World Neurosurgery News
9. Penfield W, Boldrey E: Somatic motor and sensory representations in the cerebral cortex of man as studied by electrical stimulation. Brain 60: 389-443, 1937. 10. Purdy M: $30 million project will map the brain’s wiring (Press release). Washington University School of Medicine. Available at: http://news. wustl.edu/news/Pages/21153.aspx. Accessed April 5, 2013. 11. Rocca J: Galen on the brain: anatomical knowledge and physiological speculation in the
second century AD. Stud Anc Med 26:1-313, 2003. 12. Stern A, Lindner NH: Topological quantum computation—from basic concepts to first experiments. Science 339:1179-1184, 2013. 13. Trip S, Grueber M: Economic impact of the human genome project. Battelle Memorial Institute, 2011. Available at: http://battelle.org/docs/ default-document-library/economic_impact_of_ the_human_genome_project.pdf. Accessed online January 23, 2013.
Department of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.wneu.2013.11.015
Advances in Deep Brain Stimulation for Parkinson Disease: Early and “Asleep”? Francisco A. Ponce
The use of deep brain stimulation (DBS) has expanded over recent years. Worldwide, >100,000 patients have been treated with DBS, with the most common indications being Parkinson disease (PD),
essential tremor, and primary dystonia. For patients with PD, the safety and efficacy of this therapy have been established through several large studies (3, 7, 9, 17). The labeling of DBS is for
Figure 1. Portable computed tomography scanner used intraoperatively for (A) Leksell frame registration and (B) verification of lead positioning before closing. (C) STEALTH snapshot showing deep brain stimulation contact windowing from computed tomography merged with magnetic resonance imaging, with inaccuracy calculated as 0.6 mm to target, 0.5 mm off plan. (Used with permission from Barrow Neurological Institute.)
6
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81 [1]: 2-8, JANUARY 2014 WORLD NEUROSURGERY
World Neurosurgery News
patients with advancing PD with motor complications associated with medical therapy (e.g., motor fluctuations, troublesome dyskinesias). In studies assessing the efficacy of DBS for PD, outcomes are assessed by standardized metrics, such as the Unified Parkinson’s Disease Rating Scale and 39-Item Parkinson’s Disease Questionnaire (PDQ-39), the latter of which is a measure of quality of life. DBS has been shown to provide patients with PD significant motor benefits as well as improvements in quality of life (11, 17). EARLY DBS In a trial by Schuepbach et al. (13), patients were enrolled at time points earlier in the disease than when DBS is typically introduced and randomly assigned to continued best medical therapy (BMT) or DBS. The trial enrolled 251 patients, and surgery targeted the subthalamic nucleus. Mean age was 52 years, and mean duration of disease was 7.5 years. The primary endpoint was the score on the PDQ-39 at 24 months. The results of the study indicated that DBS was superior to BMT with respect to motor disability, activities of daily living, reduction of levodopa-induced motor complications, and reduction of dyskinesias. Over the course of the trial, mean score of patients on the PDQ-39 was improved by 26% in the neurostimulation group but worsened by 1% in the BMT group. The maximum effect on the PDQ-39 was seen at 5 months. The motor portion of the Unified Parkinson’s Disease Rating Scale (Part III) improved by 53% in the DBS group. Medication use (i.e., levodopa-equivalent daily dose) was reduced by 39% in the DBS group but was increased by 21% in the BMT group. There were no significant differences between groups in cognitive outcome or in the rate of mood improved with stimulation.
REFERENCES 1. Deep Brain Stimulation (DBS) for Early Stage Parkinson’s Disease (PD). Clinical Trials 2013. Available at: http://clinicaltrials.gov/show/NCT00282152. 2. Abosch A, Timmermann L, Bartley S, Rietkerk HG, Whiting D, Connolly PJ, Lanctin D, Hariz MI: An international survey of deep brain stimulation procedural steps. Stereotact Funct Neurosurg 91: 1-11, 2013. 3. Burchiel KJ, Anderson VC, Favre J, Hammerstad JP: Comparison of pallidal and subthalamic nucleus deep brain stimulation for advanced Parkinson’s disease: results of a randomized, blinded pilot study. Neurosurgery 45:1375-1382, 1999. 4. Burchiel KJ, McCartney S, Lee A, Raslan AM: Accuracy of deep brain stimulation electrode placement using intraoperative computed tomography without microelectrode recording. J Neurosurg 119:301-306, 2013. 5. Charles PD, Dolhun RM, Gill CE, Davis TL, Bliton MJ, Tramontana MG, Salomon RM, Wang L, Hedera P, Phibbs FT, Neimat JS, Konrad PE: Deep brain stimulation in early Parkinson’s disease: enrollment experience from a pilot trial. Parkinsonism Relat Disord 18:268-273, 2012.
