Browsing by Subject "Amygdala"

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Open Access
A neural biomarker of psychological vulnerability to future life stress.
(Neuron, 2015-02-04) Swartz, J; Knodt, A; Radtke, S; Hariri, A
We all experience a host of common life stressors such as the death of a family member, medical illness, and financial uncertainty. While most of us are resilient to such stressors, continuing to function normally, for a subset of individuals, experiencing these stressors increases the likelihood of developing treatment-resistant, chronic psychological problems, including depression and anxiety. It is thus paramount to identify predictive markers of risk, particularly those reflecting fundamental biological processes that can be targets for intervention and prevention. Using data from a longitudinal study of 340 healthy young adults, we demonstrate that individual differences in threat-related amygdala reactivity predict psychological vulnerability to life stress occurring as much as 1 to 4 years later. These results highlight a readily assayed biomarker, threat-related amygdala reactivity, which predicts psychological vulnerability to commonly experienced stressors and represents a discrete target for intervention and prevention.
Open Access
Altered resting-state functional connectivity of basolateral and centromedial amygdala complexes in posttraumatic stress disorder.
(Neuropsychopharmacology, 2014-01) Brown, Vanessa M; LaBar, Kevin S; Haswell, Courtney C; Gold, Andrea L; Mid-Atlantic MIRECC Workgroup; McCarthy, Gregory; Morey, Rajendra A
The amygdala is a major structure that orchestrates defensive reactions to environmental threats and is implicated in hypervigilance and symptoms of heightened arousal in posttraumatic stress disorder (PTSD). The basolateral and centromedial amygdala (CMA) complexes are functionally heterogeneous, with distinct roles in learning and expressing fear behaviors. PTSD differences in amygdala-complex function and functional connectivity with cortical and subcortical structures remain unclear. Recent military veterans with PTSD (n=20) and matched trauma-exposed controls (n=22) underwent a resting-state fMRI scan to measure task-free synchronous blood-oxygen level dependent activity. Whole-brain voxel-wise functional connectivity of basolateral and CMA seeds was compared between groups. The PTSD group had stronger functional connectivity of the basolateral amygdala (BLA) complex with the pregenual anterior cingulate cortex (ACC), dorsomedial prefrontal cortex, and dorsal ACC than the trauma-exposed control group (p<0.05; corrected). The trauma-exposed control group had stronger functional connectivity of the BLA complex with the left inferior frontal gyrus than the PTSD group (p<0.05; corrected). The CMA complex lacked connectivity differences between groups. We found PTSD modulates BLA complex connectivity with prefrontal cortical targets implicated in cognitive control of emotional information, which are central to explanations of core PTSD symptoms. PTSD differences in resting-state connectivity of BLA complex could be biasing processes in target regions that support behaviors central to prevailing laboratory models of PTSD such as associative fear learning. Further research is needed to investigate how differences in functional connectivity of amygdala complexes affect target regions that govern behavior, cognition, and affect in PTSD.
Open Access
Amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group.
(Arch Gen Psychiatry, 2012-11) Morey, Rajendra A; Gold, Andrea L; LaBar, Kevin S; Beall, Shannon K; Brown, Vanessa M; Haswell, Courtney C; Nasser, Jessica D; Wagner, H Ryan; McCarthy, Gregory; Mid-Atlantic MIRECC Workgroup
CONTEXT: Smaller hippocampal volumes are well established in posttraumatic stress disorder (PTSD), but the relatively few studies of amygdala volume in PTSD have produced equivocal results. OBJECTIVE: To assess a large cohort of recent military veterans with PTSD and trauma-exposed control subjects, with sufficient power to perform a definitive assessment of the effect of PTSD on volumetric changes in the amygdala and hippocampus and of the contribution of illness duration, trauma load, and depressive symptoms. DESIGN: Case-controlled design with structural magnetic resonance imaging and clinical diagnostic assessments. We controlled statistically for the important potential confounds of alcohol use, depression, and medication use. SETTING: Durham Veterans Affairs Medical Center, which is located in proximity to major military bases. PATIENTS: Ambulatory patients (n = 200) recruited from a registry of military service members and veterans serving after September 11, 2001, including a group with current PTSD (n = 99) and a trauma-exposed comparison group without PTSD (n = 101). MAIN OUTCOME MEASURE: Amygdala and hippocampal volumes computed from automated segmentation of high-resolution structural 3-T magnetic resonance imaging. RESULTS: Smaller volume was demonstrated in the PTSD group compared with the non-PTSD group for the left amygdala (P = .002), right amygdala (P = .01), and left hippocampus (P = .02) but not for the right hippocampus (P = .25). Amygdala volumes were not associated with PTSD chronicity, trauma load, or severity of depressive symptoms. CONCLUSIONS: These results provide clear evidence of an association between a smaller amygdala volume and PTSD. The lack of correlation between trauma load or illness chronicity and amygdala volume suggests that a smaller amygdala represents a vulnerability to developing PTSD or the lack of a dose-response relationship with amygdala volume. Our results may trigger a renewed impetus for investigating structural differences in the amygdala, its genetic determinants, its environmental modulators, and the possibility that it reflects an intrinsic vulnerability to PTSD.
