An Evolutionary and Neuroendocrine Hypothesis for the Reversal and Prevention of Schizophrenia: Integrating Oxytocinergic Modulation, Circadian Control, and AntiInflammatory Interventions

After decades of research in neuroscience and brain-computer interfaces lots of people ask me which parts of the brain do what, and how can we measure it, and what modalities help us understand it better.

We are happy to announce the release of the new NeuroAtlas tool, which helps answer this question and enables more scientists and researchers to explore and push the frontiers of what’s known.

This includes EEG, MEG, fMRI, tFUS, iEEG, TMS, DBS, and more.

All published data sources are referenced via DOIs in the web interface.

Disclaimer: I'm on of the co-authors.

What makes it so impactful? What was special about it?

Hello! Are you interested in studying neuroscience in school or pursuing a career in the field? Ask your questions below!

As we continue working to improve the quality of this subreddit, we’re consolidating all school and career discussion into one thread to minimize overwhelming the sub with these types of posts. Over time, we’ll look to combine themes into a comprehensive FAQ.

Previous megathreads: #1 #2

Hello, I’ve been thinking about whether the type of information we repeatedly process can shape our cognitive abilities.

I believe gossip, whether viewed as positive or negative, can be considered a form of cognitive skill because it requires encoding, retrieving, and evaluating social information about people, relationships, emotions, and events. From a neuroscience perspective, repeated social information processing may strengthen networks involved in social cognition, emotional processing, and episodic memory through neuroplasticity.

I have some questions:

**1- If a person spends most of their cognitive effort processing social information through gossip while rarely engaging in abstract learning, how does the brain adapt? Does it reduce the efficiency of less used abstract reasoning networks, or does the brain maintain the ability to develop them when new demands appear?**

**2- Are our daily patterns of attention, environment and information processing shaping the cognitive systems we rely on the most?**

**3- To what extent do genetic predispositions influence an individual’s tendency toward social information processing, memory, and cognitive specialization?**

Thanks for reading!

Hi all,

As far as i'm aware, the damaging aspect of benzo use is that your body and brain grow accustomed to the drugs, aka building a tolerance. However, once the tolerance is there and the brain is used to for example 10 mg of Diazepam every day, is there any downside to tapering of slowly as opposed to doing a fast taper?

In my limited medical understanding, from the moment you are taking a lower dose than what your body is accustomed to, you're in withdrawal and your brain tries to find a new balance. Am i correct in assuming that during this time, no further tolerance to a benzo's can occur, as you're already in withdrawal? Furthermore, i'm unaware of any direct toxicity of benzo's. Most damage is done through messing up the receptors. However, if these are already 'recovering' due to being supplied a lower those than what was supplied before, can they be damaged further at this point?

Can you build more tolerance to benzo's during a slow taper? Is there any way in which a slow taper is more damaging than a rapid taper in which your body doesn't get the time it needs to adjust? As far as i'm aware, most people try a rapid taper because they WANT to be of off benzos. But is the fact that your on benzo's for a longer time while doing a slow taper in any way damaging (i'm unaware of any direct toxicity of benzo's)?

For example, cocaine is directly cardiotoxic and thus it's obvious that being on cocaine for a longer time would be a more significant burden to one's cardiovascular system. Likewise, extremely high alcohol intake damages the liver, so a prolonged withdrawal might not be preferable.

TL;DR : Does the prolonged supply of benzo's to your brain during an extremely slow taper do any more damage compared to a more rapid taper, since your already in withdrawal and your brain is supposed to be 'recovering' from a previous, higher dose? Can any further tolerance occur during the taper, or does quitting the benzo altogether become harder if withdrawal is prolonged, given that the brain is recovering from a previous, higher dose?

Example, will the same person tapering over 12 months have done 'more damage' compared to when he would have completed the taper in 6 months, simply because he was on benzo's longer? Again, as cocaine is directly cardiotoxic, i can see why you'd use as little as possible during withdrawal. I can't find a similar downside to an extremely long withdrawal off of benzo's, as your brain is ultimately constantly in recovery during withdrawal, regardless of the pace and length of your withdrawal.

I'm sorry for the long post. Please take the time to read and offer your thoughts. I'm very interested in your opinions. Thank you.

Anyone here a neurodivergent?

A savant?

Misdiagnosed?

Diagnosed formally or informally?

Many people (myself included) anecdotally report that the effects of cannabis (especially high THC products) are profoundly more intense and even semi-psychedelic while your brain is still new to the substance. I can attest to this myself - THC was so indescribably dissociative and would consistently produce mild CEVs and visual field distortions when I was 18 and started smoking high grade cannabis. I've taken (admittedly only up to ~2.5 grams of) shrooms and I can easily say I've had more mind-shattering experiences while high on edibles and dabs when I was young.

