Elevated response of human amygdala to neutral stimuli in mild post traumatic stress disorder: neural correlates of generalized emotional response

Brunetti, Marcella; Sepede, Gianna; Mingoia, Gianluca; Catani, Claudia; Ferretti, Andrea; Merla, Arcangelo; Gratta, Cosimo Del; Romani, Gian Luca; Babiloni, Claudio

doi:10.1016/j.neuroscience.2010.04.024

Cited by 83 publications

(54 citation statements)

References 33 publications

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“…50 The decreased amygdalar activation during inhibition in TBI participants suggests that emotional salience may play a less prominent role in inhibitory processes for these participants than for non-TBI controls. This is in contrast to studies of persons with PTSD, 51,52 where the opposite pattern is observed (i.e., hyperactivation of the amygdala).…”

Section: Discussioncontrasting

confidence: 98%

Neural Activation during Response Inhibition Differentiates Blast from Mechanical Causes of Mild to Moderate Traumatic Brain Injury

Fischer

Parsons

Durgerian

et al. 2014

Journal of Neurotrauma

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Military personnel involved in Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) commonly experience blastinduced mild to moderate traumatic brain injury (TBI). In this study, we used task-activated functional MRI (fMRI) to determine if blast-related TBI has a differential impact on brain activation in comparison with TBI caused primarily by mechanical forces in civilian settings. Four groups participated: (1) blast-related military TBI (milTBI; n = 21); (2) military controls (milCON; n = 22); (3) non-blast civilian TBI (civTBI; n = 21); and (4) civilian controls (civCON; n = 23) with orthopedic injuries. Mild to moderate TBI (MTBI) occurred 1 to 6 years before enrollment. Participants completed the Stop Signal Task (SST), a measure of inhibitory control, while undergoing fMRI. Brain activation was evaluated with 2 (mil, civ) · 2 (TBI, CON) analyses of variance, corrected for multiple comparisons. During correct inhibitions, fMRI activation was lower in the TBI than CON subjects in regions commonly associated with inhibitory control and the default mode network. In contrast, inhibitory failures showed significant interaction effects in the bilateral inferior temporal, left superior temporal, caudate, and cerebellar regions. Specifically, the milTBI group demonstrated more activation than the milCON group when failing to inhibit; in contrast, the civTBI group exhibited less activation than the civCON group. Covariance analyses controlling for the effects of education and selfreported psychological symptoms did not alter the brain activation findings. These results indicate that the chronic effects of TBI are associated with abnormal brain activation during successful response inhibition. During failed inhibition, the pattern of activation distinguished military from civilian TBI, suggesting that blast-related TBI has a unique effect on brain function that can be distinguished from TBI resulting from mechanical forces associated with sports or motor vehicle accidents. The implications of these findings for diagnosis and treatment of TBI are discussed.

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Section: Discussioncontrasting

confidence: 98%

Neural Activation during Response Inhibition Differentiates Blast from Mechanical Causes of Mild to Moderate Traumatic Brain Injury

Fischer

Parsons

Durgerian

et al. 2014

Journal of Neurotrauma

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“…Possibly, PTSD patients may be specifically sensitive to show greater amygdala responsiveness to the neutral, socially ambiguous faces in the happy-neutral condition. Indeed, a previous study showed elevated amygdala responses towards neutral pictures in PTSD patients compared with trauma-exposed controls (Brunetti et al, 2010). In addition, we found that PTSD patients with higher state anxiety showed more amygdala reactivity especially toward happy-neutral faces under placebo.…”

Section: Discussionsupporting

confidence: 60%

Intranasal Oxytocin Administration Dampens Amygdala Reactivity towards Emotional Faces in Male and Female PTSD Patients