Open Access
Amygdala, Hippocampus, and Ventral Medial Prefrontal Cortex Volumes Differ in Maltreated Youth with and without Chronic Posttraumatic Stress Disorder.
(Neuropsychopharmacology, 2016-02) Morey, Rajendra A; Haswell, Courtney C; Hooper, Stephen R; De Bellis, Michael D
Posttraumatic stress disorder (PTSD) is considered a disorder of recovery where individuals fail to learn and retain extinction of the traumatic fear response. In maltreated youth, PTSD is common, chronic, and associated with comorbidity. Studies of extinction-related structural volumes (amygdala, hippocampus, anterior cingulate cortex (ACC), and ventral medial prefrontal cortex (vmPFC)) and this stress diathesis, in maltreated youth were not previously investigated. In this cross-sectional study, neuroanatomical volumes associated with extinction in maltreated youth with PTSD (N=31), without PTSD (N=32), and in non-maltreated healthy volunteers (n=57) were examined using magnetic resonance imaging. Groups were sociodemographically similar. Participants underwent extensive assessments for strict inclusion/exclusion criteria and DSM-IV disorders. Maltreated youth with PTSD demonstrated decreased right vmPFC volumes compared with both maltreated youth without PTSD and non-maltreated controls. Maltreated youth without PTSD demonstrated larger left amygdala and right hippocampal volumes compared with maltreated youth with PTSD and non-maltreated control youth. PTSD symptoms inversely correlated with right and left hippocampal and left amygdala volumes. Confirmatory masked voxel base morphometry analyses demonstrated greater medial orbitofrontal cortex gray matter intensity in controls than maltreated youth with PTSD. Volumetric results were not influenced by psychopathology or maltreatment variables. We identified volumetric differences in extinction-related structures between maltreated youth with PTSD from those without PTSD. Alterations of the vmPFC may be one mechanism that mediates the pathway from PTSD to comorbidity. Further longitudinal work is needed to determine neurobiological factors related to chronic and persistent PTSD, and to PTSD resilience despite maltreatment.
Open Access
Amygdala-prefrontal cortex functional connectivity during threat-induced anxiety and goal distraction.
(Biol Psychiatry, 2015-02-15) Gold, Andrea L; Morey, Rajendra A; McCarthy, Gregory
BACKGROUND: Anxiety produced by environmental threats can impair goal-directed processing and is associated with a range of psychiatric disorders, particularly when aversive events occur unpredictably. The prefrontal cortex (PFC) is thought to implement controls that minimize performance disruptions from threat-induced anxiety and goal distraction by modulating activity in regions involved in threat detection, such as the amygdala. The inferior frontal gyrus (IFG), orbitofrontal cortex (OFC), and ventromedial PFC (vmPFC) have been linked to the regulation of anxiety during threat exposure. We developed a paradigm to determine if threat-induced anxiety would enhance functional connectivity between the amygdala and IFG, OFC, and vmPFC. METHODS: Healthy adults performed a computer-gaming style task involving capturing prey and evading predators to optimize monetary rewards while exposed to the threat of unpredictable shock. Psychophysiological recording (n = 26) and functional magnetic resonance imaging scanning (n = 17) were collected during the task in separate cohorts. Task-specific changes in functional connectivity with the amygdala were examined using psychophysiological interaction analysis. RESULTS: Threat exposure resulted in greater arousal measured by increased skin conductance but did not influence performance (i.e., monetary losses or rewards). Greater functional connectivity between the right amygdala and bilateral IFG, OFC, vmPFC, anterior cingulate cortex, and frontopolar cortex was associated with threat exposure. CONCLUSIONS: Exposure to unpredictable threat modulates amygdala-PFC functional connectivity that may help maintain performance when experiencing anxiety induced by threat. Our paradigm is well-suited to explore the neural underpinnings of the anxiety response to unpredictable threat in patients with various anxiety disorders.
