Researchers have made significant advancements in correlating aberrations in
specific brain circuits with neuropsychiatric conditions like depression.
However, it remains difficult to prove that damage to these circuits causes
the symptoms themselves and that targeting them with therapeutics could help
patients. By integrating brain lesion datasets with data on how two
treatments — deep brain stimulation (DBS) and transcranial magnetic
stimulation (TMS) — influence neuropsychiatric disorders, researchers from
Brigham and Women’s Hospital and collaborators developed a new brain mapping
approach that may help clarify the cause of a variety of neuropsychiatric
conditions and identify promising stimulation sites to target
therapeutically. Findings are published in Nature Human Behavior.
“This is a new technique that uses existing data on patients with brain
damage to develop new treatment targets for real-world patients with similar
symptoms,” said the paper’s corresponding author, Shan Siddiqi, MD, of the
Center for Brain Circuit Therapeutics at the Brigham. “In principle, this
should open the floodgates for researchers to study any stroke- or
brain-injury-associated symptom to find a new treatment target for people
who developed the same symptom without brain damage.”
The researchers developed their approach using data on depression and
Parkinson’s disease, both of which are already associated with well-defined
brain lesions and are commonly treated with DBS and TMS. They combined the
location and connectivity of 461 brain lesions, 101 DBS sites, and 151 TMS
sites, and compared patients who developed depression, patients who had
improvement in depression, and patients who had no change in mood. Using
this approach, they identified a brain circuit that is an effective
therapeutic target for both invasive and noninvasive brain stimulation
treatments. The study also indicates that brain stimulation outcomes vary
not according to the technique used — DBS versus TMS — but according to the
circuit that is targeted.
The researchers subsequently used their approach with Parkinson’s disease
data. Combining data on 29 lesions and 95 stimulation sites for tremors and
rigidity, they showed that lesions associated with the motor symptoms of
Parkinson’s disease are connected to the same circuits as the stimulation
sites that that relieve those symptoms.
The researchers are now working to refine circuit maps for other
neuropsychiatric conditions such as anxiety disorders, post-traumatic stress
disorder, mania, hallucinations, and movement disorders. Clinical trials are
still necessary to determine whether physicians can relieve patient symptoms
by targeting the brain circuits identified through the new approach. The
authors of the study are currently conducting a trial to confirm the
distinct TMS targets that they recently identified for depression and
anxiety.
“Now that we have concrete evidence that lesions map to treatment targets,
we can design more clinical trials to generate new treatments,” Siddiqi
said. “This approach gives us highly rigorous hypotheses about treatment
targets. When we don’t know much about the brain circuitry of a particular
disorder, our study shows how to find the answer to that question and turn
it into new treatment targets.”
Reference:
Brain stimulation and brain lesions converge on common causal circuits in
neuropsychiatric disease” by Shan H. Siddiqi, Frederic L. W. V. J. Schaper,
Andreas Horn, Joey Hsu, Jaya L. Padmanabhan, Amy Brodtmann, Robin F. H.
Cash, Maurizio Corbetta, Ki Sueng Choi, Darin D. Dougherty, Natalia Egorova,
Paul B. Fitzgerald, Mark S. George, Sophia A. Gozzi, Frederike Irmen, Andrea
A. Kuhn, Kevin A. Johnson, Andrew M. Naidech, Alvaro Pascual-Leone, Thanh G.
Phan, Rob P. W. Rouhl, Stephan F. Taylor, Joel L. Voss, Andrew Zalesky,
Jordan H. Grafman, Helen S. Mayberg and Michael D. Fox, 8 July 2021, Nature
Human Behavior. DOI:
10.1038/s41562-021-01161-1
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