Emotion-Specific or General? An ALE Meta-Analysis of Inhibitory Control Impairments in Patients with Depression

Abstract:      Impaired inhibitory control is considered one of the core mechanisms underlying the progression of depression. Cognitive models of depression propose that deficits in inhibitory control weaken individuals’ ability to regulate emotional information, thereby sustaining negative affect and exacerbating depressive symptoms. However, because patients with depression exhibit both emotional disturbances and widespread cognitive impairments, explaining inhibitory control deficits solely from an emotion-processing perspective may not fully capture their role in the pathophysiology of depression. Therefore, it is necessary to systematically integrate existing evidence to determine whether inhibitory control impairments in depression are primarily emotion-specific or reflect a more generalized cognitive dysfunction, thereby clarifying the pathways through which inhibitory control contributes to the onset and maintenance of depression. The present study conducted a meta-analysis to synthesize neuroimaging findings from emotional and non-emotional inhibitory control tasks in patients with depression, aiming to identify the characteristics and neural mechanisms of inhibitory control deficits.
     Specifically, this study conducted an Activation Likelihood Estimation (ALE) meta-analysis of task-related neural activation differences between patients with major depressive disorder (MDD) and healthy controls (HC) during emotional and non-emotional inhibitory control tasks. Following a systematic literature search and rigorous screening, 19 task-based fMRI studies were included, involving 393 individuals with MDD and reporting 133 activation foci. Based on task type (emotional vs. non-emotional) and the direction of activation difference(MDD > HC vs. MDD < HC), these foci were classified into four datasets: emotional–MDD > HC, emotional–MDD < HC, non-emotional–MDD > HC, and non-emotional–MDD < HC. All coordinates were transformed into Montreal Neurological Institute (MNI) space prior to analysis, with Talairach coordinates reported in the original studies converted to MNI coordinates using GingerALE 2.6.3. Single ALE analyses were performed for each dataset using an uncorrected threshold of p < 0.0001 and a minimum cluster size of 200 mm³. Because the non-emotional–MDD < HC and non-emotional–MDD > HC datasets showed no significant convergent activation, contrast analyses between emotional and non-emotional inhibitory control tasks could not be performed.
     The results showed that, during emotional inhibitory control tasks, individuals with MDD exhibited compensatory hyperactivation in the right middle frontal gyrus(34, 38, 32), and decreased activation convergence in the left middle frontal gyrus(–36, 40, 16) and right inferior frontal gyrus(50, 14, 18) relative to HC. By contrast, no significant convergent activation was observed for non-emotional inhibitory control tasks.
     This meta-analysis advances our understanding of the pathophysiology of depression by revealing the characteristics of inhibitory control deficits. The findings indicate that depression is characterized by altered recruitment of prefrontal regions during emotional inhibitory control, supporting the view that inhibitory control deficits in depression are closely linked to emotional processing dysfunction. These results highlight a potential pathway through which impaired inhibitory control may contribute to the persistence of depressive symptoms and may inform the development of targeted cognitive and neurobiological interventions.