A 7-Tesla MRI study of the periaqueductal gray: resting state and task activation under threat.

The periaqueductal gray (PAG) is a region of the midbrain implicated in a variety of behaviors including defensive responses to threat. Despite the wealth of knowledge pertaining to the differential functional roles of the PAG columns in nonhuman and human research, the basic functional connectivity of the PAG at rest has not been well characterized. Therefore, the current study utilized 7-Tesla magnetic resonance imaging (MRI) to characterize PAG functional connectivity at rest and task activation under uncertain threat. A sample of 53 neurologically healthy undergraduate participants (Mage = 22.2, s.d.age = 3.62) underwent structural and resting state functional MRI scans. Supporting previous work, voxel-wise analyses showed that the PAG is functionally connected to emotion regulation and fear networks. The comparison of functional connectivity of PAG columns did not reveal any significant differences. Thirty-five participants from the same sample also completed an uncertain threat task with blocks of three conditions-no shock, predictable shock and unpredictable shock. There were no robust activity differences within the PAG columns or the whole PAG across conditions although there was differential activity at the voxel level in the PAG and in other regions theoretically relevant to uncertain threat. Results of this study elucidate PAG connectivity at rest and activation in response to uncertain threat.

Neural impact of neighborhood socioeconomic disadvantage in traumatically injured adults.

Nearly 14 percent of Americans live in a socioeconomically disadvantaged neighborhood. Lower individual socioeconomic position (iSEP) has been linked to increased exposure to trauma and stress, as well as to alterations in brain structure and function; however, the neural effects of neighborhood SEP (nSEP) factors, such as neighborhood disadvantage, are unclear. Using a multi-modal approach with participants who recently experienced a traumatic injury (N = 185), we investigated the impact of neighborhood disadvantage, acute post-traumatic stress symptoms, and iSEP on brain structure and functional connectivity at rest. After controlling for iSEP, demographic variables, and acute PTSD symptoms, nSEP was associated with decreased volume and alterations of resting-state functional connectivity in structures implicated in affective processing, including the insula, ventromedial prefrontal cortex, amygdala, and hippocampus. Even in individuals who have recently experienced a traumatic injury, and after accounting for iSEP, the impact of living in a disadvantaged neighborhood is apparent, particularly in brain regions critical for experiencing and regulating emotion. These results should inform future research investigating how various levels of socioeconomic circumstances may impact recovery after a traumatic injury as well as policies and community-developed interventions aimed at reducing the impact of socioeconomic stressors.

Neural substrates of human fear generalization: A 7T-fMRI investigation.

Fear generalization - the tendency to interpret ambiguous stimuli as threatening due to perceptual similarity to a learned threat - is an adaptive process. Overgeneralization, however, is maladaptive and has been implicated in a number of anxiety disorders. Neuroimaging research has indicated several regions sensitive to effects of generalization, including regions involved in fear excitation (e.g., amygdala, insula) and inhibition (e.g., ventromedial prefrontal cortex). Research has suggested several other small brain regions may play an important role in this process (e.g., hippocampal subfields, bed nucleus of the stria terminalis [BNST], habenula), but, to date, these regions have not been examined during fear generalization due to limited spatial resolution of standard human neuroimaging. To this end, we utilized the high spatial resolution of 7T fMRI to characterize the neural circuits involved in threat discrimination and generalization. Additionally, we examined potential modulating effects of trait anxiety and intolerance of uncertainty on neural activation during threat generalization. In a sample of 31 healthy undergraduate students, significant positive generalization effects (i.e., greater activation for stimuli with increasing perceptual similarity to a learned threat cue) were observed in the visual cortex, thalamus, habenula and BNST, while negative generalization effects were observed in the dentate gyrus, CA1, and CA3. Associations with individual differences were underpowered, though preliminary findings suggested greater generalization in the insula and primary somatosensory cortex may be correlated with self-reported anxiety. Overall, findings largely support previous neuroimaging work on fear generalization and provide additional insight into the contributions of several previously unexplored brain regions.

Neighborhood disadvantage is associated with stable deficits in neurocognitive functioning in traumatically-injured adults.

