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Brain mapping identifies therapeutic targets for neuropsychiatric symptoms

Researchers from Brigham and Women’s Hospital have developed a new brain mapping approach that uses brain lesion datasets and data on two treatments to identify the cause of various neuropsychiatric symptoms, and identify promising simulation sites to target therapeutically.

Neuropsychiatric disorders

Clinicians use the term ‘neuropsychiatric disorder’ to describe a broad range of medical conditions that involve neurology and psychiatry. Common neuropsychiatric disorders include: seizures, palsies, migraine headaches and depression. Additionally, the main component of neuropsychiatric disorders is that the symptoms impact brain function, emotion and mood. Researchers have made significant advances in correlating damage to specific brain circuits with neuropsychiatric conditions, such as depression. However, it remains difficult to prove if it is the damage to these circuits that causes the symptoms themselves and whether targeting them with therapeutics could help patients.

Using patient data to identify targets for neuropsychiatric symptoms

To try and identify whether these damaged circuits cause the neuropsychiatric symptoms and determine whether stimulations sites could be promising therapeutic targets, researchers from the Brigham and Women’s Hospital have integrated brain lesion datasets with data on how two treatments – deep brain simulation (DBS) and transcranial magnetic simulation (TMS) – influence neuropsychiatric disorders.

This study deployed a new technique that uses existing data on patients with drain damage to identify and develop new treatment targets for real-world patients with similar symptoms. The lead researchers, Shan Siddiqi, hopes that their work will open the floodgates for researchers to study any stroke or brain injury associated symptoms to find new drug targets for people who developed the same symptoms without brain damage.

Datasets used to identify targets for neuropsychiatric symptoms

The researchers developed their approach using data on depression and Parkinson’s disease. The team chose these conditions as they are already associated with well-defined brain lesions and are commonly treated with DBS and TMS. Overall, the researchers combined the location and connectivity of 461 brain lesions, 101 DBS sites and 151 TMS sites with patients who developed depression, patients who had improved depression and patients who had no change in mood.

Using this approach, the researchers were able to identify a brain circuit that is an effective therapeutic target for antidepressant drugs and brain stimulation treatments. This study also indicated that brain stimulation outcomes vary according to the circuit targeted, not due to the technique or drug used.

Following that, the researchers applied their approach to Parkinson’s disease patient data. Combining the data on 29 lesion and 95 stimulation sites for tremors and rigidity, they showed that lesions associated with the motor symptoms of Parkinson’s disease are also connected to the same circuits as the stimulation sites targeted to relieve those symptoms.

Next steps

The team used data on brain lesions and data on the influence of DBS and TMS on neuropsychiatric symptoms to identify potential therapeutic targets. The researchers are currently working to refine circuit maps for other neuropsychiatric conditions, including anxiety and movement disorders. Clinicians need to conduct clinical trials to determine whether patient symptoms can be relieved by targeting the brain circuits identified in this approach. However, now that there is evidence that lesions map to treatment targets, researchers can design better clinical trials for new treatments.

Image credit: kjpargeter – FreePik

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