Phasic and sustained fear in humans elicits distinct patterns of brain activity

May combine two claims.

Transient activation of the ventral amygdala to unpredictable threat was present but not statistically significant after correction.

“Transient activation of the ventral amygdala was present but not statistically significant after correction.”

May combine two claims.

There were no significant differences in sustained activity in the extended amygdala between unpredictable and predictable contexts, or between predictable and no-shock contexts.

“We found no significant differences in sustained activity in the extended amygdala between unpredictable and predictable contexts, or predictable and no-shock contexts (Table 1).”

May combine two claims.

The unpredictable context produced larger SCRs than the no-shock context; its SCR difference from the predictable context was marginal (P=0.09).

“and that the unpredictable context (Ucxt) [ANX: 7.3 (0.3); SCR: 0.33 (0.06)] was more anxiogenic than the no-shock context (Ncxt) [ANX: 0.7 (0.2); t17=18.5, P<0.001; SCR: 0.14 (0.03); t17=4.8, P<0.001] and predictable context (Pcxt) [ANX: 4.3 (0.5); t17=7.7, P<0.001; SCR: 0.26 (0.04); t17=1.8, P=0.09].”

May combine two claims.

Follow-up analyses showed increased transient activity in response to unpredictable threat was significant in the right dorsal amygdala but not the left.

“Follow-up analyses indicated that increased transient activity in response to unpredictable threat was significant in the right dorsal amygdala but not the left (Fig. 5A; left, t17=0.58; P=0.57; right, t17=2.57; P=0.02).”

May combine two claims.

The predictable context generated sustained increased activity in superior and middle frontal cortex, and sustained decreased activity in the cerebellum and medial orbital cortex relative to the no-shock context.

“The predictable context also generated sustained increased activity in superior and middle frontal cortex, and sustained decreased activity in the cerebellum and medial orbital cortex relative to the no-shock context (Table 2).”

May combine two claims.

With the outlier removed, the difference in sustained activity between Ucxt and Ncxt was significant in bilateral dorsal BNST and left dorsal BNST, but not right.

“With this value temporarily removed from the analysis, the difference in sustained activity between Ucxt and Ncxt was significant in bilateral dorsal BNST (t16=2.27, P=0.037) and left dorsal BNST (left, t16=2.89, P=0.011; right, t16=1.44, P=0.17).”

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

Subjects rated the shock level used in the study as moderately painful (mean 3.4, SD 0.4) on a 1-5 scale.

“Subjects rated the shock level used in the study as moderately painful (mean=3.4; SD=0.4) based on a 1–5 scale (1, not at all; 3, moderately; 5, extremely).”

May combine two claims.

The peak coordinates of right BNST activation for predictable threat were identical to those for unpredictable threat onset, while left BNST coordinates were slightly more posteromedial and ventral.

“The peak coordinates of the right BNST (9 0 10) activation were identical to those associated with the onset of unpredictable threat, but the peak coordinates of the left BNST (−6 0 6) activation were slightly more posteromedial and ventral compared to those associated with unpredictable threat onset (−9 2 10 ).”

May combine two claims.

Unpredictable threat elicited sustained increased activity in anterior insula, frontal (superior, inferior, middle, frontopolar), inferior parietal cortical regions, and mid-cingulate.

“We also found sustained increased activity in anterior insula, frontal (superior, inferior, middle, frontopolar) and inferior parietal cortical regions, and the mid-cingulate (Table 2, Fig. 4C and D).”

May combine two claims.

No significant differences were found in sustained activity in dorsal BNST between unpredictable and predictable contexts, or predictable and no-shock contexts.

“As in the voxel-wise analyses, no significant differences were found in sustained activity in dorsal BNST between unpredictable and predictable contexts (Ucxt>Pcxt, t17=1.13, P=0.28), or predictable and no-shock contexts (Pcxt>Ncxt, t17=0.75, P=0.47).”

May combine two claims.

With the outlier removed, the linear trend in sustained activity across contexts was significant in bilateral dorsal BNST and left dorsal BNST, but not right.

