Dataset Information

Poor between-session recall of extinction learning and hippocampal activation and connectivity in children.

ABSTRACT: BACKGROUND:In healthy adults, successful between-session recall of extinction learning depends on the hippocampus and ventromedial prefrontal cortex (vmPFC), especially when tested in the extinction context. Poor extinction recall and dysfunction within hippocampal-vmPFC circuitry are associated with fear-based disorders (e.g., anxiety, posttraumatic stress disorder). Despite the early age of onset of virtually all fear-based disorders and the protracted development of the hippocampus and vmPFC across the first two decades of life, little is known about extinction recall and the underlying neural correlates in children. METHODS:Here, we tested extinction recall in 43 pre-adolescent children (ages 6-11 yrs) by coupling functional magnetic resonance imaging and virtual reality with a novel interpersonal threat-related two-day (ABBA) fear-extinction paradigm. Conditioned fear responding was assessed at behavioral, subjective, physiological, and neural levels. RESULTS:Although children demonstrated intact within-session extinction, there was poor between-session recall of extinction learning (retention index: 13.56%), evidenced by elevations in skin conductance, avoidant behavioral responses, and subjective ratings. Elevations in conditioning fear responding were accompanied by activation in the hippocampus and insula, and increased connectivity of the hippocampus with the insula and dorsal anterior cingulate cortex - regions implicated in the return of fear in adult studies. Children who kept more distance from the extinguished cue during extinction subsequently demonstrated heightened hippocampal-cingulate coupling during recall, suggesting that avoidant behavior interferes with extinction retention. CONCLUSIONS:Poor extinction recall in children may have implications for developmental vulnerability to fear-based disorders, and for the application of therapeutic strategies that rely on principles of extinction (e.g., exposure therapy) to pediatric samples.

SUBMITTER: Marusak HA

PROVIDER: S-EPMC6286149 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Poor between-session recall of extinction learning and hippocampal activation and connectivity in children.

Marusak Hilary A HA Peters Craig C Hehr Aneesh A Elrahal Farrah F Rabinak Christine A CA

Neurobiology of learning and memory 20181019

<h4>Background</h4>In healthy adults, successful between-session recall of extinction learning depends on the hippocampus and ventromedial prefrontal cortex (vmPFC), especially when tested in the extinction context. Poor extinction recall and dysfunction within hippocampal-vmPFC circuitry are associated with fear-based disorders (e.g., anxiety, posttraumatic stress disorder). Despite the early age of onset of virtually all fear-based disorders and the protracted development of the hippocampus an ...[more]

PMID: 30347237

Similar Datasets

Project description:Extinction learning refers to the phenomenon that a previously learned response to an environmental stimulus, for example the expression of an aversive behavior upon exposure to a specific context, is reduced when the stimulus is repeatedly presented in the absence of a previously paired aversive event. Extinction of fear memories has been implicated with the treatment of anxiety disease but the molecular processes that underlie fear extinctionare only beginning to emerge. Here we show that fear extinction initiates up-regulation of hippocampal insulin-growth factor 2 (Igf2) and down-regulation of insulin-growth factor binding protein 7 (Igfbp7). In line with this observation we demonstrate that IGF2 facilitates fear extinction, while IGFBP7 impairs fear extinction in an IGF2-dependent manner. Furthermore, we identify one cellular substrate of altered IGF2-signaling during fear extinction. To this end we show that fear extinction-induced IGF2/IGFBP7-signaling promotes the survival of 17-19 day-old newborn hippocampal neurons. In conclusion, our data suggests that therapeutic strategies that enhance IGF2-signaling and adult neurogenesis might be suitable to treat disease linked to excessive fear memory. We employed mice to investigate fear extinction in the hippocampus-dependent contextual fear conditioning paradigm. To this end, male C57BL/6J mice were exposed to the fear conditioning box (context) followed by an electric foot-shock which elicits the acquisition of conditioned contextual fear. For extinction training animals were repeatedly reexposed to the conditioned context on consecutive days (24h interval) without receiving the footshockagain (extinction trial, E). This procedure eventually results in the decline of the aversive freezing behavior. Mice that were exposed to the conditioning context without receiving fear conditioning training served as control groups. To gain a better understanding of the molecular processes underlying fear extinction we performed a genome-wide analysis of the hippocampal transcriptome during fear extinction. In the employed paradigm fear extinction is a gradual process. To capture the longitudinal course of fear extinction we decided to perform hippocampal microarray analysis at two time points: (1) After the first extinction trial (E1) when animals display high levels of aversive freezing behavior and (2) at the extinction trial on which the freezing behavior was significantly reduced when compared to E1. This extinction trial, in the case of this experiment E5, we termed “extinction trial low freezing” (ELF). Mice that were exposed to the conditioning context without receiving fear conditioning training served as control groups (3). For all three groups we hybridized 5 samples (biological replicates).

Project description:The hippocampus and underlying cortices are highly susceptible to pathologic change with increasing age. Using an associative face-scene (Face-Place) encoding task designed to target these regions, we investigated activation and connectivity patterns in cognitively normal older adults. Functional MRI scans were collected in 210 older participants (mean age = 76.4 yrs) in the Baltimore Longitudinal Study of Aging (BLSA). Brain activation patterns were examined during encoding of novel Face-Place pairs. Functional connectivity of the hippocampus was also examined during encoding, with seed regions placed along the longitudinal axis in the head, body and tail of the structure. In the temporal lobe, task activation patterns included coverage of the hippocampus and underlying ventral temporal cortices. Extensive activation was also seen in frontal, parietal and occipital lobes of the brain. Functional connectivity analyses during overall encoding showed that the head of the hippocampus was connected to frontal and anterior/middle temporal regions, the body with frontal, widespread temporal and occipital regions, and the tail with posterior temporal and occipital cortical regions. Connectivity limited to encoding of subsequently remembered stimuli showed a similar pattern for the hippocampal body, but differing patterns for the head and tail regions. These results show that the Face-Place task produces activation along the occipitotemporal visual pathway including medial temporal areas. The connectivity results also show that patterns of functional connectivity vary throughout the anterior-posterior extent of the hippocampus during memory encoding. As these patterns include regions vulnerable to pathologic change in early stages of Alzheimer's disease, continued longitudinal assessment of these individuals can provide valuable information regarding changes in brain-behavior relationships that may occur with advancing age and the onset of cognitive decline.

Dataset Information

Poor between-session recall of extinction learning and hippocampal activation and connectivity in children.

Publications

Poor between-session recall of extinction learning and hippocampal activation and connectivity in children.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets