Convergent neuroimaging and neuropsychological research demonstrates disrupted attention and heightened threat sensitivity in PTSD. This might be linked to aberrations in large-scale networks subserving detection of salient stimuli, i.e. the salience network (SN), and stimulus-independent, internally-focused thought, i.e. the default mode network (DMN).
Resting state brain activity was measured in returning veterans who served in Iraq or Afghanistan with (n=15) and without PTSD (n=15) and in healthy community controls (n=15). Correlation coefficients were calculated between the time course of seed regions in key SN and DMN regions (posterior cingulate, ventromedial prefrontal cortex, and bilateral anterior insula) and all other voxels of the brain.
Compared to control groups, PTSD participants showed reduced functional connectivity within DMN (between DMN seeds and other DMN regions), including rostral ACC/vmPFC (Z=3.31; p=.005, corrected) and hippocampus (Z=2.58; p=.005), and increased connectivity within SN (between insula seeds and other SN regions), including amygdala (Z=3.03; p=.01, corrected). PTSD participants also demonstrated increased cross-network connectivity. DMN seeds exhibited elevated connectivity with SN regions, including insula (Z=3.06; p=.03, corrected), putamen, and supplementary motor area (Z=4.14; Z=4.08; p<.001), and SN seeds exhibited elevated connectivity with DMN regions, including hippocampus (Z=3.10; p=.048, corrected).
During resting state scanning, PTSD participants showed reduced coupling within DMN, greater coupling within SN, and increased coupling between DMN and 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.
PTSD; default mode network; salience network; functional connectivity; resting-state; fMRI
Sexual assault (SA) is common, but the epidemiology of acute pain after SA has not previously been reported. We evaluated the severity and distribution of pain symptoms in the early aftermath of SA among women receiving sexual assault nurse examiner (SANE) care, and the treatment of pain by SANE nurses. Severe pain (≥7 on a 0–10 numeric rating scale) was reported by 53/83 women sexual assault survivors (64% [95% CI, 53%–74%]) at the time of SANE evaluation and 43/83 women (52% [95% CI, 41%–63%]) one week later. Pain in four or more body regions was reported by 44/83 women (53% [95% CI, 42%–64%]) at the time of initial evaluation and 49/83 women (59% [95% CI, 48%–70%]) at one week follow-up. Among survivors with severe pain at the time of initial post-assault evaluation, only 7/53 (13% [95% CI, 6%–26%]) received any pain medication at the time of initial SANE treatment. These findings suggest that pain is common in SA survivors in the early post-assault period, but rarely treated.
Acute pain is common after sexual assault. Practice guidelines for SANE nurses and others who provide care to sexual assault survivors in the early aftermath of assault should include specific recommendations for pain evaluation and treatment. Prospective longitudinal studies of pain outcomes among sexual assault survivors are needed.
Sexual assault; musculoskeletal pain; stress; pain; treatment
Convergent evidence suggests that individuals with posttraumatic stress disorder (PTSD) exhibit exaggerated avoidance behaviors as well as abnormalities in Pavlonian fear conditioning. However, the link between the two features of this disorder is not well understood. In order to probe the brain basis of aberrant extinction learning in PTSD, we administered a multimodal classical fear conditioning/extinction paradigm that incorporated affectively relevant information from two sensory channels (visual and tactile) while participants underwent fMRI scanning. The sample consisted of fifteen OEF/OIF veterans with PTSD. In response to conditioned cues and contextual information, greater avoidance symptomatology was associated with greater activation in amygdala, hippocampus, vmPFC, dmPFC, and insula, during both fear acquisition and fear extinction. Heightened responses to previously conditioned stimuli in individuals with more severe PTSD could indicate a deficiency in safety learning, consistent with PTSD symptomatology. The close link between avoidance symptoms and fear circuit activation suggests that this symptom cluster may be a key component of fear extinction deficits in PTSD and/or may be particularly amenable to change through extinction-based therapies.
fear conditioning; avoidance; posttraumatic stress disorder; fMRI; neuroimaging; amygdala; hippocampus
To determine the extent to which prenatal posttraumatic stress disorder (PTSD) is associated with lower birth weight and shorter gestation, and to explore the effects of childhood maltreatment as the antecedent trauma exposure.
