The impaired response inhibition and salience attribution (iRISA) model proposes that impaired response inhibition and salience attribution underlie drug seeking and taking. To update this model, we systematically reviewed 105 task-related neuroimaging studies (n > 15/group) published since 2010. Results demonstrate specific impairments within six large-scale brain networks (reward, habit, salience, executive, memory, and self-directed networks) during drug cue exposure, decision making, inhibitory control, and social-emotional processing. Addicted individuals demonstrated increased recruitment of these networks during drug-related processing but a blunted response during non-drug-related processing, with the same networks also being implicated during resting state. Associations with real-life drug use, relapse, therapeutic interventions, and the relevance to initiation of drug use during adolescence support the clinical relevance of the results. Whereas the salience and executive networks showed impairments throughout the addiction cycle, the reward network was dysregulated at later stages of abuse. Effects were similar in alcohol, cannabis, and stimulant addiction.

Reduced capacity to cognitively regulate emotional responses is a common impairment across major neuropsychiatric disorders. Brain systems supporting one such strategy, cognitive reappraisal of emotion, have been investigated extensively in the healthy population, a research focus that has led to influential meta-analyses and literature reviews. However, the emerging literature on neural substrates underlying cognitive reappraisal in clinical populations is yet to be systematically reviewed. Therefore, the goal of the current review was to summarize the literature on cognitive reappraisal and highlight common and distinct neural correlates of impaired emotion regulation in clinical populations. We performed a two-stage systematic literature search, selecting 32 studies on cognitive reappraisal in individuals with mood disorders (n=12), anxiety disorders (n=14), addiction (n=2), schizophrenia (n=2), and personality disorders (n=5). Comparing findings across these disorders allowed us to determine underlying mechanisms that were either disorder-specific or common across disorders. Results showed that across clinical populations, individuals consistently demonstrated reduced recruitment of the ventrolateral prefrontal cortex (vlPFC) and dorsolateral prefrontal cortex (dlPFC) during downregulation of negative emotion, indicating that there may be a core deficit in selection, manipulation and inhibition during reappraisal. Further, in individuals with mood disorders, amygdala responses were enhanced during downregulation of emotion, suggesting hyperactive bottom-up responses or reduced modulatory capacity. In individuals with anxiety disorders, however, emotion regulation revealed reduced activity in the dorsal anterior cingulate cortex (dACC) and inferior/superior parietal cortex, possibly indicating a deficit in allocation of attention. The reviewed studies thus provide evidence for both disorder-specific and common deficits across clinical populations. These findings highlight the role of distinct neural substrates as targets for developing/assessing novel therapeutic approaches that are geared towards cognitive regulation of emotion, as well as the importance of transdiagnostic research to identify both disorder specific and core mechanisms.

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Background: Spider phobics show an exaggerated fear response when encountering spiders. This fear response is aggravated by negative and irrational beliefs about the feared object. Cognitive reappraisal can target these beliefs, and therefore has a fear regulating effect. The presented study investigated if neurofeedback derived from functional magnetic resonance imaging (fMRI) would facilitate anxiety regulation by cognitive reappraisal, using spider phobia as a model of anxiety disorders. Feedback was provided based on activation in left dorsolateral prefrontal cortex and right insula, as indicators of engagement and regulation success, respectively.Methods: Eighteen female spider phobics participated in a randomized, controlled, single-blinded study. All participants completed a training session in the MRI scanner. Participants assigned to the neurofeedback condition were instructed to shape their regulatory strategy based on the provided feedback. Participants assigned to the control condition were asked to adapt their strategy intuitively.Results: Neurofeedback participants exhibited lower anxiety levels than the control group at the end of the training. In addition, only neurofeedback participants achieved down-regulation of insula activation levels by cognitive reappraisal. Group differences became more pronounced over time, supporting learning as a mechanism behind this effect. Importantly, within the neurofeedback group, achieved changes in insula activation levels during training predicted long-term anxiety reduction.Conclusions: The conducted study provides first evidence that fMRI neurofeedback has a facilitating effect on anxiety regulation in spider phobia.