“Note that with the previously indentified “outlier” removed from the analysis, the linear trend in sustained activity across contexts was significant in bilateral dorsal BNST (F(1, 16)=5.17, P=0.037) and left dorsal BNST (left; F(1, 16)=8.37, P=0.010; right, F(1, 16)=2.07, P=0.169).”

May combine two claims.

Both predictable and unpredictable threat contexts evoked transient activity in sACC, and thereafter unpredictable threat contexts were associated with a greater sustained decrease in sACC activity.

“Whereas both predictable and unpredictable threat contexts evoked transient activity in sACC, thereafter unpredictable threat contexts were associated with a greater sustained decrease in sACC activity.”

May combine two claims.

Rodent data suggest phasic fear responses rely on the central nucleus of the amygdala, which in humans is located in the dorsal part of the amygdala.

“Rodent data suggest that phasic fear responses rely on the central nucleus of the amygdala (CeA), which in humans is located in the dorsal part of the amygdala (Amunts et al., 2005)”

• cites Walker and Davis, 2008 sourceNot checked yet

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• cites Amunts et al., 2005 sourceNot checked yet

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May combine two claims.

A brief discrete cue that predictably signals imminent threat evokes rapid phasic fear and active defensive responses.

“a brief, discrete cue that predictably signals an imminent threat evokes a rapid apprehensive state (phasic fear) that diminishes quickly once the threat is terminated”

• cites Fanselow, 1994 sourceNot checked yet

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• cites Grillon, 2008 sourceNot checked yet

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Classified as probably not a substantial claim.

Animal models of sustained fear posit that cortical inputs from the insula may underlie sustained fear, possibly mediating cognitive components of anxious apprehension.

“animal models of sustained fear posit that cortical inputs from the insula may also underlie sustained fear, possibly mediating cognitive components of anxious apprehension (Davis et al., 2010b).”

• cites Davis et al., 2010bNot checked yet

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• cites McDonald et al., 1999 sourceNot checked yet

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

Human neuroimaging studies have implicated the amygdala in fear acquisition and extinction.

“neuroimaging studies in humans have likewise implicated the amygdala in fear acquisition and extinction (Buchel et al., 1998; LaBar et al., 1998; Milad et al., 2007; Phelps et al., 2004)”

• cites Buchel et al., 1998 sourceNot checked yet

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• cites LaBar et al., 1998 sourceNot checked yet

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• cites Milad et al., 2007 sourceNot checked yet

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Classified as probably not a substantial claim.

Somerville et al. (2010) recently examined the role of the bed nucleus of the stria terminalis in anxiety-related vigilance.

“However, Somerville et al. (2010) recently examined the role of the BNST in anxious-related vigilance.”

• cites Somerville et al. (2010) sourceNot checked yet

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Classified as probably not a substantial claim.

Rodent data suggest that highly related but partially distinct functional neuroanatomical networks may underlie phasic and sustained fear.

“Rodent data suggest that highly related but partially distinct functional neuroanatomical networks may underlie phasic and sustained fear (Davis et al., 2010b).”

• cites Davis et al., 2010bNot checked yet

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May combine two claims.

The study used a well-validated instructed threat procedure and neuroimaging methods that assured good signal detection of transient cue- and context-related responses and sustained context-related responses in the basal forebrain.

“We tested these predictions using a well-validated instructed threat procedure (Davis et al., 2010b; Grillon et al., 2004), and neuroimaging methods that assured good signal detection of transient cue- and context-related responses, as well as sustained context-related responses in the basal forebrain.”

• cites Davis et al., 2010bNot checked yet

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• cites Grillon et al., 2004 sourceNot checked yet

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May combine two claims.

Sustained fear responses depend on the bed nucleus of the stria terminalis, located in the ventromedial basal forebrain and receiving input from the central nucleus of the amygdala and the basolateral amygdala complex.

