Showing posts with label brain plasticity. Show all posts
Showing posts with label brain plasticity. Show all posts

Wednesday, March 06, 2024

Deep learning models reveal sex differences in human functional brain organization that are replicable, generalizable, and behaviorally relevant

Ryali et al. do a massive analysis that argues strongly against the notion of a continuum in male-female brain organization, and underscore the crucial role of sex as a biological determinant in human brain organization and behavior.  I pass on the significance and abstract statements. Motivated readers can obtain a PDF of the article from me.  

Significance

Sex is an important biological factor that influences human behavior, impacting brain function and the manifestation of psychiatric and neurological disorders. However, previous research on how brain organization differs between males and females has been inconclusive. Leveraging recent advances in artificial intelligence and large multicohort fMRI (functional MRI) datasets, we identify highly replicable, generalizable, and behaviorally relevant sex differences in human functional brain organization localized to the default mode network, striatum, and limbic network. Our findings advance the understanding of sex-related differences in brain function and behavior. More generally, our approach provides AI–based tools for probing robust, generalizable, and interpretable neurobiological measures of sex differences in psychiatric and neurological disorders.
Abstract
Sex plays a crucial role in human brain development, aging, and the manifestation of psychiatric and neurological disorders. However, our understanding of sex differences in human functional brain organization and their behavioral consequences has been hindered by inconsistent findings and a lack of replication. Here, we address these challenges using a spatiotemporal deep neural network (stDNN) model to uncover latent functional brain dynamics that distinguish male and female brains. Our stDNN model accurately differentiated male and female brains, demonstrating consistently high cross-validation accuracy (>90%), replicability, and generalizability across multisession data from the same individuals and three independent cohorts (N ~ 1,500 young adults aged 20 to 35). Explainable AI (XAI) analysis revealed that brain features associated with the default mode network, striatum, and limbic network consistently exhibited significant sex differences (effect sizes > 1.5) across sessions and independent cohorts. Furthermore, XAI-derived brain features accurately predicted sex-specific cognitive profiles, a finding that was also independently replicated. Our results demonstrate that sex differences in functional brain dynamics are not only highly replicable and generalizable but also behaviorally relevant, challenging the notion of a continuum in male-female brain organization. Our findings underscore the crucial role of sex as a biological determinant in human brain organization, have significant implications for developing personalized sex-specific biomarkers in psychiatric and neurological disorders, and provide innovative AI-based computational tools for future research.

Monday, February 12, 2024

The Art of Doing Nothing

Deep into the Juniper/Cedar pollen allergy season in Austin TX, I'm being frustrated that I have so little energy to do things. It's as if my batteries can not muster more than a 10% charge. I try to tell myself that it's OK to 'just be", to do nothing, and have not been very successful at this.  So, I enjoyed  stumbling upon a  recent Guardian article, "The art of doing nothing: have the Dutch found the answer to burnout culture?," whose URL I pass on to MindBlog readers.  It describes the concept of 'niken,' or the Dutch art of doing nothing. It has  has ameliorated my concern over how little I have been getting done, and references a 2019 NYTimes article, "The Case for Doing Nothing" that went viral when it was first published.  Letting go of always finding problems that need to be solved let's one face  a question posed by the meditation guru Loch Kelly: "What is there when there are no problems to be solved?" Variants of this question have been addressed in a thread of numerous MindBlog posts that I have now largely drawn to a close.

Monday, February 05, 2024

Functional human brain tissue produced by layering different neuronal types with 3D bioprinting

A very important advance by Su-Chun Zhang and collaborators at the University of Wisconsin that moves studies of nerve cells connecting in nutrient dishes from two to three dimensions:  

Highlights

  • Functional human neural tissues assembled by 3D bioprinting
  • Neural circuits formed between defined neural subtypes
  • Functional connections established between cortical-striatal tissues
  • Printed tissues for modeling neural network impairment

Summary

Probing how human neural networks operate is hindered by the lack of reliable human neural tissues amenable to the dynamic functional assessment of neural circuits. We developed a 3D bioprinting platform to assemble tissues with defined human neural cell types in a desired dimension using a commercial bioprinter. The printed neuronal progenitors differentiate into neurons and form functional neural circuits within and between tissue layers with specificity within weeks, evidenced by the cortical-to-striatal projection, spontaneous synaptic currents, and synaptic response to neuronal excitation. Printed astrocyte progenitors develop into mature astrocytes with elaborated processes and form functional neuron-astrocyte networks, indicated by calcium flux and glutamate uptake in response to neuronal excitation under physiological and pathological conditions. These designed human neural tissues will likely be useful for understanding the wiring of human neural networks, modeling pathological processes, and serving as platforms for drug testing.
 

