Neuromodulation Surgery for Psychiatric Disorders
- Author: Jonathan P Miller, MD; Chief Editor: Brian H Kopell, MD more...
Neuromodulation is a broad term that could technically be considered to cover any medical, surgical, or physiologic therapy designed to alter the function of the nervous system in some manner. In the clinical neurosciences, however, neuromodulation is understood to refer specifically to therapies that involve targeted delivery of drugs or electrical current, frequently through an implanted device, in order to effect a specific change in the function of a target neural structure.
Prior to the development of implantable devices for neurostimulation, surgical procedures designed to alter the function of the nervous system required the destruction of target tissues, with an accompanying irreversible change in function. Neuromodulation, however, provides a paradigm through which therapy can be titrated, or even turned on and off, with changes usually reversing rapidly upon cessation of therapy. While neuromodulation techniques are currently used primarily for the management of chronic pain and movement disorders, there has been considerable interest in their use for medically refractory psychiatric disease. Significant research remains to be done before any of the therapies are likely to become widespread, however. There is also substantial public trepidation about the use of surgical therapies in the treatment of psychiatric disease as a direct consequence of the abuse of psychosurgery in the mid-twentieth century, specifically the heavy human toll exacted by the careless and widespreaduse of the frontal lobotomy. It is therefore incumbent upon the medical community to ensure that research to refine the effectiveness and expand the indications for neuromodulation in psychiatric disease is conducted in multidisciplinary fashion, and with rigid adherence to the highest standards of medical ethics.
History of the Procedure
With the advent of stereotaxis (the use of special targeting and coordinate systems capable of delivering an electrode or other probe precisely into deep brain structures), surgery for psychiatric disease evolved from the open lobotomy into minimally invasive lesioning such as cingulotomy (stereotactic ablation of the anterior cingulate cortex; see the first image below), capsulotomy (surgical ablation of the anterior limb of the internal capsule; see the second image below), subcaudate tractotomy (surgical ablation of the area known as the substantia innominate, a region ventral to head of the caudate; see the third image below), and limbic leucotomy (essentially a combined subcaudate tractotomy and cingulotomy). Nevertheless, because of the mistrust for lesioning procedures that was the legacy of lobotomy, these procedures never came into widespread use and were not subject to strict experimental protocol. The lessons learned from stereotactic lesioning procedures were to play an important role,however, in the development of neuromodulatory therapies.
The two surgical neuromodulatory therapies currently in use for the treatment of psychiatric conditions are deep brain stimulation (DBS) and vagal nerve stimulation (VNS). Because both were developed for non-psychiatric indications, there had been extensive refinement of the techniques and technology prior to their initial use in psychiatric disease. The first report of DBS for a psychiatric indication, published in The Lancet in 1999, described implantation of electrodes into the bilateral anterior limbs of the internal capsule for treatment of refractory Obsessive-Compulsive Disorder (OCD) in a series of four patients. Target selection was based on the usual targeting for stereotactic cingulotomy, with the hope that electrical stimulation could generate the same effects as lesioning but modifiably and reversibly. Larger trials followed, followed by trials using DBS to treat other psychiatric diseases, particularly Major Depressive Disorder (MDD).
The use of VNS to treat MDD was inspired by the observation that VNS seemed to improve mood in patients with epilepsy in a manner that was independent of seizure reduction. Subsequent trials led to FDA approval of VNS for treatment refractory depression in 2005.
Psychiatric disease is a major source of suffering, disability, and death worldwide. Major Depressive Disorder (MDD) alone accounts for billions of dollars in direct and indirect medical costs, and was found to be the second leading cause of disability in the Global Burden of Disease 2010 study. Unfortunately, many psychiatric conditions have a high rate of resistance to pharmacologic treatment, and may remain refractory even to multimodal therapies utilizing medication, psychotherapy, and lifestyle interventions. Even patients whose disease responds to medication may not achieve remission due to side effects or dose limitations. Past surgical attempts at treatment of psychiatric disease, using open or stereotactic techniques to interrupt white matter tracts, showed some efficacy but were irreversible and led to catastrophic morbidity when misapplied. The challenges facing broader implementation of neuromodulatory techniques can therefore be broken down into three categories: 1)improving anatomic and pathophysiologic models of psychiatric illness to better identify the best substrates for stimulation, 2) optimizing stimulation parameters to maximize therapeutic effect and minimize adverse consequences, and 3) improving the patient selection process to avoid subjecting likely non-responders to the risk and expense of surgery.
