Michael Fox

We don't think it invalidates the approach.

We looked into this in our data and replicated the key result showing convergence to non-specific connectome structure. However, our results also suggest there is a practical fix that is already implemented in some LNM studies.

bsky.app/profile/pete...

This is a robust response. I particularly liked this figure - clarifying why the original critique showed what it did, and what was missing @foxmdphd.bsky.social

A recent @natneuro.nature.com paper analyzed lesion network mapping and raised concerns about the validity of the method.
See below 👇 for our response.

www.biorxiv.org/content/10.6...

For a discussion of why our conclusions may differ from those of van den Heuvel et al., please see our preprint:
www.biorxiv.org/content/10.6...

Taken together, these results suggest that LNM 1) shows symptom specificity across studies, 2) produces results that do not converge on a single map, and 3) controls for false positives with specificity testing.

Third, we tested the concern that LNM is prone to false positive results because of flawed specificity testing. We did not identify a single false positive in 1000 iterations when we compared 50 lesions randomly extracted from our database to the remaining 1040 lesions.

Second, we tested the concern that LNM results all converge to the same degree map. We found the spatial correlation between lesion networks from patients with the same symptom was higher than the spatial correlation w the degree map (median spatial r = 0.44 vs 0.16, p< 0.0001).

First, we tested the concern that LNM results are not symptom-specific. We found the spatial correlation between lesion networks from patients with the same symptom was significantly higher than between those with different symptoms (median spatial r= 0.44 vs 0.09; p < 0.0001).

A recent paper in @natureportfolio.nature.com raised concerns about the lesion network mapping method. Our team of 16 coauthors analyzed >1000 lesions and 34 symptoms and found that "The methodological foundations of lesion network mapping remain sound" www.biorxiv.org/content/10.6...

The deep brain stimulation response network in Parkinson’s disease operates in the high beta band Bahners et al. identify a brain network linked to optimal therapeutic outcomes in patients with Parkinson’s disease receiving deep brain stimulation. This

New @netstim.org publication alert: @bahnebahners.bsky.social in BRAIN out now:

academic.oup.com/brain/advanc...

A 🧵:

Lesions Causing Aphantasia are Connected to the Fusiform Imagery Node The absence of visual mental imagery, called aphantasia, occurs congenitally in up to 3% of the general population, but the brain regions responsible …

Can a brain injury make someone lose their imagination?

We describe rare cases of acquired aphantasia, people who lost the ability to visually imagine after a stroke or other brain injury. Now published in Cortex 🧠 @braincircuits.bsky.social

www.sciencedirect.com/science/arti...

Brain Medicine: Integrating the Clinical Neurosciences | Harvard Medical School Professional, Corporate, and Continuing Education Explore cutting-edge advances in brain medicine with this interdisciplinary course designed to equip clinicians with integrated tools for assessing and managing complex brain disorders, featuring expe...

One week away from launching our 2nd annual @harvardmed.bsky.social course Brain Medicine: Integrating the Clinical Neurosciences. On demand viewing for 30 days. Nearly 150 people registered. Join us! @jrbneuropsiq.bsky.social @foxmdphd.bsky.social

learn.hms.harvard.edu/programs/bra...

Spotlight on the Shingles Vaccine—Again! Two new studies add to a remarkable body of evidence for benefit

The Shingles vaccine and reduction of dementia: a new natural experiment from Canada replicated 3 others and adds to this week's link to slowing of biological aging.
erictopol.substack.com/p/spotlight-...

The Shingles vaccine has outperformed all expectations. Why?
erictopol.substack.com/p/spotlight-...

My understanding is that DIANA was a single paper, by a single group, that multiple groups then failed to replicate. In contrast, lesion network mapping is >200 papers by multiple groups, that a single group has reportedly failed to replicate.

Thanks Ravi. By “shades of Diana” does that mean you agree with the Van de Huevel critique that the lesion network mapping method is fundamentally flawed?

Methodological flaw may upend network mapping tool The lesion network mapping method, used to identify disease-specific brain networks for clinical stimulation, produces a nearly identical network map for any given condition, according to a new study.

Thanks to The Transmitter for reaching out to me for comments on this methodological challenge to lesion network mapping. Scientific debate is critical to methodological advancement - so let the debate begin!

www.thetransmitter.org/brain-imagin...

Investigating the methodological foundation of lesion network mapping - Nature Neuroscience The lesion network mapping method links diverse brain lesions to similar functional brain networks, reflecting general brain organization rather than disorder-specific circuits.

Are connectome-based network mapping methods and the >200 papers that have used it invalid?

New paper out in
@NatureNeuro
says YES. nature.com/articles/s41...