“sustained fear responses are dependent on the bed nucleus of the stria terminalis (BNST), which is located in the ventromedial basal forebrain and receives input from the CeA and the more ventrally located basolateral amygdala complex (BLC) (Walker and Davis, 2008)”

• cites Walker and Davis, 2008 sourceNot checked yet

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

Hasler et al. (2007) found that a visual threat cue increased cerebral blood flow in the left amygdala relative to a comparable safe cue.

“Hasler et al. (2007) found that a visual threat cue increased cerebral blood flow in the left amygdala relative to a comparable safe cue.”

• cites Hasler et al. (2007) sourceNot checked yet

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

The central nucleus of the amygdala and the bed nucleus of the stria terminalis project to the same neural mediators of fear symptoms, so each component of the extended amygdala can generate defensive responses.

“Because the CeA and BNST project to the same neural mediators of fear symptoms, each of these components of the extended amygdala are capable of generating defensive responses (Davis and Whalen, 2001).”

• cites Davis and Whalen, 2001 sourceNot checked yet

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

Anterior insula has strong projections to medial prefrontal cortical regions associated with regulation of emotions and visceral reactions.

“an area that also has strong projections to medial prefrontal cortical regions associated with the regulation of emotions and visceral reactions (Price and Drevets, 2010).”

• cites Price and Drevets, 2010 sourceNot checked yet

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May combine two claims.

Phelps et al. (2001) found that a threat cue, relative to a safe cue, evoked enhanced arousal and fear indexed by skin conductance and rapid short-lasting activation in left dorsal amygdala, even though no shocks were administered.

“Though no shocks were ever administered, the threat cue evoked enhanced arousal and fear as indexed by skin conductance, and relative to the safe cue, produced a rapid and short-lasting activation in left dorsal amygdala.”

• cites Phelps et al. (2001) sourceNot checked yet

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

LPC cost functional alignment provides superior spatial alignment between T2*- and T1-weighted images near ventricles compared to generic cost functionals.

“compared to generic cost functionals, provides superior spatial alignment between T2*- and T1-weighted images in brain structures near the ventricles (Saad et al., 2009).”

• cites Saad et al., 2009 sourceNot checked yet

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May combine two claims.

A multi-element surface coil array and parallel imaging allowed whole-brain fMRI at about four times higher spatial resolution (1.7 × 1.7 × 3.5 mm3) with enough sensitivity to detect BOLD signal changes.

“This allowed us to conduct whole-brain fMRI at roughly 4 times higher spatial resolution (1.7 × 1.7 × 3.5 mm3) and still have enough sensitivity to detect BOLD signal changes (Bodurka et al., 2007).”

• cites Bodurka et al., 2004 sourceNot checked yet

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• cites Bodurka et al., 2007 sourceNot checked yet

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Probably not a substantial claim: may not pass S1 (asserted).

Animal models of sustained fear hypothesize that a part of the CeA different from that involved in phasic fear may be transiently involved in initiating sustained fear.

“Because animal models of sustained fear hypothesize that a part of the CeA different from that involved in phasic fear may be transiently involved in initiating sustained fear (Davis et al., 2010b), we tested for a transient fear response to unpredictable threat in bilateral dorsal amygdala.”

• cites Davis et al., 2010bNot checked yet

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

A log transformation and range correction were performed to normalize the distribution and reduce error variance.

“A log transformation (log [1 + SCR]) was performed to normalize the distribution, and the magnitudes were range corrected (SCR/SCRmax) for each subject to attain statistical normality and to reduce error variance (Lykken and Venables, 1971).”

• cites Lykken and Venables, 1971Not checked yet

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Classified as probably not a substantial claim.

Statistical conclusions concerning the extended amygdala were based on small volume correction for multiple tests.

“statistical conclusions concerning the extended amygdala were based on small volume correction (SVC) for multiple tests (Worsley et al., 1996).”

• cites Worsley et al., 1996 sourceNot checked yet

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

Anatomical delineation of the BNST used a standardized protocol by a trained research assistant blind to subjects' identity, and adherence was assessed by the first author.