OCD is one of the most debilitating and refractory psychiatric disorders. OCD affects up to 2-3% of the US population (an estimated 2.2 million people) and almost 50 million people worldwide. Up to 40% of patients with OCD are partial responders or nonresponders. Few patients with OCD experience a complete remission of symptomatology.
MDD is the leading cause of disability in the United States for patients aged 15-44 years. In any given 1-year period, 9.5% of the population, or about 20.9 million American adults, suffer from a depressive illness. Up to 30% of these patients are refractory to treatment.
In general, insight into the pathophysiology of psychiatric disease is much less defined than the pathophysiology of movement disorders. There are many resons for this disparity, among them the complexity and heterogeneity of the underlying diseases and the lack of animal models of depression and OCD, as compared with the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of Parkinson disease. Animal models of psychiatric disease are currently being developed but are not nearly as mature as their movement disorder counterparts. The result is that most early models of psychiatric disease were derived from the observation of behavior after brain lesions in humans. This tended to favor oversimplified models reliant on "positive" versus "negative" mood centers.
Increasingly, however, models of psychiatric disease are predicated not on a "center" of mood or behavior but rather an imbalance in communication of multiple neuronal loops. Functional imaging techniques such as fMRI, PET, and MEG have played a significant role in elucidating functional abnormalities in patients suffering from psychiatric illness. For details of the involved circuitry, see the Anatomy section of this article. Different studies, however, have found different patterns of derangement within this circuitry. This may be due to the heterogeneous nature of psychiatric illness itself. It is possible that biologically distinct subtypes of depression may have different patterns of activity on functional imaging. A similar situation exists for the clinical subtypes of OCD.
Most of the currently accepted somatic treatments for MDD and OCD are thought to primarily work through the manipulation of discrete neurotransmitter systems. MDD has been primarily managed clinically through the use of medications that manipulate serotonergic, noradrenergic, and dopaminergic systems, based largely on drug response and monoamine depletion data. OCD has been managed primarily with manipulation of the serotonergic system, based largely on drug response data. These neurotranmitters likely participate in signaling within the circuits listed above, although they also play multiple other roles within the nervous system. This is again analagous to Parkinson's disease, where the neurotransmitter dopamine plays a central role in the pathophysiology of the disease, but where neuromodulation can be used to balance the activity of competing circuits without affecting unrelated circuits which happen to use the same neurotransmitter.
Obsessive-compulsive disorder (OCD) is defined by the National Institute of Mental Health as an anxiety disorder characterized by recurrent, unwanted thoughts (obsessions) and/or repetitive behaviors (compulsions). Repetitive behaviors such as handwashing, counting, checking, or cleaning are often performed with the hope of preventing obsessive thoughts or making them go away. Performing these so-called "rituals," however, provides only temporary relief, and not performing them markedly increases anxiety.
No definitive agreement exists on what constitutes medically refractory or treatment resistant OCD. The definition most commonly used is an unsatisfactory response to 2 adequate trials of serotonin reuptake inhibitors, although most would suggest a trial of cognitive behavioral therapy (CBT) prior to defining someone as treatment resistant. Determination of "failure" or an “unsatisfactory response” is made when the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score is reduced by less than 25% or when improvement is greater than 25% but the patient still experiences significant OCD-caused impairment (meaning that the obsessions or compulsions continue to cause impairment in functioning, even in their improved state). Approximately 10% of the OCD population may be candidates for neuromodulation surgery based on these criteria of treatment resistance.
Major Depressive Disorder
Major depressive disorder (MDD) is defined by the National Institute of Mental health as manifesting a combination of affective, cognitive, and behavioral symptoms that interfere with the ability to work, study, sleep, eat, and enjoy once pleasurable activities. Such a disabling episode of depression may occur only once but more commonly occurs several times in a lifetime.
Treatment-resistant depression also has no agreed upon definition. Attempts have been made to define degrees of treatment refractoriness. Thase and O’Reardon defined treatment refractory depression as treatment nonresponse (ie, persistence of significant depressive symptoms) despite at least 2 treatment trials with drugs from different pharmacologic classes, each used in an adequate dose for an adequate time period.[17, 18]
The FDA went beyond this most commonly used definition when its approved vagus nerve stimulation (VNS) for treatment-resistant depression raised the number of failed adequate trials to 4 but did not define the types or quality of trials needed. These trials may include medications, therapies, and other treatments such as electroconvulsive therapy (ECT). Approximately 10-15% of the major depressive disease (MDD) population may be candidates for neuromodulation surgery based on these criteria of treatment resistance.