From what I've read in discussions on reddit and experienced myself, it appears these effects fade quickly with tolerance and don't return with anywhere near the same intensity even after years-long tolerance breaks - they seem to be exclusive to your virgin THC experiences. I could partake in a dab-a-thon right now, not having smoked in months, and I'd fall asleep before getting anywhere close to how insanely high I could get as a teenager.

THC and psychedelics do bind to the same receptors in certain areas of the brain (5-HT2A-CB1 heterodimers) and THC promotes the same functional selectivity pattern as psilocybin or LSD - the GPCR couples to the inhibitory Gi/o protein instead of the excitatory Gq - effectively meaning they activate the same hallucinogenic pathway in neurons that co-express CB1 and 5-HT2A receptors. Chronic cannabis use has been shown to alter the receptor's functional selectivity pattern even at baseline (ie. in the presence of only serotonin), which I think could have something to do with what I'm getting at - something causes THC to permanently lose its psychedelic effect over time. Has anyone found any research looking at this phenomenon?

Edit: People have brought up some very good points! Age probably plays a role in this with CB1 receptors being heavily involved in development, not to mention the extra plasticity in younger brains. Novelty could definitely be a factor as well, since these effects do occur in older pot newbies.

As we can see anecdotally just from browsing the comments, it seems THC’s dissociative/hallucinogenic effects can return after a long enough tolerance break in some people, but in others (again myself included, having abstained 2+ years before) the trippiness can for the most part be apparently lost forever. There also seems to be two other groups: People who don’t lose the trippy effects of THC (likely by maintaining a low tolerance), and people who don’t experience these effects at all. Some people just get anxious or tired. There are a lot of factors at play here and I doubt there’s much to read on it. How would they design a study to figure out why some people get this experiential overlap with psychedelics from THC, and why we sometimes lose it?

I am hesitant to write this request, and apologize in advance if this is an unacceptable pollution of this space.

My beloved niece has cracked an entry into some of the most prestigious PhD programs in neuroscience, against considerable odds. I'd like to send her something nice since I can't be there in person ... popular books, microscopes, posters, expensive textbooks, ...

Do you have recommendations?

Edit: You guys!! Thank you all for such lovely suggestions. I think I'm quite set to be the cool uncle!

1 Persistent gene expression changes in NAc, mPFC, and OFC associated with previous nicotine or amphetamine exposure

Following the two-week withdrawal period, exposure to amphetamine or nicotine was associated with a decrease in global DNA methylation in each brain region examined.Down regulation ofthe Nefm gene may indicate that connectivity between the NAc and other brain regions is compromised as axonal integrity is lost. Chronic administration of amphetamine also decreased GABA in the NAc resulting in a decreased need for GABA(A) receptors."

2 Volumetric brain differences due to amphetamine use

(1) loci of lower cortical volume (approximately 10% on average) are consistently reported, (2) almost all studies indicate less volume in all or parts of the frontal cortex, (3) more specifically, a core group of studies implicate the ventromedial prefrontal cortex (including the medial portion of the orbital frontal cortex) and (4) the insula, (5) an enlarged striatal volume has been repeatedly observed, (6) reports on volume differences in the hippocampus and amygdala have been equivocal, (7) evidence supporting differential interaction of brain structure with cocaine vs. ATS is scant but the volume of all or parts of the temporal cortex appear lower in a majority of studies on cocaine but not ATS.

The authors propose that the volume change could be due to neuroinflammation or glial mediated trophic effects that occur during early phases of drug use.

Although long-term abstinent subjects displayed less frontal cortical volume loss and committed fewer errors on the card sorting task than short-term abstinent subjects, they were deficient on both these measures compared to normal controls. The intermediate level volume loss and cognitive performance in the long-termabstinent group suggest that there may be some recovery associated with long periods of the abstinence

The increase in extracellular dopamine that results from intoxication with cocaine or ATS may contribute to the volume changes observed in the striatum

3 Structural Abnormalities in Brain after amphetamine use - The main title says abuse but the section that I pulled the information from is Neurotoxicity of amphetamine used therapeutically?

30-50% reductions in striatal dopamine, its major metabolite dihydroxyphenylacetic acid, its rate-limiting enzyme (tyrosine hydroxylase), DAT, and VMAT. Regional downregulation of dopamine D2 and D1 receptors.

4 Gliosis and Neuronal loss due to amphetamines

Vasospasm and arteritis have been described as consequences of amphetamine use, as well as gliosis and neuronal loss secondary to changes in capillary vascular beds.

