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The Advantages of Closed-Loop DBS
Closed-loop DBS has several advantages over conventional DBS, said Dr. Foote. It reduces the amount of labor-intensive programming required, which ordinarily is based on frequent symptom assessment. Furthermore, closed-loop DBS can adapt to the fluctuating symptoms and interpatient variability that often characterize movement disorders. The technique may reduce the frequency of stimulation-related adverse events, decrease the likelihood of habituation, and extend the stimulator’s battery life, thus reducing the number of replacement surgeries required. “It is the ultimate in patient-tailored treatment,” said Dr. Foote.
In the past 15 years, electrocorticography, the measurement of local field potentials, and mathematical decoding have increased understanding of the brain greatly and enabled researchers to identify biomarkers of disease. Investigators have observed that when a person moves, high-frequency band activity in the motor cortex increases, and low-frequency band (ie, beta band) activity decreases. Beta activity appears to be a suppressive mechanism that gates motor function. These observations have been the basis for recent research in closed-loop DBS for Parkinson’s disease.
Tourette Syndrome
Dr. Foote and his colleagues are studying closed-loop DBS in patients with Tourette syndrome. They believed that the episodic nature of the syndrome’s symptoms would make closed-loop DBS a potentially beneficial treatment. The group hypothesized that if they could find a signal for the premonitory urge that patients generally have before a tic, they could deliver therapeutic stimulation as needed. They decided to target the centromedian (CM) nucleus of the thalamus for stimulation.
When Dr. Foote and colleagues failed to find a biomarker to predict tic onset, they decided to study intermittent stimulation using the NeuroPace system. Scheduled stimulation yielded statistically significant improvements in the Yale Global Tic Severity Scale total score, although they did not reach the prespecified outcome of a 50% improvement. The participant who received the most stimulation had the least improvement.
After this study was completed, the Medtronic PC+S system became available. This system has a longer battery life and improved hardware, compared with the NeuroPace system, said Dr. Foote. Using the PC+S system, he and his colleagues implanted two 24-year-old women with severe, intractable Tourette syndrome with 16 bilateral DBS electrodes on the CM thalamus. The patients also received cortical strips on both sides of the premotor cortex and motor cortex. The investigators found high levels of activity in the CM thalamus during tics, but no activity in that region during voluntary movement. The finding provides “strong evidence that the CM thalamus is participating in that pathologic network,” said Dr. Foote.
Engineers collaborating with Dr. Foote’s group used measurements of local field potentials in the CM thalamus and motor cortex to create a device that detects tics. The detector has a sensitivity of approximately 90% and a precision of 96%. When the investigators implanted the tic detector in one of the patients with Tourette syndrome who had received implantation of the NeuroPace device, it successfully initiated and terminated responsive DBS and reduced the patient’s tics.
Parkinson’s Disease
Investigators have found exaggerated phase amplitude coupling and increased beta activity in the subthalamic nucleus (STN), globus pallidus internus, and primary motor cortex of patients with Parkinson’s disease. In addition, data suggest that STN beta power correlates with the severity of bradykinesia and rigidity. Originally, researchers hypothesized that DBS provided benefit to patients with Parkinson’s disease by decreasing beta activity. A 2015 study by de Hemptinne et al, however, indicated that the main mechanism of action of DBS is disruption of phase amplitude coupling.
Patients with Tourette syndrome have the opposite problem, compared with patients with Parkinson’s disease. Therapeutic DBS reduces excessive movement in Tourette syndrome by increasing phase amplitude coupling, which is low at baseline. “We are helping [patients with Tourette syndrome] apply the brakes, because … they are failing to suppress these extra movements,” said Dr. Foote.
The tic detector has enabled the first chronic closed-loop DBS treatment for movement disorders, but many more such applications will emerge in the near future, he added. Research has suggested that phase amplitude coupling is a better biomarker in movement disorders than beta activity is. Dr. Foote and his colleagues are studying closed-loop DBS in essential tremor, and other researchers around the world are examining the treatment for Parkinson’s disease, Tourette syndrome, and obsessive–compulsive disorder.
“All DBS will be adaptive in the relatively near future,” concluded Dr. Foote. “It is just more intelligent to do it this way.”
—Erik Greb
Suggested Reading
Air EL, Ryapolova-Webb E, de Hemptinne C, et al. Acute effects of thalamic deep brain stimulation and thalamotomy on sensorimotor cortex local field potentials in essential tremor. Clin Neurophysiol. 2012;123(11):2232-2238.
de Hemptinne C, Swann NC, Ostrem JL, et al. Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson’s disease. Nat Neurosci. 2015;18(5): 779-786.
Miller KJ, Hermes D, Honey CJ, et al. Human motor cortical activity is selectively phase-entrained on underlying rhythms. PLoS Comput Biol. 2012;8(9):e1002655.
Okun MS, Foote KD, Wu SS, et al. A trial of scheduled deep brain stimulation for Tourette syndrome: moving away from continuous deep brain stimulation paradigms. JAMA Neurol. 2013;70(1):85-94.
