Treatment

Treatment of OCD includes medications in conjunction with psychotherapy or cognitive behavioral therapy. These interventions typically do not result in complete eradication of symptoms, and patients may require a variety of medications, as well as multiple sessions of cognitive behavioral therapy, to improve. The disorder is so resistant to treatment that a positive “response” in clinical trials of OCD therapy is often defined as a 35% or greater improvement measured with standardized clinical rating scales.⁵ The form of psychotherapy used in treating OCD is known as exposure/response prevention therapy. It involves exposing patients to their anxiety-producing situation (i.e., touching a “contaminated” object) and then preventing the typical response (i.e., excessive hand washing).⁶ This form of therapy is often the most effective and has been shown to induce changes in brain activity that correlate with symptomatic response.^7,8 Selective serotonin reuptake inhibitors (SSRIs) are currently the most effective medications for the treatment of OCD.⁹ If significant benefit is not achieved with adequate doses of an SSRI, other medications such as clonazepam, risperidone, buspirone, or other atypical antipsychotics may be added.¹⁰ Despite optimal medical and psychotherapeutic interventions, at least 20% of patients remain refractory to treatment. Of these individuals, half are completely debilitated by their illness.¹¹ It is these suffering patients with few treatment options who may be candidates for neurosurgical intervention.

Neural Circuitry of Obsessive-Compulsive Disorder

The neural circuitry of patients with OCD involves a number of interconnected cortical and subcortical regions that constitute a neurobehavioral network for mood and anxiety. Our understanding of this network’s components, their normal function, and impairment in OCD is being improved by anatomic and physiologic studies, animal models, responses to medications, pathophysiologic studies, and functional brain imaging.

The anatomic basis of behavior and its implications for understanding psychiatric disease have intrigued neuroscientists for a long time. Nineteenth century phrenologists such as Franz Gall attempted to attribute personality traits and faculties of the mind to the degree of development of different cerebral areas, which could be inferred from the skull’s shape and features.¹² Early animal experiments performed in the 19th century suggested that injury to the temporal lobes could alter aggressive behavior in animals. The importance of the frontal lobes to human behavior became increasingly apparent from observing patients with diseases or injuries in that region. One of the most famous examples is that of Phineas Gage, a railroad worker who suffered a frontal lobe injury when an iron rod penetrated his left skull base and exited at the vicinity of the coronal suture.^13,14 Gage survived his injury but suffered from significant changes in behavior and personality. Gage, who had previously been regarded as efficient and capable, became “irreverent, indulging in the grossest profanity and … manifesting but little deference for his fellows … that his friends and acquaintances said he was no longer Gage.”^15,16 Several decades later, Carlyle Jacobsen and John Fulton demonstrated that injury to both frontal lobes in a nonhuman primate resulted in improvement of “neurosis” and tantrum fits that would previously occur in response to frustration.^17,18 These findings provided the experimental rationale for Egaz Moniz and Almeida Lima’s exploration of frontal leukotomy as a treatment of human psychiatric illness.^19,20 Moniz’s work popularized psychosurgery and resulted in him being awarded the Nobel Prize in Medicine in 1949. Unfortunately, the rapid adoption and indiscriminate and widespread use of frontal lobotomy in the following years resulted in significant controversy that ultimately limited the proper development of surgical approaches to psychiatric disorders.

In response to this checkered history, modern research on psychosurgery is performed by multidisciplinary teams in a controlled fashion, with monitoring committees to ensure patient safety.^21,22 Significant advances have been made in understanding the key neurobehavioral networks that control anxiety, behavior, and emotions. One important network is located in the anterior frontal lobes with connections to the thalamus and basal ganglia. Another key network with important implications for surgical treatment of psychiatric disease is the limbic system. Early descriptions of the limbic lobe were made by Paul Broca in the second half of the 19th century.¹⁷ Subsequently, James Papez’s landmark 1937 publication implicated a circuit involving the hippocampus, cingulate gyrus, hypothalamus, anterior thalamus, and fornix in the elaboration and expression of emotion.^23,24 Experiments by MacLean elucidated the concept of the limbic system and described its role in the control of behavior and emotion.^25,26 The rationale for surgical interventions for OCD and other psychiatric disorders is to alter the abnormal function of the limbic system, as well as the networks connecting the prefrontal cortex to the thalamus and ventral basal ganglia, by ablation or chronic electrical stimulation.^27,28