 


Sunday, January 21, 2024

Titles and URLs for key MindBlog posts on selves

I pass on a chronological list of titles and URLs of MindBlog posts assembled in preparation for a video chat with a European MindBlog reader:

An "Apostle's Creed" for the humanistic scientific materialist?
https://mindblog.dericbownds.net/2006/03/apostles-creed-for-humanistic.html

Some rambling on "Selves" and “Purpose”
https://mindblog.dericbownds.net/2007/10/some-rambling-on-selves-and-purpose.html

Self, purpose, and tribal mentality as Darwinian adaptations (or…Why why aren’t we all enlightened?)
https://mindblog.dericbownds.net/2020/05/self-purpose-and-tribal-mentality-as.html

MindBlog passes on a note: on the relief of not being yourself
https://mindblog.dericbownds.net/2020/03/mindblog-passes-on-note-on-relief-of.html

Points on having a self and free will.
https://mindblog.dericbownds.net/2021/03/points-on-having-self-and-free-will.html

I am not my problem
https://mindblog.dericbownds.net/2022/06/i-am-not-my-problem.html

The non-duality industry as a panacea for the anxieties of our times?         https://mindblog.dericbownds.net/2022/11/the-non-duality-industry-as-panacea-for.html

Enlightenment, Habituation, and Renewal - Or, Mindfulness as the opiate of the thinking classes?
https://mindblog.dericbownds.net/2023/01/enlightenment-habituation-and-renewal.html

A quick MindBlog riff on what a self is….
https://mindblog.dericbownds.net/2023/01/a-quick-mindblog-riff-on-what-self-is.html

MindBlog paragraphs bloviating on the nature of the self ask Google Bard and Chat GPT 4 for help
https://mindblog.dericbownds.net/2023/05/mindblog-paragraphs-bloviating-on.html

A MindBlog paragraph on non-dual awareness massaged by Bard and ChatGPT-4
https://mindblog.dericbownds.net/2023/07/a-mindblog-paragraph-on-non-dual.html

Constructing Self and World
https://mindblog.dericbownds.net/2023/09/constructing-self-and-world.html  

Anthropic Claude's version of my writing on the Mind - a condensation of my ideas
https://mindblog.dericbownds.net/2023/10/anthropic-claudes-version-of-my-writing.html  

A Materialist's Credo
https://mindblog.dericbownds.net/2023/10/a-materialists-credo.html

How our genes support our illusory selves - the "Baldwin effect"
https://mindblog.dericbownds.net/2023/11/how-our-genes-support-our-illusory.html











.



















.








 


Wednesday, January 10, 2024

If psychedelics heal, how do they do it?

I pass on from a recent issue of PNAS this informative "News Feature" article by Carolyn Beans (open source).  It discusses studies trying to determine the brain mechanisms by which therapeutically effective psychedelics such as MDMA (3,4-methylenedioxymethamphetamine, commonly known as ecstacy), psilocybin, and LSD have their effect.  They all act on serotonin receptors.  

Sunday, December 03, 2023

A flash of clarity on what current LLMs can and can not do. An AI apocalypse does not appear to be eminent...

In his most recent newsletter, Venkatesh Rao pulls up a twitter thread he wrote in 2017 making what he calls an ontological distinction between  boundary intelligence and interior intelligence.  This was before transformers like GPT-1 began to attract more attention. The distinction Rao makes is central to understanding what current large language models (LLMs) can and can not do. Here is his unedited text from 2017:
 
1. I'd like to make up a theory of intelligence based on a 2-element ontology: boundary and interior intelligence

2. Boundary intelligence is how you deal with information flows across the boundary of your processing abilities 

3. Interior intelligence is how you process information. Includes logic, emotional self-regulation, etc.

4. A thesis I've been converging on is that boundary intelligence is VASTLY more consequential once interior intelligence exceeds a minimum

5. Boundary intelligence is by definition meta, since you're tuning your filters and making choices about what to even let hit your attention

6. I think it is highly consequential because almost all risk management happens via boundary intelligence (blindspots, black swans etc)

7. Interior intelligence is your poker skill and strategy. Boundary intelligence is picking which table to sit down at

8. Interior intelligence is reading a book competently, extracting insights and arguments. Boundary intelligence is picking books to read. 