ASLEEP DBS Traditionally, DBS surgery requires patients with PD to be awake and off medication, and a more recent survey reported the average time to complete the key steps of DBS surgery was 8.75 hours (2). More recent techniques have been reported using intraoperative magnetic resonance imaging (15) or computed tomography (4) to perform the surgery under general anesthesia without the use of intraoperative microelectrode recording or test stimulation. The target is identified on preoperative magnetic resonance imaging, and intraoperative imaging is used to verify anatomic accuracy of lead placement (Figure 1). Patient outcomes at 6-month follow-up evaluation after bilateral subthalamic nucleus DBS for PD using magnetic resonance imaging at the time of surgery showed significant improvement in PD symptoms, similar to what has been reported using traditional “awake” methods (12). Whether or not targeting guided by either electrophysiology or anatomy optimizes clinical benefits has been a point of debate (10). Despite the invasiveness and the use of expensive implants, DBS has been shown to be safe and cost-effective (6, 8, 14, 16). The ability to stabilize motor function at earlier time points may provide the added benefit of delaying disability in patients and possibly allowing them to remain employed. In the coming years, the optimal time point for DBS intervention in PD may trend earlier in the disease (1, 5). The volume of DBS cases might be expected to grow in the coming years. Efforts to transform the procedure from physiologic procedures performed with the patient awake to anatomic procedures performed with the patient “asleep” may render DBS more accessible to a larger number of eligible patients. Patient safety, length of surgery, and operating room costs and time use may be additional benefits, although further study is required in this regard.
6. Dams J, Siebert U, Bornschein B, Volkmann J, Deuschl G, Oertel WH, Dodel R, Reese JP: Costeffectiveness of deep brain stimulation in patients with Parkinson’s disease. Mov Disord 28:763-771, 2013. 7. Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, Daniels C, Deutschlander A, Dillmann U, Eisner W, Gruber D, Hamel W, Herzog J, Hilker R, Klebe S, Kloss M, Koy J, Krause M, Kupsch A, Lorenz D, Lorenzl S, Mehdorn HM, Moringlane JR, Oertel W, Pinsker MO, Reichmann H, Reuss A, Schneider GH, Schnitzler A, Steude U, Sturm V, Timmermann L, Tronnier V, Trottenberg T, Wojtecki L, Wolf E, Poewe W, Voges J: A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med 355:896-908, 2006. 8. Fraix V, Houeto JL, Lagrange C, Le PC, Krystkowiak P, Guehl D, Ardouin C, Welter ML, Maurel F, Defebvre L, Rougier A, Benabid AL, Mesnage V, Ligier M, Blond S, Burbaud P, Bioulac B, Destee A, Cornu P, Pollak P: Clinical and economic results of bilateral subthalamic nucleus stimulation in Parkinson’s disease. J Neurol Neurosurg Psychiatry 77:443-449, 2006. 9. Hariz MI, Rehncrona S, Quinn NP, Speelman JD, Wensing C: Multicenter study on deep brain stimulation in Parkinson’s disease: an independent
WORLD NEUROSURGERY 81 [1]: 2-8, JANUARY 2014
assessment of reported adverse events at 4 years. Mov Disord 23:416-421, 2008. 10. Montgomery EB Jr: Microelectrode recordings in DBS—still in need of reasoned discussion. Mov Disord 28:255, 2013. 11. Okun MS, Fernandez HH, Wu SS, Kirsch-Darrow L, Bowers D, Bova F, Suelter M, Jacobson CE, Wang X, Gordon CW Jr, Zeilman P, Romrell J, Martin P, Ward H, Rodriguez RL, Foote KD: Cognition and mood in Parkinson’s disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial. Ann Neurol 65: 586-595, 2009. 12. Ostrem JL, Galifianakis NB, Markun LC, Grace JK, Martin AJ, Starr PA, Larson PS: Clinical outcomes of PD patients having bilateral STN DBS using highfield interventional MR-imaging for lead placement. Clin Neurol Neurosurg 115:708-712, 2013. 13. Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L, Halbig TD, Hesekamp H, Navarro SM, Meier N, Falk D, Mehdorn M, Paschen S, Maarouf M, Barbe MT, Fink GR, Kupsch A, Gruber D, Schneider GH, Seigneuret E, Kistner A, Chaynes P, Ory-Magne F, Brefel CC, Vesper J, Schnitzler A, Wojtecki L, Houeto JL, Bataille B, Maltete D, Damier P, Raoul S, SixelDoering F, Hellwig D, Gharabaghi A, Kruger R, Pinsker MO, Amtage F, Regis JM, Witjas T,
