Lukas A. Basedow, PhD

And that's a middle of the week break 🙂. As planned, fewer psychedelic papers. But still have lots on the reading list!

A neuromodulatory circuit-to-molecular pathway for reformatting aversive memories during recall Tan et al. identify a neuromodulatory circuit-to-molecular pathway in rats that updates aversive memories when they are recalled. Noradrenaline from the locus coeruleus triggers synapse-to-nuclear tra...

Again, absolutely impressed by the complexity and thouroughness necessary for neuroscientific questions and publications. www.cell.com/neuron/fullt...

Is Ketamine an Opioid?

A great comment by @theborislab.bsky.social (www.sciencedirect.com/science/arti...) on an already great paper. Really should read both to grasp the importance of the paper. Fascinating work!
www.sciencedirect.com/science/arti...

Adolescent Cannabis Use and Risk of Psychotic, Bipolar, Depressive, and Anxiety Disorders This cohort study assesses the association of past-year cannabis use by adolescents with the risk of incident psychiatric, bipolar, depressive, and anxiety disorders by age 26 years.

While a commendable errort, I don't think the authors have reported the influence of alcohol and other substance use, even though they assessed it. My suspicion is these reported associations would also be significant for other drug use.
jamanetwork.com/journals/jam...

Overdose Prevention Centers and Neighborhood Commercial Activity in New York City This cohort study assesses whether the opening of the first publicly recognized overdose prevention centers in the US was associated with changes in foot traffic and consumer spending at local busines...

Overdose Prevention Centers are indisputably good and necessary. There really is no sensible argument against providing these services. Apparently people are concerned such centers would reduce the value of the neighborhood. Well, they don't.
jamanetwork.com/journals/jam...

Reduction or Discontinuation vs Maintenance Antipsychotics This randomized clinical trial compares early dose reduction or discontinuation vs maintenance treatment of antipsychotic medication for patients remitted from first-episode psychosis in the Netherlan...

Imo very important to do this kind of work to figure out potential ways of reducing the need for psychopharmacological agents. As, nearly, always in pharmacological trials no words on psychotherapy...
jamanetwork.com/journals/jam...

Integrating information in the brain’s EM field: the cemi field theory of consciousness A key aspect of consciousness is that it represents bound or integrated information, prompting an increasing conviction that the physical substrate of consciousness must be capable of encoding integrated information in the brain. However, as Ralph ...

I understand little of the brains electromagnetic properties and even less of the necessary physics. Still, this is the first theory of consciousness that I feel like I can grasp (not sure if thats a good thing).
pmc.ncbi.nlm.nih.gov/articles/PMC...

Vectorized instructive signals in cortical dendrites - Nature Mice learning a neurofeedback brain–computer interface task show neuron-specific teaching signals in cortical dendrites, consistent with a vectorized solution for credit assignment in the brain.

Neurons are complicated and different parts of the neuron are responsible for different kinds of signals (I guess, I really only understand parts of this work)
www.nature.com/articles/s41...

A short, German, perspective on the need of harm reduction approaches for people affected by psychotic disorders with comorbid crack use disorders.
www.thieme-connect.de/products/ejo...

Should biology put complexity first? The dictum “Everything should be made as simple as possible, but no simpler” poses a problem for biology. How simply can it be told without doing dama…

Beautifully written essay by @philipcball.bsky.social "It seems possible that the very complexity of biology engenders an undue and unhelpful determination to sustain old, simple narratives beyond the point where they are useful [...]"
www.sciencedirect.com/science/arti...

Cognitive primitives of the insect brain Understanding the mechanistic basis of human cognition is likely to benefit from investigating how it emerged through evolution. We propose that identifying and investigating fundamental brain functio...

A fascinating look into fly cognition. Always love the cross-species similarities emerging from an evolutionary perspective.
www.cell.com/trends/cogni...

Papers I have read, March 2nd - March 4th:

Toward the end of his two-volume Treatise on the Venom of the Viper, published in 1781, the Tuscan naturalist Deluxe Fontana declared: "I have made more than 6000 experiments; I have had more than 4000 animals bit; I have employed upwards of 3000 vipers and may have been deceived; some essential circumstance may have escaped me: I may have neglected some other, not thinking it necessary; my consequences may have been too general, my experiments too few in number. In a word, I may very easily have been mistaken, and it would be almost impossible that I should never have been so in a matter so difficult, so obscure, and likewise so new."

Fontana thinking his 6000+ experiments may not have been enough to feel confident in his conclusions in the 18th century while we expect our singular experiments and their standalone replications to do wonders some 250 years later... (excerpt from the intro of Jutta Schickore's About Experiment)

🤨

Only possible because my daughter likes to sleep while being bounced on a pezi ball. That's my paper reading time 🙃

Later school start times are the one extremely evidence-based change that’s likely to dramatically improve kids’ and teens’ well-being but because it’s so inconvenient for adults it’s quickly dismissed

And another week wrapped up. Definitely seeing a trend. I'm mostly reading neuroscience and psychedelic research. Will see if the next weeks mix it up a bit. Still got a long list to work through.