Prospective three-cohort study
Ann Arbor and Detroit, Michigan, United States
839 diverse nulliparas in PTSD-positive (n=255), trauma-exposed, resilient (n=307), and non-exposed to trauma (n=277) cohorts
Standardised telephone interview prior to 28 weeks to ascertain trauma history, PTSD, depression, substance use, mental health treatment history, and sociodemographics, with chart abstraction to obtain chronic condition history, antepartum complications, and prenatal care data, as well as outcomes.
Main outcome measures
Infant birth weight and gestational age per delivery record.
Women with PTSD during pregnancy had a mean birth weight 283 grams less than trauma-exposed, resilient women and 221 grams less than non-exposed women (F(3, 835) = 5.4, p = .001). PTSD was also associated with shorter gestation in multivariate models that took childhood abuse history into account. Stratified models indicated that PTSD subsequent to child abuse trauma exposure was most strongly associated with adverse outcomes. PTSD was a stronger predictor than African American race of shorter gestation and a nearly equal predictor of birth weight. Prenatal care was not associated with better outcomes among women abused in childhood.
Abuse-related PTSD may be an additional or alternative explanation for adverse perinatal outcomes associated with low socioeconomic status and African American race in the United States. Biological and interventions research is warranted along with replication studies in other nations.
Stress disorder; posttraumatic; perinatal outcomes; birth weight; gestational age; health disparities; childhood maltreatment; abuse
This review summarizes the major discussion points of a symposium on stress modulation of cognitive and affective processes, which was held during the 2010 workshop on the neurobiology of stress (Boulder, CO, USA). The four discussants addressed a number of specific cognitive and affective factors that are modulated by exposure to acute or repeated stress. Dr David Morilak discussed the effects of various repeated stress situations on cognitive flexibility, as assessed with a rodent model of attentional set-shifting task, and how performance on slightly different aspects of this test is modulated by different prefrontal regions through monoaminergic neurotransmission. Dr Serge Campeau summarized the findings of several studies exploring a number of factors and brain regions that regulate habituation of various autonomic and neuroendocrine responses to repeated audiogenic stress exposures. Dr Kerry Ressler discussed a body of work exploring the modulation and extinction of fear memories in rodents and humans, especially focusing on the role of key neurotransmitter systems including excitatory amino acids and brain-derived neurotrophic factor. Dr Israel Liberzon presented recent results on human decision-making processes in response to exogenous glucocorticoid hormone administration. Overall, these discussions are casting a wider framework on the cognitive/affective processes that are distinctly regulated by the experience of stress and some of the brain regions and neurotransmitter systems associated with these effects.
Cognitive flexibility; prefrontal cortex; decision making; habituation; extinction; fear conditioning
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.
Persons with schizophrenia often appraise other individuals as threatening or persecutory. To evaluate social appraisal in schizophrenia, we probed brain networks with a task in which subjects judged whether or not they liked face stimuli with emotional expressions. We predicted that appraising negative expressions would engage patients, more than controls, and negative faces would be related to higher levels of negative affect and produce increased activity in the medial frontal cortex, an area involved in social appraisal. Twenty-one stable outpatients with chronic non-affective psychosis (16 schizophrenic, 5 schizoaffective) and 21 healthy subjects underwent functional magnetic resonance imaging. Compared with the control subjects, patients were slower to respond, but particularly slow when they judged negatively-valenced faces, a slowness correlated with negative affect in the psychosis patients. Appraisal activated the medial prefrontal cortex (mPFC) across all face valences. For negative expressions, patients exhibited greater activation of the dorsal anterior cingulate cortex (dACC). A psychophysiological interaction analysis of the dACC revealed co-modulation of the mPFC in controls, significantly less in patients, and a trend for co-modulation of occipital cortex in the patients. Activity in occipital cortex correlated with poor social adjustment and impaired social cognition, and co-modulation of the occipital gyrus by the dACC was correlated with poorer social cognition. The findings link appraisal of negative affect with aberrant activation of the medial frontal cortex, while early sensory processing of this social cognitive task was linked with poor social function, reflecting either top down or bottom up influences.
