Source of Jennifer Fraser’s argument, around 40:00 minutes in the podcast:

“Now, Dr. Michael Merzenek, who's the father of neuroplasticity, outright said to me, plain and simple, and he said, you know, the thing about a brain scan, it doesn't lie.
So you can tell from a brain scan whether I have empathetic deterioration?
Yes.
Come on.
Yes.
What does it look like?
It looks like your empathy is eroded. That's what they can tell. That's how they know that you are in the dark triad and that you will commit evil.
That's how they know. This knowledge is out there. We're just not applying it to anything.”

From Heliograph: The Investigative Journalism Playbook: Heliograph LIVE: Jennifer Fraser on how the "gaslit brain" rewires us, Dec 4, 2025
https://podcasts.apple.com/ca/podcast/heliograph-the-investigative-journalism-playbook/id1711241442?i=1000739693006&r=2414
This material may be protected by copyright.

Hi everyone, I’m applying to neuroscience PhD programs for the second time and would appreciate any advice on my school list and application.

I applied during my last year at UC Berkeley but didn’t receive any interviews. Since graduating, I’ve been working as a research technician at MIT, where I’ll have about six months of experience by the time I apply.

A little more about my background:

• 3.4 undergraduate GPA
• Research experience at Berkeley and MIT
• One coauthored manuscript expected to be posted on bioRxiv soon
• Two additional coauthored manuscripts in preparation that likely won’t be ready during this application cycle

My research interests are in the mechanisms underlying neurological and neurodevelopmental disorders and, eventually, developing treatments.

Here’s my current list:

• UC San Diego
• UCLA
• UCSF
• Stanford
• USC
• University of Chicago
• Northwestern
• Columbia
• MIT
• Mount Sinai
• Rockefeller
• NYU
• Johns Hopkins

I know many of these programs are highly competitive, and I’m not sure how much my application has improved since last cycle. I don’t necessarily want to apply to schools just because they might be less competitive; I want to be excited about the program and the research I’d be doing.

Does this list seem too ambitious for my background? Are there other neuroscience or biomedical sciences programs with strong research in disease mechanisms and treatments that I should look into? I’d also appreciate any advice from people who applied a second time.

When we have an Orgasm The lateral orbitofrontal cortex briefly drops to zero activity. Meaning no fear, No Anxiety for a moment even if it is brief!

I'm curious. I've been thinking a lot about the whole glutamate glutamine cycle, and the destruction of astrocytes in our brain. If I understand right, the astrocytes are basically like little cleaning crew of our neocortex, and what triggers the destruction of those astrocytes is the glutamine glutamate cycle?\n So if we had a way to halt or stop the whole transferring the glutamate and glutamine and astrocyte destruction And we're still able to get rid of you know, the excess glutamine to where it wasn't building up, is it possible to stop neocortical death? I have a theory that that might be the whole 120 year. Switch that whatever, creator or whatever created us or whatever, put into s*** to where we won't live beyond a 120 years. I think that's where the mechanism probably is so I would like to know if I'm actually onto something or a complete idiot, and it won't hurt my feelings.I have no formal actual school education and neuroscience.I've done it all myself

https://www.youtube.com/watch?v=YnCoUHGk3uU&t

Popular science often repeats that "nobody knows how anesthesia works," while surveys show around 40% of adults think general anesthesia is simply deep sleep. Both claims are only half right: the molecular targets are now largely mapped, while the exact step that removes subjective experience remains unresolved.

Tracing the ~40-second window of a propofol induction against 180 years of research highlights several key turning points in how neuroscience views the anesthetized brain:

* **From Lipid Membranes to Protein Pockets:** For nearly a century after Meyer and Overton's 1900 tadpole experiments, anesthetic potency was explained by olive-oil solubility—the idea that drugs soak into the fatty membrane of nerve cells. That rule broke down with long-chain alcohols, which suddenly stop working past a certain length. In 1984, Franks and Lieb tested lipid-free firefly luciferase in a test tube and found it dimmed at anesthetic doses with the exact same size cutoff, shifting the field from membranes to hydrophobic protein pockets.

* **The Mismatched Keys:** In 2020, cryo-EM mapped propofol sitting inside the GABA-A receptor atom by atom. Yet ketamine acts on excitatory NMDA receptors, xenon is a single-atom noble gas that barely forms chemical bonds, and ether vapor reversibly halts electrical signaling and movement in a Venus flytrap—an organism with no brain at all. Because different molecular keys fit different locks, no single receptor explains the state itself.

