1. The Friedman Brain Institute
brain surgery

Living Brain Project

The Living Brain Project (LBP) is a multiscale, data-driven investigation of the living human brain that uses the full human subjects neuroscience toolkit to discover how interactions between the various levels of neurobiology, neurophysiology, and neuroanatomy give rise to neuropsychiatric functioning.

The toolkit includes clinical observation, neuropharmacology, neuroimaging, neurophysiology, neuromodulation, and molecular-cellular neuroscience. Led by Alexander Charney, MD, PhD, and Brian Kopell, MD, the study has enrolled more than 300 individuals undergoing elective deep brain stimulation (DBS) surgery for neurological or neuropsychiatric conditions including Parkinson’s disease, obsessive-compulsive disorder, essential tremor, dystonia, and depression. The project has received funding from the National Institute of Health’s National Institute on Aging. The following are some frequently asked questions about the project.

Living Brain Project Frequently Asked Questions

The LBP includes the largest known collection of brain specimens obtained from living individuals, with paired blood and skin specimens also available. This information is linked to high-dimensional clinical data (e.g., data in the electronic medical record and from cognitive tests), neuroimaging data, neuropathology data, and neurophysiology data from the same individuals. The ongoing acquisition of living brain tissue in this context positions the LBP to be able to address neuroscientific questions that cannot be addressed using other tissues or study designs, such as “What RNA transcript and protein expression patterns in a person’s brain are active when the person experiences a particular emotion?”

The first 10 years of the LBP were focused on identifying molecular relationships between living and postmortem brain tissue. In the latter situation, brain tissue is collected from individuals after death, but with typically 12-24 hours passing between death and freezing the tissue. The investigation identified widespread differences between living and postmortem tissue with respect to RNA transcript expression, RNA splicing, RNA editing, protein expression, and RNA transcript and protein co-expression. By linking gene expression data from living brain samples to neurophysiology recordings of the same individuals, the LBP also has identified a transcriptional program associated with neurotransmission in the human brain. Such knowledge will be used by the LBP team to develop therapeutics that target neural circuit activities in a precise manner to treat neurological and mental illnesses. LBP studies have also identified how dopamine and other neurotransmitter systems activate in our brains when we are making social decisions, and contributed to the development of new technologies for studying how synapses in the brain work and how to deliver gene therapy to human brain cells. The results of studies using samples from the LBP are now beginning to appear on preprint servers and peer-reviewed publications. Six such publications are available at the following URLs, and more than a dozen additional publications are in other phases of preparation:

Distribution of biopsy sizes

To demonstrate the size of the tissues obtained for the LBP, the masses of 231 biopsies were measured over a four-year period from May 2020 through May 2024, and masses were converted to volumes using the conversion factor of 1,700 milligrams per cubic centimeters, as reported in Barber et al. (PMID: 4983875). Masses were obtained using the Accuris Analytical Balance Series (Product Number W3100A-210). The distribution of the resulting volumes is shown in the histogram below and shows a mean volume = 0.04 cubic centimeters [cc], which documents the small size of the biopsies. Note a single biopsy with a volume of 0.64 cc, a clear outlier, which is suspected to be the result of a measuring error. The remaining biopsies demonstrate a tight distribution around the mean, with standard deviation of 0.01, suggesting the biopsy procedure is highly consistent and precise.

View Histogram

To demonstrate the safety of the LBP biopsy procedure, the rate of postoperative hemorrhage was assessed using a database that has been maintained since March 2012 to track clinical outcomes of DBS surgeries at Mount Sinai (i.e., a database that is maintained for quality assessment independently of the LBP). This database included outcomes from approximately 1,000 DBS electrode implantation surgeries, and a biopsy was obtained in approximately 60 percent of these surgeries. No statistically significant difference was observed in the rates of postoperative hemorrhage between surgeries when a biopsy was obtained and surgeries when a biopsy was not obtained, and observed postoperative hemorrhage rates were consistent with the low-end of rates of postoperative hemorrhage following DBS, as reported in the literature (PMID: 37232022).

Extensive multimodal data are collected and generated for LBP participants. Data collection and data generation are ongoing as LBP enrollment continues.

Enrolled participants with diagnosis Number
Tourette syndrome 2
Major depressive disorder 15+
Obsessive-compulsive disorder 20+
Dystonia 35+
Essential tremor 35+
Parkinson’s disease 300+
Total participants enrolled 410+
Average monthly enrollment ~4
Type of participant specimen Number
Intraoperative skin 330+
Prefrontal cortex 640+
Intraoperative blood 660+
Type of data Available for
snRNA-seq 25+ participants
Bulk proteomics 245+ participants
Whole-genome sequencing 250+ participants
Bulk RNA-seq 275+ specimens
Intraoperative neurophysiological electrical recordings (single cell, LFPs) All participants
Neuropsychological battery All participants
Multi-modal neuroimaging All participants
Electronic medical record All participants