schizophrenia; anterior cingulate cortex; faces; visual cortex; fMRI BOLD
Autism spectrum disorders (ASD) involve a core deficit in social functioning and impairments in the ability to recognize face emotions. In an emotional faces task designed to constrain group differences in attention, the present study used functional MRI to characterize activation in the amygdala, ventral prefrontal cortex (vPFC), and striatum, three structures involved in socio-emotional processing, in adolescents with ASD.
Twenty-two adolescents with ASD and 20 healthy adolescents viewed facial expressions (happy, fearful, sad and neutral) that were briefly presented (250ms) during functional MRI acquisition. To monitor attention, subjects pressed a button to identify the gender of each face.
The ASD group showed greater activation to the faces relative to the control group in the amygdala, vPFC and striatum. Follow-up analyses indicated that the ASD relative to control group showed greater activation in the amygdala, vPFC and striatum (p<.05 small volume corrected), particularly to sad faces. Moreover, in the ASD group, there was a negative correlation between developmental variables (age and pubertal status) and mean activation from the whole bilateral amygdala; younger adolescents showed greater activation than older adolescents. There were no group differences in accuracy or reaction time in the gender identification task.
When group differences in attention to facial expressions were limited, adolescents with ASD showed greater activation in structures involved in socio-emotional processing.
Autism; Adolescents; FMRI; Faces; Emotion
Genetic variations in the catechol-o-methyltransferase (COMT) gene have been associated with experimental pain and risk of chronic pain development, but no studies have examined genetic predictors of neck pain intensity and other patient characteristics after motor vehicle collision (MVC). We evaluated the association between COMT genotype and acute neck pain intensity and other patient characteristics in 89 Caucasian individuals presenting to the emergency department (ED) after MVC. In the ED in the hours after MVC, individuals with a COMT pain vulnerable genotype were more likely to report moderate to severe musculoskeletal neck pain (76% vs. 41%, RR = 2.11 (1.33 - 3.37)), moderate or severe headache (61% vs. 33%, RR = 3.15 (1.05 – 9.42), and moderate or severe dizziness (26% vs. 12%, RR = 1.97 (1.19 – 3.21)). Individuals with a pain vulnerable genotype also experienced more dissociative symptoms in the ED, and estimated a longer time to physical recovery (median 14 vs. 7 days, p = .002) and emotional recovery (median 8.5 vs. 7 days, p = .038). These findings suggest that genetic variations affecting stress response system function influence the somatic and psychological response to MVC, and provide the first evidence of genetic risk for clinical symptoms after MVC.
Although tailored health interventions can be more effective in eliciting positive behavior change then generic interventions, the underlying neural mechanisms are not yet understood. Ninety-one smokers participated in a functional magnetic resonance imaging (fMRI) session and a tailored smoking-cessation program. We found that increases in activations in self-related processing regions, particularly dorsomedial prefrontal cortex, to tailored messages predicted quitting during a 4-month follow-up.
Application of Single Prolonged Stress (SPS) in rats induces changes in neuroendocrine function and arousal that are characteristic of Post Traumatic Stress Disorder (PTSD). PTSD, in humans, is associated with decreased neural activity in the prefrontal cortex, increased neural activity in the amygdala complex, and reduced neuronal integrity in the hippocampus. However, the extent to which SPS models these aspects of PTSD has not been established. In order to address this, we used high-resolution magic angle spinning proton magnetic resonance spectroscopy (HR-MAS 1H MRS) ex vivo to assay levels of neurochemicals critical for energy metabolism (creatine and lactate), excitatory (glutamate and glutamine) and inhibitory (gamma amino butyric acid (GABA)) neurotransmission, and neuronal integrity (N-acetyl aspartate (NAA)) in the medial prefrontal cortex (mPFC), amygdala complex, and hippocampus of SPS and control rats. Glutamate, glutamine, and creatine levels were decreased in the mPFC of SPS rats when compared to controls, which suggests decreased excitatory tone in this region. SPS did not alter the neurochemical profiles of either the hippocampus or amygdala. These data suggest that SPS selectively attenuates excitatory tone, without a disruption of neuronal integrity, in the mPFC.