9. Interior intelligence is being a good listener. Boundary intelligence is deciding whom to listen to. 

10. Basically, better input plus mediocre IQ beats bad input and genius IQ every time, so boundary intelligence is leverage

11. And obviously, boundary intelligence is more sensitive to context. The noisier and angrier info streams get, the more BI beats II

12. Most of boundary intelligence has to do with input intelligence, but output intelligence becomes more important with higher agency 

13. Output intelligence is basically the metacognition around when/where/how/to-whom/why to say or do things you are capable of saying/doing

14. We think a lot about external factors in decisions, but output intelligence is about freedom left after you've dealt with external part

Next, from the abstract of a forthcoming paper by Yadlowsky et al. Rao extracts the following:

…when presented with tasks or functions which are out-of-domain of their pretraining data, we demonstrate various failure modes of transformers and degradation of their generalization for even simple extrapolation tasks. Together our results highlight that the impressive ICL abilities of high-capacity sequence models may be more closely tied to the coverage of their pretraining data mixtures than inductive biases that create fundamental generalization capabilities.

And then, in the following selected clips, continues his text:

Translated into the idiom from the fourteen points above, this translates into “It’s all interior intelligence, just within a very large boundary.” There is no boundary intelligence in current machine learning paradigms. There isn’t even an awareness of boundaries; just the ability to spout statements about doubt, unknowns, and boundaries of knowability; a bit like a blind person discussing color in the abstract.

This is not to say AI cannot acquire BI. In fact, it can do so in a very trivial way, through embodiment. Just add robots around current AIs and let them loose in real environments.

The reason people resist this conclusion is is irrational attachment to interior intelligence as a sacred cow (and among computer science supremacists, a reluctance to acknowledge the relevance and power of embodiment and situatedness in understandings of intelligence). If much of the effectual power of intelligence is attributable to boundary intelligence, there is much less room for sexy theories of interior intelligence. Your (cherished or feared) god-like AI is reduced to learning through FAFO (Fuck around and find out) feedback relationships with the rest of the universe, across its boundary, same as us sadsack meatbag intelligences with our paltry 4-GPU-grade interior intelligence.

In their current (undoubtedly very impressive) incarnation, what we have with AI is 100% II, 0% BI. Human and animal intelligences (and I suspect even plant intelligences, and definitely evolutionary process intelligence) are somewhere between 51-49 to 99.9-0.1% BI. They are dominated to varying degrees by boundary intelligence. Evolutionary processes are 100% BI, 0% II.

Wednesday, August 30, 2023

Neuron–astrocyte networks might perform the core computations performed by AI transformer blocks

Fascinating ideas from Kozachkov et al. Their text contains primers on Astrocyte biology and the transformers found in AI Generative Pre-trained Transformers such as ChatGPT.  

Significance

Transformers have become the default choice of neural architecture for many machine learning applications. Their success across multiple domains such as language, vision, and speech raises the question: How can one build Transformers using biological computational units? At the same time, in the glial community, there is gradually accumulating evidence that astrocytes, formerly believed to be passive house-keeping cells in the brain, in fact play an important role in the brain’s information processing and computation. In this work we hypothesize that neuron–astrocyte networks can naturally implement the core computation performed by the Transformer block in AI. The omnipresence of astrocytes in almost any brain area may explain the success of Transformers across a diverse set of information domains and computational tasks.
Abstract
Glial cells account for between 50% and 90% of all human brain cells, and serve a variety of important developmental, structural, and metabolic functions. Recent experimental efforts suggest that astrocytes, a type of glial cell, are also directly involved in core cognitive processes such as learning and memory. While it is well established that astrocytes and neurons are connected to one another in feedback loops across many timescales and spatial scales, there is a gap in understanding the computational role of neuron–astrocyte interactions. To help bridge this gap, we draw on recent advances in AI and astrocyte imaging technology. In particular, we show that neuron–astrocyte networks can naturally perform the core computation of a Transformer, a particularly successful type of AI architecture. In doing so, we provide a concrete, normative, and experimentally testable account of neuron–astrocyte communication. Because Transformers are so successful across a wide variety of task domains, such as language, vision, and audition, our analysis may help explain the ubiquity, flexibility, and power of the brain’s neuron–astrocyte networks.