Open Access
Co-activation of the amygdala, hippocampus and inferior frontal gyrus during autobiographical memory retrieval.
(Neuropsychologia, 2005) Greenberg, Daniel L; Rice, Heather J; Cooper, Julie J; Cabeza, Roberto; Rubin, David C; Labar, Kevin S
Functional MRI was used to investigate the role of medial temporal lobe and inferior frontal lobe regions in autobiographical recall. Prior to scanning, participants generated cue words for 50 autobiographical memories and rated their phenomenological properties using our autobiographical memory questionnaire (AMQ). During scanning, the cue words were presented and participants pressed a button when they retrieved the associated memory. The autobiographical retrieval task was interleaved in an event-related design with a semantic retrieval task (category generation). Region-of-interest analyses showed greater activation of the amygdala, hippocampus, and right inferior frontal gyrus during autobiographical retrieval relative to semantic retrieval. In addition, the left inferior frontal gyrus showed a more prolonged duration of activation in the semantic retrieval condition. A targeted correlational analysis revealed pronounced functional connectivity among the amygdala, hippocampus, and right inferior frontal gyrus during autobiographical retrieval but not during semantic retrieval. These results support theories of autobiographical memory that hypothesize co-activation of frontotemporal areas during recollection of episodes from the personal past.
Open Access
Emotion-attention network interactions during a visual oddball task.
(Brain Res Cogn Brain Res, 2004-06) Fichtenholtz, Harlan M; Dean, Heather L; Dillon, Daniel G; Yamasaki, Hiroshi; McCarthy, Gregory; LaBar, Kevin S
Emotional and attentional functions are known to be distributed along ventral and dorsal networks in the brain, respectively. However, the interactions between these systems remain to be specified. The present study used event-related functional magnetic resonance imaging (fMRI) to investigate how attentional focus can modulate the neural activity elicited by scenes that vary in emotional content. In a visual oddball task, aversive and neutral scenes were presented intermittently among circles and squares. The squares were frequent standard events, whereas the other novel stimulus categories occurred rarely. One experimental group [N=10] was instructed to count the circles, whereas another group [N=12] counted the emotional scenes. A main effect of emotion was found in the amygdala (AMG) and ventral frontotemporal cortices. In these regions, activation was significantly greater for emotional than neutral stimuli but was invariant to attentional focus. A main effect of attentional focus was found in dorsal frontoparietal cortices, whose activity signaled task-relevant target events irrespective of emotional content. The only brain region that was sensitive to both emotion and attentional focus was the anterior cingulate gyrus (ACG). When circles were task-relevant, the ACG responded equally to circle targets and distracting emotional scenes. The ACG response to emotional scenes increased when they were task-relevant, and the response to circles concomitantly decreased. These findings support and extend prominent network theories of emotion-attention interactions that highlight the integrative role played by the anterior cingulate.
Open Access
Emotional Modulation of Cognitive Skill Learning.
(2007-12-13) Thomas, Laura Anderson
In this set of studies the modulation of feedback-based cognitive skill learning was investigated by modulating a probabilistic classification learning (PCL) task to be either emotional or neutral. In the current task, based on the weather prediction task, cue cards were presented on the screen and subjects were asked to predict what they would come across while walking in the woods, in the emotional condition a snake/spider or in the neutral condition a flower/mushroom. Chapter 1 is a review of the animal and human literature of multiple memory systems, amygdala modulation of multiple memory systems, and sleep-dependent procedural memory consolidation.Chapter 2 examined how emotional arousal affected performance, strategy use, and sympathetic nervous system activation in our manipulated PCL task. Subjects highly fearful of the outcomes in the emotional condition showed overall greater skin conductance responses compared to the other groups, as well as retardation in initial cue-outcome acquisition. Individuals who were not fearful of the outcome stimuli used more complex (optimal) strategies after a 24-hr period of memory consolidation relative to the other groups, reflecting greater implicit knowledge of the probabilistic task structure.The purpose of the experiment in Chapter 3 was to examine consolidation-based stabilization and enhancement in an emotional cognitive skill task. There was no effect of sleep on retention or savings on percent correct or strategy use in both the emotional and neutral PCL task. These results conform to recent evidence that probabilistic learning does not show sleep-dependent performance enhancements.Chapter 4 investigated the neural correlates of emotional PCL with functional magnetic resonance imaging. There was greater amygdala and striatal activity in the emotional versus neutral group on Day 1. There was also increased activity in the striatum on Day 2, suggesting an early and lasting bias of emotion on procedural learning. Additionally, there were differences in neural recruitment by subjects using complex versus simple implicit strategies.The findings from this series of experiments have implications for the assessment of psychopathologies that show dysfunction in affective and striatal areas, such as obsessive-compulsive disorder and Tourette's syndrome, and for the development, eventually, of optimal therapies.