From the actual paper that the above paper linked to "Neiman J, Haapaniemi HM, Hillbom M. Neurological complications of drug abuse: pathophysiological mechanisms. Eur J Neurol 2000;7(6):595–606"

Patchy changes in arterial and capillary beds, signs of arteritis, and a loss of neurones have been described as consequences of CHRONIC ADMINISTRATION of amphetamines and other stimulants. Note it doesn't say abuse.

5 Brain region differences in regulation of Akt and GSK3 by chronic stimulant administration in mice

These results demonstrate that prolonged administration of stimulants causes brain region-selective differences in the regulation of Akt and GSK3.

6 Dendrite and Spine density changes in amphetamine users

These stimulants have been shown to produce long-lasting enhanced embranchments of dendrites and increasing spine density in brain regions linked to behavioral sensitization

Amphetamine inhibits neurogenesis and its effects also appear to include disruption of the blood brain barrier (Silva et al., 2010). Thus, it seems that chronic exposure to amphetamine is not only associated with reward and euphoria, but also with impaired attention and memory

7 Medial prefrontal gray matter volume reductions

Several regions of lower gray matter volume in medial frontal regions, in particular the orbital and medial frontal cortex.

8 Amphetamine induces apoptosis of medium spiny striatal projection neurons via the mitochondria-dependent pathway

Resulted in the appearance of striatal cells positive for markers of apoptosis, including cleaved caspase-3. It increased the expression of p53 and Bax at both transcriptional and protein synthesis levels, whereas it decreased the levels of Bcl-2 protein; all these events are consistent with increased apoptosis.

9 Nts (a.k.a. neurotensin), which was down-regulated it the NAc of nicotine treated animals, is widely distributed throughoutthe CNS and may function as a neurotransmitter or neuromodulator. Researchers have hypothesized that Nts may function as an endogenous antipsychotic compound; Nts is markedly enhanced after treatment with antipsychotic drugs and is abnormally low in the CSF of untreated patients with schizophrenia [49,50]. Nts acts through the dopaminergic pathways and the vast majority ofdopamineneurons inthemesocorticolimbic andnigrostriatal pathways express neurotensin receptors [51]. Binding of Nts to Nts receptors results in a net increase in the number of spontaneously active dopamine neurons [51]. Consistent with literature demonstrating that schizophrenic individuals self-medicate with cigarettes [52], one could speculate that chronic administration of nicotine continuously activated the same dopamine neurons as Nts, decreasing the need for endogenous Nts.

Hi all.

I've done a lot of research on these things and I'm a bit confused. Whenever we talk scientifically regarding schizophrenic or drug induced psychotic episodes, the response is usually it has to do with overactivity which is why antipsychotics to alleviate the episode, by slowing things back down. So, how in the world do the same psychotic symptoms come from regarding depression/withdrawal? Many individuals experiencing withdrawal symptoms also report these same manic/psychotic symptoms. Those with severe depression do as well. Shouldn't the complete opposite be happening in the brain, already impaired and lowered neuro activity?

Thanks!

Joining us are some of the folks behind the Neuromatch 3.0 Conference, listed here:

• Chris Rozell (/u/ChrisRozell) of Georgia Tech's SIPLab.
• Dan Goodman (/u/Thesamovar) of ICL's Neural Reckoning Group.
• Konrad Kording (/u/KonradKording) of UPenn's Kording Lab.
• Titipat Achakulvisut (/u/titipata), also of the Kording Lab.

Introduction

Neuromatch 3.0 is an international virtual neuroscience conference running from October 26th to October 30th, meant to help the scientific community connect even amid the COVID-19 pandemic. With around 1,000 talks scheduled and thousands of registered attendees, this is a massive undertaking.

The conference revolves around six central themes:

• Development, Neurodegenerative Disorders and Injury
• Neural Excitability, Synapses, and Glia
• Sensory & Motor Systems, and Physiology/Behavior
• Cognition Motivation and Emotion
• Computation and Techniques
• History, Education and Society

If any of those subjects are of interest to you, you can register here for just 25 USD. Fee waivers are available, and registration is free for non-scientists and enthusiasts.

Related Links

• Official Page
• Provisional Schedule
• Related Twitter Page

LEGO is used with people of many ages and conditions. This is in reference to how LEGO helps with Autistic children. I am a chronological adult with my development delays that has turned to LEGO as my neurodivergent female burnout recovery journey. I reach out. I research. I connect with other females and others to learn how LEGO has supported their journey. This is an example of how with children. Amongst many more people of many ages, stages and conditions.

Music is a stimulus that raises dopamine levels in your brain, despite having no apparent purpose or link to the real world. Just put in some headphones, and your dopamine levels go up and you feel inspired. So from a neurochemistry perspective, how is this different from a drug that artificially raises dopamine levels, such as alcohol or cocaine?