PTSD; anxiety; emotional regulation; glutamate; GABA; proton magnetic resonance spectroscopy
To estimate point prevalence and assess the association of types of trauma with posttraumatic stress disorder (PTSD) in a sociodemographically and racially mixed sample of women from both predominantly Medicaid and privately insured settings expecting their first infant.
Structured telephone diagnostic interview data were analyzed for prevalence of trauma exposure, PTSD, comorbidity, risk behaviors, and treatment-seeking among 1,581 diverse English-speaking nulliparous women.
The overall rate of lifetime PTSD was 20.2%, 17% in the predominantly private-payer settings, 23% in the predominantly public-payer settings. The overall rate of current PTSD was 7.9%, 2.9% and 13.9% respectively. Those with current PTSD were more likely to be African American, pregnant as a teen, living in poverty, with high school education or less, and living in higher crime areas. Adjusted odds of having current PTSD were highest among those whose worst trauma exposure was abuse (OR = 11.9, 95% CI 3.6, 39.9), followed by reproductive trauma (OR = 6.1, 95% CI 1.5, 24.4). Health risk behaviors and exposures were concentrated among those with PTSD.
These findings affirm that PTSD affects pregnant women. Women with PTSD in pregnancy were more like to have had exposures to childhood abuse and prior traumatic reproductive event, to have cumulative sociodemographic risk factors, comorbid depression and anxiety, and to have sought mental health treatment in the past. Obstetric risk behaviors occur more in women with PTSD. Research is needed to assess the effect of PTSD, a potentially modifiable source of perinatal morbidity, on obstetric outcomes.
Posttraumatic stress disorder (PTSD) is more prevalent in perinatal than general samples of women (6–8% versus 4–5%). To explore potential causes, we examined the symptom profiles of women belonging to two separate samples: a perinatal clinic sample (n = 1,581) and a subsample of women in a similar age range from the U. S. National Women’s Study (n = 2,000). Within the perinatal sample, risk ratios were higher for all 17 PTSD symptoms among women with current PTSD compared with unaffected women, suggesting that higher rates are not likely due to measurement error. The younger age and greater social disadvantage in the perinatal clinic sample contributed only a small proportion of variance in symptom levels compared with extent of trauma exposure and pre-existing PTSD. Compared with the national study sample’s symptom profile, the perinatal sample had higher rates of occurrence of five symptoms: detachment, loss of interest, anger and irritability, trouble sleeping, and nightmares. This analysis confirms that PTSD rates are higher in perinatal samples, which is likely due to exacerbation of pre-existing PTSD among women of a younger age and greater social disadvantage. Further elucidation is warranted, including identifying triggers and determining if there are needs for pregnancy-specific interventions.
posttraumatic stress; trauma exposure; PTSD symptom profile; pregnancy; prevalence
Although bio-psycho-social health research is an ideal, samples adequate for complex modeling require biomarker specimens from hundreds of participants. Ecological sampling departs from laboratory study norms, with implications for analysis.
This paper compares salivary cortisol levels and effect sizes of ‘focal’ psychiatric factors, such as trauma history, posttraumatic stress diagnosis, comorbidity, and chronic stress, and ‘nuisance’ factors, including endocrine disorders, medications, physiological factors, such as gestational age, and smoking, to inform ecological study designs.
This is a descriptive analysis of ecologically collected cortisol specimens, assayed in an on-going perinatal psychobiological study, addressing methodological considerations.
Focal and nuisance factors are often interdependent with similar effect sizes. Careful specimen deletion decisions and model specification are needed to achieve the hoped-for external validity while maintaining internal validity.