The functional organization of the connections among the cortex, striatum, globus pallidus, and thalamus is similar in movement disorders and psychiatric disorders. The current view that parallel basal ganglia–thalamic loops process cortical input originating in motor, oculomotor, dorsolateral prefrontal, lateral orbitofrontal, or anterior cingulate areas has been established by Alexander and colleagues.²⁹ Modern staining techniques and histologic studies led to identification of the ventral pallidal system, a key milestone in understanding parallel basal ganglia networks.^30,31 Likewise, modern histologic methods allowed identification of the extended amygdala system.³²

In the current view of the network (Fig. 88-1), the cortical-striatal-pallidal-thalamic-cortical (CSPTC) loop related to neurobehavioral and psychiatric disease originates in the prefrontal and orbital frontal cortices and, along with the parallel circuit originating at the cingulate cortex, controls behavior and emotion. In the orbitofrontal system, projections enter the basal ganglia through the ventral internal capsule and ventral striatum, which in turn project to the ventral pallidum. In addition to the corticostriatal projections, reciprocal direct connections also exist between the orbitofrontal cortex and the thalamus and are conveyed through the anterior limb of the internal capsule. Projections from the orbitofrontal cortex reach the ventral striatal area, which is composed predominantly of the ventral aspect of the caudate nucleus and the nucleus accumbens, with excitatory terminals mediated by glutamate. The ventral striatum also receives projections from the hippocampus and the amygdala and is further divided into two territories: the shell and core. In humans, the inner core is composed of calbindin-rich neurons, whereas the shell is populated predominantly by calbindin-poor cells.³³ Both the ventral pallidum and the ventral striatum are located ventral to the anterior commissure, near the anterior perforated substance. Ventral striatal projections to the ventral pallidum are mediated predominantly by substance P, enkephalin, and γ-aminobutyric acid (GABA). The external part of the ventral pallidum, like the pars externa of the dorsal component of the globus pallidus, projects preferentially to the subthalamic nucleus.^34,35 The internal segment has inhibitory projections predominantly to the mediodorsal thalamic nucleus.^33,36,37 This differs from the projections mediating motor control, which are processed through ventrolateral thalamic nuclei.

FIGURE 88-1 Projections from the prefrontal and orbitofrontal cortices enter the basal ganglia via the ventral striatum. These projections are then processed through the ventral pallidum and are relayed to the cortex via the medial dorsal thalamic nucleus. The prefrontal/orbitofrontal cortex also shares direct reciprocal connections with the medial dorsal nucleus of the thalamus.

The parallel segregated circuitry model is important for our current understanding of how information is processed through the basal ganglia and how the cortical activity associated with each domain of motor or nonmotor functioning is modulated. The segregation of these circuits, however, is not absolute. Cortical-fugal connections tend to overlap, particularly in the ventral striatum.³¹ Furthermore, recent evidence has shown specific points of connectivity among these otherwise segregated loops that allow the integration of motor, cognitive, and limbic functions.³⁸