I have concerns about this new paper's methods and conclusions, but am biased. What do others think?

Mapping the Neuroanatomy of Dystonia Using Causal Brain Lesions Dystonia is one of the most prevalent movement disorders, but its neural substrates have remained enigmatic despite decades of research. Brain lesions leading to dystonia offer unique causal inference...

New pre-print out now from Dr Daniel Corp, @jjoutsa.bsky.social and @foxmdphd.bsky.social ‘Mapping the neuroanatomy of dystonia using causal brain lesions’ !! www.medrxiv.org/content/10.6...
We map networks for the different dystonias, showing significant differences, somatotopy...and much more!!

Very interesting findings! Gliomas selectively locate within in the Action-mode Network, using glioma network mapping derived from lesion network mapping @foxmdphd.bsky.social

Check out our new work on the relationship between glioma and system-level functional networks! We identify that nearly all gliomas localize within a common brain functional network, Action-Mode Network (AMN) .

biorxiv.org/content/10.64898/2026.01.05.697608v1

Depression as a disease of white matter network disruption: Learning from Multiple Sclerosis Depression is a common and debilitating psychiatric disorder that is associated with substantial morbidity and mortality. For nearly 40 years, scientists have attempted to localize depression in the b...

Excited to share that our new review, "Depression as a disease of white matter network disruption: Learning from Multiple Sclerosis," is out now in Biological Psychiatry! We propose MS as a powerful model for studying how white matter network changes contribute to depression.

What is the burden in the US of Parkinson's, Alzheimer's and other diseases? Spoiler alert: there are surges beyond the pure numbers and we need to raise awareness for the increases in both disability and burden. Parkinson disease has shown the largest growth in burden on society.
cutt.ly/xtyUtS0D

Mongay-Ochoa et al. review advanced methods for mapping brain connections and identify common topographical patterns of pathology spread across different neurological disorders, including MS, AD and PD. tinyurl.com/3sz8ayup

Pruckner et al. show that the structural effects of neurosurgery extend beyond the resected tissue into connected networks through transneuronal degeneration. They were able to reliably predict these changes from preoperative MRI. tinyurl.com/a6rxvbey

A horizontal graphic with a teal panel on the lefthand side reading “Discovery Research Grantee ’25; University of Minnesota Medical School; Research: Precision Functional Mapping-Guided Network Stimulation for Bipolar Depression.” The right side of the graphic features headshots and titles of the research team: Lead Principal Investigator Ziad Nahas, MD, MSCR; and Co-Principal Investigators Damien Fair, PA-C, PhD; David Darrow, MD, MPH; Tay Netoff, PhD; and Alex Opitz, PhD. The BD² logo appears in the bottom lefthand corner.

🧪 Research Spotlight: Ziad Nahas, MD, MSCR, is studying how brain networks regulate mood in #BipolarDisorder & how instability drives shifts between depression & mania with PACE

👉 Goal: Test if targeting networks can improve mood & reveal mechanisms behind switches.

🔗 bit.ly/4gTbBwU

🧪 Research Spotlight: Michael Fox, MD, PhD (@foxmdphd.bsky.social) of Mass General Brigham (@mgbresearch.bsky.social) will map brain circuits driving symptoms in #BipolarDisorder

👉 Goal: Go beyond imaging correlations to identify the circuits causing symptoms.

🔗 bit.ly/4gTbBwU

A probabilistic histological atlas of the human brain for MRI segmentation - Nature NextBrain is an open source, probabilistic atlas of the entire human brain, assembled using artificial-intelligence-enabled registration and segmentation methods to reconstruct the multimodal serial h...

This is 🤯

All publicly available. Looks like an amazing new histology-based human probabilistic atlas and parcellation tool.

#neuroskyence #mri #brainmapping

A probabilistic histological atlas of the human brain for MRI segmentation | Nature share.google/5AD0iW7pxgb4...

Nice case report led by Ben Shofty's team adding prospective evidence for tract based reprogramming in deep brain stimulation for obsessive compulsive disorder out in @biologicalpsych.bsky.social:

www.biologicalpsychiatryjournal.com/article/S000...

🧵

BD² expands global effort to examine the key mechanisms of bipolar disorder Today, BD², or Breakthrough Discoveries for thriving with Bipolar Disorder, announced its third round of Discovery Research grants, totaling nearly $18 million – expanding a comprehensive global effor...

Can we identify brain circuit targets to treat symptoms of bipolar disorder? Thanks to funding from @bipolardiscoveries.org our team @braincircuits.bsky.social will be working hard to find out! Honored to be one of these excellent teams.
www.news-medical.net/news/2025102...