Koch

Zuiden

Nawijn

et al. 2015

Neuropsychopharmacol

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Post-traumatic stress disorder (PTSD) is a disabling psychiatric disorder. As a substantial part of PTSD patients responds poorly to currently available psychotherapies, pharmacological interventions boosting treatment response are needed. Because of its anxiolytic and pro-social properties, the neuropeptide oxytocin (OT) has been proposed as promising strategy for treatment augmentation in PTSD. As a first step to investigate the therapeutic potential of OT in PTSD, we conducted a double-blind, placebo-controlled, cross-over functional MRI study examining OT administration effects (40 IU) on amygdala reactivity toward emotional faces in unmedicated male and female police officers with (n = 37, 21 males) and without (n = 40, 20 males) PTSD. Trauma-exposed controls were matched to PTSD patients based on age, sex, years of service and educational level. Under placebo, the expected valence-dependent amygdala reactivity (ie, greater activity toward fearful-angry faces compared with happy-neutral faces) was absent in PTSD patients. OT administration dampened amygdala reactivity toward all emotional faces in male and female PTSD patients, but enhanced amygdala reactivity in healthy male and female traumaexposed controls, independent of sex and stimulus valence. In PTSD patients, greater anxiety prior to scanning and amygdala reactivity during the placebo session were associated with greater reduction of amygdala reactivity after OT administration. Taken together, our results indicate presumably beneficial neurobiological effects of OT administration in male and female PTSD patients. Future studies should investigate OT administration in clinical settings to fully appreciate its therapeutic potential.

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“…While a previous investigation observed no change with neutral faces following treatment, 11 our findings may be explained by increased complexity and associated increases in frontal engagement associated with appraisal processes of images that is subsequently impacted by treatment. 42,43 Our observations that a single dose of escitalopram reduced IFG activity associated with appraisal and inhibition, akin to the positive stimuli, is important given that neutral stimuli tend to be experienced negatively by clinical samples [7][8][9] and that chronic treatment is associated with viewing these stimuli more positively. 8 This finding also has implications for pharmaco-fMRI methodology in that employing neutral stimuli as a contrast against emotional stimuli may be problematic as treatment appears to impact on emotional as well as neutral stimulus categories.…”

Section: Discussionmentioning

confidence: 89%

“…[2][3][4] There is a critical need to better understand acute antidepressant action given low response and remission rates to first-line treatment, resulting in trial and error. 5,6 Though it has been established that patients with affective disorders also negatively appraise neutral stimuli, [7][8][9] investigations on the acute effects of antidepressants have yet to account for such effects on neutral stimuli. If treatment were to facilitate the processing of neutral stimuli -stimuli that patients usually perceive as negative -in addition to positive and negative stimu li, this would provide much-needed support for the proposal that treatment improves negative biases across stimuli by facilitating a positive information processing bias.…”

Section: Introductionmentioning

confidence: 99%

“…This is an important consideration given that patients with affective disorders 28,29,44 display impairments in the conscious and controlled processing of both emotional 45,46 and neutral stimuli. [7][8][9] Rather than consider the impact of acute effects of antidepressants on neutral stimuli as a condition of interest in its own right, treatment studies thus far have employed neutral stimuli to serve as a contrast against positive and negative emotional stimuli to isolate modulations in neural activity due to emotion. 10,11,31 Antidepressant treatment may not modulate amygdala activity associated with reactivity to low-arousal neutral stimuli; however, IFG activity associated with appraisal and regulation may be impacted.…”

Section: Introductionmentioning

confidence: 99%

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Impact of acute administration of escitalopram on the processing of emotional and neutral images: a randomized crossover fMRI study of healthy women

Outhred

Das

Felmingham

et al. 2014

J Psychiatry Neurosci

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Elevated response of human amygdala to neutral stimuli in mild post traumatic stress disorder: neural correlates of generalized emotional response

Cited by 83 publications

References 33 publications

Neural Activation during Response Inhibition Differentiates Blast from Mechanical Causes of Mild to Moderate Traumatic Brain Injury

Neural Activation during Response Inhibition Differentiates Blast from Mechanical Causes of Mild to Moderate Traumatic Brain Injury

Intranasal Oxytocin Administration Dampens Amygdala Reactivity towards Emotional Faces in Male and Female PTSD Patients

Impact of acute administration of escitalopram on the processing of emotional and neutral images: a randomized crossover fMRI study of healthy women

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