Patient selection is perhaps the most crucial issue facing the renewed interest in neuromodulation for psychiatric disease. Careful patient selection is the key to not recapitulating the mistakes of the lobotomy era. An emphasis is placed on a multidisciplinary approach in which a team led by psychiatrists who are expert in the treatment of refractory obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) carefully reviews all patients prior to surgical intervention.
Recent publications have given the following guidelines for forming such a team: an ethics committee, a patient assessment committee, strict adherence to accepted criteria for treatment-refractory MDD/OCD, limitation of such efforts to tertiary-care academic centers, limitation of patient selection to those patients with decision-making capacity, and the avoidance of procedures whose purpose involves law enforcement, political, or social ends.
In 1937, James Papez introduced a circuitry that included the hippocampus, the fornix, the mammillary bodies, the mammillothalamic tract, the anterior thalamic, the subgenual cingulate (Brodmann area 25 or Cg25), the parahippocampal gyrus, and the entorhinal cortex.
This circuit, known as the Papez circuit, has been an important heuristic model for psychiatric research and practice (see the image below).
In 1954, Paul McLean described a neural circuit that included cortical and subcortical structures. Known as the limbic system, this has been perhaps the most influential neuroanatomic model of psychiatric phenomena in the 20th and 21st centuries. The limbic system consists of the regions involved in the Papez circuit and adds the amygdala, the hypothalamus, the nucleus accumbens, and the orbitofrontal cortex.
Despite the prejudice it cast on the practice of surgery for psychiatric disease, lobotomy emphasized the inherent role the frontal lobe has in the genesis of psychiatric symptoms and behaviors. The evolution of this insight has been the basis of the evolution of lobotomy to stereotactic lesions and now to the use of deep brain stimulation (DBS) for psychiatric disease. The following anatomic areas within the frontal lobe have to be considered:
Orbitofrontal cortex (Brodmann areas 10, 11, 12, 47; see the image below)
- This area processes tasks related to reward and punishment and extinction behavior in response to aversive stimuli.
- This area’s role in psychiatric disease is perseverative cognitions and emotional response.
- The anatomic connections in this area include the following:
- It receives projections from every sensory modality (unique among any neocortical region).
- Its influence over the autonomic nervous system is second only to the Cg25.
- This area has extensive reciprocal connections to the dorsolateral prefrontal cortex and cingulate.
- Functional imaging data
Dorsolateral prefrontal cortex (Brodmann area 9, lateral 10, 46; see the image below)The dorsolateral prefrontal cortex. Adapted from an image from Professor Mark Dubin, University of Colorado.See the list below:
- This area processes tasks related to working memory, spatial memory and executive function, and mediation of external environment on limbic responses.
- This area’s role in psychiatric disease involves the patient’s insight into symptoms, the ability to suppress negative feelings and painful stimuli, and the psychomotor retardation of severe depression.
- Anatomic connections include extensive reciprocal connections to OFC and the cingulate.
- Functional imaging data include decreased metabolism in negative mood states and untreated depressed patients and increased metabolism with successful treatment.
Cingulate (Brodmann areas 24, 32, and 25; see the image below)The cingulate gyrus (Cg25; in green). Adapted from an image from Professor Mark Dubin, University of Colorado.See the list below:
- This area processes tasks related to attention and influence over visceromotor and vegetative functions.
- This area’s role in psychiatric disease is related to disruptions in hedonic tone and motivation.
- This area’s anatomic features include the following:
- Extensive connections to autonomic circuitry
- Extensive reciprocal connections to the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC)
- Functional imaging data include the following:
These frontal lobe regions can be organized into 2 functionally related compartments: the dorsal compartment (DLPFC/ lateral orbitofrontal cortex [LOFC]; see the first image below) and a ventral compartment (medial orbitofrontal cortex [MOFC]/cingulate; see the second image below).
