I'll direct this at Bernardo in the event he reads it, but anyone should feel free to respond.
I've just read your paper and the
LSD paper that you reference above. I've read the
2012 paper awhile back but haven't gone over it again now.
I have some questions regarding your interpretation of the LSD paper. Note, I don't claim expertise in any of this, I don't have a scientific background and had to look up most terms to figure out what they meant. What follows represents my best effort to understand the material and raise questions that I have. I'll say off the bat that on my understanding there is a serious omission in your paper and your treatment of the 2016 study, but hopefully it is one that is based on my misunderstanding of something rather than a more serious problem. My questions are not rhetorical, and hopefully my criticisms will be taken in the constructive spirit with which they are intended.
Here is what you say about it:
In the second study, localized increases in CBF were observed in the visual cortex of subjects on LSD, but magnetoencephalography (MEG)— which performs a more direct measurement of neural activity than CBF—again revealed reductions in activity throughout the brain. The slight discrepancy in CBF measurements between the two studies was explained by the researchers in the following manner: ‘One must be cautious of proxy measures of neural activity (that lack temporal resolution), such as CBF … lest the relationship between these measures, and the underlying neural activity they are assumed to index, be confounded by extraneous factors, such as a direct vascular action of the drug’ (Carhart-Harris et al 2016, 5). They proceeded to say that ‘more direct measures of neural activity (e.g., EEG and MEG) … should be considered more reliable indices of the functional brain effects of psychedelics’ (Carhart-Harris et al 2016, 6).
First of all, this isn't a big point, but I think we have to be careful about interpreting their caution as "explaining" the discrepancy. Rather, it warns us to take those findings with a grain of salt and that further research needs to be done on that score.
I'm much more concerned about why you left out the bit representing the ellipsis after (e.g. EEG and MEG) and left out any reference to the rest of the paragraph, which described the more important findings. Here is the entire passage. I'll bold the parts that were left out:
One must be cautious of proxy measures of neural activity (that lack temporal resolution), such as CBF or glucose metabolism, lest the relationship between these measures, and the underlying neural activity they are assumed to index, be confounded by extraneous factors, such as a direct vascular action of the drug (
43). For this reason, more direct measures of neural activity (e.g., EEG and MEG)
and/or more dynamic fMRI measures (e.g., RSFC) should be considered more reliable indices of the functional brain effects of psychedelics,
and it is notable in this regard that our previous MEG (9) and RSFC (16, 19, 42) findings with psilocybin are highly consistent with those observed here with LSD. Thus, rather than speculate on the above-mentioned discrepancy, it may be more progressive to highlight the advantages of EEG/MEG and dynamic fMRI and conclude that further work would be required to resolve discrepancies in the literature regarding the effects of psychedelics on metabolically related metrics that lack temporal resolution.
RSFC stands for Resting State Functional Connectivity, which according to wiki measures "regional interactions that occur when a subject is not performing an explicit task." CBF is cerebral blood flow.
The reason I think this is important is because your argument focuses solely on overall power, which are some of the findings in these studies, but ignores the parts of the study that look at how the activity in the brain shifts around, and how certain connections increase while others decrease.
Let's look at some of the findings in the LSD Study: (don't read too much into the bracketed linkages that I've added, They don't come from the paper, they are based on wiki, and I put them in there to give myself and others a general idea of what we're talking about.)
- Increased CBF in the visual cortex, the magnitude of increase correlates possitively with ratings of complex imagery on the ASC
- Increased RSFC between the primary visual cortex and a large number of cortical and subcortical brain regions.
- Decreased RSFC between the bilateral parahippocampal (PH) and the retrosplenial cortex (RSC) and posterior cingulate cortex (PCC) (areas that wiki associates with e to memory retrieval and human awareness)
- Increased between the PH and dorsal medial prefrontal cortex (PFC) and right dorsolateral PFC (linked to attention, cognition and action- wki)
- Increased RSFC between the ventromedial PFC (vmPFC) and the bilateral caudate and inferior frontal gyus (linked to processing risk and fear, inhibition of emotional responses, decision making, learning, inhibitory control, language processing, go/no go tasks).