Open Access
Functional neuroimaging of autobiographical memory.
(2010) St. Jacques, Peggy L.
Autobiographical memory (AM) refers to memory for events from our own personal past. Functional neuroimaging studies of AM are important because they can investigate the neural correlates of processes that are difficult to study using laboratory stimuli, including: complex constructive processes, subjective qualities of memory retrieval, and remote memory. Three functional magnetic resonance imaging (fMRI) studies are presented to examine these important contributions of AM. The first study investigates the neural correlates of temporal-order memory for autobiographical events using a novel photo paradigm. Participants took photographs at many campus locations over a period of several hours, and the following day they were scanned while making temporal-order judgments to pairs of photographs from different locations. It was found that temporal-order decisions associated with recollection recruited left prefrontal (PFC) and left posterior parahippocampal cortex, whereas temporal-order decisions relying on familiarity recruited greater activity in the right PFC. The second study examines self-projection, the capacity to re-experience the personal past and to mentally infer another person’s perspective. A novel camera technology was used to examine self-projection by prospectively generating dynamic visuospatial images taken from a first-person perspective. Participants were literally asked to self-project into the personal past or into the life of another person. Self-projection of one’s own past self recruited greater ventral medial PFC (mPFC), and self-projection of another individual recruited dorsal mPFC. Activity in ventral vs. dorsal mPFC was also sensitive to the ability to relive or understand the perspective taken on each trial. Further, task-related functional connectivity analysis revealed that ventral mPFC contributed to the medial temporal lobe network linked to memory processes, whereas dorsal mPFC contributed to the frontoparietal network linked to controlled processes. The third study focuses on the neural correlates underlying age-related differences in the recall of episodically rich AMs. Age-related attenuation in the episodic richness of AM was linked to reductions in activity elicited during elaboration. Age effects on AM were more pronounced during elaboration than search, with older adults showing less sustained recruitment of the hippocampus and ventrolateral PFC for less episodically rich AMs. Further, there was an age-related reduction in the top-down modulation of the PFC on the hippocampus by episodic richness, possibly reflecting fewer controlled processes operating on the recovery of information in the hippocampus. Ultimately, the goal of all memory research is to understand how memory operates in the real-world; the present research highlights the important contribution of functional neuroimaging studies of AM in attaining this goal.
Open Access
Individual Differences in Neural Reward and Threat Processing: Identifying Pathways of Risk and Resilience for Psychopathology
(2014) Nikolova, Yuliya
The goal of this dissertation is two-fold: 1) to identify novel biological pathways implicating individual differences in reward and threat processing in the emergence of risk and resilience for psychopathology, 2) to identify novel genetic and epigenetic predictors of the inter-individual variability in these biological pathways. Four specific studies are reported wherein blood oxygen-level dependent functional magnetic resonance imaging (BOLD fMRI) was used to measure individual differences in threat-related amygdala reactivity and reward-related ventral striatum (VS) reactivity; self-report was used to measure of mood and psychopathology as well as the experience of stressful life events. In addition, DNA was derived from peripheral tissues to identify specific genetic and epigenetic markers.
Results from Study 1 demonstrate that individuals with relatively low reward-related VS reactivity show stress-related reductions in positive affect, while those with high VS reactivity remain resilient to these potentially depressogenic effects. Heightened VS reactivity was, however, associated with stress-related increases in problem drinking in Study 2. Importantly, this effect only occurred in individuals showing concomitantly reduced threat-related amygdala reactivity. Study 3 demonstrates that using a multilocus genetic profile capturing the cumulative impact of five functional polymorphic loci on dopamine signaling increases power to explain variability in reward-related VS reactivity relative to an approach considering each locus independently. Finally, Study 4 provides evidence that methylation in the proximal promoter of the serotonin transporter gene is negatively correlated with gene expression and positively correlated with threat-related amygdala reactivity above and beyond the effects of commonly studied functional DNA-sequence based variation in the same genomic vicinity.