Evidence shows that neuronal ensemble oscillation and resonance between the thalamus and the cortex is "deeply related to the emergence of brain functions." The thalamocortical (TC) loop is thought to be the basic building block of behaviors that span from motor activity to psychiatric phenomena. Each TC loop consists of a specific region of cerebral cortex and its reciprocal excitatory connections with a specific target within the thalamus. Derangement in these loops can result in neurologic disorders.
In the case of motor disorders such as Parkinson disease, the TC loop in question involves the cortical regions of the motor cortex, the premotor cortex, and the supplementary motor area and the ventral lateral thalamic motor nucleus (VL). With regard to psychiatric disease, the following 2 TC loops are important: an associative loop that consists of the dorsal frontal lobe compartment and its reciprocal projections to the ventral anterior (VA) and the parvocellular dorsomedial thalamic nuclei (DMpc) and a limbic loop that consists of the ventral frontal lobe compartment and its reciprocal projections to the magnocellular portion of the dorsomedial thalamus (DMmc; see the images below).
In 1986, Alexander and Delong described a series of 5 loops of information, from cortex to basal ganglia and back to cortex. Each loop activity courses through the basal ganglia in parallel direct and indirect pathways. These heuristic schemes provided the basis for modern movement disorder surgery. In the case of movement disorders, the motor loop is of importance. For psychiatric disease, the dorsolateral, orbitofrontal, and anterior cingulate loops are important. Each loop has a direct and indirect component (see the image below).
One of the features of these basal ganglia loops is that information is segregated according to the anatomic areas of their components. The primary cortical association of the associative loop is the dorsal compartment. Most of the information in the dorsal compartment flows through central striatal regions, such as the head of the caudate and portions of the NA core. The primary cortical association of the limbic loop is the ventral compartment. Most of the information in the ventral compartment flows through ventromedial striatal regions, such as the NA core and the NA shell. Like other cortico-striato-pallido-thalamocortical (CSPTC) loops, information travels through parallel indirect and direct pathways, with the output structures being the globus pallidus pars interna (GPi) and substantia nigra pars reticularis (SNr).
The third anatomic circuitry that must be discussed is the interface of these thalamocortical and basal ganglia loops with the hypothalamic-pituitary axis. Via direct and indirect connections, the associative and limbic loops have access to autonomic machinery via the amygdala, the NA shell, the hypothalamus, and the serotonergic midbrain. The autonomic circuitry is especially important to the so-called vegetative aspects of psychiatric disease, such as wake/sleep cycles, feeding aberrances, and anxiety manifestations (see the image below).
Currently, 7 targets for neuromodulation surgery have been published: Cg25, the anterior internal capsule (AIC), the nucleus accumbens (NA), the ventral striatum (VS), the inferior thalamic peduncle (ITP), the subthalamic nucleus (StN) and the left vagus nerve. Each of these regions can be seen as nodes in the aforementioned circuitry. Putative modulation at these nodes is the basis of the current efforts investigating neuromodulation surgery for refractory psychiatric disease. The highlighted areas of the images below show how neuromodulation at each target may influence the aforementioned circuitry.
Tierney TS, Vasudeva VS, Weir S, Hayes MT. Neuromodulation for neurodegenerative conditions. Front Biosci (Elite Ed). 2013 Jan 1. 5:490-9. [Medline].
Robison RA, Taghva A, Liu CY, Apuzzo ML. Surgery of the mind, mood, and conscious state: an idea in evolution. World Neurosurg. 2013 Sep-Oct. 80(3-4):S2-26. [Medline].
Kopell BH, Greenberg B, Rezai AR. Deep brain stimulation for psychiatric disorders. J Clin Neurophysiol. 2004 Jan-Feb. 21(1):51-67. [Medline].
Leiphart JW, Valone FH 3rd. Stereotactic lesions for the treatment of psychiatric disorders. J Neurosurg. 2010 Dec. 113(6):1204-11. [Medline].
Nuttin B, Cosyns P, Demeulemeester H, Gybels J, Meyerson B. Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder. Lancet. 1999 Oct 30. 354(9189):1526. [Medline].
Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman G, Murray CJ, et al. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med. 2013 Nov. 10(11):e1001547. [Medline]. [Full Text].
McIntyre RS, Filteau MJ, Martin L, Patry S, Carvalho A, Cha DS. Treatment-resistant depression: Definitions, review of the evidence, and algorithmic approach. J Affect Disord. 2014 Mar. 156:1-7. [Medline].