“Anatomical delineation of the BNST was performed using a standardized protocol by a trained research assistant blind to the subjects' identity and adherence to the protocol was assessed by the first author.”

May combine two claims.

The results confirm that under predictable threat, the cue elicited a phasic apprehensive state greater than other cues and greater than the predictable context without a cue.

“These results also confirm that under predictable threat, the cue elicited a phasic apprehensive state that was greater than that elicited by other cues, and greater than the predictable context in the absence of a cue.”

May combine two claims.

The absence of cues in the predictable context may have signaled relative safety, but the predictable context was not safe in an absolute sense because it was associated with cue-related shock.

“Therefore, the absence of cues in Pcxt may have signaled relative safety; however, unlike Ncxt, Pcxt was not a safe context in an absolute sense because Pcxt was associated with cue-related shock, much like the context in background contextual conditioning studies (Calandreau et al., 2005).”

• cites Calandreau et al., 2005 sourceNot checked yet

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

AlphaSim correction resulted in a minimum cluster size threshold of 40 mm3 for the extended amygdala and 120 mm3 for other brain regions.

“The above correction procedures resulted in a minimum cluster size threshold of 40 mm3 for the extended amygdala, and a minimum cluster size threshold of 120 mm3 for all other brain regions.”

Classified as probably not a substantial claim.

EPI data were not spatially filtered or smoothed to optimize detection of fMRI signal changes from small brain structures and avoid reduction in spatial resolution.

“To optimize our ability to detect fMRI signal changes from small brain structures and to avoid any reduction in spatial resolution, we did not spatially filter or smooth the EPI data.”

Classified as probably not a substantial claim.

Context onset was unlikely to be associated with any specific cue within a context because entry occurred at several locations.

“Since entry into each context occurred at several locations within the VR environment, it is unlikely that the onset of a context would be associated with any specific cue within a context.”

May combine two claims.

Imaging at higher spatial resolution can decrease partial volume effects but can reduce MRI signal-to-noise ratio.

“Imaging at a higher spatial resolution can decrease partial volume effects but can come at the cost of a reduced MRI signal-to-noise ratio (SNR) (Edelstein et al., 1986).”

• cites Edelstein et al., 1986 sourceNot checked yet

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

Retrospective fear ratings obtained immediately after scanning were used to confirm understanding of the threat instructions.

“Retrospective fear ratings obtained immediately following scanning were used to confirm understanding of the threat instructions.”

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

Previous studies of instructed fear using simple threat cues have associated phasic fear responses with a left hemisphere bias.

“Previous studies of instructed fear using simple threat cues (e.g., colored squares) have associated phasic fear responses with a left hemisphere bias (Phelps et al., 2001; Funayama et al., 2001; Hasler et al., 2007).”

• cites Phelps et al., 2001 sourceNot checked yet

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• cites Funayama et al., 2001 sourceNot checked yet

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• cites Hasler et al., 2007 sourceNot checked yet

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

Four subjects were excluded because of excessive shock-related head motion (n=1), failure of the shock delivery system (n=2), and scanner malfunction (n=1).

“Besides the 18 subjects included in the study, 4 were excluded because of excessive shock-related head motion (n=1), failure of the shock delivery system (n=2), and scanner malfunction (n=1).”

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

All subjects exhibited minimal head motion during imaging (mean 2.1 mm, SD 1.6).

“All subjects in the study exhibited minimal head motion during imaging (mean= 2.1 mm, SD=1.6).”

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

Similarly constructed VR stimuli are effective for studying context manipulations in the MRI environment.

“Previous research in our laboratory has shown that similarly constructed VR stimuli are effective for studying context manipulations in the MRI environment (Alvarez et al., 2008).”

• cites Alvarez et al., 2008 sourceNot checked yet

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

To ensure subjects understood the threat procedure, they were exposed to the VR contexts and tone before the study and required to paraphrase the shock and no-shock contingencies.

“To ensure that subjects understood the threat procedure, they were exposed to the VR contexts and tone prior to the study, and were required to paraphrase the shock and no-shock contingencies.”

