Zach Rosenthal

Psychedelic 5-HT2A receptor agonism alters neurovascular coupling and differentially affects neuronal and hemodynamic measures of brain function Nature Neuroscience - Padawer-Curry et al. show that the hallucinogenic 5-HT2A receptor agonist DOI alters neurovascular coupling in mice, with implications for the interpretation of human fMRI...

🚨 New science alert! Our cross-species study, now in Nature Neuroscience, demonstrates psychedelics distort how we should interpret functional brain imaging.
👇🧵

nature.com/articles/s41...
#Neuroscience #Psychedelics #BrainImaging

Thank you! Great question – it seems that global infraslow dynamics continue during transitional states for sleep and anesthesia (i.e., where you see these spatial maps persisting). Some interesting perspectives on this: doi.org/10.1016/j.co... doi.org/10.1016/j.ne... doi.org/10.1016/j.ce...

Arousal as a universal embedding for spatiotemporal brain dynamics - Nature Reframing of arousal as a latent dynamical system can reconstruct multidimensional measurements of large-scale spatiotemporal brain dynamics on the timescale of seconds in mice.

Super proud of this collaboration with rockstar Ryan Raut - born out of playing in the sandbox in our last year of grad school! Multi-scale brain activity can be predicted from a simple measure of arousal like pupil diameter. Out with linear causality, in with dynamic systems to explain neurobiology

WOW this is the honor of a lifetime, Vienna (Airport Conference Center) here I come!

Toward a Better Understanding of Electroconvulsive Therapy When we don't understand how something works, we often fear it. That has been the case with electroconvulsive therapy (ECT), but new research may be shedding needed light.

Toward a Better Understanding of Electroconvulsive Therapy | Psychology Today www.psychologytoday.com/us/blog/deny...

The Baller Lab is thrilled to announce that @elenaccooper.bsky.social just had her first first-author publication! “Investigating mood and cognition in people with multiple sclerosis: a prospective cross-sectional study protocol” is now published on BMJ Open: bmjopen.bmj.com/content/15/5/e094733! 🧠

Cutting the NIH—The $8 Trillion Health Care Catastrophe This JAMA Forum discusses the recent budget cuts to National Institutes of Health (NIH), the effects of these cuts on scientific research and health of individuals in the US, and the prospects for cha...

Two Harvard economists forecast the impact of the administration’s proposed NIH budget cuts- stunning losses in new therapies, life expectancy, and economic output with a “social cost 16 times greater than the savings the administration is attempting to achieve."

jamanetwork.com/journals/jam...

Electroconvulsive therapy's 'hard reset' effect: Brain wave discovery challenges long-held assumption During his third-year psychiatry clerkship as a medical student, Zach Rosenthal, MD, Ph.D., was part of a team providing care to a young man with schizophrenia and severe catatonia.

New evidence shows electroconvulsive therapy triggers a brain event called cortical spreading depolarization, challenging previous assumptions about how ECT achieves its therapeutic effects. doi.org/g9mnvt

Northwestern has not received any NIH funds since March. No written communication about why or what can be done. Thank you Ben Singer for raising awareness at #ATS2025

There is no replacement (yet) for animal models in medical research The NIH is “reducing animal use in research.” But there is no replacement for animal models.

It is beyond disturbing when the NIH and HHS Directors do not understand that animal models are essential in research

www.statnews.com/2025/05/19/a...

Takeaway: We have been missing a huge brain event during ECT. Further research can help us learn more to optimize stimulation and outcomes for this life-saving treatment. If CSD proves central to the mechanism of ECT, we could develop novel brain stimulation therapies that don’t require seizure!

ECT can cause side effects, most often temporary memory issues. As with any treatment, we discuss this risk with patients and weigh against potential benefits, so that patients can make informed decisions. We are now testing if memory effects might also be modulated by spreading depolarization.

ECT is stigmatized and misrepresented in popular media and by anti-psychiatry activists. The reality is ECT is not painful, violent, or a form of punishment. Patients are asleep and immobilized with general anesthesia during the seizure. There is no evidence that ECT causes ‘brain damage’.

We are now testing if CSD mediates the clinical effects of ECT. This hypothesis could explain:
- why seizure intensity predicts therapeutic effects
- why stimulation parameters modulate outcomes
- why ECT is inhibitory and raises seizure thresholds (CSD is an intrinsic anti-seizure mechanism)

We then showed that CSD waves also occur in routine ECT treatments in human patients. This required a novel tool – bedside, non-invasive optical monitoring of brain hemodynamics – developed by our colleagues in the Penn Physics dept!

