Kerry L. Kinney

Predicting cognitive behavioral therapy response in social anxiety disorder with anterior cingulate cortex and amygdala during emotion regulation

Background Cognitive Behavioral Therapy (CBT) for social anxiety disorder (SAD) and other internalizing conditions attempts to improve emotion regulation. Accumulating data indicate anterior cingulate cortex (ACC), and to a lesser extent amygdala, activation in various tasks predicts treatment outcome. However, little is known about ACC and amygdala activation to emotion regulation in predicting clinical improvement following CBT in SAD. Methods Before treatment, 38 SAD patients completed implicit and explicit emotion regulation paradigms during fMRI. Implicit regulation involved attentional control over negative distractors. Explicit regulation comprised cognitive reappraisal to negative images. Pre-CBT brain activity was circumscribed to anatomical-based ACC sub-regions (rostral, dorsal) and amygdala masks, which were submitted to ROC curves to examine predictive validity as well as correlational analysis to evaluate prognostic change in symptom severity. Results More rostral (rACC) activity in implicit regulation and less rACC activity during explicit regulation distinguished responders (34%) from non-responders. Greater amygdala response in implicit regulation also foretold responder status. Baseline rACC and amygdala activity during attentional control correlated with pre-to-post CBT change in symptom severity such that more activation was related to greater decline in symptoms. No significant correlations were observed for explicit regulation. Conclusions Across forms of regulation, rACC activity predicted responder status whereas amygdala as a neuromarker was limited to implicit regulation. While the direction of effects (enhanced vs. reduced) in rACC activity was task-dependent, results suggest SAD patients with deficient regulation benefited more from CBT. Findings support previous studies involving patients with depression and suggest the rACC may be a viable marker of clinical improvement in SAD.

Threat distractor and perceptual load modulate test-retest reliability of anterior cingulate cortex response

ABSTRACT Accumulating data from fMRI studies implicate the rostral anterior cingulate cortex (rACC) in inhibition of attention to threat distractors that compete with task‐relevant goals for processing resources. However, little data is available on the reliability of rACC activation. Our aim in the current study was to examine test‐retest reliability of rACC activation over a 12‐week period, in the context of a validated emotional interference paradigm that varied in perceptual load. During functional MRI, 23 healthy volunteers completed a task involving a target letter in a string of identical letters (low load) or in a string of mixed letters (high load) superimposed on angry, fearful, and neutral face distractors. Intraclass correlation coefficients (ICCs) indicated that under low, but not high perceptual load, rACC activation to fearful vs. neutral distractors was moderately reliable. Conversely, regardless of perceptual load, rACC activation to angry vs. neutral distractors was not reliable. Regarding behavioral performance, ICCs indicated that accuracy was not reliable regardless of distractor type or perceptual load. Although reaction time (RT) was similarly not reliable regardless of distractor type under low perceptual load, RT to angry vs. neutral distractors and to fearful vs. neutral distractors was reliable under high perceptual load. Together, results indicate the test‐retest reliability of rACC activation and corresponding behavioral performance are context dependent; reliability of the former varies as a function of distractor type and level of cognitive demand, whereas reliability of the latter depends on behavioral index (accuracy vs. RT) and level of cognitive demand but not distractor type. HIGHLIGHTS23 adults completed an emotional interference task twice across 12 weeks during fMRI.rACC activation to fearful distractors was reliable under low perceptual load.rACC activation to angry distractors was not reliable regardless of perceptual load.task accuracy was not reliable regardless of distractor type or perceptual load.task reaction time was reliable under high but not low perceptual load.