Results of multivariate models support the validity and usefulness of an ecological approach to incorporating biomarkers in health research.
ecological validity; salivary cortisol; methodology; posttraumatic stress; community-based research
Human communication and survival depend on effective social information processing. Abundant behavioral evidence has shown that humans efficiently judge preferences for other individuals, a critical task in social interaction, yet the neural mechanism of this basic social evaluation, remains less than clear. Using a social-emotional preference task and connectivity analyses (psycho-physiological interaction) of fMRI data, we first demonstrated that cortical midline structures (medial prefrontal and posterior cingulate cortices) and the task-positive network typically implicated in carrying out goal-directed tasks (pre-supplementary motor area, dorsal anterior cingulate and bilateral frontoparietal cortices) were both recruited when subjects made a preference judgment, relative to gender identification, to human faces. Connectivity analyses further showed network interactions among these cortical midline structures, and with the task-positive network, both of which vary as a function of social preference. Overall, the data demonstrate the involvement of cortical midline structures in forming social preference, and provide evidence of network interactions which might reflect a mechanism by which an individual regularly forms and expresses this fundamental decision.
fMRI BOLD; cortical midline structures; social cognition; functional connectivity; psycho-physiological interaction
Smoking leads to illnesses including addiction, cancer, and cardiovascular and respiratory diseases. Different intervention programs have become available. In the past decade, providing tailored smoking cessation messages has been shown to be more effective in inducing smoking cessation than one-size-fits-all interventions. However, little is known about the brain responses of smokers when they receive tailored smoking cessation messages.
A neuroimaging study using blocked and event-related designs examined neural activity in 24 smokers exposed to high-tailored and low-tailored smoking cessation messages. RESULTS: In both blocked and event-related conditions, rostral medial prefrontal cortex and precuneus/posterior cingulate were engaged more during the processing of high-tailored smoking cessation messages than low-tailored smoking cessation messages.
The activation patterns of smokers to tailored cessation messages show involvement of brain areas commonly implicated in self-related processing. Results seem to add support to the suggested role of self-relevance in tailored cessation programs, where previous studies have shown a potential mediating role of self-relevance on smoking abstinence. The findings are relevant to understanding the cognitive mechanisms underlying tailored message processing and may point to new directions for testing response to health communications programming.
smoking cessation; fMRI; nicotine; tailoring; self; addiction
The hypothalamic-pituitary adrenal (HPA) axis is critical for biobehavioral adaptation to challenge and appears dysregulated in a range of psychiatric disorders. Its precise role in psychopathology remains unclear and discrepant and difficult to explain findings abound in the clinical literature. Basic research suggests this system is sensitive to psychosocial cues, but psychosocial milieu factors are rarely controlled or examined in psychiatric studies using biological probes of the HPA axis. To test the hypothesis that psychological factors might complicate HPA study results even in direct, pharmacological challenge paradigms, endocrine responses to corticotropin-releasing hormone (CRH) were examined under two different cognitive preparation conditions.
Healthy subjects (n=32) received standard instructions or a cognitive intervention (CI) prior to injection with CRH and placebo, given on separate days in random order. The CI combined access to control over drug exposure with novelty reduction and coping enhancement. Blood samples were obtained via intravenous catheter before and after CRH.
Cognitive intervention reduced corticotropin (ACTH) levels, but only when CRH was given first (intervention by order interaction). It did not reduce cortisol response. The CI and visit (1st or 2nd) both impacted cortisol levels on placebo day.
Modifiable psychological factors may amplify or inhibit HPA axis activity in pharmacological activation paradigms, including CRH stimulation tests. The factors manipulated by the CI (novelty/familiarity, control and coping) may have particular salience to the HPA axis. Differential sensitivity to such factors could impact results in studies applying biological HPA probes to psychiatric populations.
stress; cortisol; ACTH, corticotropin-releasing hormone; control; coping
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.
