The Stop Signal Task (SST) is a measure that has been used widely to assess response inhibition. We conducted a meta-analysis of studies that examined SST performance in patients with various psychiatric disorders to determine the magnitude and generality of deficient inhibition. A five-item instrument was used to assess the methodological quality of studies. We found medium deficits in stop signal reaction time (SSRT), reflecting the speed of the inhibitory process, for attention-deficit hyperactivity disorder (ADHD) (g = 0.62), obsessive compulsive disorder (OCD) (g = 0.77) and schizophrenia (SCZ) (g = 0.69). SSRT was less impaired or normal for anxiety disorder (ANX), autism, major depressive disorder (MDD), oppositional defiant disorder/conduct disorder (ODD/CD), pathological gambling, reading disability (RD), substance dependence, and Tourette syndrome. We observed a large SSRT deficit for comorbid ADHD + RD (g = 0.82). SSRT was less than moderately impaired for ADHD + ANX and ADHD + ODD/CD. Study quality did not significantly affect SSRT across ADHD studies. This confirms an inhibition deficit in ADHD, and suggests that comorbid ADHD has different effects on inhibition in patients with ANX, ODD/CD, and RD. Further studies are needed to firmly establish an inhibition deficit in OCD and SCZ.

Response inhibition, defined as the ability to withhold a response, is considered to be a core deficit in various mental illnesses. Measures of response inhibition have been used to define functional deficits, as markers of genetic risk, in neuroimaging studies, and for diagnostic purposes in these disorders. However, the magnitude of the deficit across psychopathologies has not been systematically assessed. We conducted a systematic review and meta-analysis of performance on commonly used measures of the ability to withhold a response: go/no-go task, Conners' continuous performance task (CCPT), and sustained attention to response task (SART). The primary variable of interest in each of these tasks was commission errors (CE), which provides an index of one's ability to correctly withhold a response. In addition, we examined omission errors (OE) which are an index of sustained attention; and mean reaction time (RT; MRT). Three-hundred and 18 studies in 11 different psychiatric disorders met inclusion criteria. Weighted mean effect sizes (ESs) were calculated to measure the magnitude of the deficit. In general, we found low-to-medium ESs for commission errors ranging from g = -0.10 for anxiety disorder to medium ESs of g = 0.52 for bipolar disorder. Small-to-medium deficits in withholding were found in various disorders. Results indicate that deficits in withholding are insufficiently sensitive or specific to be used individually as a diagnostic measure or biomarker in most disorders.

ADHD is associated with altered dopamine regulated reinforcement learning on prediction errors. Despite evidence of categorically altered error processing in ADHD, neuroimaging advances have largely investigated models of normal reinforcement learning in greater detail. Further, although reinforcement leaning critically relies on ventral striatum exerting error magnitude related thresholding influences on substantia nigra (SN) and dorsal striatum, these thresholding influences have never been identified with neuroimaging. To identify such thresholding influences, we propose that error magnitude related activities must first be separated from opposite activities in overlapping neural regions during error detection. Here we separate error detection from magnitude related adjustment (post-error slowing) during inhibition errors in the stop signal task in typically developing (TD) and ADHD adolescents using fMRI. In TD, we predicted that: 1) deactivation of dorsal striatum on error detection interrupts ongoing processing, and should be proportional to right frontoparietal response phase activity that has been observed in the SST; 2) deactivation of ventral striatum on post-error slowing exerts thresholding influences on, and should be proportional to activity in dorsal striatum. In ADHD, we predicted that ventral striatum would instead correlate with heightened amygdala responses to errors. We found deactivation of dorsal striatum on error detection correlated with response-phase activity in both groups. In TD, post-error slowing deactivation of ventral striatum correlated with activation of dorsal striatum. In ADHD, ventral striatum correlated with heightened amygdala activity. Further, heightened activities in locus coeruleus (norepinephrine), raphe nucleus (serotonin) and medial septal nuclei (acetylcholine), which all compete for control of DA, and are altered in ADHD, exhibited altered correlations with SN. All correlations in TD were replicated in healthy adults. Results in TD are consistent with dopamine regulated reinforcement learning on post-error slowing. In ADHD, results are consistent with heightened activities in the amygdala and non-dopaminergic neurotransmitter nuclei preventing reinforcement learning.

Inhibition, the ability to suppress inappropriate cognitions or behaviors, can be measured using computer tasks and questionnaires. Inhibition depends on the frontal cortex, but the role of the underlying white matter (WM) is unclear. We assessed the specific impact of frontal WM damage on inhibition in 29 children with moderate-to-severe traumatic brain injury (15 with and 14 without frontal WM damage), 21 children with orthopedic injury, and 29 population controls. We used the Stop Signal Task to measure response inhibition, the Behavior Rating Inventory of Executive Function to assess everyday inhibition, and T2 fluid-attenuated inversion recovery magnetic resonance imaging to identify lesions. Children with frontal WM damage had impaired response inhibition compared with all other groups and poorer everyday inhibition than the orthopedic injury group. Frontal WM lesions most often affected the superior frontal gyrus. These results provide evidence for the critical role of frontal WM in inhibition.