Neural correlates of experimental trauma memory retrieval

May combine two claims.

In the contrast of experimental trauma > control and film pictures > negative IAPS pictures, the retrosplenial cortex and precuneus remained significantly different, but the PCC and ACC were not found.

“When looking at experimental trauma > control group and specifically at the film pictures > negative IAPS pictures contrast, the retrosplenial cortex and the precuneus were still significantly different.However, the PCC and ACC were not found in this contrast”

• AssumptionRests on an assumption: The emotional distractors in the Sternberg task are assumed to trigger only implicit memories of the film.

May combine two claims.

Implicit experimental trauma retrieval specifically involved the retrosplenial cortex and ACC, while both retrieval tasks produced trauma-related activity in the PCC and precuneus.

“We show that implicit experimental trauma retrieval specifically involved the retrosplenial cortex and the anterior cingulate cortex (ACC), while both retrieval tasks resulted in trauma-related activity in the posterior cingulate cortex (PCC) and the precuneus.”

• AssumptionRests on an assumption: The emotional distractors in the Sternberg task are assumed to trigger only implicit memories of the film.

May combine two claims.

Sternberg task performance did not differ significantly between the two experimental groups or across picture types (all P>0.10).

“Performances in the Sternberg task did not differ significantly, neither between the two experimental groups nor between pictures types (all P > 0.10).”

May combine two claims.

The trauma film group gave higher negative and arousal ratings to film pictures than to neutral IAPS pictures (t(20)=6.6, P<0.001), whereas the control group did not.

“In addition, participants from the experimental trauma group rated the film pictures as more negative and more arousing than neutral IAPS pictures (t 20 5 6.6, P < 0.001), while participants from the control group did not do that.”

May combine two claims.

There was a significant interaction between film type and picture type for valence (F(3,120)=7.80, P=0.003) and arousal (F(3,120)=5.44, P<0.001).

“The pattern was substantiated by a significant interaction effect in the between-subject factor of film type (experimental trauma vs. neutral) and picture type (negative, neutral film and scrambled pictures; valence F 3,120 5 7.80, P 5 0.003 and arousal F 3,120 5 5.44, P < 0.001).”

May combine two claims.

Activity in the brain soon after experimental trauma predicted the later emergence of intrusions, with separate contributions from the retrosplenial cortex during implicit retrieval and the PCC during explicit retrieval.

“Importantly, neural activity early after experimental trauma exposure predicted later intrusion development, with independent contributions from activity in the retrosplenial cortex (implicit retrieval) and the PCC (explicit retrieval).”

• AssumptionRests on an assumption: The seven-day intrusion diary is assumed to validly measure intrusive memories.

May combine two claims.

No increases in brain activity were found in the control group relative to the experimental trauma group in either the implicit or the explicit retrieval task.

“No increases in brain activity were observed in the control group compared to the experimental trauma group, neither in the implicit nor the explicit retrieval task.”

May combine two claims.

In the implicit retrieval task, a bilateral amygdala seed showed greater connectivity with the supplementary motor area, precentral and paracentral lobule for film pictures compared with scrambled pictures, and this connectivity was stronger in control participants than in the experimental trauma group.

“In the implicit retrieval task, PPI analyses with a bilateral amygdala seed revealed a higher connectivity with the supplementary motor area, precentral and paracentral lobule for film pictures > scrambled pictures (p FWE.cluster < 0.05, see Supporting Information Fig. 1), that was significantly stronger in the control group compared to the experimental trauma group.”

May combine two claims.

The trauma film group rated film pictures as more arousing and more negatively valenced than the neutral film group (t(40)=3.5, P=0.001).

“As expected, participants who had seen the traumatic film (experimental trauma group) rated the film pictures as more arousing and negatively valenced as the neutral film group (t (40) 5 3.5 P 5 0.001), see Figure 1B”

May combine two claims.

Activation in the experimental trauma retrieval network predicted later intrusion development in a highly specific manner: retrosplenial cortex activation predicted intrusions when retrieval was implicit, while PCC activation independently predicted intrusive memories under explicit retrieval.

“Finally, we show that activation in the experimental trauma retrieval network predicted later intrusion development in a highly specific manner: While activation in the retrosplenial cortex predicted intrusions when experimental trauma memory retrieval was implicit, activation in the PCC independently predicted intrusive memories under explicit retrieval conditions.”

May combine two claims.

There was overlap between implicit and explicit memory, with the strongest overlap in the PCC.

“However, there was also an overlap between implicit and explicit memory.The strongest overlap of both types of memory retrieval access was observed in the PCC.”

May combine two claims.

Anxiety ratings, arousal ratings, and valence ratings did not contribute to the prediction model.