Classified as probably not a substantial claim.

Quality of coregistration between EPI and anatomical datasets was visually verified for each subject.

“The quality of coregistration between EPI and anatomical datasets was visually verified for each subject.”

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

Context assignment was counterbalanced across subjects for which environment was associated with predictable versus unpredictable shock; the restaurant was always the no-shock context.

“Context assignment was reversed for the remaining subjects so as to counterbalance across subjects which environment was associated with predictable and unpredictable shock; the virtual restaurant was always the no-shock context.”

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

SCRs contaminated by a shock or an early cue were omitted from analyses, so SCR data were not affected by nuisance factors.

“SCRs to cue and context onset that were contaminated by a shock, or an early cue in the case of a context, were omitted from analyses, assuring that the SCR data were not affected by nuisance factors.”

May combine two claims.

Phasic and sustained fear in humans may manifest similar signs of distress but appear associated with different patterns of neural activity in the human basal forebrain.

“these results provide evidence that phasic and sustained fear in humans may manifest similar signs of distress, but appear to be associated with different patterns of neural activity in the human basal forebrain.”

Classified as probably not a substantial claim.

Because subjects were forewarned of the threat associated with each cue, subjects encountering a predictable cue would be expected to engage in conscious appraisal of imminent threat.

“Because subjects in the present study were forewarned of the threat associated with each cue, subjects encountering a predictable cue would be expected to engage in conscious appraisal of imminent threat.”

Classified as probably not a substantial claim.

Previous studies show a rapid reduction in amygdala activation over time in fear conditioning and threat of shock.

“It is also consistent with previous studies showing a rapid reduction in amygdala activation over time in fear conditioning (Buchel et al., 1998; LaBar et al., 1998) and threat of shock (Phelps et al., 2001).”

• cites Buchel et al., 1998 sourceNot checked yet

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• cites LaBar et al., 1998 sourceNot checked yet

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• cites Phelps et al., 2001 sourceNot checked yet

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Classified as probably not a substantial claim.

Studies in rodents, primates, and humans demonstrate a role for the CeA in mediating behavioral and physiological responses evoked by conditioned and unconditioned stimuli including contexts.

“This result is consistent with studies in rodents, primates, and humans that demonstrate a role for the CeA in mediating behavioral and physiological responses evoked by conditioned and unconditioned stimuli including contexts (Davis and Whalen, 2001; Kalin et al., 2004; LeDoux, 2000).”

• cites Davis and Whalen, 2001 sourceNot checked yet

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• cites Kalin et al., 2004 sourceNot checked yet

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• cites LeDoux, 2000 sourceNot checked yet

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

Any conclusions regarding fMRI signals in the CeA must remain tentative.

“Hence, any conclusions regarding fMRI signals in the CeA must remain tentative.”

May combine two claims.

Research indicates that the BLC is well positioned to receive incoming sensory information concerning threats and to convey this information to output areas including the CeA and BNST.

“This conjecture is supported by research indicating that the BLC is well positioned to receive incoming sensory information concerning threats in the environment, and to convey this information to output areas including the CeA and BNST (Amaral et al., 1992; Dong et al., 2001).”

• cites Amaral et al., 1992Not checked yet

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• cites Dong et al., 2001 sourceNot checked yet

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

The null finding is perplexing considering that ROIs typically increase the power to detect an effect.

“This null finding is perplexing considering that ROIs typically increase the power to detect an effect.”

Classified as probably not a substantial claim.

The posterior cingulate and precuneus are part of a cortical midline network associated with self-referential processing in the spatial domain.

“The posterior cingulate and precuneus are part of a cortical midline network associated with self-referential processing in the spatial domain (Northoff et al., 2006)”

• cites Northoff et al., 2006 sourceNot checked yet

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

It has been suggested that anterior insula might mediate cognitive aspects of worry.

“It has been suggested that anterior insula might mediate cognitive aspects of worry (Walker and Davis, 2008).”