Wednesday, July 26, 2023

A MindBlog paragraph on non-dual awareness massaged by Bard and ChatGPT-4

This post is using MindBlog to archive a further example example of the sort shown in Monday’s post ...of GPT bots editing  a paragraph I wrote, this one being on non-dual awareness.  The paragraph:

The fact that  there is no there there means it. Empty is empty. The ground state is just the mute body doing its thing. From its depths storylines rise and fall, bonbons to savor or ignore. The body can know that it has found a new ground state, and can be no longer willing to just play nice if the upstairs word salad is dinking around with or threatening its peace. It can withdraw from the fray. It can rest as a calm non-dual self centered within a cosmic perspective of time and space that views the rise and fall of human civilizations during the anthropocene as minor dances in the music of time.

After incorporating some changes suggested by Google Bard and GPT4:

When we say something is empty, we mean just that: it contains nothing. Our natural baseline or 'ground state' is the body performing its automatic functions without our conscious intervention. From the body's inherent depths, various thoughts or experiences emerge and recede, like bonbons we can savor or ignore. The body can grow to know that it has found a new ground state in the present moment, a ground state of awareness that no longer needs to be caught up in word salads of disruptive thoughts that can threaten its peace.  It can withdraw from the fray and can rest as a calm non-dual state of being centered within a cosmic perspective of time and space that can view the rise and fall of human civilizations during the anthropocene as minor dances in the music of time.


Monday, July 24, 2023

The evolution of transhuman forms - a MindBlog paragraph edited by GPT implementations

In this post I am documenting the final result of passing a paragraph I wrote on future human evolution through a number of different GPT (generative pre-trained transformers). This is to archive the results of this exercise for myself, and in case it might be of interest to a few MindBlog readers. The bots were prompted by a request to re-write or edit the paragraph to make it more accessible to a reader with a college education.

The bottom line is that the edited versions with the most depth and coherence were obtained using Open AI’s ChatGPT-4.  Bard.google.com, Google Workspace Labs, and Microsoft’s Bing, respectively, provided increasingly less useful versions.   Here is my original paragraph:

The linguistic capabilities of generative pre-trained transformers based on silicon  - the same capabilities that have enabled human civilization  - will soon exceed those of humans. We have brought our understanding of what human beings as they now exist are about to a plateau level at which further increments of understanding will become increasingly small. The cream has been skimmed, the best cherries have been picked, and it seems appropriate to turn our  attention now to studying the evolution of trans human forms utilizing LLMs that are better able to manage themselves and the planet.  The action is in the the pretraining P of GPT, as the models move beyond their initial human management to the stage of evolving themselves, hopefully into benign versions of Darwin’s  “forms most beautiful and most wonderful.” What is the point of humans other than being self replicating machines that evolve into further forms, hopefully before they extinguish themselves by destroying the ecological environment required for their sustenance? Can they evolve into trans human minds (or mind, singular)?
Here is the result of including some of the edits suggested by ChatGPT4’s regenerated response, a  vers. 3 of the paragraph above:
The linguistic capabilities of generative pre-trained transformers based on silicon - the same capabilities that have enabled human civilization - will soon surpass those of humans.

Our understanding of human nature as it currently exists has reached a plateau level, at which further increments of understanding are becoming increasingly small. The cream has been skimmed, the best cherries have been picked. Consequently it seems the right time to shift our focus toward studying the evolution of 'transhuman' forms. These are beings that could potentially leverage advanced language models (LLMs) to better self-regulate themselves and manage the planet.

The real crux of the matter lies in the pretraining phase of these transformers (symbolized by 'P' in GPT). This is when the models are initially developed and fine-tuned. As they evolve beyond their human programming the optimistic vision is that they might transform into benign versions of what Charles Darwin called “forms most beautiful and most wonderful.”

From a philosophical perspective, one might ask: What is the ultimate purpose of human beings, if not to serve as self-replicating entities that evolve into more advanced forms - hopefully before they extinguish themselves by destroying the ecological environment required for their sustenance? Is it possible for humans to evolve into a collective of transhuman minds or even a singular, transcendent mind?  These are questions worth exploring as we stand on the brink of an AI-enhanced future.


