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ABSTRACT: Dehydroepiandrosterone (DHEA) is a neurosteroid with anxiolytic, antidepressant, and antiglucocorticoid properties. It is endogenously released in response to stress, and may reduce negative affect when administered exogenously. Although there have been multiple reports of DHEA's antidepressant and anxiolytic effects, no research to date has examined the neural pathways involved. In particular, brain imaging has not been used to link neurosteroid effects to emotion neurocircuitry. To investigate the brain basis of DHEA's impact on emotion modulation, subjects were administered 400 mg of DHEA (N=14) or placebo (N=15) and underwent 3 T fMRI while performing the Shifted-Attention Emotional Appraisal Task (SEAT), a test of emotional processing and regulation. Compared to placebo, DHEA reduced activity in the amygdala and hippocampus, enhanced connectivity between the amygdala and hippocampus, and enhanced activity in the rACC. These activation changes were associated with reduced negative affect. DHEA also reduced memory accuracy for emotional stimuli, and reduced activity in regions associated with conjunctive memory encoding. These results demonstrate that DHEA reduces activity in regions associated with generation of negative emotion and enhances activity in regions linked to regulatory processes. Considering that activity in these regions is altered in mood and anxiety disorders, our results provide initial neuroimaging evidence that DHEA may be useful as a pharmacological intervention for these conditions and invite further investigation into the brain basis of neurosteroid emotion regulatory effects.Neuropsychopharmacology accepted article preview online, 3 April 2013; doi:10.1038/npp.2013.79.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 04/2013; · 6.99 Impact Factor
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ABSTRACT: Objective
Convergent research demonstrates disrupted attention and heightened threat sensitivity in posttraumatic stress disorder (PTSD). This might be linked to aberrations in large-scale networks subserving the detection of salient stimuli (i.e., the salience network [SN]) and stimulus-independent, internally focused thought (i.e., the default mode network [DMN]).Methods
Resting-state brain activity was measured in returning veterans with and without PTSD (n = 15 in each group) and in healthy community controls (n = 15). Correlation coefficients were calculated between the time course of seed regions in key SN and DMN regions and all other voxels of the brain.ResultsCompared with control groups, participants with PTSD showed reduced functional connectivity within the DMN (between DMN seeds and other DMN regions) including the rostral anterior cingulate cortex/ventromedial prefrontal cortex (z = 3.31; p = .005, corrected) and increased connectivity within the SN (between insula seeds and other SN regions) including the amygdala (z = 3.03; p = .01, corrected). Participants with PTSD also demonstrated increased cross-network connectivity. DMN seeds exhibited elevated connectivity with SN regions including the insula (z = 3.06; p = .03, corrected), and SN seeds exhibited elevated connectivity with DMN regions including the hippocampus (z = 3.10; p = .048, corrected).Conclusions
During resting-state scanning, participants with PTSD showed reduced coupling within the DMN, greater coupling within the SN, and increased coupling between the DMN and the SN. Our findings suggest a relative dominance of threat-sensitive circuitry in PTSD, even in task-free conditions. Disequilibrium between large-scale networks subserving salience detection versus internally focused thought may be associated with PTSD pathophysiology.
Psychosomatic Medicine 10/2012; · 3.97 Impact Factor
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ABSTRACT: Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure.
Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD.
Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC.
Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non-combat related PTSD.
These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD.
Journal of psychiatry & neuroscience: JPN 02/2012; 37(4):241-9. · 5.34 Impact Factor
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ABSTRACT: Advanced magnetic resonance imaging (MRI) techniques provide the means of studying both the structural and the functional properties of various brain regions, allowing us to address the relationship between the structural changes in human brain regions and the activity of these regions. However, analytical approaches combining functional (fMRI) and structural (sMRI) information are still far from optimal. In order to improve the accuracy of measurement of structural properties in active regions, the current study tested a new analytical approach that repeated a surface-based analysis at multiple planes crossing different depths of cortex. Twelve subjects underwent a fear conditioning study. During these tasks, fMRI and sMRI scans were acquired. The fMRI images were carefully registered to the sMRI images with an additional correction for cortical borders. The fMRI images were then analyzed with the new multiple-plane surface-based approach as compared to the volume-based approach, and the cortical thickness and volume of an active region were measured. The results suggested (1) using an additional correction for cortical borders and an intermediate template image produced an acceptable registration of fMRI and sMRI images; (2) surface-based analysis at multiple depths of cortex revealed more activity than the same analysis at any single depth; (3) projection of active surface vertices in a ribbon fashion improved active volume estimates; and (4) correction with gray matter segmentation removed non-cortical regions from the volumetric measurement of active regions. In conclusion, the new multiple-plane surface-based analysis approaches produce improved measurement of cortical thickness and volume of active brain regions. These results support the use of novel approaches for combined analysis of functional and structural neuroimaging.