The results from these studies implicate novel biological pathways, namely reward-related VS reactivity and threat-related amygdala reactivity, as predictors of relative risk or resilience for psychopathology particularly in response to stressful life events. Moreover, the results suggest that genetic and epigenetic markers may serve as easily accessible peripheral tissue proxies for these neural phenotypes and, ultimately, risk and resilience. Such markers may eventually be harnessed to identify vulnerable individuals and facilitate targeted early intervention or prevention efforts.
Open Access
Induction of hippocampal long-term potentiation during waking leads to increased extrahippocampal zif-268 expression during ensuing rapid-eye-movement sleep.
(J Neurosci, 2002-12-15) Ribeiro, Sidarta; Mello, Claudio V; Velho, Tarciso; Gardner, Timothy J; Jarvis, Erich D; Pavlides, Constantine
Rapid-eye-movement (REM) sleep plays a key role in the consolidation of memories acquired during waking (WK). The search for mechanisms underlying that role has revealed significant correlations in the patterns of neuronal firing, regional blood flow, and expression of the activity-dependent gene zif-268 between WK and subsequent REM sleep. Zif-268 integrates a major calcium signal transduction pathway and is implicated by several lines of evidence in activity-dependent synaptic plasticity. Here we report that the induction of hippocampal long-term potentiation (LTP) during WK in rats leads to an upregulation of zif-268 gene expression in extrahippocampal regions during subsequent REM sleep episodes. This upregulation occurs predominantly in the amygdala, entorhinal, and auditory cerebral cortices during the first REM sleep episodes after LTP induction and reaches somatosensory and motor cerebral cortices as REM sleep recurs. We also show that hippocampal inactivation during REM sleep blocks extrahippocampal zif-268 upregulation, indicating that cortical and amygdalar zif-268 expression during REM sleep is under hippocampal control. Thus, expression of an activity-dependent gene involved in synaptic plasticity propagates gradually from the hippocampus to extrahippocampal regions as REM sleep recurs. These findings suggest that a progressive disengagement of the hippocampus and engagement of the cerebral cortex and amygdala occurs during REM sleep. They are also consistent with the view that REM sleep constitutes a privileged window for hippocampus-driven cortical activation, which may play an instructive role in the communication of memory traces from the hippocampus to the cerebral cortex.
Open Access
Neural Mechanisms of Young Adult Sexual Decision-Making and Risk Behavior
(2016) Victor, Elizabeth Christine
Sexual risk behavior among young adults is a serious public health concern; 50% will contract a sexually transmitted infection (STI) before the age of 25. The current study collected self-report personality and sexual history data, as well as neuroimaging, experimental behavioral (e.g., real-time hypothetical sexual decision making data), and self-report sexual arousal data from 120 heterosexual young adults ages 18-26. In addition, longitudinal changes in self-reported sexual behavior were collected from a subset (n = 70) of the participants. The primary aims of the study were (1) to predict differences in self-report sexual behavior and hypothetical sexual decision-making (in response to sexually explicit audio-visual cues) as a function of ventral striatum (VS) and amygdala activity, (2) test whether the association between sexual behavior/decision-making and brain function is moderated by gender, self-reported sexual arousal, and/or trait-level personality factors (i.e., self-control, impulsivity, and sensation seeking) and (3) to examine how the main effects of neural function and interaction effects predict sexual risk behavior over time. Our hypotheses were mostly supported across the sexual behavior and decision-making outcome variables, such that neural risk phenotypes (heightened reward-related ventral striatum activity coupled with decreased threat-related amygdala activity) were associated with greater lifetime sexual partners at baseline measured and over time (longitudinal analyses). Impulsivity moderated the relationship between neural function and self-reported number of sexual partners at baseline and follow up measures, as well as experimental condom use decision-making. Sexual arousal and sensation seeking moderated the relationship between neural function and baseline and follow up self-reports of number of sexual partners. Finally, unique gender differences were observed in the relationship between threat and reward-related neural reactivity and self-reported sexual risk behavior. The results of this study provide initial evidence for the potential role for neurobiological approaches to understanding sexual decision-making and risk behavior. With continued research, establishing biomarkers for sexual risk behavior could help inform the development of novel and more effective individually tailored sexual health prevention and intervention efforts.