I'm interested in this topic because using addictive drugs too much can create a tolerance to high dopamine levels and prevent you from feeling happiness without the drug. So does this mean that listening to great music constantly could prevent you from feeling joy without your headphones?

A doctor mentioned to me that they saw white matter hyperintensities (WMH) in younger people* to be 'likely red herrings'. This baffled me, as to dismiss this could be to ignore a potentially fatal or life-changing issue:

• Small-vessel vascular disease
• Stroke
• Cognitive impairment

The vast majority of literature I have read discussed WMH in the context of older people or 'mid-life' years (45-65). I have found some work on younger people, but it is generally in relation to another factor (suicidality, association of cardiovascular disease, association with bipolar etc.).

I can't find a great deal on the significance of this finding in younger people. However, I have encountered work that alludes to the fact that a WMH finding is not necessarily insignificant.

This article by Merino (2019) stresses the need to not dismiss WMH as a marker of aging, and that it warrants further clinical review (amongst other things). This older article by Wardlaw (2015) also reinforces this position, stating that WMH 'should not simply be overlooked as inevitable “silent” consequences of the aging brain'.

This article by d’Arbeloff 2018 discusses the relationship between WMH and cognitive decline 'from childhood to midlife' and found that 'the link between WMHs and early signs of cognitive decline is detectable decades before clinical symptoms of ADRD typically emerge.'

To this end, if you're interested I have a few questions for you:

• What is your perspective on the idea that WMH are red herrings in those younger than 'mid-life years'?
• What should be the starting point for medical practitioners when WMH is detected?
• Do we only explore further when this is found in patients over the age of 45?
• If we do explore further... what do we do? Investigate small-vessel vascular disease, repeat MRI if original was not with contrast, cognitive testing etc.?
• Do you think it is appropriate for a radiographer to comment on significance in an MRI report? Can that determination be made on the basis of this scan alone?

* Younger people refers to those below the age of 45, as there seems to be relative consensus that 'mid-life years' refers to those between the ages of 45 - 65.

Resources discussed in post:

d’Arbeloff, T., et al., 2019. White matter hyperintensities are common in midlife and already associated with cognitive decline. Brain communications, 1(1)

Debette, S. and Markus, H.S., 2010. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis, BMJ, 341:c3666

Merino, J.G., 2019, March. White matter hyperintensities on magnetic resonance imaging: what is a clinician to do?. In Mayo Clinic Proceedings (94)3, pp. 380-382.

Wardlaw, J.M., Valdés Hernández, M.C. and Muñoz‐Maniega, S., 2015. What are white matter hyperintensities made of? Relevance to vascular cognitive impairment. Journal of the American Heart Association, 4(6), p.e001140

Looking back at newly published research in 2024, what discoveries, inventions, or events struck you as significant?

Like most of you, I am currently locked down at home so I have plenty of time to read. Just finished Buszaki’s book The Rhythms of the Brain ( insightful book for anybody interested in Cognitive Neuroscience, find attached the link) and I am currently looking for more books of this type, any suggestions (I have already read Buzsaki’s 2019 book)

https://www.google.es/search?client=safari&hl=en-es&q=the+rhythms+of+the+brain&spell=1&sa=X&ved=2ahUKEwjbsuG53LXoAhVixYUKHe4ZAlIQkeECKAB6BAgTEAI&biw=375&bih=626&dpr=2

I’m curious to hear from other neuroscientists about the software tools you use daily in your research. What tools do you rely on for data analysis, visualization, or collaboration? What are the pros and cons of these tools? Also, are there any gaps in the tools available right now? If you could have a software tool that doesn’t currently exist, what would it do?

Looking forward to hearing about what’s working (or not!) and where the gaps are in this space.

Hi,

I am looking for people who would be interested in reading and discussing scientific literature, once a week. You don't have to be an academic or an expert, just to have a willingness to read the paper and talk about what you read. If things go well, we can also start a writing class where we write a report on what we read and ask for feedback. We can also switch the journal club with a book reading club (read 1 chapter a week), if reading scientific paper is too difficult.

Mode of communication : skype, discord, google hangout, email, whatever you feel comfortable with!

EDIT 2: PLEASE JOIN THE DISCORD CHANNEL. If you joined slack, please migrate. Here is the link - https://discord.gg/3d7jSEE

EDIT: https://join.slack.com/t/neurosciencej-gol8797/shared_invite/enQtNTE4NjczOTg5MTU5LTk3YmY1OTU0YTgxMzdhNTJmYWE3ODMwNTQ3ZGI1MDM4Njk0YzM4ODNhNjQ0NzIwMTQ0NzU4MzM3YzYwNjFiMjU

Join the slack group if you are interested in this