Principal component analysis and neural predictors of emotion regulation

&NA; Reappraisal, a cognitive approach intended to alter an emotional response, is generally associated with prefrontal cortical recruitment and decreased limbic activity. However, the extent to which neurofunctional activity predicts successful reappraisal is unclear. During fMRI, 60 healthy participants completed a reappraisal paradigm, which included reappraising negative images to reduce emotional reactivity (‘ReappNeg’) and viewing negative images and experiencing the negative affect they evoke (‘LookNeg’). After each trial, participants rated their emotional response on a Likert‐type scale where higher values indicated more negative affect. Reappraisal ability was based on a difference value (&Dgr;ReappNeg‐LookNeg) such that negative values signified successful reappraisal (‘SR’; n = 38) and positive values, unsuccessful reappraisal (‘USR’; n = 22). Neural activity based on ReappNeg‐LookNeg conditions from 37 regions of interest encompassing cortical and limbic areas was submitted to Principal Component Analysis (PCA). Resulting PCA factors were submitted to discriminant function analysis to evaluate which factor(s) predicted SR and USR groups. Results showed a factor with high loadings for certain frontal areas (e.g., left dorsomedial prefrontal cortex) and limbic regions (e.g., bilateral amygdala) predicted 71.1% of cases in the SR group and 68.2% of cases in the USR group. Additionally, successful reappraisal corresponded with more activation in the factor with high loadings for frontal areas and less activity in the factor associated with limbic regions. Results are consistent with studies of individual differences where more prefrontal engagement and less limbic activity is associated with effectual reappraisal, but for the first time, a neural ‘signature’ for successful reappraisal has been demonstrated.

Reactivity to unpredictable threat as a treatment target for fear-based anxiety disorders

BACKGROUND Heightened reactivity to unpredictable threat (U-threat) is a core individual difference factor underlying fear-based psychopathology. Little is known, however, about whether reactivity to U-threat is a stable marker of fear-based psychopathology or if it is malleable to treatment. The aim of the current study was to address this question by examining differences in reactivity to U-threat within patients before and after 12-weeks of selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy (CBT). METHODS Participants included patients with principal fear (n = 22) and distress/misery disorders (n = 29), and a group of healthy controls (n = 21) assessed 12-weeks apart. A well-validated threat-of-shock task was used to probe reactivity to predictable (P-) and U-threat and startle eyeblink magnitude was recorded as an index of defensive responding. RESULTS Across both assessments, individuals with fear-based disorders displayed greater startle magnitude to U-threat relative to healthy controls and distress/misery patients (who did not differ). From pre- to post-treatment, startle magnitude during U-threat decreased only within the fear patients who received CBT. Moreover, within fear patients, the magnitude of decline in startle to U-threat correlated with the magnitude of decline in fear symptoms. For the healthy controls, startle to U-threat across the two time points was highly reliable and stable. CONCLUSIONS Together, these results indicate that startle to U-threat characterizes fear disorder patients and is malleable to treatment with CBT but not SSRIs within fear patients. Startle to U-threat may therefore reflect an objective, psychophysiological indicator of fear disorder status and CBT treatment response.

Trait attentional control modulates neurofunctional response to threat distractors in anxiety and depression

Accumulating data suggest attentional control capability varies across psychiatric diagnostic boundaries. The Attentional Control Scale (ACS) assesses self-reported trait attentional control (TAC) and tracks the anterior attention system. Greater TAC is associated with less negative affect, however, its mechanisms in anxiety and depression are poorly understood. Therefore, we examined whether individual differences in TAC modulated top-down mechanisms in a clinical sample. During fMRI, 104 patients with social anxiety, generalized anxiety, and/or major depression and 34 healthy participants completed a validated attentional control paradigm comprising strings of letters superimposed on threatening and neutral face distractors. In the low perceptual load condition, a target letter was in a string of identical letters. In the high load condition, a target letter was in a mixed letter string. Whole-brain regression results for low load revealed more activation to threat (vs. neutral) distractors in the pregenual anterior cingulate cortex was predicted by better TAC (i.e., higher ACS scores). For high load, regression results showed less activation to threat (vs. neutral) distractors in the inferior frontal gyrus was predicted by better TAC. An exploratory whole-brain ANOVA revealed a main effect of group in the superior temporal gyrus and a main effect of perceptual load in parietal, frontal, and limbic regions. No other effects were detected and activation derived from significant ANOVA results did not correlate with ACS scores. In conclusion, regression findings suggest individual differences in brain-behavioral ACS-related activity in frontal structures may be useful in identifying phenotypes in internalizing conditions.