Open Access
Preschool anxiety disorders predict different patterns of amygdala-prefrontal connectivity at school-age.
(PLoS One, 2015) Carpenter, Kimberly LH; Angold, Adrian; Chen, Nan-Kuei; Copeland, William E; Gaur, Pooja; Pelphrey, Kevin; Song, Allen W; Egger, Helen L
OBJECTIVE: In this prospective, longitudinal study of young children, we examined whether a history of preschool generalized anxiety, separation anxiety, and/or social phobia is associated with amygdala-prefrontal dysregulation at school-age. As an exploratory analysis, we investigated whether distinct anxiety disorders differ in the patterns of this amygdala-prefrontal dysregulation. METHODS: Participants were children taking part in a 5-year study of early childhood brain development and anxiety disorders. Preschool symptoms of generalized anxiety, separation anxiety, and social phobia were assessed with the Preschool Age Psychiatric Assessment (PAPA) in the first wave of the study when the children were between 2 and 5 years old. The PAPA was repeated at age 6. We conducted functional MRIs when the children were 5.5 to 9.5 year old to assess neural responses to viewing of angry and fearful faces. RESULTS: A history of preschool social phobia predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces. Preschool generalized anxiety predicted less functional connectivity between the amygdala and dorsal prefrontal cortices in response to fearful faces. Finally, a history of preschool separation anxiety predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces and greater school-age functional connectivity between the amygdala and dorsal prefrontal cortices to angry faces. CONCLUSIONS: Our results suggest that there are enduring neurobiological effects associated with a history of preschool anxiety, which occur over-and-above the effect of subsequent emotional symptoms. Our results also provide preliminary evidence for the neurobiological differentiation of specific preschool anxiety disorders.
Open Access
Reduced hippocampal and amygdala activity predicts memory distortions for trauma reminders in combat-related PTSD.
(J Psychiatr Res, 2011-05) Hayes, Jasmeet Pannu; LaBar, Kevin S; McCarthy, Gregory; Selgrade, Elizabeth; Nasser, Jessica; Dolcos, Florin; VISN 6 Mid-Atlantic MIRECC workgroup; Morey, Rajendra A
Neurobiological models of posttraumatic stress disorder (PTSD) suggest that altered activity in the medial temporal lobes (MTL) during encoding of traumatic memories contribute to the development and maintenance of the disorder. However, there is little direct evidence in the PTSD literature to support these models. The goal of the present study was to examine MTL activity during trauma encoding in combat veterans using the subsequent memory paradigm. Fifteen combat veterans diagnosed with PTSD and 14 trauma-exposed control participants viewed trauma-related and neutral pictures while undergoing event-related fMRI. Participants returned one week after scanning for a recognition memory test. Region-of-interest (ROI) and voxel-wise whole brain analyses were conducted to examine the neural correlates of successful memory encoding. Patients with PTSD showed greater false alarm rates for novel lures than the trauma-exposed control group, suggesting reliance on gist-based representations in lieu of encoding contextual details. Imaging analyses revealed reduced activity in the amygdala and hippocampus in PTSD patients during successful encoding of trauma-related stimuli. Reduction in left hippocampal activity was associated with high arousal symptoms on the Clinician-Administered PTSD Scale (CAPS). The behavioral false alarm rate for traumatic stimuli co-varied with activity in the bilateral precuneus. These results support neurobiological theories positing reduced hippocampal activity under conditions of high stress and arousal. Reduction in MTL activity for successfully encoded stimuli and increased precuneus activity may underlie reduced stimulus-specific encoding and greater gist memory in patients with PTSD, leading to maintenance of the disorder.
Open Access
Relationship of trauma symptoms to amygdala-based functional brain changes in adolescents.