Kopell BH, Rezai AR. Psychiatric neurosurgery: a historical perspective. Neurosurg Clin N Am. 2003 Apr. 14(2):181-97, vii. [Medline].
Eisen K Rasmussen S. Phenomenology of Obsessive Compulsive Disorder in Textbook of Anxiety Disorders. Edited by Stein, Hollander. American Psychiatric Publishing. 2002.
Hollander E, Alterman R, Dell'Osso, B. Approaching Treatment-Resistant Obsessive-compulsive Disorder With Brain Stimulation Interventions:. The State of the Art. Psychiatric Annals 36:. 2006. 7:480-488.
Murray C, Lopez A. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries and Risk Factors in 1990 and Projected to 2020. Cambridge, MA: Harcourt University Press. (1996).
Robins LN, Regier DA (Eds). Psychiatric Disorders in America, The Epidemiologic Catchment Area Study. New York: The Free Press; 1990.
Hirschfeld RM, Montgomery SA, Aguglia E, Amore M, Delgado PL, Gastpar M. Partial response and nonresponse to antidepressant therapy: current approaches and treatment options. J Clin Psychiatry. 2002 Sep. 63(9):826-37. [Medline].
Goodman WK, McDougle CJ, Barr LC, Aronson SC, Price LH. Biological approaches to treatment-resistant obsessive compulsive disorder. J Clin Psychiatry. 1993 Jun. 54 Suppl:16-26. [Medline].
Greenberg BD, Malone DA, Friehs GM, Rezai AR, Kubu CS, Malloy PF, et al. Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology. 2006 Nov. 31(11):2384-93. [Medline].
Sackeim HA, Rush AJ, George MS, Marangell LB, Husain MM, Nahas Z, et al. Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology. 2001 Nov. 25(5):713-28. [Medline].
O'Reardon JP, Amsterdam JD. Overview of treatment-resistant depression and its management. In: Treatment-Resistant Mood Disorders: Diagnosis and Treatment, Amsterdam JD, Hornig M, Nierenberg AA, eds. Cambridge, U.K.: Cambridge University Press,. (2001). pp30-45.
Greenberg BD, Price LH, Rauch SL, Friehs G, Noren G, Malone D, et al. Neurosurgery for intractable obsessive-compulsive disorder and depression: critical issues. Neurosurg Clin N Am. 2003 Apr. 14(2):199-212. [Medline].
Fins JJ, Rezai AR, Greenberg BD. Psychosurgery: avoiding an ethical redux while advancing a therapeutic future. Neurosurgery. 2006 Oct. 59(4):713-6. [Medline].
Deckersbach T, Dougherty DD, Rauch SL. Functional imaging of mood and anxiety disorders. J Neuroimaging. 2006 Jan. 16(1):1-10. [Medline].
Rauch SL, Dougherty DD, Malone D, Rezai A, Friehs G, Fischman AJ, et al. A functional neuroimaging investigation of deep brain stimulation in patients with obsessive-compulsive disorder. J Neurosurg. 2006 Apr. 104(4):558-65. [Medline].
Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA, et al. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry. 1999 May. 156(5):675-82. [Medline].
Dougherty DD, Weiss AP, Cosgrove GR, Alpert NM, Cassem EH, Nierenberg AA, et al. Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for treatment of major depression. J Neurosurg. 2003 Dec. 99(6):1010-7. [Medline].
Llinas RR, Ribary U, Jeanmonod D, Kronberg E, Mitra PP. Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci U S A. 1999 Dec 21. 96(26):15222-7. [Medline].
Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci. 1986. 9:357-81. [Medline].
Machado A, Rezai AR, Kopell BH, Gross RE, Sharan AD, Benabid AL. Deep brain stimulation for Parkinson's disease: surgical technique and perioperative management. Mov Disord. 2006 Jun. 21 Suppl 14:S247-58. [Medline].
Rush AJ, Marangell LB, Sackeim HA, George MS, Brannan SK, Davis SM, et al. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry. 2005 Sep 1. 58(5):347-54. [Medline].
Rezai AR, Kopell BH, Gross RE et al. Deep Brain Stimulation for Movement Disorders: Surgical Issues. Mov Disord. 2006. 21 (Suppl 14):S197-S218.
