DBS
Precision Deep Brain Stimulation Shows Initial Promise for Severe Depression
Posted on by Dr. Francis Collins
For many people struggling with depression, antidepressants and talk therapy can help to provide relief. But for some, the treatments don’t help nearly enough. I’m happy to share some early groundbreaking research in alleviating treatment-resistant depression in a whole new way: implanting a pacemaker-like device capable of delivering therapeutic electrical impulses deep into the brain, aiming for the spot where they can reset the depression circuit.
What’s so groundbreaking about the latest approach—so far, performed in just one patient—is that the electrodes didn’t simply deliver constant electrical stimulation. The system could recognize the specific pattern of brain activity associated with the patient’s depressive symptoms and deliver electrical impulses to the brain circuit where it could provide the most relief.
While much more study is needed, this precision approach to deep brain stimulation (DBS) therapy offered immediate improvement to the patient, a 36-year-old woman who’d suffered from treatment-resistant major depressive disorder since childhood. Her improvement has lasted now for more than a year.
This precision approach to DBS has its origins in clinical research supported through NIH’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative. A team, led by Edward Chang, a neurosurgeon at the University of California San Francisco’s (UCSF) Epilepsy Center, discovered while performing DBS that the low mood in some patients with epilepsy before surgery was associated with stronger activity in a “subnetwork” deep within the brain’s neural circuitry. The subnetwork involved crosstalk between the brain’s amygdala, which mediates fear and other emotions, and the hippocampus, which aids in memory.
Researchers led by Andrew Krystal, UCSF, Weill Institute for Neurosciences, attempted in the latest work to translate this valuable lead into improved care for depression. Their results were published recently in the journal Nature Medicine [1].
Krystal and colleagues, including Chang and Katherine Scangos, who is the first author of the new study, began by mapping patterns of brain activity in the patient that was associated with the onset of her low moods. They then customized an FDA-approved DBS device to respond only when it recognized those specific patterns. Called NeuroPace® RNS®, the device includes a small neurostimulator and measures about 6 by 3 centimeters, allowing it to be fully implanted inside a person’s skull. There, it continuously monitors brain activity and can deliver electrical stimulation via two leads, as shown in the image above [2].
Researchers found they could detect and predict high symptom severity best in the amygdala, as previously reported. The next question was where the electrical stimulation would best relieve those troubling brain patterns and associated symptoms. They discovered that stimulation in the brain’s ventral capsule/ventral striatum, part of the brain’s circuitry for decision-making and reward-related behavior, led to the most consistent and sustained improvements. Based on these findings, the team devised an on-demand and immediate DBS therapy that was unique to the patient’s condition.
It will be important to learn whether this precision approach to DBS is broadly effective for managing treatment-resistant depression and perhaps other psychiatric conditions. It will take much more study and time before such an approach to treating depression can become more widely available. Also, it is not yet clear just how much it would cost. But these remarkable new findings certainly point the way toward a promising new approach that will hopefully one day bring another treatment option for those in need of relief from severe depression.
References:
[1] Closed-loop neuromodulation in an individual with treatment-resistant depression. Scangos KW, Khambhati AN, Daly PM, Makhoul GS, Sugrue LP, Zamanian H, Liu TX, Rao VR, Sellers KK, Dawes HE, Starr PA, Krystal AD, Chang EF. Nat Med. 2021 Oct;27(10):1696-1700
[2] The NeuroPace® RNS® System for responsive neurostimulation, NIH BRAIN Initiative.
Links:
Depression (National Institute of Mental Health/NIH)
Deep Brain Stimulation for Parkinson’s Disease and other Movement Disorders (National Institute of Neurological Disorders and Stroke/NIH)
Andrew Krystal (University of California San Francisco)
Katherine Scangos (UCSF)
Edward Chang (UCSF)
NIH Support: National Institute of Neurological Disorders and Stroke
The Amazing Brain: Deep Brain Stimulation for OCD
Posted on by Dr. Francis Collins
The winners of the “Show Us Your BRAINs!” Photo and Video contest are chosen each year based on their eye-catching ability to capture the creative spirit of the Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative. This year’s first-place video certainly fits the bill while highlighting encouraging efforts to help people with the most severe and hard-to-treat form of obsessive compulsive disorder (OCD), a psychiatric illness marked by recurrent unwanted or distressing thoughts and repetitive behaviors.
Most cases of OCD can be effectively treated with a combination of pharmacotherapy and cognitive behavioral therapy. But for a small subset of individuals with severe, intractable, and debilitating OCD, other approaches are needed.
The video shows a 360-degree view of the brain of a person with severe OCD. At about 15 seconds into the video, the brain’s outer surface fades away to reveal the critical brain structures that serve as landmarks for targeting the disorder.
These include the anterior commissure (orange), helping to transfer information between the brain’s two hemispheres; caudate nucleus (dark blue), involved in various higher neurological functions, such as learning and memory; putamen (light blue), which plays a role in learning and motor control; and ventral striatum (yellow), part of the brain’s circuitry for decision-making and reward-related behavior.
This person is a participant in a clinical trial to alleviate OCD symptoms using deep brain stimulation (DBS). In DBS, electrodes are implanted deep in the brain to deliver electrical impulses that regulate abnormal, repetitive brain impulses. The straight lines (purple) are wire leads, each bearing a single electrode topped with an electrical contact (white). These leads connect to a pacemaker-like device implanted in the chest (not shown) that delivers electrical impulses that ease the patient’s distressing thoughts and unwanted behaviors.
