Hippocampal Network Connectivity and Activation Differentiates Post-Traumatic Stress Disorder From Generalized Anxiety Disorder

Abstract

Anxiety disorders are a diverse group of clinical states. Post-traumatic stress disorder (PTSD) and generalized anxiety disorder (GAD), eg, share elevated anxiety symptoms, but differ with respect to fear-related memory dysregulation. As the hippocampus is implicated in both general anxiety and fear memory, it may be an important brain locus for mapping the similarities and differences among anxiety disorders. Anxiety and fear also functionally associate with different subdivisions of the hippocampus along its longitudinal axis: the human posterior (rodent dorsal) hippocampus is involved in memory, through connectivity with the medial prefrontal-medial parietal defaultmode network, whereas the anterior (rodent ventral) hippocampus is involved in anxiety, through connectivity with limbic-prefrontal circuits. We examined whether differential hippocampal network functioning may help account for similarities and differences in symptoms in PTSD and GAD. Network-sensitive functional magnetic resonance imaging-based resting-state intrinsic connectivity methods, along with task-based assessment of posterior hippocampal/default-mode network function, were used. As predicted, in healthy subjects resting-state connectivity dissociated between posterior hippocampal connectivity with the default-mode network, and anterior hippocampal connectivity to limbic-prefrontal circuitry. The posterior hippocampus and the associated default-mode network, across both resting-state connectivity and task-based measures, were perturbed in PTSD relative to each of the other groups. By contrast, we found only modest support for similarly blunted anterior hippocampal connectivity across both patient groups. These findings provide new insights into the neural circuit-level dysfunctions that account for similar vs different features of two major anxiety disorders, through a translational framework built on animal work and carefully selected clinical disorders.

Mobilization of Medial and Lateral Frontal-Striatal Circuits in Cocaine Users and Controls: An Interleaved TMS/BOLD Functional Connectivity Study

“…Interestingly, however, in the present study DLPFC stimulation also led to a reciprocal decrease in medial orbitofrontal (BA 10) BOLD signal in the controls, but not the cocaine users. The reciprocal relationship between the DLPFC and BA 10 in controls is consistent with other studies, which have revealed negative connectivity between the central executive network and the salience network (Chen and Etkin, 2013a;Liston et al, 2014). It is also consistent with PET studies showing that 10 Hz rTMS to the left DLPFC effects dopamine release in the medial orbitofrontal cortex and anterior cingulate cortex, as revealed by [(11)C]FLB 457 binding, a ligand sensitive to D2 receptors (Cho and Strafella, 2009).…”

Childhood Poverty and Stress Reactivity Are Associated with Aberrant Functional Connectivity in Default Mode Network

“…Another study noted that financial hardship (but not childhood poverty) reduced hippocampal volume in middle-aged adults (Butterworth et al, 2012). Decreased connectivity between hippocampus and PCC has also been associated with heightened anxiety in individuals with posttraumatic stress disorder (Chen and Etkin, 2013;Sripada et al, 2012). However, one study of healthy adolescents found that reduced connectivity between hippocampus and DMN was associated with reduced anxiety and cortisol output in the scanner, as well as reduced cortisol during TSST (Thomason et al, 2013).…”

Hippocampal and Insular Response to Smoking-Related Environments: Neuroimaging Evidence for Drug-Context Effects in Nicotine Dependence

“…In view of the functional heterogeneity of the HPC along the anterior-posterior axis (Poppenk et al, 2013;Strange et al, 2014), separate hippocampal region of interests (ROIs) were generated for anterior and posterior HPC. Bilateral aHPC and pHPC ROIs were defined following a prior study of aHPC and pHPC connectivity (Chen and Etkin, 2013), taking the anterior-most third and posterior-most third of an HPC ROI consisting of voxels with a 460% likelihood of being in HPC (as defined by the Harvard-Oxford probabilistic structural axis). The following additional ROIs, chosen a priori based on preclinical research (Bossert et al, 2011;Fuchs et al, 2005;McLaughlin and See, 2003;Otis et al, 2014), our previous neuroimaging studies (McClernon et al, 2005(McClernon et al, , 2007(McClernon et al, , 2009) and metaanalysis (Engelmann et al, 2012;Kuhn and Gallinat, 2011;Tang et al, 2012) of cue-reactivity, were created in PickAtlas (Maldjian et al, 2003): (1) ventral striatum (5 mm radius sphere centered on ± 6,4, − 5); (2) amygdala (anatomical); (3) insula (5 mm radius sphere centered on ± 38,10,6); (4) mPFC inclusive of portions of rostral anterior cingulate cortex (5 × 10 × 10 mm box centered on ± 5, 40, 10); and (5) PCC (5 × 5 × 10 mm box centered on ± 5, − 60,20).…”