Shapira NA, Okun MS, Wint D, Foote KD, Byars JA, Bowers D, et al. Panic and fear induced by deep brain stimulation. J Neurol Neurosurg Psychiatry. 2006 Mar. 77(3):410-2. [Medline].
Nuttin BJ, Gabriels LA, Cosyns PR, Meyerson BA, Andreewitch S, Sunaert SG, et al. Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder. Neurosurgery. 2003 Jun. 52(6):1263-72; discussion 1272-4. [Medline].
Rush AJ, George MS, Sackeim HA, Marangell LB, Husain MM, Giller C, et al. Vagus nerve stimulation (VNS) for treatment-resistant depressions: a multicenter study. Biol Psychiatry. 2000 Feb 15. 47(4):276-86. [Medline].
Sackeim HA, Keilp JG, Rush AJ, George MS, Marangell LB, Dormer JS, et al. The effects of vagus nerve stimulation on cognitive performance in patients with treatment-resistant depression. Neuropsychiatry Neuropsychol Behav Neurol. 2001 Jan. 14(1):53-62. [Medline].
Rezai AR, Friehs G, Malone DA et al. Deep Brain Stimulation for the Treatment of Intractable Major Depression: Preliminary Results from a Multicenter Prospective Trial. AANS 2006 annual meeting, San Diego California. 2006.
Anderson D, Ahmed A. Treatment of patients with intractable obsessive-compulsive disorder with anterior capsular stimulation. Case report. J Neurosurg. 2003 May. 98(5):1104-8. [Medline].
Abelson JL, Curtis GC, Sagher O, Albucher RC, Harrigan M, Taylor SF, et al. Deep brain stimulation for refractory obsessive-compulsive disorder. Biol Psychiatry. 2005 Mar 1. 57(5):510-6. [Medline].
Sturm V, Lenartz D, Koulousakis A, Treuer H, Herholz K, Klein JC, et al. The nucleus accumbens: a target for deep brain stimulation in obsessive-compulsive- and anxiety-disorders. J Chem Neuroanat. 2003 Dec. 26(4):293-9. [Medline].
Aouizerate B, Cuny E, Martin-Guehl C, Guehl D, Amieva H, Benazzouz A, et al. Deep brain stimulation of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depression. Case report. J Neurosurg. 2004 Oct. 101(4):682-6. [Medline].
Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, et al. Deep brain stimulation for treatment-resistant depression. Neuron. 2005 Mar 3. 45(5):651-60. [Medline].
Lozano AM, Mayberg HS, Giacobbe P, Hamani C, Craddock RC, Kennedy SH. Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry. 2008 Sep 15. 64(6):461-7. [Medline].
Lozano AM, Giacobbe P, Hamani C, Rizvi SJ, Kennedy SH, Kolivakis TT, et al. A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment-resistant depression. J Neurosurg. 2012 Feb. 116(2):315-22. [Medline].
Jimenez F. Electrical Stimulation of the Inferior Thalamic Peduncle. Presented at the 14th WSSFN society meeting, Rome, Italy. Wednesday June 15, 2005.
Mallet L, Mesnage V, Houeto JL, Pelissolo A, Yelnik J, Behar C, et al. Compulsions, Parkinson's disease, and stimulation. Lancet. 2002 Oct 26. 360(9342):1302-4. [Medline].
Mallet L, Polosan M, Jaafari N, Baup N, Welter ML, Fontaine D, et al. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med. 2008 Nov 13. 359(20):2121-34. [Medline].
Nahas Z, Marangell LB, Husain MM, Rush AJ, Sackeim HA, Lisanby SH, et al. Two-year outcome of vagus nerve stimulation (VNS) for treatment of major depressive episodes. J Clin Psychiatry. 2005 Sep. 66(9):1097-104. [Medline].
Lipsman N, Mendelsohn D, Taira T, Bernstein M. The contemporary practice of psychiatric surgery: results from a survey of North American functional neurosurgeons. Stereotact Funct Neurosurg. 2011. 89(2):103-10. [Medline].
Mendelsohn D, Lipsman N, Lozano AM, Taira T, Bernstein M. The contemporary practice of psychiatric surgery: results from a global survey of functional neurosurgeons. Stereotact Funct Neurosurg. 2013. 91(5):306-13. [Medline].
Schneider TM, Beynon C, Sartorius A, Unterberg AW, Kiening KL. Deep brain stimulation of the lateral habenular complex in treatment-resistant depression: traps and pitfalls of trajectory choice. Neurosurgery. 2013 Jun. 72(2 Suppl Operative):ons184-93; discussion ons193. [Medline].
