Task-related dissociation in ERN amplitude as a function of obsessive–compulsive symptoms

Abstract

Hyperactive cortico-striatal circuits including the anterior cingulate cortex (ACC) have been implicated to underlie obtrusive thoughts and repetitive behaviors in obsessive–compulsive disorder (OCD). Larger error-related negativities (ERNs) in OCD patients during simple flanker tasks have been proposed to reflect an amplified error signal in these hyperactive circuits. Such amplified error signals typically are associated with an adaptive change in response, yet in OCD these same repetitive responses persist to the point of distress and impairment. In contrast to this repetitive character of OC behavior, larger ERN amplitudes have been linked to better avoidance learning in reinforcement learning tasks. Study I thus investigated if OC symptomatology in non-patients predicted an enhanced ERN after suboptimal choices in a probabilistic learning task. Absent any behavioral differences, higher OC symptoms predicted smaller ERNs. Study II replicated this effect in an independent sample while also replicating findings of a larger ERN in a flanker task. There were no relevant behavioral differences in reinforcement learning or error monitoring as a function of symptom score. These findings implicate different, yet overlapping neural mechanisms underlying the negative deflection in the ERP following the execution of an erroneous motor response and the one following a suboptimal choice in a reinforcement learning paradigm. OC symptomatology may be dissociated in these neural systems, with hypoactivity in a system that enables learning to avoid maladaptive choices, and hyperactivity in another system that enables the same behavior to be repeated when it was assessed as not quite good enough the first time.

Introduction

Obsessive–compulsive disorder (OCD) is a common psychiatric condition characterized by intrusive and recurrent unwanted thoughts, ideas or impulses (obsessions) and the urge to perform repetitive, ritualistic behavior (compulsions) to reduce anxiety or distress (DSM-IV, 1994). The lifetime prevalence is estimated to be as high as 2–3.5% (Angst et al., 2004, Kessler et al., 2005, Weissman et al., 1994) but the recognized clinical prevalence is estimated to be much lower (Fireman, Koran, Leventhal, & Jacobson, 2001). Neuroimaging studies of OCD patients have revealed greater activity at rest and after symptom provocation in the anterior cingulate cortex (ACC: Adler et al., 2000, Baxter, 1999, Breiter and Rauch, 1996, Cottraux et al., 1996, Kim et al., 2003, Perani et al., 1995, Rauch et al., 1994; Swedo, Rapoport, Leonard, Lenane, & Cheslow, 1989; van den Heuvel et al., 2005) the orbito-frontal cortex (OFC: Baxter, Schwartz, Guze, Bergman, & Szuba, 1990; Swedo et al., 1989) and the striatum (van den Heuvel et al., 2005). Since the ACC, OFC and striatum are interconnected in recurrent loops, hyperactivity in this cortico-striatal circuit is thought to contribute to the pathophysiology of OCD (Remijnse et al., 2006). Given that cortico-striatal circuits are involved in action selection, goal-directed behavior, and performance monitoring (Balleine, Delgado, & Hikosaka, 2007; Ito, Stuphorn, Brown, & Schall, 2003; Nicola, 2007), hyperactivity in this system is proposed to underlie a persistent high error signal (Pitman, 1987). This hyperactive error monitoring hypothesis suggests that patients receive malfunctioning error signals after not completing their goals (e.g., hands are not quite clean enough), leading them to repeat their compulsive behaviors.

Pitman's (1987) hypothesis of a persistent and enhanced cortico-striatal error signal in OCD was tested by Gehring, Himle, and Nisenson (2000) using the error-related negativity (ERN), an electrophysiological voltage potential occurring ∼80 ms following errors of motor commission (Falkenstein, Hohnsbein, Hoormann, & Blanke, 1991; Gehring, Coles, Meyer, & Donchin, 1990). EEG source localization and EEG-informed functional Magnetic Resonance Imaging (fMRI) have both implicated the caudal ACC as the proposed neural generator of the ERN (Debener et al., 2005; Dehaene, Posner, & Tucker, 1994; Ullsperger & von Cramon, 2004). Convergent evidence from multiple fields of neuroimaging have implicated a hyperactive error system in the ACC where OCD patients are characterized by greater hemodynamic responses in the ACC following errors (Fitzgerald et al., 2005; Maltby, Tolin, Worhunsky, O’Keefe, & Kiehl, 2005; Ursu, Stenger, Shear, Jones, & Carter, 2003) or a larger ERN (Endrass, Klawohn, Schuster, & Kathmann, 2008; Gehring et al., 2000; Hajcak, Franklin, Foa, & Simons, 2008; Johannes et al., 2001, Ruchsow et al., 2005) but see Nieuwenhuis, Nielen, Mol, Hajcak, and Veltman (2005) who utilized a reinforcement learning paradigm. Two studies have also shown that greater OC symptom scores in non-patients predict a larger ERN (Hajcak & Simons, 2002; Santesso, Segalowitz, & Schmidt, 2006), indicating that this relationship may be reliably present in non-clinical populations. Although these investigations demonstrate a reliable effect of an enhanced ERN as a function of OCD or OC symptoms, an unresolved issue is the degree to which a putative hyperactive error signal affects action selection and goal-directed behavior. Differences in post-error behaviors are rarely found between OC and control groups even in the context of larger ERN amplitudes.

Conditions in which enhanced ERN amplitudes have been found in OC populations involve instructed response conflict tasks with speeded responses (Flanker task: Endrass et al., 2008, Ruchsow et al., 2005, Santesso et al., 2006; Stroop task: Gehring et al., 2000, Hajcak and Simons, 2002; Simon task: Hajcak et al., 2008; choice reaction time task: Johannes et al., 2001). The sole task investigating reinforcement learning, however, failed to find an effects on fronto-central scalp potentials in OCD patients (Nieuwenhuis, Nielen, et al., 2005). Importantly, the ERN in this reinforcement learning task was defined as the voltage deflection following a probabilistic suboptimal response, one which the participant must learn over time through the use of valenced feedback (Holroyd & Coles, 2002). In these goal directed reinforcement learning tasks, larger error signals have been associated with a greater tendency to avoid making the same action that preceded the error, sometimes termed NoGo learning (Frank, D’Lauro, & Curran, 2007; Frank, Woroch, & Curran, 2005; Holroyd & Coles, 2002). The larger ERNs in OC groups, putatively reflecting hyperactive error monitoring circuits, should thus lead to better learning among OC patients to avoid making the choices that led to the error; i.e., a NoGo bias.

Therefore, it would be predicted that a larger ERN deflection in OCD patients would predict enhanced NoGo learning; yet it is unclear if findings of an enhanced ERN would extend to uncertain environments in which adaptive responses are needed to achieve optimal performance goals. Indeed, the prediction of enhanced avoidance learning may stand in sharp contrast to the repetitive character of OC behaviors. To investigate a possible association between action monitoring and reinforcement learning as a function of OC symptomatology, this study utilized a reinforcement learning paradigm previously shown to elicit response-locked negative deflections in fronto-central scalp potentials after suboptimal choices or similar feedback-locked deflections following negative performance feedback (here termed ERN and FRN, respectively (Frank, Seeberger, & O’Reilly, 2004; Frank et al., 2005). Due to unexpected findings from this investigation, a second study was run to replicate the findings with the probabilistic learning task, and to compare them to findings using a standard response conflict flanker task, that has robustly elicited larger ERNs in OC populations. The findings demonstrate that the relationship between medio-frontal activation and error processing in OCD is task-dependent, with hyper activity in a response conflict task, but hypo activity in reinforcement learning.