“Further variables such as anxiety ratings, and arousal and valence ratings did not contribute to the model.”

Classified as probably not a substantial claim.

Earlier PTSD research found altered neural activity during trauma-related stimuli and trauma memory across several brain regions, most notably the amygdala, ventromedial prefrontal cortex, ACC, and insula.

“Previous research focusing on traumatic memory retrieval was mainly conducted in patients with full psychiatric manifestations of PTSD.It revealed altered neural correlates during the presentation of trauma-related stimuli and trauma memory in a variety of brain regions.Most prominent are brain activations in the amygdala, ventromedial prefrontal cortex, anterior cingulate cortex (ACC) and insular”

• cites Pitman et al., 2012Not checked yet

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Classified as probably not a substantial claim.

Participants were randomly assigned to a trauma film group or a control film group.

“Participants were randomly allocated to either a trauma film group or a control film group which was presented inside the MR scanner.”

Classified as probably not a substantial claim. May combine two claims.

Traumatic memories are brought back involuntarily by internal or external cues and are experienced as highly intrusive and distressing.

“Traumatic memories represent a major distress to patients as they are reactivated involuntarily after exposure to internal or external cues.They are rendered highly intrusive and disturbing [APA, 2013].”

• cites APA, 2013Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

The trauma-film paradigm has been validated in more than 70 studies in recent years.

“The trauma-film paradigm was first developed over 50 years ago [Horowitz, 1969;Lazarus, 1964] and has been validated in over 70 studies only in the past years [James et al., 2016].”

• cites James et al., 2016Not checked yet

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May combine two claims.

A prior fMRI study of encoding an experimental traumatic event found activity in the amygdala, striatum, thalamus, and ACC, and these regions predicted later experimental trauma intrusions.

“Concerning the neural correlates in analogue studies, there has only been one functional magnetic resonance imaging (fMRI) study focusing on the encoding of an experimental traumatic event itself [Bourne et al., 2013].Neural correlates during encoding involved brain regions of the amygdala, striatum, thalamus and anterior cingulate cortex.These brain regions significantly predicted development of”

• cites Bourne et al., 2013Not checked yet

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Classified as probably not a substantial claim. May combine two claims.

PTSD can be understood as a disorder of memory, with traumatic memories insufficiently integrated into the autobiographical memory network.

“In sum, several theoretical accounts describe PTSD as a memory disorder [Brewin, 2014], mainly associated with a reduced integration of traumatic memories in the autobiographical memory network.”

• cites Brewin, 2014Not checked yet

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May combine two claims.

Traumatic memories are a central symptom of PTSD and are involved in the disorder's onset and persistence.

“Traumatic memories are a crucial symptom of posttraumatic stress disorder (PTSD) and play a major role in the development and maintenance of PTSD [APA, 2013;Elbert and Schauer, 2002;Michael et al., 2005].”

• cites APA, 2013Not checked yet

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• cites Elbert and Schauer, 2002Not checked yet

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• cites Michael et al., 2005Not checked yet

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May combine two claims.

The trauma-film paradigm reliably produces responses in healthy people that resemble real-life trauma, including core PTSD symptoms such as physiological arousal, intrusive memories, negative cognitions, and negative mood.

“Responses comparable to real-life trauma have been systematically observed in healthy subjects after an experimental trauma (i.e., trauma film) [James et al., 2016].Responses include hallmark symptoms of PTSD [James et al., 2016].Specifically, physiological arousal, intrusive memories, negative cognitions and mood have been reported [APA, 2013;Butler et al., 1995;Holmes et al., 2004;James et al.,”

• cites James et al., 2016Not checked yet

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• cites APA, 2013Not checked yet

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• cites Butler et al., 1995Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

A meta-analysis of PTSD trauma memory found greater activation in the retrosplenial cortex, precuneus, ACC, and amygdala.

“A recent meta-analysis of trauma memory in PTSD revealed an increased activation in the retrosplenial cortex, precuneus, ACC and amygdala [Sartory et al., 2013].”

• cites Sartory et al., 2013Not checked yet

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May combine two claims.

People with PTSD tend to show stronger recall of trauma-related cues, altered autobiographical memory retrieval to cue words, and enhanced implicit memory in complex tasks.

“PTSD patients typically exhibit an enhanced recall of trauma-related stimuli, an altered retrieval of autobiographical memories in response to cue words and also show an enhanced implicit memory in complex tasks.[McNally, 1997].”

• cites McNally, 1997Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Three participants were excluded because of technical problems, leaving 42 healthy female participants in the analyzed sample.

