / low-ability-to-impact-downstream-areas / whatever). And that that problem is basically unfixable in almost all schizophrenic people, absent miraculous future medical advances. And it’s not the kind of problem that I expect to come and go, I think. It’s structural.
But that communication channel, lousy as it is, can still transmit the information if the source-cortex is “shouting” long enough and loud enough. So I think the only viable approach that treating psychosis is to reduce the ratio B/A.
Not sure about stiffness but “general reluctance to do stuff” is totally what I would expect from “less B”. I don’t follow how you connect it to A.
I think so! I have an example in my previous post.
Yeah, moving my arm is just one of many types of cortical output.
Another is subvocalizing / inner speech. I don’t understand all the details, but AFAICT producing a subvocalization involves sending signals to brainstem motor areas, and “hearing” your own subvocalization “activates similar areas of the auditory cortex that are involved in listening” (wiki). So my working hypothesis is that “hearing voices” in psychosis involves inner speech feeling like it’s external. Same diagram. (Low confidence though—again, I’m kinda confused about the mechanics of inner speech / subvocalization.)
Yet another type of cortical output is “attentional”—one part of the cortex can exert (metacognitive) control over the information flows and activities of other parts of the cortex (via signals to various subcortical areas). If you visualize a pen, it activates the same neurons in your temporal lobe as if you see a similar pen. You can flip back and forth by (among other things) voluntary metacognitive control. Nevertheless, for a neurotypical person, you don’t get confused about whether the thing you’re attending to is real or imagined. But I think things can get very screwy when one part of the cortex is manipulating the levers on metacognition / attention-control, and other parts of the cortex are not getting advanced notice that this metacognition / attention-control is happening. So basically, I think a visual hallucination would happen when the metacognitive / attention-control parts of the cortex (prefrontal probably) set part of the visual system (temporal lobe) to imagination-mode rather than attend-to-what’s-in-front-of-you mode, but other parts of the cortex don’t get the memo that we’re in imagination-mode right now, and they interpret the (imagined) current contents of the visual system as a reflection of what’s directly in sight and coming up through V1/V2/etc.
(Or something like that.)