* **Three Separate Effects:** Going under is not a single switch. Immobility is handled mostly in the spinal cord (isolated brain experiments in goats required more than twice the dose to stop movement), amnesia occurs at much lower doses while patients can still speak with a nurse, and the loss of experience happens in the brain.

* **Cortical Fragmentation:** Intracranial recordings in epilepsy patients show the brain doesn't shut off at loss of responsiveness. Instead, slow waves (~1 Hz) roll through the cortex, restricting neural firing to brief bursts and throwing distant brain regions out of phase. Primary auditory cortex still responds to spoken words, but the signals fade before propagating further.

* **Unresponsive vs. Unconscious (The TMS Echo):** When a magnetic pulse taps the cortex (TMS-EEG), an awake brain produces a rich, complex echo that travels far. Under propofol or xenon, the echo stays short and local, similar to deep sleep. Under ketamine, however, volunteers stop responding to the outside world, yet their cortical echo remains rich and wake-like—matching their post-anesthesia reports of vivid dreams.

* **The Thalamocortical Hub:** In 2020 and 2021, sending electrical pulses into a specific hub in the thalamus woke anesthetized macaques even while the drug was still flowing, and pulled desynchronized cortical activity back toward normal—though stimulating other brain sites can also reverse the state.

While behavior and memory recall can be tested directly, subjective experience between going under and waking up can only be inferred through clues like the cortical echo. Whether these system-wide brain changes actually cause consciousness to fade—or merely reflect what a brain looks like once the person is already gone—is still an open question.

This video explores the 180-year scientific search to understand how general anesthesia alters brain function. It examines the mechanisms of the forty-second induction window and how different drugs affect neural activity.

In this talk, Philip Ball explores the emerging shift from the traditional 20th-century view of biology to a "New Biology" that abandons the idea of life as a deterministic machine programmed by a rigid genetic blueprint.

Key Concepts of the New Biology:

• Agency and Goal-Directedness: Ball argues that a defining characteristic of living systems is agency—the ability to manipulate the environment to reach self-determined goals (2:51-12:53).
• Redefining the Genome: Instead of a "blueprint," the genome should be viewed as a flexible source of molecular resources that cells deploy in context-specific ways (18:14).
• Fuzzy Logic in Gene Regulation: Eukaryotic gene regulation is highly combinatorial and "fuzzy," relying on non-adjacent enhancers, chromatin loops, and 3D nuclear organization rather than simple, digital-like switches (21:10-34:33).
• Biomolecular Condensates: These membraneless structures act as compartments that integrate contextual information, enabling cells to make complex decisions without fixed algorithmic pathways (34:33-38:46).
• Proteomic Complexity: The prevalence of intrinsically disordered proteins and alternative splicing allows for significant functional versatility, further supporting an open, non-machine-like view of information flow in life (38:46-50:20).

Ball concludes that while reductionist and organicist perspectives are often seen as mutually exclusive, they can be reconciled by understanding how these molecular mechanisms facilitate high-level, robust biological agency (55:06-56:34).

While the crows worked at the task, the team recorded from 248 neurons in the NCL (nidopallium caudolaterale)—a region at the top of the avian processing hierarchy that is widely regarded as the functional counterpart of the primate prefrontal cortex, despite being built differently.

Birds and mammals parted evolutionary ways more than 360 million years ago, and bird brains evolved a different architecture. The mammalian cortex is arranged as stacked sheets of cells, while the equivalent tissue in a bird is organized into dense clusters, with no layering at all. This alternative architecture, Nieder’s study found, proved faster.

Measured from the moment that the dots appeared to the moment the bird’s head started turning to peck at the button, the crows averaged 235 milliseconds. In closely matched versions of the task, monkeys took roughly 410, 490, and 600 milliseconds in three studies. The obvious question was whether the birds simply sacrificed accuracy for speed, but it turned out they did not.

Paper published in Science:

https://doi.org/10.1126/science.aed6459

I’m following SKY-0515 and votoplam closely, particularly their potential to slow Huntington’s disease before noticeable symptoms develop.
SKY-0515 has reported up to 69% mutant huntingtin lowering in blood, alongside encouraging preliminary clinical findings.
My question for neuroscientists, biostatisticians, and clinical researchers is:
If future randomized trials demonstrate reduced caudate and putamen atrophy, lower neurofilament light, and slower clinical deterioration, could researchers use those measurements to develop a validated mathematical model predicting 10–30 additional symptom-free years?
Are there existing models that could support such projections, and what evidence would be needed before scientists could estimate the probability of 20+ years of sustained neurological protection?
I’d particularly appreciate links to peer-reviewed studies or research tools. Thank you!