Reduced Anterior Temporal and Hippocampal Functional Connectivity During Face Processing Discriminates Individuals with Social Anxiety Disorder from Healthy Controls and Panic Disorder, and Increases Following Treatment

Abstract

Group functional magnetic resonance imaging (fMRI) studies suggest that anxiety disorders are associated with anomalous brain activation and functional connectivity (FC). However, brain-based features sensitive enough to discriminate individual subjects with a specific anxiety disorder and that track symptom severity longitudinally, desirable qualities for putative disorder-specific biomarkers, remain to be identified. Blood oxygen level-dependent (BOLD) fMRI during emotional face perceptual tasks and a new, large-scale and condition-dependent FC and machine learning approach were used to identify features (pair-wise correlations) that discriminated patients with social anxiety disorder (SAD, N ¼ 16) from controls (N ¼ 19). We assessed whether these features discriminated SAD from panic disorder (PD, N ¼ 16), and SAD from controls in an independent replication sample that performed a similar task at baseline (N: SAD ¼ 15, controls ¼ 17) and following 8-weeks paroxetine treatment (N: SAD ¼ 12, untreated controls ¼ 7). High SAD vs HCs discrimination (area under the ROC curve, AUC, arithmetic mean of sensitivity and specificity) was achieved with two FC features during unattended neutral face perception (AUC ¼ 0.88, Po0.05 corrected). These features also discriminated SAD vs PD (AUC ¼ 0.82, P ¼ 0.0001) and SAD vs HCs in the independent replication sample (FC during unattended angry face perception, AUC ¼ 0.71, P ¼ 0.01). The most informative FC was left hippocampus-left temporal pole, which was reduced in both SAD samples (replication sample P ¼ 0.027), and this FC increased following the treatment (post4pre, t (11) ¼ 2.9, P ¼ 0.007). In conclusion, SAD is associated with reduced FC between left temporal pole and left hippocampus during face perception, and results suggest promise for emerging FC-based biomarkers for SAD diagnosis and treatment effects.

Neural Correlates of Procedural Variants in Cognitive-Behavioral Therapy: A Randomized, Controlled Multicenter fMRI Study

“…In line with our findings, the hippocampus has been found to be relevant also for other anxiety disorders [62,63], conditioning paradigms [35,49,64,65,66,67,68,69] and seems to be sensitive to exposure [70], CBT treatment [30,71,72], therapy response [30] or recovery in general [73]. Furthermore, the hippocampus has been discussed with regard to the potential contribution to acquisition of irregularities in PD [15] and the optimization of exposure therapy and related learning processes [26].…”

Empathic Care and Distress: Predictive Brain Markers and Dissociable Brain Systems

“…We assessed both the sensitivity and relative specificity of each marker—the extent to which it tracked the emotion it was trained to track, and did not track the other emotion (Chang et al, 2015; Kassam et al, 2013; Koutsouleris et al, 2015; Kragel & LaBar, 2015; Pantazatos, Talati, Schneier, & Hirsch, 2014; Peelen, Atkinson, & Vuilleumier, 2010; Saarimaki et al, 2015; Wager et al, 2013; Woo et al, 2014). Because predictions were unbiased (tested in independent participants), two likely outcomes were that a marker would (a) track only the emotion it was trained on, demonstrating emotion-specificity; or (b) track both emotions, thus capturing aspects of emotional engagement common to both care and distress (Figure 1b).…”

Working memory dysfunction associated with brain functional deficits and cellular metabolic changes in patients with generalized anxiety disorder

“…The HIP is involved in storage and retrieval of memory, and is inter-related with the prefrontal cortex to yield various cognitive functions (McNaughton, 1997). Pantazatos et al (2014) reported that the HIP could be modulated by threat stimuli in various cognitive reappraisal strategies in patients with anxiety disorder. In an anxiety-inducing animal model study (Crestani et al, 1999), hippocampal activation was increased in response to fearful or threatening stimuli, due to reduction of secretion of γ-amino benzoic acid, an inhibitory neurotransmitter.…”