• cites Walker and Davis, 2008 sourceNot checked yet

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

According to this model, cortical and subcortical input converge on the basolateral amygdala and lateral CeA, which project to the lateral BNST and trigger a cascade of neurochemical release, resulting in a relatively long-lasting apprehensive state.

“According to this model, cortical and subcortical input converge on the basolateral amygdala and lateral CeA, which in turn project to the lateral BNST and trigger a cascade of neurochemical release, resulting in a relatively long-lasting apprehensive state.”

• cites Davis et al., 2010bNot checked yet

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

The supracapsular BNST is a small basal forebrain structure that is relatively well developed in humans.

“The supracapsular BNST is a small basal forebrain structure that is relatively well developed in humans (Strenge et al., 1977).”

• cites Strenge et al., 1977Not checked yet

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

A comparable area of the BNST has been associated with hypervigilant threat monitoring.

“A comparable area of the BNST has been associated with hypervigilant threat monitoring (Somerville et al., 2010).”

• cites Somerville et al., 2010 sourceNot checked yet

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May combine two claims.

Imminent threats likely evoke greater phasic fear than temporally unpredictable threats, but the latter may give rise to greater vigilance.

“suggesting that imminent threats likely evoke greater phasic fear than temporally unpredictable threats, but the latter may give rise to greater vigilance.”

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

Straube et al. (2007) interpreted their finding as evidence for BNST involvement in anticipatory anxiety because enhanced activity occurred during an anticipatory period of 10-28 s.

“Because enhanced activity in the BNST occurred during an anticipatory period of 10–28 s, Straube et al. (2007) interpreted their finding as evidence for BNST involvement in anticipatory anxiety.”

• cites Straube et al. (2007) sourceNot checked yet

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

This proposal is compatible with a recently described neural model of sustained fear.

“This proposal is compatible with a recently described neural model of sustained fear (Davis et al., 2010b).”

• cites Davis et al., 2010bNot checked yet

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May combine two claims.

The supracapsular and lateral BNST share a similar cellular and neurochemical makeup, and the supracapsular BNST merges into and shares afferent and efferent pathways with the lateral BNST.

“The supracapsular and lateral BNST share a similar cellular and neurochemical makeup, and the supracapsular BNST merges into and shares afferent and efferent pathways with the lateral BNST (Shammah-Lagnado et al., 2000)”

• cites Shammah-Lagnado et al., 2000 sourceNot checked yet

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Classified as probably not a substantial claim.

Conscious appraisal processes have been hypothesized to involve a neural circuit including the dmPFC/dACC.

“Conscious appraisal processes have been hypothesized to involve a neural circuit including the dmPFC/dACC (Mechias et al., 2010).”

• cites Mechias et al., 2010 sourceNot checked yet

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Classified as probably not a substantial claim.

This may account for the dynamic pattern of activation observed in sACC in response to unpredictable threat.

“This may account for the dynamic pattern of activation observed in sACC in response to unpredictable threat.”

May combine two claims.

Contexts that signal a longer duration threat initially elicit transient activity in the ventral amygdala/hippocampus and dorsal amygdala, with the former structures possibly being responsible for activation of the latter.

“Contexts that signal a longer duration threat initially elicit transient activity in the ventral amygdala/hippocampus and dorsal amygdala, with the former structures possibly being responsible for activation of the latter.”

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

Subgenual anterior cingulate cortex is central to the medial prefrontal network associated with mood and anxiety dysregulation and implicated in regulation of visceral responses during stress and anxiety.

“Subgenual anterior cingulate cortex (sACC) is central to the medial prefrontal network that has been associated with mood and anxiety dysregulation, and has been implicated in the regulation of visceral responses during stress and anxiety (Price and Drevets, 2010).”

• cites Price and Drevets, 2010 sourceNot checked yet

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May combine two claims.

Long-duration states of anxiety engender hypervigilance mediated by frontoparietal networks, and modulation of visceral function via mechanisms within anterior insula, pACC and sACC.

“In addition, we suggest that long-duration states of anxiety engender hypervigilance mediated by frontoparietal networks, and modulation of visceral function via mechanisms within anterior insula, pACC and sACC.”