“Due to technical problems, three participants had to be discarded from the experiment (one participant fell asleep in the scanner and data of two participants could not be analyzed due to technical difficulties), leaving forty-two healthy participants in the sample (mean age 23.3, range 19-33 years).”

Probably not a substantial claim: may not pass S3 (load-bearing).

In PTSD patients, implicit processing of trauma stimuli during a working memory task with trauma-related distractors was linked to greater activity in the fusiform gyrus, ventrolateral prefrontal cortex, and amygdala.

“Moreover, patients who implicitly processed trauma stimuli exhibited an increased activation in the amygdala, ventrolateral prefrontal cortex and fusiform gyrus [Morey et al., 2009] in a working memory task with traumarelated distractors.”

• cites Morey et al., 2009Not checked yet

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May combine two claims.

In PTSD patients, explicit trauma focus during script-driven imagery was linked to greater activation in the thalamus, ACC, and medial frontal gyrus, and to stronger connectivity in the PCC, parietal lobe, and occipital lobe, especially on the right.

“In contrast, patients who explicitly focused on a trauma during a script-driven imagery task exhibited increased brain activation in thalamus, ACC and medial frontal gyrus and enhanced connectivity in the posterior cingulate cortex (PCC), parietal lobe and occipital lobe, specifically in the right hemisphere [Lanius et al., 2001[Lanius et al., , 2004]].”

• cites Lanius et al., 2001Not checked yet

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• cites Lanius et al., 2004Not checked yet

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Classified as probably not a substantial claim.

Statistical significance was defined as p FWE.cluster < 0.05 with a cluster-defining threshold of P = 0.001.

“Statistical significance was set at p FWE.cluster < 0.05, with a cluster defining threshold (CDT) of P 5 0.001 [Eklund et al., 2016].”

• cites Eklund et al., 2016Not checked yet

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Probably not a substantial claim: may not pass S4 (based).

Before this study, the brain areas and processes involved in early retrieval of traumatic memories and their link to intrusion development had not been identified.

“In contrast, brain areas and processes involved in early retrieval attempts of traumatic memories and their relation to traumatic intrusion development as a predictor variable have not yet been identified.”

May combine two claims.

Symptoms after an experimental trauma last only hours or days and decline within one week.

“However, in contrast to PTSD, symptoms after an experimental trauma only last for hours or days and finally decrease within one week [Holmes et al., 2004;James et al., 2016].”

• cites Holmes et al., 2004Not checked yet

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• cites James et al., 2016Not checked yet

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May combine two claims.

Witnessing trauma can cause behavioral impairments in rats and can lead to PTSD in humans.

“Witnessing trauma can result in behavioral impairments in both rats [Patki et al., 2014] and humans [Al-Nuaimi et al., 2015;Atwoli et al., 2015].”

• cites Patki et al., 2014Not checked yet

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• cites Al-Nuaimi et al., 2015Not checked yet

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• cites Atwoli et al., 2015Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Freezing or fainting during trauma exposure and reliving can be observed in PTSD patients, as suggested by dissociation theories.

“The displayed phenomenon can be observed in PTSD patients, where freezing or fainting occurs during trauma exposure and reliving, as suggested by dissociations theories in PTSD [Schauer and Elbert, 2010].”

• cites Schauer and Elbert, 2010Not checked yet

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Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

A possible intervention targeting memory integration may be found by enhancing memory consolidation and integration during sleep.

“A possible intervention that targets memory integration can be potentially found by enhancing memory consolidation and integration during sleep [Kleim et al., 2016;Stickgold, 2002].”

• cites Kleim et al., 2016Not checked yet

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• cites Stickgold, 2002Not checked yet

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May combine two claims.

Retrosplenial cortex and precuneus appeared specific to experimental trauma material, whereas ACC and PCC were more associated with overall heightened responses to negative stimuli during the implicit memory task.

“Interestingly, the retrosplenial cortex and precuneus seem to be specific for the experimental trauma material, whereas the ACC and PCC were rather associated with overall heightened responses to negative stimuli during the implicit memory task.”

Probably not a substantial claim: may not pass S2 (checkable).

With identification of the relevance of PCC and retrosplenial cortex, preventive and targeted treatment can be developed.

“With the identification of the relevance of PCC and retrosplenial cortex, preventive and targeted treatment can be developed.”

Classified as probably not a substantial claim.

The ACC has been associated with detection of unfavorable outcomes, response errors, response conflict, and decision uncertainty.

“Interestingly, the ACC has been associated with detection of unfavorable outcomes, response errors, response conflict and decision uncertainty [Ridderinkhof et al., 2004]”

• cites Ridderinkhof et al., 2004Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

The PCC has been reported to be involved in processing emotional salience.

“Furthermore, the PCC has been reported to be implicated in the processing of emotional salience [Maddock et al., 2003].”