A very specific read by @janw.bsky.social but outlines the problems arising from this specific research design quite well. Definitely learned a lot!
osf.io/preprints/ps...

Action Potentials for February 1: A new GWAS of schizophrenia is notable for including a substantial number of people of African ancestry, with 13.5K such cases and 65K controls.

If you're interested in neuroscience I highly recommend signing up for the Action Potential newsletter (neurobiology.substack.com/p/action-pot...). While recently a lot of cryonic research is featured, which i mainly ignore, the other highlights are always fascinating!

Neuroplastogen TSND-201 for the Treatment of PTSD This randomized clinical trial investigates if TSND-201 (methylone) is efficacious and safe in people with posttraumatic stress disorder (PTSD).

Another industry-sponsored trial. I think the term "psychoplastogen" is quite disingenuous. However the results are pretty impressive. Also interesting is the quite pronounced placebo response.
jamanetwork.com/journals/jam...

Statistical Modeling: The Two Cultures (with comments and a rejoinder by the author) There are two cultures in the use of statistical modeling to reach conclusions from data. One assumes that the data are generated by a given stochastic data model. The other uses algorithmic models and treats the data mechanism as unknown. The statistical community has been committed to the almost exclusive use of data models. This commitment has led to irrelevant theory, questionable conclusions, and has kept statisticians from working on a large range of interesting current problems. Algorithmic modeling, both in theory and practice, has developed rapidly in fields outside statistics. It can be used both on large complex data sets and as a more accurate and informative alternative to data modeling on smaller data sets. If our goal as a field is to use data to solve problems, then we need to move away from exclusive dependence on data models and adopt a more diverse set of tools.

I didn't read the whole thing, but it did inspire some thoughts for upcoming analyses.
projecteuclid.org/journals/sta...

Psychedelic Therapy as Form of Life - Neuroethics In the historical context of a crisis in biological psychiatry, psychedelic drugs paired with psychotherapy are globally re-emerging in research clinics as a potential transdiagnostic therapy for trea...

Such a great paper, showcasing the neccessity of trans-disciplinary perspectives. Would love to see similar work for "normal" psycho- and pharmacotherapy.
link.springer.com/article/10.1...

Kappa opioid receptor control of motivated behavior revisited - Neuropsychopharmacology Neuropsychopharmacology - Kappa opioid receptor control of motivated behavior revisited

Third @npp-journal.bsky.social paper in a row. Seems I have a type. Another fantastic and well-written review. Even hints at an explanation for the hallucinogenic effects of Salvinorin A, a KOR agonist, that have always baffled me.
www.nature.com/articles/s41...

Infant sensory gating and a developmental cascade to autistic traits and anxiety - Neuropsychopharmacology Neuropsychopharmacology - Infant sensory gating and a developmental cascade to autistic traits and anxiety

Learned a lot but this bit was particularly fascinating: "Prenatally, widespread expression of the chloride ion transporter NKCC1 causes GABA to function as an excitatory rather than inhibitory neurotransmitter."
www.nature.com/articles/s41...

Synergistic pathways to psychosis: understanding developmental risk and resilience factors - Neuropsychopharmacology Neuropsychopharmacology - Synergistic pathways to psychosis: understanding developmental risk and resilience factors

Very extensive review (over 400 references) with a clear message: it's all very complicated!
www.nature.com/articles/s41...

Part 2 of this weeks paper haul (Feb 27th - March 1st):

1. ITT vs. actually received treatment: important discussion which still needs to be done for the pediatric antidepressant (TADS) trial regarding rates of treatment emergent suicidality.
Fluoxetine vs. placebo: ITT: 15 vs. 11%, n.s.
Actually treated with fluoxetine: 11% vs. 2.7% (p < 0.02)

Time for a middle of the week cut. Will continue on sunday 😎

The Research Deficit and Expert Disagreement Regarding Music Selection for Psychedelic Assisted Therapy Prior research has determined that music plays a central role in psychedelic assisted therapy (PAT). While there is a general consensus of the importance of music during PAT, there are only three empi...

Way less research on this than I suspected! Time for more science.
pubs.acs.org/doi/10.1021/...

Dopamine dynamics during stimulus-reward learning in mice can be explained by performance rather than learning - Nature Communications VTA dopamine activity control movement-related performance, not reward prediction errors. Here, authors show that behavioral changes during Pavlovian learning explain DA activity regardless of reward ...

From social science back to hardcore neuroscience. In my (limited) understanding this proposes a fresh look on the function of dopamine signaling.
www.nature.com/articles/s41...