“Targeted neuromodulation tailored to individual patients’ distinctive symptoms is an increasingly common way of correcting misfiring brain circuits in people with epilepsy or Parkinson’s disease. Now, scientists at UC San Francisco’s Dolby Family Center for Mood Disorders and Weill Institute for Neurosciences have demonstrated a novel personalized neuromodulation approach that – at least in one patient – was able to provide relief from symptoms of severe treatment-resistant depression within minutes.
The approach is being developed specifically as a potential treatment for the significant fraction of people with debilitating depression who do not respond to existing therapies and are at high risk of suicide.
‘The brain, like the heart, is an electrical organ, and there is a growing acceptance in the field that the faulty brain networks that cause depression – just like epilepsy or Parkinson’s disease – could be shifted into a healthier state by targeted stimulation,’ said Katherine Scangos, MD, PhD, an assistant professor in the Department of Psychiatry and Behavioral Sciences and corresponding author of the new study. ‘Prior attempts to develop neuromodulation for depression have always applied stimulation in the same site in all patients, and on a regular schedule that fails to specifically target the pathological brain state. We know depression affects different people in very different ways, but the idea of mapping out individualized sites for neuromodulation that match a patient’s particular symptoms had not been well explored.’
In a case study published Jan. 18, 2021, in Nature Medicine, Scangos and colleagues mapped the effects of mild stimulation of several mood-related brain sites in a patient with severe treatment-resistant depression. They found that stimulation at different sites could alleviate distinct symptoms of the brain disease – reducing anxiety, boosting energy levels, or restoring pleasure in everyday activities – and, notably, that the benefits of different stimulation sites depended on the patient’s mental state at the time.
The proof-of-concept study lays the groundwork for a major five-year clinical trial Scangos is leading, called the PRESIDIO trial, that will evaluate the effectiveness of personalized neuromodulation in 12 patients with severe treatment-resistant depression. The trial will build on the current study by identifying brain signatures that reflect individual participants’ symptoms. With this information, neuromodulation devices can be programmed to respond in real time to these faulty network states with targeted stimulation that brings patients’ brain circuits back into balance.
‘We’ve developed a framework for how to go about personalizing treatment in a single individual, showing that the distinctive effects of stimulating different brain areas are reproducible, long-lasting and state-dependent,’ said co-senior author Andrew Krystal, MD, director of UCSF’s Dolby Center and the Ray and Dagmar Dolby Distinguished Professor of Psychiatry and Behavioral Sciences. ‘Our trial is going to be groundbreaking in that every person in the study is potentially going to get a different, personalized treatment, and we will be delivering treatment only when personalized brain signatures of a depressed brain state indicate treatment is needed.’
Epilepsy Studies Laid Groundwork for Depression Trial
Depression is among the most common psychiatric disorders, affecting as many as 264 million people worldwide and leading to hundreds of thousands of deaths per year. But as many as 30 percent of patients do not respond to standard treatments such as medication or psychotherapy. Some of these individuals respond positively to electroconvulsive therapy (ECT), but stigma and side effects make ECT undesirable for many, and one in ten patients experience little benefit even from ECT.
Previous research by Edward Chang, MD, co-senior author of the new study, has demonstrated the potential of brain mapping to identify promising sites for mood-boosting brain stimulation. These studies were conducted at UCSF Epilepsy Center in patients with and without clinical depression who already had electrode arrays implanted in their brains to map seizures ahead of epilepsy surgery.
‘Our prior work showed a proof of principle for targeted stimulation across brain areas to treat mood symptoms, but an outstanding question has been whether the same approach would hold true for patients with depression alone,’ said Chang, who is the Joan and Sanford I. Weill Chair of the UCSF Department of Neurological Surgery and Jeanne Robertson Distinguished Professor.”
View the whole story here: https://www.ucsf.edu/news/2021/01/419616/personalized-brain-stimulation-alleviates-severe-depression-symptoms