- Decreased RSFC between the vmPFC and the PCC.
- Increased RSFC between the primary visual cortex and other significant regions correlated with VAS ratings of simple hallucinations and ASC rating of elementary and complex imagery
- Decreased RSFC between PH and significant regions correlated with VAS ratings of ego-dissolution and altered-meaning on the ASC.
- Increased visual cortex CBF and primary visual cortex RSFC correlated more with visual hallucinatory aspect of the drug experience than altered meaning/ego dissolution aspect
- Opposite true for decreased PH RSFC.
- Changes in cmPFC RSFC did not correlate with any ratings.
They then look at activity in 12 resting state networks (RSNs) and found:
- Increases in CBF were only found in the visual RSNs, nowhere else.
- Decreases in other activity was more pronounced and universal.
- default-mode network (DMN) disintegration was correlated with ego-dissolution ratings (consistent with psilocybin study), compared against testing of correlations in the other RSN produced no significant correlation. (DMNs are networks of interacting brain regions with high correlational activity, distinct from other networks in the brain).
- Disintegration of visual RSNs did not correlated with ratings of visual hallucinations.
- RSFC between the RSNs or RSN segregation was markedly modulated by LSD (although decreased RSN segregation did not correlate with ego-dissolution ratings)
MEG analysis:
- Decreased oscillatory power under LSD in four frequency bands (muscle artifact may have confounded these results)
- Significant relationships were found between ego-dissolution, and decreased delta and alpha power
- Significant relationships found between simple hallucinations and decreased alpha power.
- Distribution of power was decreased across a broad frequency range under LSD.
- Peak alpha rhythm was reduced in amplitude and of higher frequency.
- While power decreased throughout the brain, there were certain areas that decreased much more: the decreases were not evenly distributed throughout the brain with significant effects in the PCC/precuneus (theta, alpha, and beta) and other high-level cortical regions (delta-beta) (If you look at the chart in the appendix, you can see much bigger decreases in those areas than in the others)
They found certain correlations between the various imaging outcomes between
- increased CBF in visual cortex and decreases in alpha power in psoterior (occipital) cortex sensors.
- increased RSFC between the primary visual cortex and other significant regions with decreased posterior-sensor alpha power.
- (plus some other findings I'm not going to summarize.)
Bernardo, if I'm reading you right, the only parts of this you address is the increase in CBF in the visual cortex, and the overall decrease in power. This leaves out a lot of findings, in particular the ones the authors suggest are more reliable (the RSFC and MEG findings). The RSFC findings if I understand correctly are extremely important because they describe the changes in connections between areas and we see a number of areas with increased connections, and others with decreased.
The discussion section goes into more detail on the significance of these changes, in particular the findings of increased connections between the primary visual cortex and other areas of the brain which they suggest demonstrates that a far greater proportion of brain contributes to visual processing while under the effects of LSD.
Interestingly, the relationship between the increased visual activity correlated to the hallucinations but not ego-dissolution. On the other hand, there was a specific relationship between DMN disintegration and ego-dissolution (also consistent with the 2012 study) linking DMN integrity with our sense of self. There was another very strong relationship between bilateral parahippocampal and retrosplenial cortex decoupling with the altered meaning factor on the ASC (an area associated with spiritual experience and insightfulness in other studies).
They conclude that psychedelics seem induce network disintegration and desegregation. Consistent with other studies.
Now, the authors note some limitations of the study and it is clear that more research will need to be done to confirm these findings and further explore these relationships. I can't speak as to the soundness of their findings or the level of significance of the results. There may be some legitimate discussion to be had there. The problem is, that you don't go into that at all You only deal with the increased CBF finding by refering to a warning that there could be confounding factors there (but not really addressing the relationships that were seen) and refer very generally to the overall decrease in power. You don't look at all at the changes within the brain network, the areas where there is seen to be more visual activity correlating with hallucinations, or network disintegration in some areas being correlated with a decreased sense of self, or any of the other findings that the authors consider important.
You may have arguments to address this (I hope so) but I still can't understand why you left out mention of any of this, even breaking up a quote to take out the parts the authors considered most important.