BACKGROUND: In trauma-exposed adults, the relationship between an individual's socioeconomic position (SEP) and post-traumatic stress disorder (PTSD) has been well demonstrated. One potential mechanism by which the stress associated with lower SEPs may impact trauma outcomes is through changes in neurocognition. In both healthy and clinical samples, area-level factors also appear to be independently related to neurocognition. Far less is known about how neighborhood socioeconomic disadvantage, may impact cognition in traumatically-injured adults. The current study employed hierarchical linear modeling to longitudinally investigate whether neighborhood disadvantage was associated with neurocognitive functioning in five domains: processing speed, sustained attention, controlled attention, cognitive flexibility, and response inhibition. METHODS: One-hundred and ninety-five socioeconomically diverse traumatically-injured subjects (mean age = 32.8, 52.8% female) were recruited from an Emergency Department. Two-weeks, three-months, and six-months post-trauma, participants completed self-report measures and a computerized test battery to evaluate neurocognition. An Area Deprivation Index (ADI) score, a measure of a neighborhood's socioeconomic disadvantage, was derived from each participants' home address. RESULTS: Greater neighborhood disadvantage was significantly related to lower scores in all domains. Results of hierarchical linear models revealed neighborhood disadvantage was significantly associated with processing speed, controlled attention, cognitive flexibility, and response inhibition across time, even after adjusting for individual annual household income, baseline PTSD symptoms, and previous adverse life experiences. This relationship was stable for all domains except sustained attention, which varied across time. CONCLUSION: These findings indicate neighborhood disadvantage contributes uniquely to neurocognitive functioning and, for the majority of domains, these contributions are stable across time. The relationship between area-level variables and cognitive function may underlie individual vulnerability to developing psychiatric disorders. Future work should continue to examine the interaction between socioenvironmental stressors and PTSD symptoms longitudinally.

High-Resolution Resting-State Functional Connectivity of the Extended Amygdala.

The extended amygdala has been implicated as a critical region in the neurocircuitry underlying anxiety. The circuitry of the extended amygdala, including the central (CeA) and basolateral (BLA) nuclei of the amygdala and the bed nucleus of the stria terminalis (BNST), has been well defined in nonhuman animals; however, much less is known about the roles and interactions of these structures in humans given their small size. Therefore, this study used high-resolution 7-Tesla magnetic resonance imaging to define, compare, and contrast functional connectivity (FC) of these structures in 57 neurologically healthy young adults. In addition, FC was investigated in relation to self-reported measures of anxiety and intolerance of uncertainty, a key feature of anxiety. Results of the FC analysis of each of the nuclei largely replicated previous work. Conjunction analyses showed that nuclei of the extended amygdala shared FC with hippocampal, cingulate, medial prefrontal, and subgenual cortices. Comparison of seed-to-voxel time series correlation maps demonstrated that compared with the BNST, the CeA and BLA were more strongly coupled with parahippocampal, temporal, fusiform, and occipital gyri. Relative to the CeA and BLA, the BNST was more strongly coupled with the anterior caudate and anterior cingulate cortex. Finally, trait anxiety and intolerance of uncertainty were not robustly related to FC of the extended amygdala at rest. Results of this study extend previous work to provide more clarity of the nuances of extended amygdala resting FC and its relationship with anxiety.

Effects of anticipated emotional category and temporal predictability on the startle reflex.

Anticipated emotional category and temporal predictability are key characteristics that have both been shown to impact psychophysiological indices of defensive motivation (e.g., the startle reflex). To date, research has primarily examined these features in isolation, and it is unclear whether they have additive or interactive effects on defensive motivation. In the present study, the startle reflex was measured in anticipation of low arousal neutral, moderate arousal pleasant, and high arousal unpleasant pictures that were presented with either predictable or unpredictable timing. Linear mixed-effects modeling was conducted to examine startle magnitude across time, and the intercept at the beginning and end of the task. Across the entire task, the anticipation of temporally unpredictable (relative to predictable) pictures and emotional (relative to neutral) pictures potentiated startle magnitude, but there was no interaction between the two features. However, examination of the intercept at the beginning of the task indicated a Predictability by Emotional Category interaction, such that temporal unpredictability enhanced startle potentiation in anticipation of unpleasant pictures only. Examination of the intercept at the end of the task indicated that the effects of predictability and emotional category on startle magnitude were largely diminished. The present study replicates previous reports demonstrating that emotional category and temporal predictability impact the startle reflex, and provides novel evidence suggesting an interactive effect on defensive motivation at the beginning of the task. This study also highlights the importance of examining the time course of the startle reflex.