Anxiety disorders are a significant problem in the community, and recent neuroimaging research has focused on determining the brain circuits that underlie them. Research on the neurocircuitry of anxiety disorders has its roots in the study of fear circuits in animal models and the study of brain responses to emotional stimuli in healthy humans. We review this research, as well as neuroimaging studies of anxiety disorders. In general, these studies have reported relatively heightened amygdala activation in response to disorder-relevant stimuli in post-traumatic stress disorder, social phobia, and specific phobia. Activation in the insular cortex appears to be heightened in many of the anxiety disorders. Unlike other anxiety disorders, post-traumatic stress disorder is associated with diminished responsivity in the rostral anterior cingulate cortex and adjacent ventral medial prefrontal cortex. Additional research will be needed to (1) clarify the exact role of each component of the fear circuitry in the anxiety disorders, (2) determine whether functional abnormalities identified in the anxiety disorders represent acquired signs of the disorders or vulnerability factors that increase the risk of developing them, (3) link the findings of functional neuroimaging studies with those of neurochemistry studies, and (4) use functional neuroimaging to predict treatment response and assess treatment-related changes in brain function.
amygdala; fMRI; PET; anterior cingulate; insula; hippocampus
Individuals with generalized social anxiety disorder (GSAD) exhibit exaggerated amygdala reactivity to aversive social stimuli. These findings could be explained by microstructural abnormalities in white matter (WM) tracts that connect the amygdala and prefrontal cortex, which is known to modulate the amygdala’s response to threat. The goal of this study was to investigate brain frontal WM abnormalities by using diffusion tensor imaging (DTI) in patients with social anxiety disorder.
A Turboprop DTI sequence was used to acquire diffusion tensor images in thirty patients with GSAD and thirty matched healthy controls. Fractional anisotropy, an index of axonal organization, within WM was quantified in individual subjects and an automated voxel-based, whole-brain method was used to analyze group differences.
Compared to healthy controls, patients had significantly lower fractional anisotropy localized to the right uncinate fasciculus WM near the orbitofrontal cortex. There were no areas of higher fractional anisotropy in patients than controls.
These findings point to an abnormality in the uncinate fasciculus, the major WM tract connecting the frontal cortex to the amygdala and other limbic temporal regions, in GSAD which could underlie the aberrant amygdala-prefrontal interactions resulting in dysfunctional social threat processing in this illness.
Neural regulation of stress responses, and the feedback of stress hormones to the brain, reflect complex brain-body interactions that may underlie the effects of psychological stress on health. Elucidating the brain circuitry involved in the cortical control of limbic-hypothalamic-pituitary-adrenal axis, and the cortical “targets” of cortisol that in turn modulates brain function, requires careful assessment of glucocorticoid hormones, in the context of the neuroimaging paradigms. Here we discuss approaches for assessment of endocrine function in the context of neuroimaging, including methods of blood and saliva specimen collection, and methods for drug/hormone administration. We also briefly discuss important temporal considerations, including appropriate timing of sample collections for hormones with different time-courses of activation (e.g. ACTH vs. cortisol), the pharmacokinetics of both endogenous hormones and administered agents, and circadian considerations. These are crucial to experimental designs of rhythmic hormonal systems and multiple feedback loops. We briefly address psychological/behavioral ‘activation’ paradigms used for inducing endogenous LHPA axis responses within or in proximity to scanner, as well as strategies for administration of exogenous hormones or secretagogues. Finally, we discuss some of the analyses issues in terms of hormone responses (e.g. response and area under curve, diurnal variability) and strategies for linking measured levels of peripheral humoral factor to brain activity (e.g. hormone responses as between subject regressors of BOLD activations, hormone levels as within subject regressors in analyses of covariance of brain activity over time, etc.).
Individuals with generalized social anxiety disorder tend to make overly negative and distorted predictions about social events, which enhance perceptions of threat and contribute to excessive anxiety in social situations. Here, we coupled functional magnetic resonance imaging and a multiround economic exchange game (‘trust game’) to probe mentalizing, the social-cognitive ability to attribute mental states to others. Relative to interactions with a computer, those with human partners (‘mentalizing’) elicited less activation of medial prefrontal cortex in generalized social anxiety patients compared with matched healthy control participants. Diminished medial prefrontal cortex function may play a role in the social-cognitive pathophysiology of social anxiety.
anxiety; functional magnetic resonance imaging; mentalizing; social cognition; trust