Error-Related Brain Activity in Anxiety Disorders: The Hyperactivity of the ERN

Abnormalities in the anterior cingulate cortex (ACC) have been reported in anxiety disorders. The error-related negativity (ERN), a component of the event-related brain potential (ERP), has been found to be increased in both adults and children with anxiety disorders, such as in people with Obsessive-Compulsive Disorder (OCD). The purpose of this study was to assess the ERN and behavioral correlates during an Eriksen flanker task in anxiety probands compared to other groups. The dataset consisted of participants aged 8-17; 25 probands with a lifetime diagnosis of OCD, 8 probands diagnosed with social, separation, or generalized anxiety disorder (SSGAD) and 43 healthy controls. ERN during correctand error-trials was larger in the SSGAD group than the OCD group or controls. ERROR-RELATED BRAIN ACTIVITY 4 Error-Related Brain Activity in Anxiety Disorders: The Hyperactivity of the ERN The study of mental disorders is one that has been of great interest in psychology but has not yet been conquered. Anxiety disorders have come to be known as the most prevalent class of mental disorders. Thayer and Lane (2000) asserted that anxiety disorders represented a failure to either elect an adaptive response or to inhibit a maladaptive response given a situation. Anxiety disorders, while being a diverse set of phenotypes, are alike in that they all involve excessive negative effect typically in the form of fear and anxiety. There are many varieties and types within the disorder; the most commonly known ones include social anxiety, separation anxiety, generalized anxiety, obsessive-compulsive disorder (OCD) ̧ and a wide array of phobias. One of the most recognized anxiety disorders is OCD, a disorder that is characterized by recurrent intrusive thoughts, or obsessions, which result in repetitive and ritualistic behaviors, also known as compulsions (Rosenberg & Keshavan, 1998). Obsessive-compulsive disorder is a debilitating disorder for those who suffer from it. Due to their obsessions, people feel driven to carry out their compulsive acts, which may take several hours a day to complete. Some examples are washing their hands repeatedly or checking to see if their doors are locked numerous times. These acts, which must be performed precisely and according to rules, are done to reduce anxiety stemming from their obsessions. This disorder very commonly emerges in childhood; as many as 80% of all cases of anxiety have their onset in childhood and adolescence (Pauls et al., 1995). This is a serious illness because in severe cases of anxiety, it is usually associated with other psychiatric disorders. In the study by Hanna (1995), over 80% of the subjects were diagnosed with at least one additional psychiatric disorder. These psychopathologies included lifetime depressive ERROR-RELATED BRAIN ACTIVITY 5 disorder, other anxiety disorders, disruptive behavior disorders (such as attentional-deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder), and lifetime tic disorder. OCD, which is comorbid with anxiety, is produced in individuals with OCD due to their obsessions. In children with anxiety disorder, error signals in the brain are generated during the course of doing a flanker task. In control children, there is no appearance of these error signals (Ladouceur, Dahl, Birmaher, Axelson, & Ryan, 2006). This is noteworthy since the error signals are typically observed in midto lateadolescence but they are shown in anxious children. Despite its high prevalence and the attendant morbidity, the pathophysiology of anxiety disorders remains unclear with a plethora of theories and a lack of well-replicated findings. In the study by Rosenberg and Keshavan (1998), they utilize a series of neurobiological studies aimed at testing the hypothesis that neurodevelopmental abnormalities of ventral prefrontalstriatal circuits may be involved in and contribute to the etiology and presentation of the illness. Ventral prefrontal cortical (VPFC) abnormalities early in illness and the lack of association between illness duration and anterior cingulate volume suggest that VPFC abnormalities may have a neurodevelopmental basis in anxiety. The prefrontal cortex matures throughout childhood and adolescence up until the mid-twenties. The positive correlation between age and anterior cingulate volumes in controls, but not in anxious patients, further supports the neurodevelopmental model for anxiety. Further research has been done using genetic and imaging strategies in anxiety for potential implications for treatment development. Disturbances in VPFC-striatal interactions are believed to be involved in causing anxiety. Damage to the VPFC circuits results in impairment in the ability to inhibit context-inappropriate emotional responses, leading to inappropriate ERROR-RELATED BRAIN ACTIVITY 6 behaviors (Rosenberg & Keshavan, 1998). Volumetric abnormalities in VPFC-striatal-thalamic circuitry may be associated