Kuldeep Kumar

Neuroscience needs engineers—for more reasons than you think Adopting an engineering mindset will help the field focus its research priorities.

Many of our big insights into brain function come from trying to mimic it, writes @timothyoleary.bsky.social. This lesson should guide how we organize research programs.

www.thetransmitter.org/systems-neur...

#neuroskyence

Polygenic and developmental profiles of autism differ by age at diagnosis - Nature A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

This was a fantastic collaboration with lots of people including @hilarycmartin.bsky.social @jakobgrove.bsky.social, Experts by Experience, and several others who I can't seem to find on this app.

Article: www.nature.com/articles/s41...

This is figure 1, which shows the trajectory analyses in three of the four birth cohorts.

The age that autism is diagnosed may partly reflect underlying biological and developmental differences among individuals with autism, according to a study in Nature. go.nature.com/4gQ5gSV 🧬 🧪

Autism-linked copy number variants always boost autism likelihood By contrast, varied doses of the same genes decrease or increase the odds of five other conditions, with distinct biological consequences, two new preprints show.

The same genes can have disparate, sometimes opposing, effects on neuropsychiatric conditions, a study finds.

By Natalia Mesa

www.thetransmitter.org/spectrum/aut...

p-Tau 217, Tau PET, and Cognition in Preclinical Alzheimer Disease This diagnostic/prognostic study examines longitudinal data from studies of older patients without cognitive impairment to consider whether plasma phosphorylated tau 217 and tau positron emission tomo...

p-tau217 predicts cognitive changes prior to any cognitive impairment (again)
"The era of disease-modifying therapy in Alzheimer's disease is just starting."
jamanetwork.com/journals/jam...
jamanetwork.com/journals/jam...

New paper🥳

🧠 In TLE, brain changes go beyond the temporal lobe & beyond normal aging.

Our ENIGMA study (769 patients, 18 sites) found widespread gray & white matter decline, especially after 55. By Judy Chen and a terrific intl' team

Time for earlier diagnosis & deeper research
bit.ly/3HRYeQt

Age-related cerebello-thalamo-cortical white matter degradation and executive function performance across the lifespan https://www.biorxiv.org/content/10.1101/2025.08.22.671779v1

Latest processing of UK Biobank brain imaging data - now with 82,000 usable first-scan datasets. Correlating brain IDPs with 13,000 non-imaging variables gives a rich manhattan-stye plot. 324,000 Bonferroni-significant associations.

The overlapping genetic architecture of psychiatric disorders and cortical brain structure - Nature Mental Health This study highlights sex differences in major depressive disorder using resting-state functional magnetic resonance imaging. Findings suggest hormonal fluctuations influence onset, emphasizing the ne...

💥🧠🧬Finally out!! Our new paper on the overlapping genetic basis of brain structures and psychiatric disorders has been published in Nature Mental Health. The full list of shared genetic loci is also available online. Thank you so much, Aaron and all co-authors.
www.nature.com/articles/s44...

Brain Surfaces of 70 primate species

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To predict the behaviour of a primate, would you rather base your guess on a closely related species or one with a similar brain shape? We looked at brains & behaviours of 70 species, you’ll be surprised!

🧵Thread on our new preprint with @r3rt0.bsky.social , doi.org/10.1101/2025...

For me, this work is a classic @ohbmofficial.bsky.social story: In 2023 I wasn't working with @bttyeo.bsky.social but I overheard him at his poster pointing to some accuracy curves saying "I don't why they have this particular shape". That kicked off the collab that led to these results.

The field of neuroscience views the goal of human genetics as "finding genes". This is an outdated view. In whole genome studies of rare variants, finding genes is the easy part. The more interesting and important goal is to map out the causal pathway from genes to brain function to cognitive traits

As we have learned, genes have dose-dependent effects on psychiatric traits. DOSAGE, it turns out, is a key element that helps unravel mechanisms of gene → pathway → cell type → brain region → diagnosis. Here we developed a framework to characterize cellular processes that mediate genetic effects.

PGC-CNV paper led by Bank and @sebatlab.bsky.social et al. using Gene Set Burden Analysis across 6 disorders.

"Psychiatric disorders converge on common pathways but diverge in cellular context, spatial distribution, and directionality of genetic effects"

www.medrxiv.org/content/10.1...

The Psychiatric Genomics Consortium: discoveries and directions Research by the Psychiatric Genomics Consortium (PGC) has advanced the discovery of common and rare genetic variations that contribute to the susceptibility to many psychiatric disorders and neurodeve...

What's going on in psychiatric genetics? The @pgcgenetics.bsky.social have now published our latest progress review in @thelancetpsych.bsky.social, highlighting discovery, and laying out a map for moving forwards!

www.thelancet.com/journals/lan...

Heads-up for major new faculty search at KI — with great startup packages and a wide range of subject areas.

A new combination technique enables DNA sequencing and high-resolution imaging in intact cells — offering new insights into progeria and aging. broad.io/expansion-in-situ @jbuenrostro.bsky.social

Stimulants rescue cognition and brain functional architecture if you didn’t sleep enough … short term: www.biorxiv.org/content/10.1... Is it possible that this is a true rescue, or is it just a temporary cover up and there will be a price to pay … maybe decades later? Asking for a friend.

My med school textbook says stimulants like Ritalin treat hyperactivity by “stimulating” the brain’s attention and cognitive control systems. We studied children taking stimulants in the ABCD Study, and the largest differences were actually in arousal and reward networks! Check out our preprint!

Cortical differences across psychiatric disorders and associated common and rare genetic variants https://www.medrxiv.org/content/10.1101/2025.04.16.25325971v1

Gene dosage architecture across complex traits https://www.medrxiv.org/content/10.1101/2025.02.25.25322833v1

"Gene dosage architecture across complex traits".

Excited to share our work led by the excellent @KazemSayeh (joint co-author).

We will post a detailed 🧵 in the coming days. Please reach out if you have any questions.

www.medrxiv.org/content/10.1...

#CNVs #GeneDosage #UKBB

The effect of spherical projections on spin tests for brain maps | biorxiv.org/content/10.1...

Spin tests are the de facto null model for map-to-map comparisons in brain imaging. Why don't they perfectly control false positives? @vincebaz.bsky.social explores ⤵️

Interested in how cortical alterations in neurodevelopmental & psychiatric disorders (ASD, ADHD, BD, SCZ,...) relate to those observed in rare genetic risk for these conditions.
Visit our poster tomorrow @acnporg.bsky.social

We show discordance between CT/SA, impact of medication, age of onset..

scPrediXcan integrates advances in deep learning and single-cell data into a powerful cell-type–specific transcriptome-wide association study framework Transcriptome-wide association studies (TWAS) help identify disease causing genes, but often fail to pinpoint disease mechanisms at the cellular level because of the limited sample sizes and sparsity ...

check out our new preprint led by Charles Zhou and supervised by Mengjie Chen and me doi.org/10.1101/2024... where we present scPrediXcan which integrates deep learning and single cell expression data into a powerful cell type specific TWAS framework

"Integrating the RNA sequencing data and morphological profiles uncovered a novel biological link between altered expression of specific cell adhesion molecules and observed changes in mitochondrial morphology in 22q11.2 deletion astrocytes."