Deep brain stimulation for obsessive-compulsive disorder: past, present, and future

Mian, Matthew K.; Campos, Michael; Sheth, Sameer A.; Eskandar, Emad N.

doi:10.3171/2010.4.focus10107

Cited by 97 publications

(48 citation statements)

References 82 publications

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“…The combination of the latter two, the limbic leukotomy, was later used by Kelly and colleagues. 13,14 Recently DBS, motivated by the success of lesioning procedures, 9,11,18 has emerged as a promising treatment for OCD. The encouraging initial results of DBS for OCD led to the approval of this procedure under a humanitarian device exemption from the FDA.…”

Section: Discussionmentioning

confidence: 99%

Limbic system surgery for treatment-refractory obsessive-compulsive disorder: a prospective long-term follow-up of 64 patients

Sheth¹,

Neal²,

Tangherlini³

et al. 2013

JNS

Self Cite

103

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O bsessive-cOmpulsive disorder is a psychiatric illness characterized by intrusive, recurrent thoughts (obsessions) coupled with repetitive behaviors that are performed in an attempt to reduce anxiety (compulsions). These obsessions and compulsions can cause severe emotional distress, financial hardship, and social isolation. With a lifetime prevalence of approximately 2%-3%, 22 OCD is among the most common mental illnesses in the US, and of patients in whom OCD is diagnosed, one-half experience severe symptoms.15 Obsessive-compulsive disorder is also associated with high rates of comorbid MDD and suicidal ideations. 21Standard treatment for patients with OCD includes a combination of psychotherapy and pharmacotherapy; however, 40%-60% of patients do not respond satisfac- Object. Obsessive-compulsive disorder (OCD) is a common and disabling psychiatric illness, and in a significant proportion of patients with OCD the disease is refractory to conventional pharmacotherapy and psychotherapy. For more than half a century, patients with severe, treatment-resistant OCD have been treated with stereotactic limbic system lesions, including dorsal anterior cingulotomy. The authors present their results describing the efficacy and durability of limbic system surgery for OCD, characterizing a large cohort of patients treated at a single institution with a mean follow-up of more than 5 years.Methods. The authors identified 64 consecutive patients undergoing cingulotomy for refractory OCD at the Massachusetts General Hospital between 1989 and 2009. Changes in OCD and major depressive disorder symptom severity were assessed at both the initial and most recent postoperative follow-up by using the Yale-Brown Obsessive Compulsive Scale and the Beck Depression Inventory, respectively. Full and partial OCD symptom responses were defined as Yale-Brown Obsessive Compulsive Scale score reductions of ≥ 35% and 25%-34%, respectively.Results. Regarding OCD symptom improvement, at the first postoperative follow-up (mean 10.7 months), 35% of patients demonstrated a full response and 7% were partial responders. Thirty patients had a subsequent procedure (repeat cingulotomy or subcaudate tractotomy). By the most recent follow-up (mean 63.8 months), rates climbed to 47% and 22% for full and partial responses, respectively. Of the 24 patients with at least a partial response at initial follow-up, 20 (83%) retained at least a partial response at final follow-up. Comorbid major depressive disorder severity decreased by 17% at the most recent follow-up.Conclusions. Limbic system surgery based on initial cingulotomy offers a durable and effective treatment option for appropriately selected patients with severe OCD who have not responded to conventional pharmacotherapy or psychotherapy. See the corresponding editorial in this issue, pp 489-490.

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Section: Discussionmentioning

confidence: 99%

Limbic system surgery for treatment-refractory obsessive-compulsive disorder: a prospective long-term follow-up of 64 patients

Sheth¹,

Neal²,

Tangherlini³

et al. 2013

JNS

Self Cite

103

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“…In DBS, chronic high-frequency stimulation of specific sites reduces symptoms in medically intractable illness. DBS of the ventral capsule and the adjacent ventral striatum (VC/VS) has been used to treat refractory obsessive-compulsive disorder (OCD) in the European Union and the United States (7)(8)(9)(10). Little is known about how DBS acts in OCD, emphasizing the need for translational animal studies.…”

Section: Eep Brain Stimulation (Dbs) Is a Neurosurgical Techniquementioning

confidence: 99%

Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear

Rodríguez-Romaguera

Monte

Quirk

2012

Proc. Natl. Acad. Sci. U.S.A.