NeuroImage 11/2009; 49(4):3075-85. · 5.89 Impact Factor
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ABSTRACT: Background: The memory deficit hypothesis has been used to explain the maintenance of repetitive behavior in individuals with obsessive–compulsive disorder, yet the majority of studies focusing on verbal memory show mixed results. These studies primarily evaluated memory accuracy via the inclusion or omission of previously encountered material, as opposed to false recognition (i.e., the inclusion of erroneous material). We evaluated false memories and memory processes in individuals with obsessive–compulsive washing symptoms (OC), individuals matched on depression and anxiety without OC symptoms (D/A), and in nonanxious individuals (NAC). Methods: Twenty-eight OC, 28 D/A, and 29 NAC individuals read OC-threat relevant, positive, and neutral scenarios and then performed a recognition test. Erroneous recognition of words associated to encoded, but not previously viewed, scenarios were classified as false memories. To evaluate processes underlying memory, participants completed a modified remember/know task to examine whether the OC individuals differed from the other individuals in recollective clarity for false memories of OC-relevant (e.g., germs), positive (e.g., lottery), and neutral (e.g., bread) material. Results: The OC individuals used “know” more than the D/A and NAC individuals for false memories of threat. For veridical memories, the OC individuals used “know” more than the NAC, but not, D/A individuals. Conclusions: The greater reliance on “know” (i.e., feelings of familiarity) in general and false threat memories in particular in individuals with OC symptoms may add to feelings of uncertainty for threat-relevant material, which may contribute to compulsive behavior. Depression and Anxiety, 2009. ©2008 Wiley-Liss, Inc.
Depression and Anxiety 04/2009; 26(5):396 - 402. · 4.18 Impact Factor
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ABSTRACT: Neuroimaging provides a powerful means to understand the mechanisms that mediate emotional processing in healthy individuals
as well as the dysregulation of these processes in post-traumatic stress disorder (PTSD). Reviewed are neuroimaging findings
in PTSD, with a focus on studies utilizing symptom provocation, cognitive activation, and functional connectivity. These studies
highlight the role of the medial prefrontal cortex (mPFC), insula, amygdala, sublenticular extended amygdala (SLEA), and hippocampus
in mediating symptom formation in PTSD. In addition, new and emerging foci in neuroimaging research relevant to PTSD involve
psychological processes like fear conditioning, habituation, extinction recall; cognitive-emotional interactions; and self-related
and social-emotional processing. Findings linking neurocircuitry subserving these processes to the abnormalities associated
with PTSD are highlighted, suggesting that the mPFC is implicated in a number of these processes. It is proposed that the
mPFC plays a role in the “contextualization” of stimuli, and dysregulation of contextualization processes might play a key
role in the generation of PTSD symptoms.
KeywordsContextualization–emotional appraisal–fear conditioning–fMRI–mPFC–neuroimaging–PTSD–self-related processing
12/2008: pages 297-317;
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ABSTRACT: The memory deficit hypothesis has been used to explain the maintenance of repetitive behavior in individuals with obsessive-compulsive disorder, yet the majority of studies focusing on verbal memory show mixed results. These studies primarily evaluated memory accuracy via the inclusion or omission of previously encountered material, as opposed to false recognition (i.e., the inclusion of erroneous material). We evaluated false memories and memory processes in individuals with obsessive-compulsive washing symptoms (OC), individuals matched on depression and anxiety without OC symptoms (D/A), and in nonanxious individuals (NAC).
Twenty-eight OC, 28 D/A, and 29 NAC individuals read OC-threat relevant, positive, and neutral scenarios and then performed a recognition test. Erroneous recognition of words associated to encoded, but not previously viewed, scenarios were classified as false memories. To evaluate processes underlying memory, participants completed a modified remember/know task to examine whether the OC individuals differed from the other individuals in recollective clarity for false memories of OC-relevant (e.g., germs), positive (e.g., lottery), and neutral (e.g., bread) material.
The OC individuals used "know" more than the D/A and NAC individuals for false memories of threat. For veridical memories, the OC individuals used "know" more than the NAC, but not, D/A individuals.
The greater reliance on "know" (i.e., feelings of familiarity) in general and false threat memories in particular in individuals with OC symptoms may add to feelings of uncertainty for threat-relevant material, which may contribute to compulsive behavior.
Depression and Anxiety 11/2008; 26(5):396-402. · 4.18 Impact Factor
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Kyoung-Uk Lee,
Hyun Soo Khang,
Ki-Tae Kim,
Young-Joo Kim,
Yong-Sil Kweon,
Yong-Wook Shin,
Jun Soo Kwon,
Shao-Hsuan Ho, Sarah N Garfinkel,
Jeong-Ho Chae,
Israel Liberzon
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ABSTRACT: We investigated the neural basis underlying the effect of race on incidental facial emotional processing using functional MRI. Thirteen healthy Korean men underwent functional MRI while viewing photographs of Korean (own-race) and Caucasian (other-race) emotional faces while performing a sex discrimination task. Responses to other-race relative to own-race neutral faces replicated previous studies: activations were obtained in dorsolateral prefrontal cortex/medial frontal cortex. Direct contrasts between-race emotional faces (happy and sad) also showed differential effects: the contrast of own-race relative to other-race had more activations in limbic areas (amygdala and hippocampus), whereas the contrast of other-race relative to own-race had more activations in frontal, occipital, and parietal lobes. Our findings provide evidence for differential processing of emotional faces as a function of race.
Neuroreport 08/2008; 19(10):1021-5. · 1.66 Impact Factor