Clinically, ECT stimulation parameters are known to modulate outcomes. Here, we found that electrode placement shapes where seizure is most intense and where CSD is triggered. Increasing pulse current and frequency increase seizure amplitude, which in turn predicts the likelihood of triggering CSD.

Why has this gone undetected for nearly 86 years? CSD wavefronts travel very slowly (millimeters per minute), such that when they are subjected to routine low frequency EEG filtering (our mainstay tool for brain monitoring during ECT), they’re rendered virtually invisible (right video panel).

In a mouse model, we observed that seizure is followed by a slow-traveling wave of maximal neural and hemodynamic activation followed by suppression, consistent with cortical spreading depolarization (CSD). Only high amplitude seizures cross the threshold of triggering this all-or-none event.

ECT remains the most effective treatment for severe, medication-resistant depression, achieving rapid remission in 60-80% of patients. It also works for psychosis, mania, catatonia, and more, when other treatments have failed. Why electrically-induced seizure is therapeutic has remained a mystery.

Electroconvulsive therapy generates a postictal wave of spreading depolarization in mice and humans - Nature Communications The underlying mechanism of electroconvulsive therapy remains not fully understood. Here, the authors use optical neuroimaging in mice and humans to show that electroconvulsive therapy elicits a secon...

Hot off the press! We found that electroconvulsive therapy (ECT) induces a previously undescribed, second brain event after seizure, called cortical spreading depolarization (CSD), using optical neuroimaging in both a mouse model to human patients. 🧵 below!

doi.org/10.1038/s414...

Takeaway: We have been overlooking a huge brain event during ECT due to understudy. Research can help us optimize stimulation and outcomes for this life-saving treatment. If CSD proves central to the mechanism of ECT, we could develop novel brain stimulation therapies that don’t require seizure!

ECT can cause side effects, most often temporary memory issues. As with any treatment, we discuss this risk with patients and weigh against potential benefits, so that patients can make informed decisions. We are now testing if memory effects might also be modulated by spreading depolarization.

ECT is stigmatized and misrepresented in popular media and by anti-psychiatry activists. The reality is ECT is not painful, violent, or a form of punishment. Patients are asleep and immobilized with general anesthesia during the seizure. There is no evidence that ECT causes ‘brain damage’.

We are now testing if CSD mediates the clinical effects of ECT. This hypothesis could explain:
- why seizure intensity predicts therapeutic effects
- why stimulation parameters modulate outcomes
- why ECT is inhibitory and raises seizure thresholds (CSD is an intrinsic anti-seizure mechanism)

We then showed that CSD waves also occur in routine ECT treatments in human patients. This required a novel tool – bedside, non-invasive optical monitoring of brain hemodynamics – developed by our colleagues in the Penn Physics dept!

Clinically, ECT stimulation parameters are known to modulate outcomes. Here, we found that electrode placement shapes where seizure is most intense and where CSD is triggered. Increasing pulse current and frequency increase seizure amplitude, which in turn predicts the likelihood of triggering CSD.

Why has this gone undetected for nearly 86 years? CSD wavefronts travel very slowly (millimeters per minute), such that when they are subjected to routine low frequency EEG filtering (our mainstay tool for brain monitoring during ECT), they’re rendered virtually invisible (right video panel).

In a mouse model, we observed that seizure is followed by a slow-traveling wave of maximal neural and hemodynamic activation followed by suppression, consistent with cortical spreading depolarization (CSD). Only high amplitude seizures cross the threshold of triggering this all-or-none event.

ECT remains the most effective treatment for severe, medication-resistant depression, achieving rapid remission in 60-80% of patients. It also works for psychosis, mania, catatonia, and more, when other treatments have failed. Why electrically-induced seizure is therapeutic has remained a mystery.

Light-microscopy-based connectomic reconstruction of mammalian brain tissue - Nature A technique called LICONN (light-microscopy-based connectomics) allows mapping of brain tissue at synapse level and simultaneous measurement of molecular information, thus enabling quantification of c...

Thanks to expansion microscopy, clever labeling, and modern segmentation approaches, doing connectomics with #light #microscopy has become feasible - huge congratulations Mojtaba & the Danzl lab at @istaresearch.bsky.social !
www.nature.com/articles/s41...