(J Trauma Stress, 2013-12) Nooner, Kate B; Mennes, Maarten; Brown, Shaquanna; Castellanos, F Xavier; Leventhal, Bennett; Milham, Michael P; Colcombe, Stanley J
In this pilot study, amygdala connectivity related to trauma symptoms was explored using resting-state functional magnetic resonance imaging (R-fMRI) in 23 healthy adolescents ages 13-17 years with no psychiatric diagnoses. Adolescents completed a self-report trauma symptom checklist and a R-fMRI scan. We examined the relationship of trauma symptoms to resting-state functional connectivity of the amygdala. Increasing self-report of trauma symptoms by adolescents was associated with increasing functional connectivity with the right amygdala and a local limbic cluster and decreasing functional connectivity with the amygdala and a long-range frontoparietal cluster to the left amygdala, which can be a hallmark of immaturity. These pilot findings in adolescents provide preliminary evidence that even mild trauma symptoms can be linked to the configuration of brain networks associated with the amygdala.
Open Access
Serotonin transporter gene polymorphisms and brain function during emotional distraction from cognitive processing in posttraumatic stress disorder.
(BMC Psychiatry, 2011-05-05) Morey, Rajendra A; Hariri, Ahmad R; Gold, Andrea L; Hauser, Michael A; Munger, Heidi J; Dolcos, Florin; McCarthy, Gregory
BACKGROUND: Serotonergic system dysfunction has been implicated in posttraumatic stress disorder (PTSD). Genetic polymorphisms associated with serotonin signaling may predict differences in brain circuitry involved in emotion processing and deficits associated with PTSD. In healthy individuals, common functional polymorphisms in the serotonin transporter gene (SLC6A4) have been shown to modulate amygdala and prefrontal cortex (PFC) activity in response to salient emotional stimuli. Similar patterns of differential neural responses to emotional stimuli have been demonstrated in PTSD but genetic factors influencing these activations have yet to be examined. METHODS: We investigated whether SLC6A4 promoter polymorphisms (5-HTTLPR, rs25531) and several downstream single nucleotide polymorphisms (SNPs) modulated activity of brain regions involved in the cognitive control of emotion in post-9/11 veterans with PTSD. We used functional MRI to examine neural activity in a PTSD group (n = 22) and a trauma-exposed control group (n = 20) in response to trauma-related images presented as task-irrelevant distractors during the active maintenance period of a delayed-response working memory task. Regions of interest were derived by contrasting activation for the most distracting and least distracting conditions across participants. RESULTS: In patients with PTSD, when compared to trauma-exposed controls, rs16965628 (associated with serotonin transporter gene expression) modulated task-related ventrolateral PFC activation and 5-HTTLPR tended to modulate left amygdala activation. Subsequent to combat-related trauma, these SLC6A4 polymorphisms may bias serotonin signaling and the neural circuitry mediating cognitive control of emotion in patients with PTSD. CONCLUSIONS: The SLC6A4 SNP rs16965628 and 5-HTTLPR are associated with a bias in neural responses to traumatic reminders and cognitive control of emotions in patients with PTSD. Functional MRI may help identify intermediate phenotypes and dimensions of PTSD that clarify the functional link between genes and disease phenotype, and also highlight features of PTSD that show more proximal influence of susceptibility genes compared to current clinical categorizations.
Open Access
Stress-induced cortisol response is associated with right amygdala volume in early childhood.
(Neurobiology of stress, 2021-05) Fowler, Carina H; Bogdan, Ryan; Gaffrey, Michael S
Rodent research suggests that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and the resulting cortisol stress response can alter the structure of the hippocampus and amygdala. Because early-life changes in brain structure can produce later functional impairment and potentially increase risk for psychiatric disorder, it is critical to understand the relationship between the cortisol stress response and brain structure in early childhood. However, no study to date has characterized the concurrent association between cortisol stress response and hippocampal and amygdala volume in young children. In the present study, 42 young children (M _age = 5.97, SD = 0.76), completed a frustration task and cortisol response to stress was measured. Children also underwent magnetic resonance imaging (MRI), providing structural scans from which their hippocampal and amygdala volumes were extracted. Greater cortisol stress response was associated with reduced right amygdala volume, controlling for whole brain volume, age, sex, and number of cortisol samples. There were no significant associations between cortisol stress response and bilateral hippocampus or left amygdala volumes. The association between right amygdala volume and cortisol stress response raises the non-mutually exclusive possibilities that the function of the HPA axis may shape amygdala structure and/or that amygdala structure may shape HPA axis function. As both cortisol stress response and amygdala volume have been associated with risk for psychopathology, it is possible that the relationship between cortisol stress response and amygdala volume is part of a broader pathway contributing to psychiatric risk.