| 1. |
- Björkstrand, Johannes, et al.
(författare)
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Disrupting Reconsolidation Attenuates Long-Term Fear Memory in the Human Amygdala and Facilitates Approach Behavior
- 2016
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 26:19, s. 2690-95
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Tidskriftsartikel (refereegranskat)abstract
- Memories become labile and malleable to modification when recalled [1]. Fear-conditioning experiments in both rodents and humans indicate that amygdala-localized short-term fear memories can be attenuated by disruption of their reconsolidation with extinction training soon after memory activation [2-7]. However, this may not be true for natural long-term fears. Studies in rodents indicate that although it is possible to disrupt the reconsolidation of older memories [8-11], they appear to be more resistant [1, 3, 9, 12, 13]. In humans, 1-week-old conditioned fear memories have been attenuated by behaviorally induced disruption of reconsolidation [14], but it remains to be seen whether this is possible for naturally occurring long-term fears and whether the underlying neural mechanisms are similar to those found in experimental fear-conditioning paradigms. Using functional brain imaging in individuals with a lifelong fear of spiders, we show that fear memory activation followed by repeated exposure to feared cues after 10 min, which disrupts reconsolidation, attenuates activity in the basolateral amygdala at re-exposure 24 hr later. In contrast, repeated exposure 6 hr after fear memory activation, which allows for reconsolidation, did not attenuate amygdala activity. Disrupted, but not undisrupted, reconsolidation facilitated approach behavior to feared cues, and approach behavior was inversely related to amygdala activity during re-exposure. We conclude that memory activation immediately preceding exposure attenuates the neural and behavioral expression of decades-old fear memories and that, similar to experimentally induced fear memories, the basolateral amygdala is crucially involved in this process.
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| 2. |
- Björkstrand, Johannes, et al.
(författare)
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Disruption of Memory Reconsolidation Erases a Fear Memory Trace in the Human Amygdala : An 18-Month Follow-Up.
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7, s. e0129393-
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Tidskriftsartikel (refereegranskat)abstract
- Fear memories can be attenuated by reactivation followed by disrupted reconsolidation. Using functional magnetic resonance imaging we recently showed that reactivation and reconsolidation of a conditioned fear memory trace in the basolateral amygdala predicts subsequent fear expression over two days, while reactivation followed by disrupted reconsolidation abolishes the memory trace and suppresses fear. In this follow-up study we demonstrate that the behavioral effect persists over 18 months reflected in superior reacquisition after undisrupted, as compared to disrupted reconsolidation, and that neural activity in the basolateral amygdala representing the initial fear memory predicts return of fear. We conclude that disrupting reconsolidation have long lasting behavioral effects and may permanently erase the fear component of an amygdala-dependent memory.
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| 3. |
- Björkstrand, Johannes, et al.
(författare)
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Think twice, it's all right : Long lasting effects of disrupted reconsolidation on brain and behavior in human long-term fear
- 2017
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 324, s. 125-129
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Tidskriftsartikel (refereegranskat)abstract
- Memories can be modified when recalled. Experimental fear conditioning studies support that amygdala-localized fear memories are attenuated when reconsolidation is disrupted through extinction training immediately following memory activation. Recently, using functional brain imaging in individuals with lifelong spider fears, we demonstrated that fear memory activation followed by repeated exposure to feared cues after 10 min, thereby disrupting reconsolidation, attenuated activity in the amygdala during later re-exposure, and also facilitated approach behavior to feared cues. In contrast, repeated exposure 6 h after fear memory activation, allowing for reconsolidation, did not attenuate amygdala activity and resulted in less approach behavior as compared to the group that received disrupted reconsolidation. We here evaluated if these effects are stable after 6 months and found that amygdala activity was further reduced in both groups, with a tendency towards greater reductions in the 10 min than the 6 h group. Hence, disrupted reconsolidation results in long lasting attenuation of amygdala activity. The behavioral effect, with more approach towards previously feared cues, in the 10 min than the 6 h group also persisted. Thus, the brain effect of disrupted reconsolidation is stable over 6 months and the behavioral effect also remained. We therefore conclude that disrupted reconsolidation result in a long-lasting diminished fear memory representation in the amygdala which may have clinical importance.
