Consolidation of extinction learning is a primary mechanism disrupted in posttraumatic stress disorder (PTSD), associated with hypoactivity of the ventromedial prefrontal cortex and hippocampus. A role for rapid eye movement (REM) sleep disturbances in this failure to consolidate extinction learning has been proposed. We performed functional magnetic resonance imaging (fMRI) with simultaneous skin conductance response (SCR) measurements in 16 healthy participants during conditioning/extinction and later recall of extinction. The visual stimuli were basic geometric forms and electrical shocks functioned as the unconditioned stimulus. Between the conditioning/extinction and recall sessions, participants received a 90-min sleep window in the sleep laboratory. This daytime sleep was polysomnographically recorded and scored by professionals blind to the study design. Only seven out of 16 participants had REM sleep; participants without REM sleep had a significantly slower decline of both SCR and neural activity of the laterodorsal tegmentum in response to electrical shocks during conditioning. At recall of fear extinction, participants with preceding REM sleep had a reduced SCR and stronger activation of the left ventromedial prefrontal cortex and bilateral lingual gyrus in response to the extinguished stimulus than participants lacking REM sleep. This study indicates that trait-like differences in shock reactivity/habituation (mediated by the brainstem) are predictive of REM sleep disruption, which in turn is associated with impaired consolidation of extinction (mediated by the ventromedial prefrontal cortex). These findings help understand the neurobiological basis and the temporal sequence of the relationship between shock exposure, disturbed sleep and impaired consolidation of extinction, as observed in PTSD.
"Accordingly, we expected reduced CRs at the ROF test in the L-DOPA as compared to the placebo group. At a neural level, we expected reduced CS responses at test in the L-DOPA group in regions of interest involved in ROF, specifically the amygdala, the posterior hippocampus and the dorsal anterior cingulate/ dorsomedial prefrontal cortex (dACC/dmPFC) (Agren et al., 2012; Kalisch et al., 2009, 2006; Milad et al., 2009) as well as enhanced responses in extinction-related regions, specifically the vmPFC and the anterior hippocampus (Kalisch et al., 2006; Milad et al., 2009, 2007; Phelps et al., 2004; Spoormaker et al., 2010). "
"For example, a daytime nap session was found to promote physiological intersession habituation to repeatedly presented, aversive images, an effect that was reduced by the occurrence of REM sleep (Pace-Schott et al. 2011). In a different study, subjects who showed diminished habituation in their skin conductance response (SCR) to electrical shocks during fear conditioning did not achieve REM sleep during a subsequent nap opportunity (Spoormaker et al. 2010). Given that the hypothalamus plays a critical role in sleep regulation, it is likely that the sudomotor fibers that project from the hypothalamus to the ventrolateral spinal sympathetic tract mediate these effects (Boucsein 2012). "
[Show abstract][Hide abstract] ABSTRACT: Sleep disturbances are prevalent in clinical anxiety but it remains unclear whether they are cause and/or consequence of this condition. Fear conditioning constitutes a valid laboratory model for the acquisition of normal and pathological anxiety. To explore the relationship between disturbed sleep and anxiety in more detail, the present study evaluated the effect of partial sleep deprivation (SD) on fear conditioning in healthy individuals. The neural correlates of (1) non-associative learning and physiological processing, and (2) associative learning (differential fear conditioning) were addressed. Measurements entailed simultaneous functional magnetic resonance imaging (fMRI), electroencephalography (EEG), skin conductance response (SCR) and pulse recordings. Regarding non-associative learning (1), partial SD resulted in a generalized failure to habituate during fear conditioning as evidenced by reduced habituation of SCR and hypothalamus responses to all stimuli. Furthermore, SCR and hypothalamus activity were correlated, supporting their functional relationship. Regarding associative learning (2) effects of partial SD on the acquisition of conditioned fear were weaker and did not reach statistical significance. The hypothalamus plays an integral role in the regulation of sleep and autonomic arousal. Thus, sleep disturbances may play a causal role in the development of normal and, possibly, pathological fear by increasing the susceptibility of the sympathetic nervous system to stressful experiences.
Journal of Neurophysiology 06/2014; 112(6). DOI:10.1152/jn.00657.2013 · 2.89 Impact Factor
"Table 1 ROI center coordinates and literature sources ROI x y z References vmPFC 0 40 À12 Phelps et al. (2004) Kalisch et al. (2006) Milad et al. (2007) Milad et al. (2009) Spoormaker et al. (2010) dmPFC 0 43 29 Kalisch et al. (2009) Milad et al. (2009) "
[Show abstract][Hide abstract] ABSTRACT: Human context conditioning studies have focused on acquisition and extinction. Subsequent long-term changes in fear behaviors not only depend on associative learning processes during those phases but also on memory consolidation processes and the later ability to retrieve and express fear and extinction memories. Clinical theories explain relapse after successful exposure-based treatment with return of fear memories and remission with stable extinction memory expression. We probed contextual fear and extinction memories one week (day8) after conditioning (day1) and subsequent extinction (day2) by presenting conditioned contexts before (Test1) and after (Test2) a reinstatement manipulation. We find consistent activation patterns in two independent samples: activation of a subgenual part of the ventromedial prefrontal cortex (vmPFC) before reinstatement (Test1) and (albeit with different temporal profiles between samples) of the amygdala after reinstatement (Test2) as well as up-regulation of anterior hippocampus activity after reinstatement (Test2>Test1). These areas have earlier been implicated in the expression of cued extinction and fear memories. The present results suggest a general role for these structures in defining the balance between fear and extinction memories, independent of the conditioning-mode. The results are discussed in the light of hypotheses implicating the anterior hippocampus in the processing of situational ambiguity.
Social Cognitive and Affective Neuroscience 02/2014; DOI:10.1093/scan/nsu018 · 7.37 Impact Factor
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