The video took a true team effort. Nicole Provenza, a graduate student in the lab of David Borton, Brown University, Providence, RI, produced it with the project’s principal investigator Wayne Goodman, lead neurosurgeon Sameer Sheth, and research assistant Raissa Mathura, all at Baylor College of Medicine, Houston. Another vital contributor was Noam Peled, MGH/HST Martinos Center for Biomedical Imaging, Charlestown, MA.
The team produced the video primarily to help explain how DBS works for people with OCD. But such visualizations are also helping them to see where exactly in the brain electrodes have been placed during surgery in each of their study participants.
Right now, the location of DBS electrodes can’t be imaged using MRI. So CT scans must be taken after surgery that combine X-ray images from different angles. The researchers then carefully align the MRI and CT scans and load them into special software called Multi-Modality Visualization Tool (MMVT). The software enables simultaneous 3D visualization and analysis of brain imaging data captured in different ways.
Using MMVT, Provenza and colleagues labelled the brain regions of interest and spun the image around to see just where those leads were placed in this particular individual with OCD. They then captured many still images, which they stitched together to produce this remarkable video.
Deep brain stimulation is used to treat Parkinson’s disease and other movement disorders. But earlier attempts to treat severe and intractable OCD with DBS haven’t yet succeeded in the way researchers had hoped. This innovative team seeks to change that in the future by using more responsive and adaptive systems, capable of sensing the abnormal brain impulses as they happen and responding at just the right time [1].
Reference:
[1] The case for adaptive neuromodulation to treat severe intractable mental disorders. Provenza NR, Matteson ER, Allawala AB, Barrios-Anderson A, Sheth SA, Viswanathan A, McIngvale E, Storch EA, Frank MJ, McLaughlin NCR, Cohn JF, Goodman WK, Borton DA. Front Neurosci. 2019 Feb 26;13:152.
Links:
Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative (NIH)
Obsessive-Compulsive Disorder (National Institute of Mental Health/NIH)
Deep Brain Stimulation for Parkinson’s Disease and other Movement Disorders (National Institute of Neurological Disorders and Stroke/NIH)
Borton Lab (Brown University, Providence, RI)
Wayne Goodman (Baylor College of Medicine, Houston)
Noam Peled (MGH/HST Martinos Center for Biomedical Imaging, Charlestown, MA)
Show Us Your BRAINs! Photo and Video Contest (BRAIN Initiative/NIH)
NIH Support: National Institute of Neurological Disorders and Stroke; National Institute of Mental Health
The Amazing Brain: Deep Brain Stimulation
Posted on by Dr. Francis Collins
August is here, and many folks have plans to enjoy a well-deserved vacation this month. I thought you might enjoy taking a closer look during August at the wonder and beauty of the brain here on my blog, even while giving your own brains a rest from some of the usual work and deadlines.
Some of the best imagery—and best science—comes from the NIH-led Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, a pioneering project aimed at revolutionizing our understanding of the human brain. Recently, the BRAIN Initiative held a “Show Us Your Brain Contest!”, which invited researchers involved in the effort to submit their coolest images. So, throughout this month, I’ve decided to showcase a few of these award-winning visuals.
Let’s start with the first-place winner in the still-image category. What you see above is an artistic rendering of deep brain stimulation (DBS), an approach now under clinical investigation to treat cognitive impairment that can arise after a traumatic brain injury and other conditions.
The vertical lines represent wire leads with a single electrode that has been inserted deep within the brain to reach a region involved in cognition, the central thalamus. The leads are connected to a pacemaker-like device that has been implanted in a patient’s chest (not shown). When prompted by the pacemaker, the leads’ electrode emits electrical impulses that stimulate a network of neuronal fibers (blue-white streaks) involved in arousal, which is an essential component of human consciousness. The hope is that DBS will improve attention and reduce fatigue in people with serious brain injuries that are not treatable by other means.
Andrew Janson, who is a graduate student in Christopher Butson’s NIH-supported lab at the Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, composed this image using a software program called Blender. It’s an open-source, 3D computer graphics program often used to create animated films or video games, but not typically used in biomedical research. That didn’t stop Janson.
With the consent of a woman preparing to undergo experimental DBS treatment for a serious brain injury suffered years before in a car accident, Janson used Blender to transform her clinical brain scans into a 3D representation of her brain and the neurostimulation process. Then, he used a virtual “camera” within Blender to capture the 2D rendering you see here. Janson plans to use such imagery, along with other patient-specific modeling and bioelectric fields simulations, to develop a virtual brain stimulation surgery to predict the activation of specific fiber pathways, depending upon lead location and stimulation settings.
DBS has been used for many years to relieve motor symptoms of certain movement disorders, including Parkinson’s disease and essential tremor. More recent experimental applications include this one for traumatic brain injury, and others for depression, addiction, Alzheimer’s disease, and chronic pain. As the BRAIN Initiative continues to map out the brain’s complex workings in unprecedented detail, it will be exciting to see how such information can lead to even more effective applications of to DBS to help people living with a wide range of neurological conditions.
Links:
Deep Brain Stimulation for Movement Disorders (National Institute of Neurological Disorders and Stroke/NIH)
Video: Deep Brain Stimulation (University of Utah, Salt Lake City)
Deep Brain Stimulation for the Treatment of Parkinson’s Disease and Other Movement Disorders (NINDS/NIH)
Butson Lab (University of Utah)
Show Us Your Brain! (BRAIN Initiative/NIH)
Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative (NIH)
NIH Support: National Institute of Neurological Disorders and Stroke