The neuroanatomic CSPTC circuit has served as a substrate for mechanistic models of the pathophysiology of OCD. Modell and collaborators proposed that pathologic states may arise when the orbitofrontal and corticothalamocortical loops, which exchange reciprocal excitatory connections via the anterior limb of the internal capsule, lose their physiologic modulation. Normally, this modulation is maintained by projections through the ventral striatum and pallidum. The net effect of this longer modulatory loop is thalamic inhibition through the pallidothalamic GABAergic projections. In the normal state, this inhibition serves to “damp the excitatory orbitofrontal-thalamic reciprocating circuit.”³⁹ However, in OCD, there is a lack of regulation of the excitatory loop that results in an overactive orbitofrontal cortex. Neuroimaging studies in patients with OCD have provided support for this model. Baxter and colleagues identified increased orbitofrontal and striatal metabolic activity in patients with OCD undergoing fluorodeoxyglucose positron emission tomography (PET).⁴⁰ Subsequent studies have provided further supportive evidence for the model by demonstrating hyperactivity of the caudate nucleus in patients with OCD. More importantly, a reduction in this hyperactivity was observed in OCD patients who responded well to behavioral therapy.⁴¹ Functional magnetic resonance imaging (fMRI) has also contributed to our understanding of the neural circuitry of OCD. Study paradigms have included a comparison of hemodynamic responses in different cortical and subcortical structures, with and without provocation of symptoms^42,43 and during cognitive tasks.⁴⁴ Activation of several cortical areas, including the cingulate cortex, temporal lobes, and orbitofrontal areas, has been demonstrated,⁴⁵ again corroborating the participation of these networks in the pathogenesis of OCD. Recent functional neuroimaging studies have explored the possibility that discrete behavioral features of OCD could be predominantly modulated by different anatomic substrates.⁴⁶ Mataix-Cols and coworkers assessed the response of OCD patients and normal volunteers to images depicting scenes related to contamination or washing and checking or hoarding behavior.⁴⁷ In response to pictures depicting washing, patients demonstrated greater activation in the ventromedial prefrontal regions and right caudate nucleus than controls did. Images related to checking behavior increased activation of the lentiform nucleus and thalamus, whereas those related to hoarding resulted in increased activation of the right orbitofrontal region. This study supports previous knowledge indicating the relevance of the CSPTC loop to the genesis of OCD and demonstrates that different anatomic substrates may be involved in discrete OCD symptoms. fMRI studies have also been performed in OCD patients with externalized deep brain stimulation (DBS) leads to allow exploration of the effects of stimulation of the targeted area on the pathologic circuit.⁴⁸

In summary, advances in our understanding of the neural circuitry of OCD is occurring as a result of anatomic and pathophysiologic studies using high-resolution MRI, fMRI, PET, and MR spectroscopy. The prevailing concepts regarding the underlying OCD circuitry involve dysfunction and lack of regulation of anxiety and behavior control networks. The regions implicated in this circuit include the orbitofrontal cortex, the prefrontal cortex, the dorsomedial thalamus, the cortical-striatal-pallidal-thalamic loops, and the circuit of Papez. The orbitofrontal and thalamic circuitry appear to be hyperactive at baseline, accentuated during aggravation of symptoms, and reduced with medication or behavioral therapy, or both. The various components of this circuit and specifically the ventral anterior internal capsule have been the most common anatomic targets for neurosurgical intervention for OCD. The ventral anterior internal capsule with the associated ventral striatum (VC/VS) is an important region or node through which white matter fibers interconnect large parts of the circuit course.

Ablative Procedures for Obsessive-Compulsive Disorder

Surgery for OCD and other psychiatric disorders has a long and complex history marked by initial enthusiasm, widespread and indiscriminate use, lack of rigorous patient selection criteria and outcome measures, and severe and underreported complications, which resulted in its demise and current social stigma. Yet despite the stigma, a number of centers have pressed on with ablative surgery for psychiatric illness with some positive results.

Prefrontal leukotomy was an early, undeveloped surgical approach that represented the initial human extension of early-stage animal research.^49,50 The initial Moniz experience¹⁹ was deemed sufficient and the procedure was quickly adopted and performed widely for various conditions without standardized indications, outcome measures, or follow-up.⁵¹

Modern approaches have focused on the creation of smaller, more targeted stereotactic lesions with an eye toward enhancing the safety and efficacy of the procedure, especially with regard to the preservation of cognitive function. Modern lesioning surgeries include cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leukotomy.