The Advantages of Closed-Loop DBS
Closed-loop DBS has several advantages over conventional DBS, said Dr. Foote. It reduces the amount of labor-intensive programming required, which ordinarily is based on frequent symptom assessment. Furthermore, closed-loop DBS can adapt to the fluctuating symptoms and interpatient variability that often characterize movement disorders. The technique may reduce the frequency of stimulation-related adverse events, decrease the likelihood of habituation, and extend the stimulator’s battery life, thus reducing the number of replacement surgeries required. “It is the ultimate in patient-tailored treatment,” said Dr. Foote.
In the past 15 years, electrocorticography, the measurement of local field potentials, and mathematical decoding have increased understanding of the brain greatly and enabled researchers to identify biomarkers of disease. Investigators have observed that when a person moves, high-frequency band activity in the motor cortex increases, and low-frequency band (ie, beta band) activity decreases. Beta activity appears to be a suppressive mechanism that gates motor function. These observations have been the basis for recent research in closed-loop DBS for Parkinson’s disease.
Tourette Syndrome
Dr. Foote and his colleagues are studying closed-loop DBS in patients with Tourette syndrome. They believed that the episodic nature of the syndrome’s symptoms would make closed-loop DBS a potentially beneficial treatment. The group hypothesized that if they could find a signal for the premonitory urge that patients generally have before a tic, they could deliver therapeutic stimulation as needed. They decided to target the centromedian (CM) nucleus of the thalamus for stimulation.
When Dr. Foote and colleagues failed to find a biomarker to predict tic onset, they decided to study intermittent stimulation using the NeuroPace system. Scheduled stimulation yielded statistically significant improvements in the Yale Global Tic Severity Scale total score, although they did not reach the prespecified outcome of a 50% improvement. The participant who received the most stimulation had the least improvement.
After this study was completed, the Medtronic PC+S system became available. This system has a longer battery life and improved hardware, compared with the NeuroPace system, said Dr. Foote. Using the PC+S system, he and his colleagues implanted two 24-year-old women with severe, intractable Tourette syndrome with 16 bilateral DBS electrodes on the CM thalamus. The patients also received cortical strips on both sides of the premotor cortex and motor cortex. The investigators found high levels of activity in the CM thalamus during tics, but no activity in that region during voluntary movement. The finding provides “strong evidence that the CM thalamus is participating in that pathologic network,” said Dr. Foote.
Engineers collaborating with Dr. Foote’s group used measurements of local field potentials in the CM thalamus and motor cortex to create a device that detects tics. The detector has a sensitivity of approximately 90% and a precision of 96%. When the investigators implanted the tic detector in one of the patients with Tourette syndrome who had received implantation of the NeuroPace device, it successfully initiated and terminated responsive DBS and reduced the patient’s tics.
Parkinson’s Disease
Investigators have found exaggerated phase amplitude coupling and increased beta activity in the subthalamic nucleus (STN), globus pallidus internus, and primary motor cortex of patients with Parkinson’s disease. In addition, data suggest that STN beta power correlates with the severity of bradykinesia and rigidity. Originally, researchers hypothesized that DBS provided benefit to patients with Parkinson’s disease by decreasing beta activity. A 2015 study by de Hemptinne et al, however, indicated that the main mechanism of action of DBS is disruption of phase amplitude coupling.
Patients with Tourette syndrome have the opposite problem, compared with patients with Parkinson’s disease. Therapeutic DBS reduces excessive movement in Tourette syndrome by increasing phase amplitude coupling, which is low at baseline. “We are helping [patients with Tourette syndrome] apply the brakes, because … they are failing to suppress these extra movements,” said Dr. Foote.
The tic detector has enabled the first chronic closed-loop DBS treatment for movement disorders, but many more such applications will emerge in the near future, he added. Research has suggested that phase amplitude coupling is a better biomarker in movement disorders than beta activity is. Dr. Foote and his colleagues are studying closed-loop DBS in essential tremor, and other researchers around the world are examining the treatment for Parkinson’s disease, Tourette syndrome, and obsessive–compulsive disorder.
“All DBS will be adaptive in the relatively near future,” concluded Dr. Foote. “It is just more intelligent to do it this way.”
—Erik Greb
Suggested Reading
Air EL, Ryapolova-Webb E, de Hemptinne C, et al. Acute effects of thalamic deep brain stimulation and thalamotomy on sensorimotor cortex local field potentials in essential tremor. Clin Neurophysiol. 2012;123(11):2232-2238.
de Hemptinne C, Swann NC, Ostrem JL, et al. Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson’s disease. Nat Neurosci. 2015;18(5): 779-786.
Miller KJ, Hermes D, Honey CJ, et al. Human motor cortical activity is selectively phase-entrained on underlying rhythms. PLoS Comput Biol. 2012;8(9):e1002655.
Okun MS, Foote KD, Wu SS, et al. A trial of scheduled deep brain stimulation for Tourette syndrome: moving away from continuous deep brain stimulation paradigms. JAMA Neurol. 2013;70(1):85-94.