www.WORLDNEUROSURGERY.org
7
World Neurosurgery News
Thobois S, Mertens P, Kloss M, Hartmann A, Oertel WH, Post B, Speelman H, Agid Y, SchadeBrittinger C, Deuschl G: Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 368:610-622, 2013. 14. Spottke EA, Volkmann J, Lorenz D, Krack P, Smala AM, Sturm V, Gerstner A, Berger K, Hellwig D, Deuschl G, Freund HJ, Oertel WH, Dodel RC: Evaluation of healthcare utilization and health status of patients with Parkinson’s disease treated with deep brain stimulation of the subthalamic nucleus. J Neurol 249:759-766, 2002. 15. Starr PA, Martin AJ, Ostrem JL, Talke P, Levesque N, Larson PS: Subthalamic nucleus deep brain stimulator placement using high-field interventional
magnetic resonance imaging and a skull-mounted aiming device: technique and application accuracy. J Neurosurg 112:479-490, 2010. 16. Valldeoriola F, Morsi O, Tolosa E, Rumia J, Marti MJ, Martinez-Martin P: Prospective comparative study on cost-effectiveness of subthalamic stimulation and best medical treatment in advanced Parkinson’s disease. Mov Disord 22: 2183-2191, 2007. 17. Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJ Jr, Rothlind J, Sagher O, Reda D, Moy CS, Pahwa R, Burchiel K, Hogarth P, Lai EC, Duda JE, Holloway K, Samii A, Horn S, Bronstein J, Stoner G, Heemskerk J, Huang GD: Bilateral deep brain stimulation vs best medical
therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA 301: 63-73, 2009.
Division of Neurological Surgery, Barrow Neurological Institute and St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, USA 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.wneu.2013.11.018
Studying Obsessive-Compulsive Disorder Using Light Harrison Whyte and M. Yashar S. Kalani
It is estimated that 1%e2% of people worldwide have obsessivecompulsive disorder (OCD). More recent research has shown that patients with OCD have hyperactivity in orbitofrontal cortex (OFC)estriatal circuits; this was the target area for Ahmari et al. (1) in their study on OFC-ventromedial striatum (VMS) activity in mice. Using optogenetics, the team stereotactically injected a vector containing the gene for channel-rhodopsin (ChR2), an ion channel activated by blue light, to stimulate the OFC-VMS circuit. ChR2 was infused with a fluorescent yellow protein for tracking and was to be stimulated by fiberoptic implants able to emanate 473-nm lasers. The team expected to see increases in OCD-related behaviors (grooming and anxiety). Although the areas of the brain containing the introduced ChR2 were stimulated, no increases in grooming were noted. However, the
REFERENCE 1. Ahmari SE, Spellman T, Douglass NL, Kheirbek MA, Simpson HB, Deisseroth K, Gordon JA, Hen R: Repeated cortico-striatal stimulation generates persistent OCD-like behavior. Science 340:1234-1239, 2013.
8
www.SCIENCEDIRECT.com
repeated stimulation led to an overall major increase in stimulation-independent grooming. Psychopathologic abnormalities may be induced or facilitated by repeated instances of incorrect circuit activity. The mice tested in the study by Ahmari et al. (1) did not show any increases in anxiety or prepulse inhibition deficits at any point, indicating that the OFCVMS circuit is related solely to repetitive tendencies in regard to OCD. Finally, the investigators tested the effects of fluoxetine treatment on the mice while continuing the stimulation regimen. No change was noted during the first week, but grooming habits gradually returned to normal during the following weeks. Similar studies are expected to continue to shed light on the specific complexities of the problems caused by OCD, and it is hoped that these studies will uncover potential treatments for OCD and other psychological disorders.