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| 4. |
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| 5. |
- Faria, Vanda, et al.
(författare)
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Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder : A Randomized Trial
- 2017
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 24, s. 179-188
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Tidskriftsartikel (refereegranskat)abstract
- Background: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but their efficacy relative to placebo has been questioned. We aimed to test how manipulation of verbally induced expectancies, central for placebo, influences SSRI treatment outcome and brain activity in patients with social anxiety disorder (SAD).Methods: We did a randomized clinical trial, within an academic medical center (Uppsala, Sweden), of individuals fulfilling the DSM-IV criteria for SAD, recruited through media advertising. Participants were 18 years or older and randomized in blocks, through a computer-generated sequence by an independent party, to nine weeks of overt or covert treatment with escitalopram(20 mg daily). The overt group received correct treatment information whereas the covert group was treated deceptively with the SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist was necessarily unmasked while the research staff was masked from intervention assignment. Treatment efficacy was assessed primarily with the self-rated Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9, also yielding a dichotomous estimate of responder status (clinically significant improvement). Before and at the last week of treatment, brain activity during an emotional face-matching task was assessed with functional magnetic resonance imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also assessed with the Spielberger State-Trait Anxiety Inventory - State version (STAI-S). Analyses included all randomized patients with outcome data at posttreatment. This study is registered at ISRCTN, number 98890605.Findings: Between March 17th 2014 and May 22nd 2015, 47 patients were recruited. One patient in the covert group dropped out after a few days of treatment and did not provide fMRI data, leaving 46 patients with complete outcome data. After nine weeks of treatment, overt (n = 24) as compared to covert (n = 22) SSRI administration yielded significantly better outcome on the LSAS-SR (adjusted difference 21.17, 95% CI 10.69–31.65, p < 0.0001) with more than three times higher response rate (50% vs. 14%; χ2(1) = 6.91, p = 0.009) and twice the effect size (d = 2.24 vs. d = 1.13) from pre-to posttreatment. There was no significant between-group difference on anticipatory speech anxiety (STAI-S), both groups improving with treatment. No serious adverse reactions were recorded. On fMRI outcomes, there was suggestive evidence for a differential neural response to treatment between groups in the posterior cingulate, superior temporal and inferior frontal gyri (all z thresholds exceeding 3.68, p ≤ 0.001). Reduced social anxiety with treatment correlated significantly with enhanced posterior cingulate (z threshold 3.24, p = 0.0006) and attenuated amygdala (z threshold 2.70, p = 0.003) activity.Interpretation: The clinical and neural effects of escitalopram were markedly influenced by verbal suggestions. This points to a pronounced placebo component in SSRI-treatment of SAD and favors a biopsychosocial over a biomedical explanatory model for SSRI efficacy.
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| 6. |
- Frick, Andreas, et al.
(författare)
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Enlargement of visual processing regions in social anxiety disorder is related to symptom severity
- 2014
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 583, s. 114-119
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Tidskriftsartikel (refereegranskat)abstract
- Social anxiety disorder (SAD) is associated with altered brain function and structure, but most structural studies include small samples and findings are mixed. This study compared regional gray matter volume between 48 SAD patients and 29 healthy controls (HC) as well as the relationship between volume and symptom severity. Structural magnetic resonance images from SAD patients and HC were evaluated using standard voxel-based morphometry (VBM) processing in the SPM8 software package. Social anxiety symptom severity was rated in SAD patients by a clinician using the Liebowitz Social Anxiety Scale (LSAS). SAD patients had greater regional gray matter volume in the lingual gyrus and lateral occipital cortex than the controls, and within the SAD group a positive correlation was found between symptom severity and regional gray matter volume in the lingual gyrus and the retrosplenial cortex. These findings replicate and extend earlier reports of enlarged visual processing areas in SAD. Increased gray matter volume in regions involved in visual processing and self-consciousness could underlie, or be the result of, abnormal emotional information processing and self-focused attention previously demonstrated in patients with SAD.
