Response inhibition and interference control in obsessive-compulsive spectrum disorders

Abstract

Over the past 20 years, motor response inhibition and interference control have received considerable scientific effort and attention, due to their important role in behavior and the development of neuropsychiatric disorders. Results of neuroimaging studies indicate that motor response inhibition and interference control are dependent on cortical-striatal-thalamic-cortical (CSTC) circuits. Structural and functional abnormalities within the CSTC circuits have been reported for many neuropsychiatric disorders, including obsessive-compulsive disorder (OCD) and related disorders, such as attention-deficit hyperactivity disorder, Tourette's syndrome, and trichotillomania. These disorders also share impairments in motor response inhibition and interference control, which may underlie some of their behavioral and cognitive symptoms. Results of task-related neuroimaging studies on inhibitory functions in these disorders show that impaired task performance is related to altered recruitment of the CSTC circuits. Previous research has shown that inhibitory performance is dependent upon dopamine, noradrenaline, and serotonin signaling, neurotransmitters that have been implicated in the pathophysiology of these disorders. In this narrative review, we discuss the common and disorder-specific pathophysiological mechanisms of inhibition-related dysfunction in OCD and related disorders.

Keywords: Tourette’s syndrome; attention-deficit hyperactivity disorder; interference control; obsessive–compulsive disorder; response inhibition; trichotillomania.

Figure 1

Examples of interference control and motor response inhibition tasks. The Flanker task is a test in which subjects are asked to respond to a target stimulus by pressing a button to indicate the direction of the target stimulus. The target, however, is flanked by non-target distracter stimuli, which are presented in the same or in the opposite direction as the target (congruent and incongruent trials, respectively). During a Simon task, participants are asked to press a button depending on the orientation of the arrow, irrespective of the location of the arrow. Orientation and location can either be congruent of incongruent. In the Stroop task names of colors are presented in either the same (congruent) or a different color (incongruent). Subjects are instructed to name to color of the word but not the word itself. In the Go/No-go task, subjects need to respond as fast as possible when letters are presented (Go-trials), but must withhold the response when a certain letter (e.g., “X”) is presented (Stop-trials). In a Stop-signal task, the participant is asked to respond as fast as possible by pressing a button to a stimulus (Go-trials) that is presented. On a minority of trials, a stop-signal is presented and the subject is asked to suppress the response when the stop-signal occurs. Task demands gradually increase from interference control to action cancelation.

Figure 2

Shift in the inverted U-shaped relation between task load and inhibition-related activity. Inhibition-related neural circuit activity gradually increases with task load (green to red gradient). However, when task demands become too high the compensatory activity starts to fail and behavioral performance becomes impaired (solid red). In obsessive– compulsive and related disorders performance impairments and failure of compensatory neural activation occur at a lower task load than in healthy controls (visualized as a shift of the inverted U-shaped curve to the left).

Figure 3

Inverted U-shaped relation between dopamine levels and inhibitory control. The ability to control behaviors, impulses, and urges is influenced by dopamine, and both reduced and increased dopamine levels (green to red gradient) have a detrimental effect on inhibitory control. Current evidence suggests that ADHD is a hypodopaminergic disorder, while OCD, TTM, and TS are considered hyperdopaminergic disorders. Inhibitory deficits are also evident in patients with Parkinson’s disease, a prototypical hypodopaminergic disease. Pharmacotherapeutics used to treat the symptoms of these disorders are listed and are thought to normalize dopamine levels and thereby ameliorate response inhibition (indicated by the arrows). PD, Parkinson’s disease; ADHD, attention-deficit hyperactivity disorder; OCD, obsessive–compulsive disorder; TTM, trichotillomania; TS, Tourette’s syndrome. NB. Since comparison studies across OCD, TTM, and TS are in short supply, the spacing between these disorders on the U-shaped curve is arbitrary and does not necessarily represent actual differences in dopamine levels between these disorders.