A comprehensive map of the brain's "dysfunctome"—the regions that become dysfunctional during various neurological conditions—has been created by neuroscientists for the first time. The research offers hope for millions of patients, paving the way toward more tailored treatments based on specific dysfunctionality in certain areas of the brain.
Dysfunctionality in key brain areas can result in a range of debilitating conditions, including Parkinson's disease, obsessive-compulsive disorder (OCD), dystonia (a movement disorder where the muscles contract involuntarily) and Tourette's syndrome.
These disorders have a broad spectrum of different symptoms, from information processing and mood disorders to motor deficits. But the one thing they all have in common is an underlying malfunction in brain circuitry.
Deep brain stimulation—that is, delivering an electric current directly to specific areas of the brain using small electrodes—can target these brain circuits and has been shown to alleviate symptoms for various conditions. However, this treatment method is not always successful, and even small discrepancies in electrode placement can significantly dampen its efficacy. Also, it is not always clear which brain circuits need to be stimulated to achieve optimal outcomes.
But in a new study, published in the journal Neuroscience, a team of researchers led by Berlin's Charité – Universitätsmedizin and Boston's Brigham and Women's Hospital used deep brain simulations data from 261 patients around the world to pinpoint specific circuits in the brain's prefrontal cortex involved in symptom alleviation for Parkinson's disease, OCD, dystonia and Tourette's.
"Our goal was to better understand where in the brain possible 'brakes' can be released through neuromodulation to normalize the symptoms of Parkinson's disease, for example," study co-author Ningfei Li, a researcher in the Movement Disorders and Neuromodulation Unit at the Charité – Universitätsmedizin's Department of Neurology, said in a statement.
Using this technology, the team was able to identify specific brain circuits that had become dysfunctional for each of the four disorders.
"The circuits we identified partially overlapped, which to us implies that the malfunctions reflected in the symptoms studied are not wholly independent from each other," said Barbara Hollunder, the study's first author, in a statement.
By applying this approach across a range of different disorders, the researchers were gradually able to develop a map of specific brain circuits and their association with different neurological symptoms.
"By analogy to the terms 'connectome,' which describes a comprehensive map of all neural connections existing in the brain, and 'genome,' which is used for the full set of genetic information found in an organism, we have coined the term human 'dysfunctome,'" said Hollunder, a Ph.D. fellow at the Einstein Center for Neurosciences at Charité – Universitätsmedizin.
"One day, we hope the dysfunctome will describe the entirety of brain circuits that may typically become dysfunctional as a result of network disorders," she said.
These findings not only improve our understanding of these neurological and neuropsychiatric disorders but also open up new avenues for more tailored therapies in the future.
"We plan to refine this technique and zero in even more precisely on dysfunctional brain circuits for specific symptoms. For example, we could isolate the circuits involved in obsessions or compulsions in OCD, or other comorbid symptoms commonly found in these patients, like depression and anxiety disorders, to individualize treatment further," Li said.
Correction 02/28/2024 12:41 ET: This article was updated to correct Ningfei Li's affiliated academic institution.
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