Classified as probably not a substantial claim.

Frontoparietal areas are involved in sustained attention.

“The finding that unpredictable threat induced sustained activity of frontoparietal areas involved in sustained attention (Pardo et al., 1991), is consistent with previous neuroimaging studies linking unpredictable threat to hypervigilance (Carlsson et al., 2006; Hasler et al., 2007).”

• cites Pardo et al., 1991 sourceNot checked yet

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

pACC differs from sACC in its cytological and transmitter receptor architecture.

“In the present study, unpredictable threat contexts compared to predictable threat contexts elicited greater transient activity in pregenual anterior cingulate cortex (pACC), a cingulate subregion that differs from sACC in its cytological and transmitter receptor architecture (Palomero-Gallagher, et al., 2008).”

• cites Palomero-Gallagher, et al., 2008 sourceNot checked yet

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May combine two claims.

The activations observed in the medial prefrontal network are consistent with previous imaging studies implicating medial prefrontal cortex in distal threat, and suggest that contextually induced sustained anxiety may involve complex oscillations in neural activity in key prefrontal regions such as pACC and sACC.

“Although the medial prefrontal network was not the focus of this study, the activations observed in this network are consistent with previous imaging studies implicating medial prefrontal cortex in distal threat (Mobbs et al., 2009), and suggest that contextually induced sustained anxiety may involve complex oscillations in neural activity in key prefrontal regions such as pACC and sACC.”

• cites Mobbs et al., 2009 sourceNot checked yet

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

Previous neuroimaging findings indicate that contextual fear conditioning elicits sustained activity in anterior insula.

“Previous neuroimaging findings indicating that contextual fear conditioning elicits sustained activity in anterior insula are consistent with this interpretation (Alvarez et al., 2008).”

• cites Alvarez et al., 2008 sourceNot checked yet

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May combine two claims.

The present study conducted whole-brain fMRI at about 4 times higher spatial resolution than typical fMRI studies, yet still had sufficient sensitivity to detect small signal changes in the basal forebrain.

“Notwithstanding the limitations of this investigation, the present study took advantage of recent advances in fMRI data acquisition and processing, allowing us to conduct whole-brain fMRI at about 4 times higher spatial resolution than typical fMRI studies, yet still have sufficient sensitivity to detect small signal changes in the basal forebrain.”

Classified as probably not a substantial claim.

Clinical studies indicate that metabolism in sACC is elevated in the depressed phase relative to the remitted phase of the same patients with major depressive disorder.

“Clinical studies indicate that metabolism in sACC is elevated in the depressed phase relative to the remitted phase of the same patients with major depressive disorder (Drevets et al., 2008).”

• cites Drevets et al., 2008 sourceNot checked yet

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May combine two claims.

Predictable and unpredictable threats can induce phasic and sustained fear in humans, and these apprehensive states elicit distinct patterns of activation in the basal forebrain including, potentially, the extended amygdala.

“To sum up, the present study suggests that predictable and unpredictable threats can induce phasic and sustained fear in humans, and that these apprehensive states elicit distinct patterns of activation in the basal forebrain including, potentially, the extended amygdala.”

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

Previous neuroimaging studies link unpredictable threat to hypervigilance.

“The finding that unpredictable threat induced sustained activity of frontoparietal areas involved in sustained attention (Pardo et al., 1991), is consistent with previous neuroimaging studies linking unpredictable threat to hypervigilance (Carlsson et al., 2006; Hasler et al., 2007).”

• cites Carlsson et al., 2006 sourceNot checked yet

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• cites Hasler et al., 2007 sourceNot checked yet

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Classified as probably not a substantial claim.

The present study provides further support for this hypothesis.

“The present study provides further support for this hypothesis.”

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

Conscious appraisal of predictable threat cues may activate threat evaluation processes in dmPFC/dACC.

“Conscious appraisal of predictable threat cues may activate threat evaluation processes in dmPFC/dACC.”