122

128

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Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces symptoms of intractable obsessive-compulsive disorder (OCD), but the mechanism of action is unknown. OCD is characterized by avoidance behaviors that fail to extinguish, and DBS could act, in part, by facilitating extinction of fear. We investigated this possibility by using auditory fear conditioning in rats, for which the circuits of fear extinction are well characterized. We found that DBS of the VS (the VC/VS homolog in rats) during extinction training reduced fear expression and strengthened extinction memory. Facilitation of extinction was observed for a specific zone of dorsomedial VS, just above the anterior commissure; stimulation of more ventrolateral sites in VS impaired extinction. DBS effects could not be obtained with pharmacological inactivation of either dorsomedial VS or ventrolateral VS, suggesting an extrastriatal mechanism. Accordingly, DBS of dorsomedial VS (but not ventrolateral VS) increased expression of a plasticity marker in the prelimbic and infralimbic prefrontal cortices, the orbitofrontal cortex, the amygdala central nucleus (lateral division), and intercalated cells, areas known to learn and express extinction. Facilitation of fear extinction suggests that, in accord with clinical observations, DBS could augment the effectiveness of cognitive behavioral therapies for OCD.prefrontal cortex | anxiety disorders | posttraumatic stress disorder | phosphorylated extracellular signal-regulated kinase | accumbens D eep brain stimulation (DBS) is a neurosurgical technique that has become the standard of care for movement disorders (1-3) and is under investigation in major depression (4-6). In DBS, chronic high-frequency stimulation of specific sites reduces symptoms in medically intractable illness. DBS of the ventral capsule and the adjacent ventral striatum (VC/VS) has been used to treat refractory obsessive-compulsive disorder (OCD) in the European Union and the United States (7-10). Little is known about how DBS acts in OCD, emphasizing the need for translational animal studies. A prominent feature observed in most OCD patients is repetitive avoidance behaviors to perceived threats (11,12). The persistent avoidance in OCD suggests a deficit in circuits that regulate fear extinction (11). Given the strong parallels between fear circuits in rodents and humans (13), well-characterized rodent models of fear conditioning could shed light on DBS mechanisms in OCD and related illnesses that feature pathological anxiety.The DBS target for OCD is the VC/VS (14), which contains fiber bundles interconnecting cortical areas implicated in fear extinction, such as the ventromedial prefrontal cortex, the dorsal anterior cingulate cortex, and the orbitofrontal cortex (OFC), with subcortical areas implicated in conditioned fear, such as the amygdala (15). Previous studies in anesthetized rats (16,17) have shown that DBS of the VS modifies the excitability of the OFC as well as prelimbic (PL) and infralimbic (IL) prefron...

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“…and colleagues [37] , and 3 of the patients displayed beneficial outcomes. Currently, there are 3 targets for DBS in treatment of OCD: the rostral-caudal dimension of the anterior limb of the internal capsule and ventral capsule/ventral striatum, the subthalamic nucleus, and the inferior thalamic peduncle [38] . TMS is a noninvasive technique that delivers magnetic pulses directly to the scalp.…”

Section: Hippocampus-amygdala Complexmentioning

confidence: 99%

Review of structural neuroimaging in patients with refractory obsessivecompulsive disorder

Atmaca

2011

Neurosci. Bull.

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Abstract:The notion that some special brain regions may be involved in the pathogenesis of obsessive-compulsive disorder (OCD) dates back to the beginning of the twentieth century. Structural neuroimaging studies in the past 2 decades have revealed important findings that facilitate understanding of OCD pathogenesis. Current knowledge based on functional and structural neuroimaging investigations largely emphasizes abnormalities in fronto-striatal-thalamic-cortical and orbitofronto-striato-thalamic circuits in the pathophysiology of OCD. However, these neuroimaging studies did not focus on refractory OCD. The present review mainly focused on structural neuroimaging performed in OCD, which had been ignored previously, and highlighted current evidence supporting that orbito-frontal cortex and thalamus are key brain regions, and that the hippocampus-amygdala complex is associated with refractoriness to the available treatment strategies.However, to fully reveal the neuroanatomy of refractoriness, longitudinal studies with larger samples are required.

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Deep brain stimulation for obsessive-compulsive disorder: past, present, and future

Cited by 97 publications

References 82 publications

Limbic system surgery for treatment-refractory obsessive-compulsive disorder: a prospective long-term follow-up of 64 patients

Limbic system surgery for treatment-refractory obsessive-compulsive disorder: a prospective long-term follow-up of 64 patients

Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear

Review of structural neuroimaging in patients with refractory obsessivecompulsive disorder

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