The Advantages of Closed-Loop DBS
Closed-loop DBS has several advantages over conventional DBS, said Dr. Foote. It reduces the amount of labor-intensive programming required, which ordinarily is based on frequent symptom assessment. Furthermore, closed-loop DBS can adapt to the fluctuating symptoms and interpatient variability that often characterize movement disorders. The technique may reduce the frequency of stimulation-related adverse events, decrease the likelihood of habituation, and extend the stimulator’s battery life, thus reducing the number of replacement surgeries required. “It is the ultimate in patient-tailored treatment,” said Dr. Foote.
In the past 15 years, electrocorticography, the measurement of local field potentials, and mathematical decoding have increased understanding of the brain greatly and enabled researchers to identify biomarkers of disease. Investigators have observed that when a person moves, high-frequency band activity in the motor cortex increases, and low-frequency band (ie, beta band) activity decreases. Beta activity appears to be a suppressive mechanism that gates motor function. These observations have been the basis for recent research in closed-loop DBS for Parkinson’s disease.
Tourette Syndrome
Dr. Foote and his colleagues are studying closed-loop DBS in patients with Tourette syndrome. They believed that the episodic nature of the syndrome’s symptoms would make closed-loop DBS a potentially beneficial treatment. The group hypothesized that if they could find a signal for the premonitory urge that patients generally have before a tic, they could deliver therapeutic stimulation as needed. They decided to target the centromedian (CM) nucleus of the thalamus for stimulation.
When Dr. Foote and colleagues failed to find a biomarker to predict tic onset, they decided to study intermittent stimulation using the NeuroPace system. Scheduled stimulation yielded statistically significant improvements in the Yale Global Tic Severity Scale total score, although they did not reach the prespecified outcome of a 50% improvement. The participant who received the most stimulation had the least improvement.
After this study was completed, the Medtronic PC+S system became available. This system has a longer battery life and improved hardware, compared with the NeuroPace system, said Dr. Foote. Using the PC+S system, he and his colleagues implanted two 24-year-old women with severe, intractable Tourette syndrome with 16 bilateral DBS electrodes on the CM thalamus. The patients also received cortical strips on both sides of the premotor cortex and motor cortex. The investigators found high levels of activity in the CM thalamus during tics, but no activity in that region during voluntary movement. The finding provides “strong evidence that the CM thalamus is participating in that pathologic network,” said Dr. Foote.
Engineers collaborating with Dr. Foote’s group used measurements of local field potentials in the CM thalamus and motor cortex to create a device that detects tics. The detector has a sensitivity of approximately 90% and a precision of 96%. When the investigators implanted the tic detector in one of the patients with Tourette syndrome who had received implantation of the NeuroPace device, it successfully initiated and terminated responsive DBS and reduced the patient’s tics.
Parkinson’s Disease
Investigators have found exaggerated phase amplitude coupling and increased beta activity in the subthalamic nucleus (STN), globus pallidus internus, and primary motor cortex of patients with Parkinson’s disease. In addition, data suggest that STN beta power correlates with the severity of bradykinesia and rigidity. Originally, researchers hypothesized that DBS provided benefit to patients with Parkinson’s disease by decreasing beta activity. A 2015 study by de Hemptinne et al, however, indicated that the main mechanism of action of DBS is disruption of phase amplitude coupling.
Patients with Tourette syndrome have the opposite problem, compared with patients with Parkinson’s disease. Therapeutic DBS reduces excessive movement in Tourette syndrome by increasing phase amplitude coupling, which is low at baseline. “We are helping [patients with Tourette syndrome] apply the brakes, because … they are failing to suppress these extra movements,” said Dr. Foote.
The tic detector has enabled the first chronic closed-loop DBS treatment for movement disorders, but many more such applications will emerge in the near future, he added. Research has suggested that phase amplitude coupling is a better biomarker in movement disorders than beta activity is. Dr. Foote and his colleagues are studying closed-loop DBS in essential tremor, and other researchers around the world are examining the treatment for Parkinson’s disease, Tourette syndrome, and obsessive–compulsive disorder.
“All DBS will be adaptive in the relatively near future,” concluded Dr. Foote. “It is just more intelligent to do it this way.”
—Erik Greb
Suggested Reading
Air EL, Ryapolova-Webb E, de Hemptinne C, et al. Acute effects of thalamic deep brain stimulation and thalamotomy on sensorimotor cortex local field potentials in essential tremor. Clin Neurophysiol. 2012;123(11):2232-2238.
de Hemptinne C, Swann NC, Ostrem JL, et al. Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson’s disease. Nat Neurosci. 2015;18(5): 779-786.
Miller KJ, Hermes D, Honey CJ, et al. Human motor cortical activity is selectively phase-entrained on underlying rhythms. PLoS Comput Biol. 2012;8(9):e1002655.
Okun MS, Foote KD, Wu SS, et al. A trial of scheduled deep brain stimulation for Tourette syndrome: moving away from continuous deep brain stimulation paradigms. JAMA Neurol. 2013;70(1):85-94.