Lipsman N, Woodside DB, Giacobbe P, Hamani C, Carter JC, Norwood SJ, et al. Subcallosal cingulate deep brain stimulation for treatment-refractory anorexia nervosa: a phase 1 pilot trial. Lancet. 2013 Apr 20. 381(9875):1361-70. [Medline].
Wu H, Van Dyck-Lippens PJ, Santegoeds R, van Kuyck K, Gabriëls L, Lin G. Deep-brain stimulation for anorexia nervosa. World Neurosurg. 2013 Sep-Oct. 80(3-4):S29.e1-10. [Medline].
Li N, Wang J, Wang XL, Chang CW, Ge SN, Gao L, et al. Nucleus accumbens surgery for addiction. World Neurosurg. 2013 Sep-Oct. 80(3-4):S28.e9-19. [Medline].
Heldmann M, Berding G, Voges J, Bogerts B, Galazky I, Müller U, et al. Deep brain stimulation of nucleus accumbens region in alcoholism affects reward processing. PLoS One. 2012. 7(5):e36572. [Medline]. [Full Text].
Nahas Z, Anderson BS, Borckardt J, Arana AB, George MS, Reeves ST. Bilateral epidural prefrontal cortical stimulation for treatment-resistant depression. Biol Psychiatry. 2010 Jan 15. 67(2):101-9. [Medline].
Kopell BH, Halverson J, Butson CR, Dickinson M, Bobholz J, Harsch H, et al. Epidural cortical stimulation of the left dorsolateral prefrontal cortex for refractory major depressive disorder. Neurosurgery. 2011 Nov. 69(5):1015-29; discussion 1029. [Medline].
Anderson RJ, Frye MA, Abulseoud OA, Lee KH, McGillivray JA, Berk M, et al. Deep brain stimulation for treatment-resistant depression: efficacy, safety and mechanisms of action. Neurosci Biobehav Rev. 2012 Sep. 36(8):1920-33. [Medline].
George MS, Rush AJ, Marangell LB, Sackeim HA, Brannan SK, Davis SM, et al. A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression. Biol Psychiatry. 2005 Sep 1. 58(5):364-73. [Medline].
Malone DA Jr, Dougherty DD, Rezai AR, Carpenter LL, Friehs GM, Eskandar EN, et al. Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biol Psychiatry. 2009 Feb 15. 65(4):267-75. [Medline]. [Full Text].
Nangunoori R, Tomycz ND, Quigley M, Oh MY, Whiting DM. Deep brain stimulation for psychiatric diseases: a pooled analysis of published studies employing disease-specific standardized outcome scales. Stereotact Funct Neurosurg. 2013. 91(6):345-54. [Medline].
Nemeroff CB, Mayberg HS, Krahl SE, McNamara J, Frazer A, Henry TR, et al. VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology. 2006 Jul. 31(7):1345-55. [Medline].
Olchanski N, McInnis Myers M, Halseth M, Cyr PL, Bockstedt L, Goss TF, et al. The economic burden of treatment-resistant depression. Clin Ther. 2013 Apr. 35(4):512-22. [Medline].
Oluigbo CO, Salma A, Rezai AR. Deep brain stimulation for neurological disorders. IEEE Rev Biomed Eng. 2012. 5:88-99. [Medline].
Rezai AR, Kopell BH, Gross RE, Vitek JL, Sharan AD, Limousin P, et al. Deep brain stimulation for Parkinson's disease: surgical issues. Mov Disord. 2006 Jun. 21 Suppl 14:S197-218. [Medline].
Rush AJ, Sackeim HA, Marangell LB, George MS, Brannan SK, Davis SM, et al. Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biol Psychiatry. 2005 Sep 1. 58(5):355-63. [Medline].
Sackeim HA. The definition and meaning of treatment-resistant depression. J Clin Psychiatry. 2001. 62 Suppl 16:10-7. [Medline].
Sackeim HA, Rush AJ, Marangell LB, George MS, Brannan SK. (2004). Long-term antidepressant effects of vagus nerve stimulation (VNS) in treatment-resistant depression. Poster presented at 43rd American College of Neuropsychopharmacology AnnualMeeting. San Juan, PR, December 12-16. 2004.