Division of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona, USA 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.wneu.2013.11.016
81 [1]: 2-8, JANUARY 2014 WORLD NEUROSURGERY
9. Penfield W, Boldrey E: Somatic motor and sensory representations in the cerebral cortex of man as studied by electrical stimulation. Brain 60: 389-443, 1937. 10. Purdy M: $30 million project will map the brain’s wiring (Press release). Washington University School of Medicine. Available at: http://news. wustl.edu/news/Pages/21153.aspx. Accessed April 5, 2013. 11. Rocca J: Galen on the brain: anatomical knowledge and physiological speculation in the
second century AD. Stud Anc Med 26:1-313, 2003. 12. Stern A, Lindner NH: Topological quantum computation—from basic concepts to first experiments. Science 339:1179-1184, 2013. 13. Trip S, Grueber M: Economic impact of the human genome project. Battelle Memorial Institute, 2011. Available at: http://battelle.org/docs/ default-document-library/economic_impact_of_ the_human_genome_project.pdf. Accessed online January 23, 2013.
Department of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.wneu.2013.11.015
Advances in Deep Brain Stimulation for Parkinson Disease: Early and “Asleep”? Francisco A. Ponce
The use of deep brain stimulation (DBS) has expanded over recent years. Worldwide, >100,000 patients have been treated with DBS, with the most common indications being Parkinson disease (PD),
essential tremor, and primary dystonia. For patients with PD, the safety and efficacy of this therapy have been established through several large studies (3, 7, 9, 17). The labeling of DBS is for
Figure 1. Portable computed tomography scanner used intraoperatively for (A) Leksell frame registration and (B) verification of lead positioning before closing. (C) STEALTH snapshot showing deep brain stimulation contact windowing from computed tomography merged with magnetic resonance imaging, with inaccuracy calculated as 0.6 mm to target, 0.5 mm off plan. (Used with permission from Barrow Neurological Institute.)
6
www.SCIENCEDIRECT.com
81 [1]: 2-8, JANUARY 2014 WORLD NEUROSURGERY
World Neurosurgery News
patients with advancing PD with motor complications associated with medical therapy (e.g., motor fluctuations, troublesome dyskinesias). In studies assessing the efficacy of DBS for PD, outcomes are assessed by standardized metrics, such as the Unified Parkinson’s Disease Rating Scale and 39-Item Parkinson’s Disease Questionnaire (PDQ-39), the latter of which is a measure of quality of life. DBS has been shown to provide patients with PD significant motor benefits as well as improvements in quality of life (11, 17). EARLY DBS In a trial by Schuepbach et al. (13), patients were enrolled at time points earlier in the disease than when DBS is typically introduced and randomly assigned to continued best medical therapy (BMT) or DBS. The trial enrolled 251 patients, and surgery targeted the subthalamic nucleus. Mean age was 52 years, and mean duration of disease was 7.5 years. The primary endpoint was the score on the PDQ-39 at 24 months. The results of the study indicated that DBS was superior to BMT with respect to motor disability, activities of daily living, reduction of levodopa-induced motor complications, and reduction of dyskinesias. Over the course of the trial, mean score of patients on the PDQ-39 was improved by 26% in the neurostimulation group but worsened by 1% in the BMT group. The maximum effect on the PDQ-39 was seen at 5 months. The motor portion of the Unified Parkinson’s Disease Rating Scale (Part III) improved by 53% in the DBS group. Medication use (i.e., levodopa-equivalent daily dose) was reduced by 39% in the DBS group but was increased by 21% in the BMT group. There were no significant differences between groups in cognitive outcome or in the rate of mood improved with stimulation.
REFERENCES 1. Deep Brain Stimulation (DBS) for Early Stage Parkinson’s Disease (PD). Clinical Trials 2013. Available at: http://clinicaltrials.gov/show/NCT00282152. 2. Abosch A, Timmermann L, Bartley S, Rietkerk HG, Whiting D, Connolly PJ, Lanctin D, Hariz MI: An international survey of deep brain stimulation procedural steps. Stereotact Funct Neurosurg 91: 1-11, 2013. 3. Burchiel KJ, Anderson VC, Favre J, Hammerstad JP: Comparison of pallidal and subthalamic nucleus deep brain stimulation for advanced Parkinson’s disease: results of a randomized, blinded pilot study. Neurosurgery 45:1375-1382, 1999. 4. Burchiel KJ, McCartney S, Lee A, Raslan AM: Accuracy of deep brain stimulation electrode placement using intraoperative computed tomography without microelectrode recording. J Neurosurg 119:301-306, 2013. 5. Charles PD, Dolhun RM, Gill CE, Davis TL, Bliton MJ, Tramontana MG, Salomon RM, Wang L, Hedera P, Phibbs FT, Neimat JS, Konrad PE: Deep brain stimulation in early Parkinson’s disease: enrollment experience from a pilot trial. Parkinsonism Relat Disord 18:268-273, 2012.