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| 7. |
- Frick, Andreas, Docent, et al.
(författare)
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Neuroimaging, genetic, clinical, and demographic predictors of treatment response in patients with social anxiety disorder
- 2020
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 261, s. 230-237
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Tidskriftsartikel (refereegranskat)abstract
- Background: Correct prediction of treatment response is a central goal of precision psychiatry. Here, we tested the predictive accuracy of a variety of pre-treatment patient characteristics, including clinical, demographic, molecular genetic, and neuroimaging markers, for treatment response in patients with social anxiety disorder (SAD). Methods: Forty-seven SAD patients (mean±SD age 33.9 ± 9.4 years, 24 women) were randomized and commenced 9 weeks’ Internet-delivered cognitive behavior therapy (CBT) combined either with the selective serotonin reuptake inhibitor (SSRI) escitalopram (20 mg daily [10 mg first week], SSRI+CBT, n = 24) or placebo (placebo+CBT, n = 23). Treatment responders were defined from the Clinical Global Impression-Improvement scale (CGI-I ≤ 2). Before treatment, patients underwent functional magnetic resonance imaging and the Multi-Source Interference Task taxing cognitive interference. Support vector machines (SVMs) were trained to separate responders from nonresponders based on pre-treatment neural reactivity in the dorsal anterior cingulate cortex (dACC), amygdala, and occipital cortex, as well as molecular genetic, demographic, and clinical data. SVM models were tested using leave-one-subject-out cross-validation. Results: The best model separated treatment responders (n = 24) from nonresponders based on pre-treatment dACC reactivity (83% accuracy, P = 0.001). Responders had greater pre-treatment dACC reactivity than nonresponders especially in the SSRI+CBT group. No other variable was associated with clinical response or added predictive accuracy to the dACC SVM model. Limitations: Small sample size, especially for genetic analyses. No replication or validation samples were available. Conclusions: The findings demonstrate that treatment outcome predictions based on neural cingulate activity, at the individual level, outperform genetic, demographic, and clinical variables for medication-assisted Internet-delivered CBT, supporting the use of neuroimaging in precision psychiatry.
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| 8. |
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| 9. |
- Gingnell, Malin, et al.
(författare)
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Combining escitalopram and cognitive–behavioural therapy for social anxiety disorder : randomised controlled fMRI trial
- 2016
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 209:3, s. 229-235
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSelective serotonin reuptake inhibitors (SSRIs) and cognitive–behavioural therapy (CBT) are often used concomitantly to treat social anxiety disorder (SAD), but few studies have examined the effect of this combination.AimsTo evaluate whether adding escitalopram to internet-delivered CBT (ICBT) improves clinical outcome and alters brain reactivity and connectivity in SAD.MethodDouble-blind, randomised, placebo-controlled neuroimaging trial of ICBT combined either with escitalopram (n = 24) or placebo (n = 24), including a 15-month clinical follow-up (trial registration: ISRCTN24929928).ResultsEscitalopram+ICBT, relative to placebo+ICBT, resulted in significantly more clinical responders, larger reductions in anticipatory speech state anxiety at post-treatment and larger reductions in social anxiety symptom severity at 15-month follow-up and at a trend-level (P = 0.09) at post-treatment. Right amygdala reactivity to emotional faces also decreased more in the escitalopram+ICBT combination relative to placebo+ICBT, and in treatment responders relative to non-responders.ConclusionsAdding escitalopram improves the outcome of ICBT for SAD and decreased amygdala reactivity is important for anxiolytic treatment response.
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