with the clinical presentation of anxiety and represent a central developmental neurobiological deficit in the illness. Hyperactivity in the VPFC is directly linked to structures of the basal ganglia and thalamus in a parallel circuit that mediates the expression and manifestation of anxiety symptoms (Rosenberg & Hanna, 2000). There is also substantial evidence for a genetic contribution to the etiology of anxiety disorder. Twins have a greater chance of having OCD if the other has it, and the likelihood is even greater for monozygotic twins. Analyses have provided a heritability estimate of 47% for obsessional symptoms. Due to the evidence, there have been studies which tried to identify chromosomal regions which were likely to contain susceptibility alleles for early-onset OCD (Hanna et al., 2002). Regardless of whether there is a genetic susceptibility to this disorder, a consensus in literature shows that there is a functional and neural basis behind it. There is a great deal of research that illustrates hyperactivity in certain regions of the brain, which is associated with symptoms of anxiety. Neuroimaging and electrophysiological studies have revealed an overactivity of fronto-striatal brain regions including the orbitofrontal cortex, the caudate nucleus, the thalamus, and most notably, the anterior cingulate cortex (ACC). These structures are thought to make up a circuit in which connections form a positive feedback loop, thus causing excessive activity to produce the symptoms of anxiety. In individuals with anxiety, the error signals are larger and persist for a longer period of time than in people without the disorder. As can be seen from the error signals, an individual with anxiety feels that something is wrong and that action is needed to correct the problem; therefore, the error signals contribute to nervousness, doubt, feeling of incompleteness, and ERROR-RELATED BRAIN ACTIVITY 7 compulsive behavior. The system forms a positive feedback loop; the individual is unable to reduce the error signals so they repeat the actions (such as in OCD), which generate further error signals. Gehring et al. (2000) explored the hypothesis that the excessive neural activity involved in OCD symptomatology represents “hyperactive error signals”. According to this notion, the brain maintains internal standards that represent desired internal and environmental states. It compares these standards with environmental stimuli, internal stimuli (such as thoughts or feelings), and actions. When conflicts are detected, this comparator system generates an error signal which alerts cognitive, motoric, and affective systems of the need to correct this problem. These systems then determine whether and how to act, depending on the level of error signal and the motivational significance of the alerting information. This study was the first to examine electrophysiological indicators of performance monitoring (PM) in OCD patients. Enhanced error-related negativity (ERN) amplitudes were found in OCD patients compared with controls in a Stroop task. The correlation between ERN amplitude and symptom severity supports the view that OCD is related to excessive performance monitoring. Performance monitoring has been examined using event-related potentials (ERPs). The ERN, a component of the ERP, has been identified as specifically related to incorrect response execution. It is characterized by a fronto-central negative deflection, arising shortly (< 100 ms) after the execution of an incorrect response and is generated in the ACC (Gehring, Goss, Coles, Meyer, & Donchin, 1993). Several studies reported a smaller negative ERP component following a correct response, the correct-related negativity (CRN, Ford, 1999); however, the presence of a negativity after correct responses is controversial since the CRN is not as consistently observed as the ERN (Gehring et al., 1993). ERROR-RELATED BRAIN ACTIVITY 8 Endrass et al. (2008) examined whether performance monitoring is altered in anxious patients. Earlier studies illustrated that errors were associated with increased ERN amplitudes in patients with OCD. Endrass and colleagues were also interested in whether the CRN amplitudes are also altered in patients. OCD patients are concerned with their errors but also with the correctness of their actions so it was hypothesized that CRN amplitudes should also be enhanced in OCD patients. The analysis of response-locked correct trials revealed substantial CRN amplitudes in both groups. Stimulus-locked data of correct trials varying in response time showed a second negative deflection which appears synchronously with the onset of the correct response. This clearly indicates that the CRN is not a mere stimulus artifact since the patients showed enhanced CRN amplitudes compared with controls. The significance of OCD patients showing an amplitude enhancement for response-related negativities that is not specific to error processing is that it illustrates that response monitoring m