ASLEEP DBS Traditionally, DBS surgery requires patients with PD to be awake and off medication, and a more recent survey reported the average time to complete the key steps of DBS surgery was 8.75 hours (2). More recent techniques have been reported using intraoperative magnetic resonance imaging (15) or computed tomography (4) to perform the surgery under general anesthesia without the use of intraoperative microelectrode recording or test stimulation. The target is identified on preoperative magnetic resonance imaging, and intraoperative imaging is used to verify anatomic accuracy of lead placement (Figure 1). Patient outcomes at 6-month follow-up evaluation after bilateral subthalamic nucleus DBS for PD using magnetic resonance imaging at the time of surgery showed significant improvement in PD symptoms, similar to what has been reported using traditional “awake” methods (12). Whether or not targeting guided by either electrophysiology or anatomy optimizes clinical benefits has been a point of debate (10). Despite the invasiveness and the use of expensive implants, DBS has been shown to be safe and cost-effective (6, 8, 14, 16). The ability to stabilize motor function at earlier time points may provide the added benefit of delaying disability in patients and possibly allowing them to remain employed. In the coming years, the optimal time point for DBS intervention in PD may trend earlier in the disease (1, 5). The volume of DBS cases might be expected to grow in the coming years. Efforts to transform the procedure from physiologic procedures performed with the patient awake to anatomic procedures performed with the patient “asleep” may render DBS more accessible to a larger number of eligible patients. Patient safety, length of surgery, and operating room costs and time use may be additional benefits, although further study is required in this regard.
6. Dams J, Siebert U, Bornschein B, Volkmann J, Deuschl G, Oertel WH, Dodel R, Reese JP: Costeffectiveness of deep brain stimulation in patients with Parkinson’s disease. Mov Disord 28:763-771, 2013. 7. Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, Daniels C, Deutschlander A, Dillmann U, Eisner W, Gruber D, Hamel W, Herzog J, Hilker R, Klebe S, Kloss M, Koy J, Krause M, Kupsch A, Lorenz D, Lorenzl S, Mehdorn HM, Moringlane JR, Oertel W, Pinsker MO, Reichmann H, Reuss A, Schneider GH, Schnitzler A, Steude U, Sturm V, Timmermann L, Tronnier V, Trottenberg T, Wojtecki L, Wolf E, Poewe W, Voges J: A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med 355:896-908, 2006. 8. Fraix V, Houeto JL, Lagrange C, Le PC, Krystkowiak P, Guehl D, Ardouin C, Welter ML, Maurel F, Defebvre L, Rougier A, Benabid AL, Mesnage V, Ligier M, Blond S, Burbaud P, Bioulac B, Destee A, Cornu P, Pollak P: Clinical and economic results of bilateral subthalamic nucleus stimulation in Parkinson’s disease. J Neurol Neurosurg Psychiatry 77:443-449, 2006. 9. Hariz MI, Rehncrona S, Quinn NP, Speelman JD, Wensing C: Multicenter study on deep brain stimulation in Parkinson’s disease: an independent
WORLD NEUROSURGERY 81 [1]: 2-8, JANUARY 2014
assessment of reported adverse events at 4 years. Mov Disord 23:416-421, 2008. 10. Montgomery EB Jr: Microelectrode recordings in DBS—still in need of reasoned discussion. Mov Disord 28:255, 2013. 11. Okun MS, Fernandez HH, Wu SS, Kirsch-Darrow L, Bowers D, Bova F, Suelter M, Jacobson CE, Wang X, Gordon CW Jr, Zeilman P, Romrell J, Martin P, Ward H, Rodriguez RL, Foote KD: Cognition and mood in Parkinson’s disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial. Ann Neurol 65: 586-595, 2009. 12. Ostrem JL, Galifianakis NB, Markun LC, Grace JK, Martin AJ, Starr PA, Larson PS: Clinical outcomes of PD patients having bilateral STN DBS using highfield interventional MR-imaging for lead placement. Clin Neurol Neurosurg 115:708-712, 2013. 13. Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L, Halbig TD, Hesekamp H, Navarro SM, Meier N, Falk D, Mehdorn M, Paschen S, Maarouf M, Barbe MT, Fink GR, Kupsch A, Gruber D, Schneider GH, Seigneuret E, Kistner A, Chaynes P, Ory-Magne F, Brefel CC, Vesper J, Schnitzler A, Wojtecki L, Houeto JL, Bataille B, Maltete D, Damier P, Raoul S, SixelDoering F, Hellwig D, Gharabaghi A, Kruger R, Pinsker MO, Amtage F, Regis JM, Witjas T,