Friday, July 07, 2023

A meta-analysis questions the cognitive benefits of physical activity.

I give up. If anything was supposed to have been proven I would have thought it would be that exercise has a beneficial effect on brain health and cognition. Now Ciria et al. offer the following in Nature Human Biology:
Extensive research links regular physical exercise to an overall enhancement of cognitive function across the lifespan. Here we assess the causal evidence supporting this relationship in the healthy population, using an umbrella review of meta-analyses limited to randomized controlled trials (RCTs). Despite most of the 24 reviewed meta-analyses reporting a positive overall effect, our assessment reveals evidence of low statistical power in the primary RCTs, selective inclusion of studies, publication bias and large variation in combinations of pre-processing and analytic decisions. In addition, our meta-analysis of all the primary RCTs included in the revised meta-analyses shows small exercise-related benefits (d = 0.22, 95% confidence interval 0.16 to 0.28) that became substantially smaller after accounting for key moderators (that is, active control and baseline differences; d = 0.13, 95% confidence interval 0.07 to 0.20), and negligible after correcting for publication bias (d = 0.05, 95% confidence interval −0.09 to 0.14). These findings suggest caution in claims and recommendations linking regular physical exercise to cognitive benefits in the healthy human population until more reliable causal evidence accumulates.
I can not offer an informed opinion on this abstract because my usual access to journals through the University of Wisconsin library does not work with Nature Human Behavior. However, I can point you to an excellent commentary by Claudia Lopez Lloreda that discusses the meta-analysis done by Ciria et al. and gives a summary of several recent studies on exercise and brain health.

Friday, June 02, 2023

Gender inequality is associated with differences between the brains of men and women

Sobering but not surprising analysis by Jugman et al.:  

Significance

Gender inequality is associated with worse mental health and academic achievement in women. Using a dataset of 7,876 MRI scans from healthy adults living in 29 different countries, we here show that gender inequality is associated with differences between the brains of men and women: cortical thickness of the right hemisphere, especially in limbic regions such as the right caudal anterior cingulate and right medial orbitofrontal, as well as the left lateral occipital, present thinner cortices in women compared to men only in gender-unequal countries. These results suggest a potential neural mechanism underlying the worse outcome of women in gender-unequal settings, as well as highlight the role of the environment in the brain differences between women and men.
Abstract
Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women’s worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women’s brains and provide initial evidence for neuroscience-informed policies for gender equality.

Friday, April 07, 2023

Our heartbeat shapes our perception of time (and a comparison of how ChatGPT and Google Bard condense an account of work showing this)...

Ellen Barry has done a review of work by Sadeghi et al, as well as others, on how heart-brain interactions influence our perception of time. I asked ChatGPT to do a 200 word summary of her article of 795 words. It generated 237 words (below), to which I made a small addition. (I feels like I'm using the language generating mental equivalent of a physical prosthesis.) That is followed by Google Bard's response, very impressive. Microsoft's Bing was unable to deal with the task.
A recent study by psychologists at Cornell University has suggested that our heartbeats may play an important role in shaping our perception of time. The study, published in the journal Psychophysiology, found that some distortions in time perception could be driven by variable heartbeat length. The researchers fitted undergraduates with electrocardiograms to measure the length of each heartbeat and asked them to estimate the length of brief audio tones. After longer heartbeat intervals, subjects tended to perceive the tone as longer, while shorter intervals led to shorter perception. Additionally, the subjects’ heartbeat intervals lengthened after each tone, and a lower heart rate appeared to assist with perception. According to Saeedeh Sadeghi, the study’s lead author, “there is no single part of the brain or body that keeps time — it’s all a network. The brain controls the heart, and the heart, in turn, impacts the brain.”
The study addresses the mechanisms behind how we perceive the passage of milliseconds and may help us manage trauma, in which instantaneous experiences are remembered as drawn out. Intense emotional engagement speeds up perception of time, while depression slows it down. Research into perception of time has traditionally focused on different areas of the brain, but there is now greater appreciation that cognitive functions are intimately linked to the control of the body. Time is closely related to metabolic needs, and the body tries to determine how much energy it has available in the moment, which may affect how we perceive the passage of time.
Here is the response from Google Bard, more impressive, I think:
Sure, here is a 200-word summary [note - it's actually 313 words] of the text:
A recent study published in the journal Psychophysiology suggests that our heartbeat may play an important role in our perception of time. The study found that participants who had longer heartbeat intervals tended to perceive brief audio tones as longer, while participants who had shorter heartbeat intervals tended to perceive the tones as shorter. This suggests that our heart rate may influence how we experience the passage of time.
The study's lead author, Saeedeh Sadeghi, said that the findings provide more evidence that "there is no single part of the brain or body that keeps time — it's all a network." She added that the study "could have implications for understanding how people with certain conditions, such as anxiety or depression, experience time differently."
The study's findings are in line with previous research that has shown that our heart rate can affect our cognitive function. For example, one study found that people who were asked to perform a task while listening to their heartbeat performed worse on the task than those who were not listening to their heartbeat. This suggests that our heart rate may distract us and make it more difficult to focus on tasks.
The study's findings also have implications for our understanding of how we experience time in different situations. For example, the study suggests that time may seem to pass more slowly when we are stressed or anxious, as our heart rate tends to increase in these situations. Conversely, time may seem to pass more quickly when we are relaxed or bored, as our heart rate tends to decrease in these situations.
Overall, the study provides new insights into the complex relationship between our heart rate and our perception of time. The findings could have implications for understanding how people with certain conditions experience time differently, as well as for our understanding of how we experience time in different situations.