• cites Maddock et al., 2003Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Both PCC and retrosplenial cortex have been proposed as mediators of the interaction between emotions and memory.

“Both the PCC and the retrosplenial cortex have been proposed as mediators for the interaction between emotions and memory [Maddock, 1999;Maddock et al., 2003].”

• cites Maddock, 1999Not checked yet

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• cites Maddock et al., 2003Not checked yet

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May combine two claims.

Both implicit and explicit experimental trauma memory retrieval activities significantly predicted later intrusion development, but they explained distinct aspects of the variance.

“Thus, both brain activities during implicit and explicit experimental trauma memory retrieval significantly predict later intrusion development, but they explain distinct aspects of the variance.”

May combine two claims.

This absence of amygdala activation applied to both implicit and explicit retrieval and might indicate stronger emotional reactivation during exposure to traumatic cues in patients compared with healthy females.

“This accounts for both implicit and explicit retrieval, which might point to a stronger emotional reactivation during exposure to traumatic cues in patients compared to healthy females.”

May combine two claims.

The decrease in amygdala-SMA connectivity was observed only in the control > experimental trauma contrast and therefore cannot be uniquely ascribed to the effects of the trauma film.

“Moreover, the decrease in connectivity has only been observed in the control > experimental trauma contrast and therefore cannot be uniquely ascribed to the effects of the trauma film.”

Classified as probably not a substantial claim.

When fight or flight is impossible, reduced supplementary motor area activity can be seen as a consequence of that inability.

“In case of an inability to either fight or flee, less activity in the supplementary motor area can be seen as a consequence of this inability.”

Classified as probably not a substantial claim.

The supplementary motor area has been associated with readiness for action in previous literature.

“The supplementary motor area has been associated with readiness for action in previous literature [Cunnington et al., 2005].”

• cites Cunnington et al., 2005Not checked yet

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May combine two claims.

All identified brain regions have previously been implicated in retrieval of trauma memories in PTSD patients; a meta-analysis reported activation in retrosplenial cortex, precuneus, and ACC.

“Importantly, all of the identified brain regions have been previously implicated also in retrieval of trauma memories in patients suffering from PTSD: A recent meta-analysis of trauma memory in PTSD patients with full psychiatric manifestation reported also activation in the retrosplenial cortex, precuneus, and ACC [Sartory et al., 2013].”

• cites Sartory et al., 2013Not checked yet

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Probably not a substantial claim: may not pass S2 (checkable).

A possible change in activity in these brain regions might be highly relevant for early intervention strategies.

“a possible change in activity in these brain regions might be highly relevant for early intervention strategies.”

May combine two claims.

The experimental trauma memory retrieval network depended on retrieval type: implicit and automatic retrieval activated retrosplenial cortex, precuneus, ACC, and PCC, while explicit and intentional retrieval activated PCC and precuneus.

“In addition, this experimental trauma memory retrieval network also depended on the type of retrieval access: while implicit and automatic retrieval activated the retrosplenial cortex, precuneus and the ACC as well as PCC, explicit and intentional retrieval activated the PCC and the precuneus.”

May combine two claims.

Increased participation of brain regions involved in long-term memory storage might avoid or reduce overconsolidation and decontextualisation, which might underlie intrusive and uncontrollable traumatic memories.

“Increased participation of the brain regions involved in long-term memory storage might thereby avoid or at least reduce the chance of distinct”

May combine two claims.

The study was not able to address whether pre-existing neural differences affect processing, which limits relevance of findings.

“As we were not able to address this topic in our study, this further limits the relevance of our findings.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The retrosplenial cortex and PCC have been strongly implicated in self-referential processing and episodic memory encoding and retrieval, particularly autobiographical memories.

“Particularly the retrosplenial cortex and the PCC have been strongly implicated in selfreferential processing as well as in episodic memory encoding and retrieval, more precisely with respect to autobiographical memories [Foster et al., 2013;Maddock et al., 2001].”

• cites Foster et al., 2013Not checked yet

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• cites Maddock et al., 2001Not checked yet

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May combine two claims.

This network was specific to experimental trauma memory retrieval because activation depended on having a memory representation of the traumatic film: it occurred only in participants who saw and witnessed traumatic scenes, not in controls who saw neutral scenes from the same film and did not witness a traumatic event.

“This network was specific for retrieval of experimental trauma memories, as the activation in this network critically depended on the existence of memory representation of the traumatic film: The activation only occurred in participants that saw and witnessed traumatic scenes compared to a control group that was presented with neutral scenes from the same film and thus”

• Also stated in: § DISCUSSION · plain

  “did not witness a traumatic event.”