www.WORLDNEUROSURGERY.org
7
World Neurosurgery News
Thobois S, Mertens P, Kloss M, Hartmann A, Oertel WH, Post B, Speelman H, Agid Y, SchadeBrittinger C, Deuschl G: Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 368:610-622, 2013. 14. Spottke EA, Volkmann J, Lorenz D, Krack P, Smala AM, Sturm V, Gerstner A, Berger K, Hellwig D, Deuschl G, Freund HJ, Oertel WH, Dodel RC: Evaluation of healthcare utilization and health status of patients with Parkinson’s disease treated with deep brain stimulation of the subthalamic nucleus. J Neurol 249:759-766, 2002. 15. Starr PA, Martin AJ, Ostrem JL, Talke P, Levesque N, Larson PS: Subthalamic nucleus deep brain stimulator placement using high-field interventional
magnetic resonance imaging and a skull-mounted aiming device: technique and application accuracy. J Neurosurg 112:479-490, 2010. 16. Valldeoriola F, Morsi O, Tolosa E, Rumia J, Marti MJ, Martinez-Martin P: Prospective comparative study on cost-effectiveness of subthalamic stimulation and best medical treatment in advanced Parkinson’s disease. Mov Disord 22: 2183-2191, 2007. 17. Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJ Jr, Rothlind J, Sagher O, Reda D, Moy CS, Pahwa R, Burchiel K, Hogarth P, Lai EC, Duda JE, Holloway K, Samii A, Horn S, Bronstein J, Stoner G, Heemskerk J, Huang GD: Bilateral deep brain stimulation vs best medical
therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA 301: 63-73, 2009.
Division of Neurological Surgery, Barrow Neurological Institute and St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, USA 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.wneu.2013.11.018
Studying Obsessive-Compulsive Disorder Using Light Harrison Whyte and M. Yashar S. Kalani
It is estimated that 1%e2% of people worldwide have obsessivecompulsive disorder (OCD). More recent research has shown that patients with OCD have hyperactivity in orbitofrontal cortex (OFC)estriatal circuits; this was the target area for Ahmari et al. (1) in their study on OFC-ventromedial striatum (VMS) activity in mice. Using optogenetics, the team stereotactically injected a vector containing the gene for channel-rhodopsin (ChR2), an ion channel activated by blue light, to stimulate the OFC-VMS circuit. ChR2 was infused with a fluorescent yellow protein for tracking and was to be stimulated by fiberoptic implants able to emanate 473-nm lasers. The team expected to see increases in OCD-related behaviors (grooming and anxiety). Although the areas of the brain containing the introduced ChR2 were stimulated, no increases in grooming were noted. However, the
REFERENCE 1. Ahmari SE, Spellman T, Douglass NL, Kheirbek MA, Simpson HB, Deisseroth K, Gordon JA, Hen R: Repeated cortico-striatal stimulation generates persistent OCD-like behavior. Science 340:1234-1239, 2013.
8
www.SCIENCEDIRECT.com
repeated stimulation led to an overall major increase in stimulation-independent grooming. Psychopathologic abnormalities may be induced or facilitated by repeated instances of incorrect circuit activity. The mice tested in the study by Ahmari et al. (1) did not show any increases in anxiety or prepulse inhibition deficits at any point, indicating that the OFCVMS circuit is related solely to repetitive tendencies in regard to OCD. Finally, the investigators tested the effects of fluoxetine treatment on the mice while continuing the stimulation regimen. No change was noted during the first week, but grooming habits gradually returned to normal during the following weeks. Similar studies are expected to continue to shed light on the specific complexities of the problems caused by OCD, and it is hoped that these studies will uncover potential treatments for OCD and other psychological disorders.
Division of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona, USA 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.wneu.2013.11.016
81 [1]: 2-8, JANUARY 2014 WORLD NEUROSURGERY