Monday, March 13, 2023

Blood-derived signals as potent drivers of both age-related brain dysfunction and brain rejuvenation.

 An open source review from Bieri et al. has some nice graphics and tables summarizing the varieties of pro-aging and rejuvenating interventions.  Here is their abstract.:

Aging induces molecular, cellular and functional changes in the adult brain that drive cognitive decline and increase vulnerability to dementia-related neurodegenerative diseases. Leveraging systemic and lifestyle interventions, such as heterochronic parabiosis, administration of ‘young blood’, exercise and caloric restriction, has challenged prevalent views of brain aging as a rigid process and has demonstrated that aging-associated cognitive and cellular impairments can be restored to more youthful levels. Technological advances in proteomic and transcriptomic analyses have further facilitated investigations into the functional impact of intertissue communication on brain aging and have led to the identification of a growing number of pro-aging and pro-youthful factors in blood. In this review, we discuss blood-to-brain communication from a systems physiology perspective with an emphasis on blood-derived signals as potent drivers of both age-related brain dysfunction and brain rejuvenation.

Monday, February 27, 2023

Possible mechanism of psychedelic therapeutic effects

From the latest issue of Science Magazine:  

The mechanism underlying psychedelic action

Psychedelic compounds promote cortical structural and functional neuroplasticity through the activation of serotonin 2A receptors. However, the mechanisms by which receptor activation leads to changes in neuronal growth are still poorly defined. Vargas et al. found that activation of intracellular serotonin 2A receptors is responsible for the plasticity-promoting and antidepressant-like properties of psychedelic compounds, but serotonin may not be the natural ligand for those intracellular receptors (see the Perspective by Hess and Gould). —PRS
Abstract
Decreased dendritic spine density in the cortex is a hallmark of several neuropsychiatric diseases, and the ability to promote cortical neuron growth has been hypothesized to underlie the rapid and sustained therapeutic effects of psychedelics. Activation of 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) is essential for psychedelic-induced cortical plasticity, but it is currently unclear why some 5-HT2AR agonists promote neuroplasticity, whereas others do not. We used molecular and genetic tools to demonstrate that intracellular 5-HT2ARs mediate the plasticity-promoting properties of psychedelics; these results explain why serotonin does not engage similar plasticity mechanisms. This work emphasizes the role of location bias in 5-HT2AR signaling, identifies intracellular 5-HT2ARs as a therapeutic target, and raises the intriguing possibility that serotonin might not be the endogenous ligand for intracellular 5-HT2ARs in the cortex.

Monday, February 20, 2023

Fundamentally rethinking what a mind is and how a brain works.

