Tuesday, March 5, 2024

Deep brain stimulation

In a study led by scientists at Mass General Brigham, deep brain stimulation (DBS) was able to pinpoint dysfunctions in the brain that are responsible for four cognitive disorders: Parkinson’s disease, dystonia (a muscle disorder condition that causes repetitive or twisting movements), obsessive compulsive disorder (OCD) and Tourette's syndrome.

The discovery, published in Nature Neuroscience on Feb. 22, could potentially help doctors determine new treatments for these disorders.

The study included 261 patients worldwide — 70 had dystonia, 127 were Parkinson’s disease patients, 50 had been diagnosed with OCD and 14 had Tourette’s syndrome.

The researchers implanted electrodes into the brains of each participant and used special software to determine which brain circuits were dysfunctional in each of the four disorders.

"In simplified terms, when brain circuits become dysfunctional, they may act as brakes for the specific brain functions that the circuit usually carries out," Andreas Horn, M.D., PhD, associate professor of neurology at Brigham and Women's Hospital, said in a press release.

"Applying DBS may release the brake and may in part restore functionality."

Horn, one of the 39 researchers from 16 institutions who co-authored the study, went into more detail in a conversation with Fox News Digital.

"Based on the present findings, we can better understand why deep stimulation to a small subcortical structure in the brain has been helping patients with various disorders," he said.

For each of the disorders, a different brain network was identified as "dysfunctional," leading to the condition, the doctor said.

"Identifying these ‘malfunctioning networks’ may help us better understand the four disorders and better target neuromodulation to help patients by alleviating symptoms," he noted.

In three cases, the researchers found that applying DBS led to "preliminary improved results."

At Massachusetts General Hospital, one female patient in her early 20s was diagnosed with severe, treatment-resistant OCD.

After receiving electrode implantation and targeted stimulation, the researchers measured a "significant improvement" in her symptoms one month after treatment, according to the release.

Dr. Shannon Dean, a pediatric neurologist with the Kennedy Krieger Institute in Maryland, was not involved in the study but shared her reaction to the findings.

"This study is an elegant demonstration of how treatment-focused and basic mechanism-based research can help guide each other," she told Fox News Digital.

"The authors used deep brain stimulation electrodes, which is an invasive surgical treatment for a variety of neurological disorders when medications alone are not enough," Dean went on.

"I was interested to see the researchers then used their findings to refine exactly how they were treating several patients — and saw their patients' symptoms improve as a result," she said.

Given the small number of participants, Dean stressed the need for caution in interpreting the results.

"What the authors found for those disorders will need to be replicated for us to be sure the conclusions are right," she said.

"However, what they have found is exciting and makes sense based on what we already know about these disorders. This points us to where future studies should be looking."

"This research provides hope for people living with these diseases who are resistant to standard medical therapy," she added.

Dr. Arif Dalvi, a neurologist on staff at St. Mary's Medical Center in Florida, also commented on the study as an outside expert.

"Even though deep brain stimulation has been part of the standard of care for neurological conditions such as Parkinson's disease and tremors for decades, the technology continues to evolve," he told Fox News Digital.

"This research provides hope for people living with these diseases who are resistant to standard medical therapy."

"This analysis identified ‘sweet spots’ within these circuits that could significantly alleviate symptoms, demonstrating the efficacy of DBS in modulating neural activity."

The findings highlight the need for personalized therapies, Dalvi noted.

"This emphasizes a need for neurologists to carefully evaluate each patient as a unique individual and tailor a specific treatment plan, rather than working off generic best practices or therapeutic guidelines," he said.

This research is seen as the first step in what will be a long process, Horn said.

"The study is based on retrospective data — main results should be confirmed by prospective trials, which represent the gold standard to accumulate evidence in science and medicine," he told Fox News Digital.

The study’s sample size was also relatively small, he said, especially for Tourette’s.

"Even globally, not many patients have undergone deep brain stimulation surgery for this disorder," Horn said.

This study is the first step in defining what the researchers call the "human dysfunctome," the set of connections that may become dysfunctional in specific neurological or psychiatric disorders of the human brain.

"We first paint a picture of the dysfunctome, but need additional data to complete the picture and map other symptoms onto the circuits of the human brain," Horn said.

While the study findings might not lead to drastic changes just yet, Horn said they may help experienced clinicians fine-tune their approaches to neurology treatments.

"It could give additional clarity or small refinements here and there to make interventions more successful," Horn said. "However, the information should not be followed blindly, but instead should be validated in prospective studies."

The researchers are already starting to plan for clinical trials to validate the results.

As Dalvi pointed out, developing more sophisticated mapping techniques and understanding the long-term effects of deep brain stimulation will be crucial.

"Additionally, expanding this approach to other brain regions and disorders could uncover new therapeutic avenues, marking a new era in the treatment of neurological conditions," he added.

https://www.foxnews.com/health/researchers-sources-four-brain-disorders-new-treatments

Hollunder B, Ostrem JL, Sahin IA, Rajamani N, Oxenford S, Butenko K, Neudorfer C, Reinhardt P, Zvarova P, Polosan M, Akram H, Vissani M, Zhang C, Sun B, Navratil P, Reich MM, Volkmann J, Yeh FC, Baldermann JC, Dembek TA, Visser-Vandewalle V, Alho EJL, Franceschini PR, Nanda P, Finke C, Kühn AA, Dougherty DD, Richardson RM, Bergman H, DeLong MR, Mazzoni A, Romito LM, Tyagi H, Zrinzo L, Joyce EM, Chabardes S, Starr PA, Li N, Horn A. Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation. Nat Neurosci. 2024 Feb 22. doi: 10.1038/s41593-024-01570-1. Epub ahead of print. PMID: 38388734.

Abstract

Frontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By analyzing which connections were modulated for optimal therapeutic response across these disorders, we segregated the frontal cortex into circuits that had become dysfunctional in each of them. Dysfunctional circuits were topographically arranged from occipital to frontal, ranging from interconnections with sensorimotor cortices in dystonia, the primary motor cortex in Tourette's syndrome, the supplementary motor area in Parkinson's disease, to ventromedial prefrontal and anterior cingulate cortices in obsessive-compulsive disorder. Our findings highlight the integration of deep brain stimulation with brain connectomics as a powerful tool to explore couplings between brain structure and functional impairments in the human brain.

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