What causes OCD?
Researchers have had much recent success in elucidating the neural circuitry involved in obsessive-compulsive disorder (OCD). Advances in functional neuroimaging have identified robust alterations in neural activity within particular functional circuits in individuals with the disorder (Graybiel & Rauch, 2000). Specifically, OCD is associated with pervasive disruptions in frontal subcortical circuitry (Luxenberg et al., 1988; Robinson et al., 1995). Before we discuss abnormalities in this circuitry related to OCD, it is worth reviewing the generalities of this neural system.
Frontal subcortical circuitry in OCD
According to Tekin and Cummings (2002), frontal subcortical circuits share several commonalities. They often “originate in prefrontal cortex, project to the striatum (caudate, putamen, ventral striatum), connect to the globus pallidus and substantia nigra and from there connect to the thalamus. There is a final link back to the frontal cortex [such that] each circuit forms a closed loop” . The prefrontal cortex (PFC) can be subdivided into several regions including the dorsolateral prefrontal cortex (DLPFC), the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC); and these subregions are involved in separate circuits (the DLPF circuit, the OF circuit, and the AC circuit, respectively).
These circuits have been implicated in various functional tasks. Individuals with dysfunction in DLPFC areas often exhibit deficits in attention, reasoning, and mental flexibility. Damage to OFC has been associated with personality changes including behavioral disinhibition and impaired judgment (Tekin & Cummings, 2002). Work by Damasio and colleagues (1996; 1990) indicates that insults to OFC result in deficits in reward expectancies and preferences. The ACC is closely interconnected with the limbic system and is thought to support motivation and affective behavior. Due to its association with motor cortex, the ACC presumably mediates emotionally-motivated movement. Together, the ACC and OFC influence the emotional value of stimuli and the selection of behavior based on possible reward.
Saxena and Rauch (2000) have suggested that excess positive feedback within frontal subcortical circuits might drive the repetitive symptoms that characterize OCD. What evidence supports this theory? In individuals with OCD, resting hyperactivity within frontal subcortical loops has been observed reliably, and this activity is potentiated by symptom provocation (Saxena, Brody, Schwartz, & Baxter, 1998). Interestingly, following either successful pharmacologic or behavioral treatment for OCD, this hyperactivity diminishes to normal levels. Empirical evidence implicating frontal subcortical circuitry in the etiology of OCD also includes work by Kelly (1980) who showed that lesions of the cingulate gyrus can reduce obsessive-compulsive symptomatology, presumably by disrupting interconnectivity between orbito-striatal areas or between frontal cortex and the thalamic nuclei that convey limbic input into this region. Psychosurgical procedures that interfere directly with striatal circuitry also are effective for ameliorating symptoms of OCD.
Error-related negativity in OCD
Psychophysiological studies looking at a component of the event-related potential known as error-related negativity (ERN) also provide independent evidence of abnormalities in frontal-subcortical circuitry. ERN has been defined as the negative polarity component of the event-related potential that can be observed 30-150ms following the commission of an error (or, as some have suggested, the violation of expectancies; Donkers & van Boxtel, 2005) on simple reaction time tasks. This potential largely is due to activity in the ACC.
Electroencephalogram acquired from electrodes placed near the medial-frontal scalp has indicated that ERN magnitudes in individuals with OCD are significantly greater than in controls, suggesting enhanced action-monitoring in OCD (Gehring, Himle, & Nisenson, 2000; Ruchsow et al., 2005). Using a similar choice reaction time experiment, Johannes et al. (2001) observed shorter P3 latencies and ERN deflections that were enhanced in amplitude and longer in duration in non-medicated, non-depressed individuals with OCD relative to controls. Hajcak and Simons (2002) subsequently replicated and extended these findings using a subclinical “OCD-like” sample of undergraduates who endorsed a high degree of OCD-relevant behaviors on a measure of OC symptomatology.
Gehring, Himle, and Nisenson (2000) have advanced an intriguing theory regarding the relationship between frontal subcortical hyperactivity and obsessive-compulsive symptoms. They posit that OCD symptoms arise from hyperactive “error signals” generated by the ACC that represent a mismatch between preferred and experienced internal/environmental states. In response to this error signal, the system effects changes in behavior. According to this model, individuals with OCD perform repetitive, compulsive behaviors because they experience large and persistent error signals that manifest affectively as feelings of wrongness.
Compulsive behaviors thus are the means by which the system seeks to reduce the perceived discrepancy between preferred and experienced internal/environmental states. However, these error signals remain relatively unaffected by changes in environmental context and behavior due to continued ACC hyperactivity. As a result, individuals with OCD experience persistent feelings of anxiety, doubt, and the urge to engage in behaviors that might neutralize these emotions. Although this theory remains speculative, it provides an interesting link between abnormalities in frontal-subcortical circuitry and the phenomenology of OCD.
My next post discusses cognitive deficits associated with OCD.
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