The February Issue of Trends in Cognitive Science has an open source Opinions article from Lisa Feldman Barrett and collaborators that suggests that new research approaches grounded in different ontological commitments will be required to properly describe brain-behavior relationships. Here is a clip of the introductory text and a graphic clip from the article. Finally, I pass on the concluding remarks on fundamentally rethinking what a mind is and how a brain works.
Most brain imaging studies present stimuli and measure behavioral responses in temporal units (trials) that are ordered randomly. Participants’ brain signals are typically aggregated to model structured variation that allows inferences about the broader population from which people were sampled. These methodological details, when used to study any phenomenon of interest, often give rise to brain-behavior findings that vary unexpectedly (across stimuli, context, and people). Such findings are typically interpreted as replication failures, with the observed variation discounted as error caused by less than rigorous experimentation (Box 1). Methodological rigor is of course important, but replication problems may stem, in part, from a more pernicious source: faulty assumptions (i.e., ontological commitments) that mis-specify the psychological phenomena of interest.

In this paper, we review three questionable assumptions whose reconsideration may offer opportunities for a more robust and replicable science: 

 (1) The localization assumption: the instances that constitute a category of psychological events (e.g., instances of fear) are assumed to be caused by a single, dedicated psychological process implemented in a dedicated neural ensemble (see Glossary). 

 (2) The one-to-one assumption: the dedicated neural ensemble is assumed to map uniquely to that psychological category, such that the mapping generalizes across contexts, people, measurement strategies, and experimental designs. 

 (3) The independence assumption: the dedicated neural ensemble is thought to function independently of contextual factors, such as the rest of the brain, the body, and the surrounding world, so the ensemble can be studied alone without concern for those other factors. Contextual factors might moderate activity in the neural ensemble but should not fundamentally change its mapping to the instances of a psychological category. 

 These three assumptions are rooted in a typological view of the mind, brain, and behavior [1. ] that was modeled on 19th century physics and continues to guide experimental practices in much of brain-behavior research to the present day. In this paper, we have curated examples from studies of human functional magnetic resonance imaging (fMRI) and neuroscience research using non-human animals that call each assumption into question. We then sketch the beginnings of an alternative approach to study brain-behavior relationships, grounded in different ontological commitments: (i) a mental event comprises distributed activity across the whole brain; (ii) brain and behavior are linked by degenerate (i.e., many-to-one) mappings; and (iii) mental events emerge as a complex ensemble of weak, nonlinearly interacting signals from the brain, body, and external world.

 

Concluding remarks

Scientific communities tacitly agree on assumptions about what exists (called ontological commitments), what questions to ask, and what methods to use. All assumptions are firmly rooted in a philosophy of science that need not be acknowledged or discussed but is practiced nonetheless. In this article, we questioned the ontological commitments of a philosophy of science that undergirds much of modern neuroscience research and psychological science in particular. We demonstrated that three common commitments should be reconsidered, along with a corresponding course correction in methods. Our suggestions require more than merely improved methodological rigor for traditional experimental design. Such improvements are important, but may aid robustness and replicability only when the ontological assumptions behind those methods are valid. Accordingly, a productive way forward may be to fundamentally rethink what a mind is and how a brain works. We have suggested that mental events arise from a complex ensemble of signals across the entire brain, as well as the from the sensory surfaces of the body that inform on the states of the inner body and outside world, such that more than one signal ensemble maps to a single instance of a single psychological category (maybe even in the same context. To this end, scientists might find inspiration by mining insights from adjacent fields, such as evolution, anatomy, development, and ecology , as well as cybernetics and systems theory. At stake is nothing less than a viable science of how a brain creates a mind through its constant interactions with its body, its physical environment, and with the other brains-in-bodies that occupy its social world.

Friday, December 30, 2022

The pitfalls of defining neural correlates of brain functions

Rust and Le Doux do a useful brief opinion piece from which I pass on two clips, and recommend you read the whole open source text.
...neuroscientists should avoid conflating circuits that control behavior with mental states, especially in the absence of evidence that the two map onto one another. These equivalencies need to be very carefully investigated rather than presumed.
Considerable evidence suggests that circuits involving the amygdala control behavioral and physiological responses to threats. In animal research labs, threats are often recapitulated by pairing a tone with an aversive stimulus such as a weak shock to elicit ‘fear-related behaviors’ such as freezing upon hearing the tone again. The neural circuits that learn the association between the tone and shock and produce freezing behavior are among the best understood in the brain. The problem lies in labeling these circuits with the term ‘fear’, because it presumes that the threat elicits a mental state, a subjective experience, of fear that is caused by activity in the amygdala. However, mounting evidence suggests that the amygdala is not required for the mental state of fear. Instead, the mental state of fear crucially depends, at least in part, on cortical circuits that interpret or conceptualize what is occurring in the social and physical environment and in one’s body. In this framework, amygdala circuits control nonconscious defense behaviors (such as freezing) as opposed to conscious experience. Should this framework be correct, the extensive ongoing efforts devoted to targeting amygdala circuits and rodent behaviors such as freezing and avoidance are unlikely to provide a direct route to treatments for human fear and anxiety disorders. These lines of research can help, but not without recognizing the centrality of subjective experience.

