Neuroimaging cognitive reappraisal in clinical populations to define neural targets for enhancing emotion regulation. A systematic review

Abstract

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.

Keywords: Anxiety disorder; Depression; EEG; Emotion regulation; RDoC; fMRI.

Figure 1. Proportion of studies investigating reappraisal by diagnosis

Of the selected studies, 34% of the selected studies were conducted in individuals with mood disorders, 40% in individuals with anxiety disorders and 26% in other disorders, including addiction, schizophrenia and personality disorders. Abbreviations: MDD = Major Depressive Disorder, BD = Bipolar Disorder, PTSD = Posttraumatic Stress Disorder, GAD = Generalized Anxiety Disorder, PD = Panic Disorder, SAD = Social Anxiety Disorder, OCD = Obsessive Compulsive Disorder, CUD = Cocaine use Disorder, ND = Nicotine Dependence, Sz = Schizophrenia, BPD = Borderline Personality Disorder, AvPD = Avoidant Personality Disorder

Figure 2. Proportion of fMRI studies reporting group differences by reappraisal instruction

While 87% of studies reported differences during downregulation of negative emotion, only 56% found differential upregulation of emotion (both positive and negative), and 66% showed different brain activation patterns during regulation of positive emotion.

Figure 3. Proportion of studies reporting group differences (patients vs. controls) when downregulating negative emotion based on self-report, EEG, and fMRI

Significant group differences in achieved regulation success during downregulation of negative emotion were reported in only 16% of studies based on self-report and 25% of studies employing EEG (n=1). However, 87% of studies employing fMRI reported group differences in brain activation patterns.

Figure 4. Observed group differences during downregulation of negative emotion reported by fMRI studies

All peak coordinates of brain regions showing either an increased or a decreased brain response in patients relative to controls during downregulation of negative emotion (as reported in table 2) are represented in MNI space. The regions are color coded according to the labelling used throughout this review. If the original coordinates were reported in Talairach space, they were converted using Brett’s algorithm (http://www.sdmproject.com/utilities/). The main findings of the current review are indicated by arrows (filled arrows = common findings across all clinical populations).