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. 2016 Nov 17:10:222.
doi: 10.3389/fnbeh.2016.00222. eCollection 2016.

Implicit Learning in Transient Global Amnesia and the Role of Stress

Affiliations

Implicit Learning in Transient Global Amnesia and the Role of Stress

Frauke Nees et al. Front Behav Neurosci. .

Abstract

Transient global amnesia (TGA) is a disorder with reversible anterograde disturbance of explicit memory, frequently preceded by an emotionally or physically stressful event. By using magnetic resonance imaging (MRI) following an episode of TGA, small hippocampal lesions have been observed. Hence it has been postulated that the disorder is caused by the stress-related transient inhibition of memory formation in the hippocampus. In experimental studies, stress has been shown to affect both explicit and implicit learning-the latter defined as learning and memory processes that lack conscious awareness of the information acquired. To test the hypothesis that impairment of implicit learning in TGA is present and related to stress, we determined the effect of experimental exposure to stress on hippocampal activation patterns during an implicit learning paradigm in patients who suffered a recent TGA and healthy matched control subjects. We used a hippocampus-dependent aversive learning procedure (context conditioning with the phases habituation, acquisition, and extinction) during functional MRI following experimental stress exposure (socially evaluated cold pressor test). After a control procedure, controls showed successful learning during the acquisition phase, indicated by increased valence, arousal and contingency ratings to the paired (CON+) vs. the non-paired (CON-) conditioned stimulus, and successful extinction of the conditioned responses. Following stress, acquisition was still successful, however extinction was impaired with persistently increased contingency ratings. In contrast, TGA patients showed impairment of conditioned responses and insufficient extinction after the control procedure, indicated by a lack of significant differences between CON+ and CON- for valence and arousal ratings after the acquisition phase and by significantly increased contingency ratings after the extinction. After stress, aversive learning was not successful with non-significant ratings of all parameters. Concerning brain activation patterns after the control procedure, controls showed increased hippocampal response during acquisition after the control procedure. This was not seen after stress exposure. In TGA patients, we observed an increased response in the right ventral striatum in the acquisition phase following stress. These findings suggest that alterations in implicit learning processes, including impaired hippocampal and increased striatal responses, might play a role in TGA pathophysiology, partly related to acute stress.

Keywords: aversive conditioning; context; hippocampus; striatum; transient global amnesia.

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Figures

Figure 1
Figure 1
Contextual fear conditioning paradigm. CON1/+, conditioned stimulus paired with the unconditioned stimulus; CON2/−, conditioned stimulus never paired with the unconditioned stimulus, US, unconditioned stimulus.
Figure 2
Figure 2
Subjective ratings of valence, arousal and contingency during the acquisition phase of the contextual fear conditioning paradigm. (A) In the control group, (B) in the TGA group, following the control procedure and the SECPT. *p < 0.05. CON+, conditioned stimulus paired with the unconditioned stimulus; CON−, conditioned stimulus never paired with the unconditioned stimulus; SECPT, Socially Evaluated Cold Pressor Test; TGA, transient global amnesia.
Figure 3
Figure 3
Subjective ratings of valence, arousal and contingency during the extinction phase of the contextual fear conditioning paradigm. (A) In the control group, (B) in the TGA group, following the control procedure and the SECPT. *p < 0.05. CON+, conditioned stimulus paired with the unconditioned stimulus; CON−, conditioned stimulus never paired with the unconditioned stimulus; SECPT, Socially Evaluated Cold Pressor Test; TGA, transient global amnesia.
Figure 4
Figure 4
Whole brain activation patterns (pFWE < 0.05). Contrast CON+ > CON− during the acquisition phase of the contextual fear conditioning paradigm (A) following the control procedure, (B) following the SECPT. Activation in control group indicated in green, TGA group in blue. CON+, conditioned stimulus paired with the unconditioned stimulus; CON−, conditioned stimulus never paired with the unconditioned stimulus; SECPT, Socially Evaluated Cold Pressor Test; TGA, transient global amnesia.
Figure 5
Figure 5
(A) ROI based analysis of brain activation (pFWE < 0.05) in the TGA group. Contrast SECPT > control procedure during acquisition phase (CON+ > CON−) of the contextual fear conditioning paradigm showing a stronger activation of the right ventral striatum (x = 19, y = 3, z = −5; T = 3.83) after the SECPT. (B) ROI based analysis of brain activation (pFWE < 0.05) following the SECPT. Contrast TGA > control group during the acquisition phase (CON+ > CON−) of the contextual fear conditioning paradigm showing a stronger activation of the right ventral striatum (x = 19, y = 17, z = −11; T = 3.53) in the TGA group. ROI, region of interest; CON+, conditioned stimulus paired with the unconditioned stimulus; CON−, conditioned stimulus never paired with the unconditioned stimulus; SECPT, Socially Evaluated Cold Pressor Test; TGA, transient global amnesia.

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