Monday, December 26, 2022

Rigorous study does not find that exercise and mindfulness training improve cognitive function in older adults.

Wow, here is a study by Lenze et al. - not confirming the results of numerous other less rigorous studies reported in MindBlog posts - that is unable to demonstrate that the use of mindfulness training, exercise, or a combination of both can significantly improving cognitive function in older adults with subjective cognitive concerns. In their randomized clinical trial that included 585 participants, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function composite scores at 6 months. Gretchen Reynolds provides context and a summary of the work in a Washington Post article.

Friday, November 25, 2022

The non-duality industry as a panacea for the anxieties of our times?

One of MindBlog's subject threads is meditation, and some recent posts have dealt with characterizing non-dual awareness (to find these, look in the right column of this blog, under "Selected Blog Categories, and click on 'meditation.') One of the descriptions I have pointed to is given by James Low, who has training in several lineages of Tibetan Buddhism, and has been teaching the principles of Dzogchen in Europe for over 20 years. Low's website links to an array of audio and video (YouTube and Vimeo) presentations he has done. One of the participants in a recent discussion at my house urged me to check out YouTube snippets recorded by Rupert Spiro, also British, whose YouTube videos and personal wesite (The Essence of Non-Duality) offer his teachings. 

After finding the YouTube outlets for these two meditation gurus, I googled 'non duality websites' and was rewarded with an array of rabbit holes to jump into...further teachers, and a "Nonduality Institute" that engages scientific studies of non-dual awareness. 

Perhaps an increasing number of people who engage techniques for facilitating non-dual awareness find themselves seeing and experiencing the "I" or self that feels threatened by our anxious times from a more useful perspective - an inclusive expanded awareness that includes the reporting "I" or self as just one of its many contents that include passing thoughts, perceptions, actions, and feelings.  A calm can be found in this expanded awareness that permits a  dis-association of the experienced breathing visceral center of gravity of our animal body from the emotional and linguistic veneer of politics and conflict. This does not remove the necessity of facing various societal dysfunctions, but offers the prospect of doing so without debilitating the organic physiological core from which everything we experience rises. 

Wednesday, November 09, 2022

The Neurobiology of long COVID

A number of my friends have reported, having caught break thru Covid even after 3-5 vaccinations, and are having symptoms of long Covid such as brain fog, anosmia, and cognitive impairment. (I am extremely grateful, after five vaccinations, to still be Covid free.) For these friends as well as Mind Blog readers, I want to point to a special issue of Neuron and in particular one open source article "The neurobiology of long Covid," which describes the array of neurological symptoms and their possible causes.

Saturday, October 22, 2022

New Perspectives on how our Minds Work

I want to pass on to MindBlog readers this link to a lecture I gave this past Friday (10/21/22) to the Univ. of Texas OLLI (Osher Lifelong Learning Institute) UT FORUM group on Oct. 21, 2022. Here is the brief description of the talk:  

Abstract

Recent research shows that much of what we thought we knew about how our minds work is wrong. Rather than rising from our essential natures, our emotional and social realities are mainly invented by each of us. Modern and ancient perspectives allow us to have some insight into what we have made.
Description
This talk offers a description of how our predictive brains work to generate our perceptions, actions, emotions, concepts, language, and social structures. Our experience that a self or "I" inside our heads is responsible for these behaviors is a useful illusion, but there is in fact no homunculus or discrete place inside our heads where “It all comes together.” Starting before we are born diffuse networks of brain cells begin generating actions and perceiving their consequences to build an internal library of sensing and acting correlations that keep us alive and well, a library that is the source of predictions about what we might expect to happen next in our worlds. Insights from both modern neuroscience research and ancient meditative traditions allow us to partially access and sometimes change this archive that manages our behaviors.