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Anterior cingulate activity to salient stimuli is modulated by autonomic arousal in Posttraumatic Stress Disorder
Abstract
Reduced ventral anterior cingulate (vACC) activity to threat is thought to reflect an impairment in regulating arousal networks in posttraumatic stress disorder (PTSD). Concurrent functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) recording were used to examine neural functioning when arousal networks are engaged. Eleven participants with PTSD and 11 age- and sex-matched non-traumatized controls performed an oddball task that required responding to salient, non-trauma-related auditory target tones embedded in lower frequency background tones. Averaged target-background analyses revealed significantly greater dorsal ACC, supramarginal gyrus, and hippocampal activity in PTSD relative to control participants.With-SCR target responses resulted in increased vACC activity in controls, and dorsal ACC activity in PTSD. PTSD participants had reduced vACC activity relative to controls to target tones when SCR responses were present. This reduction in vACC in PTSD relative to controls was not apparent in without-SCR responses. These findings suggest that a reduction in vACC in PTSD occurs specifically when arousal networks are engaged.
... The inclusion criteria were met by nine studies whose methods and results are summarized in Table 1. Specifically, for the cognitive domain explored, seven studies focused on attention and response inhibition (11,12,14,(16)(17)(18)(19), one study explored memory functions (13), and one study investigated autonomic arousal (15). ...
... Furthermore, the authors also found a significant correlation between PTSD symptoms, specifically avoidance and numbing, and the reduction of left hippocampal activity in PTSS subjects. Finally, Felmingham et al. (15) investigated the neural correlates associated with autonomic arousal in 11 PTSD subjects and 11 HC in response to salient stimuli in an Auditory Oddball task (AOT). The authors explored the Orienting Responses (ORs) that are critical markers of the registration of new or significant stimuli and mobilization of attention and motor responses (22). ...
... Finally, two studies found impairments in the autonomic arousal (15) and in the memory domain (13) in PTSD patients. ...
IntroductionPost-Traumatic Stress Disorder (PTSD) is often associated with impairments in emotional and cognitive domains. Contrarily to the emotional sphere, neural basis underpinnings to cognitive impairments are still not well known.Methods
We performed a bibliographic search on PUBMED of all the studies investigating the cognitive impairments in PTSD individuals. We considered only studies that applied cognitive tasks using a functional Magnetic Resonance Imaging technique. The inclusion criteria were met by nine studies.ResultsOverall, PTSD individuals reported significant impairments in the dorsolateral prefrontal cortex, anterior cingulate cortex, inferior frontal gyrus, insula, inferior temporal cortex, supplement motor area, and Default Mode Network (DMN). Moreover, abnormal activity was reported in subcortical structures (e.g. hippocampus, amygdala, thalamus) and in the cerebellum.LimitationsCognitive functioning was assessed using different cognitive tasks. Potential confounding factors such as age, sex, symptoms intensity, and comorbidities might have influenced the results.Conclusion
So far, the evidence reported that PTSD is characterized by cognitive impairments in several domains, such as attention, memory and autonomic arousal, which may be due to selective dysfunctions in brain regions that are part of cortical networks, the limbic system and DMN. However, further studies are needed in order to better assess the role of cognitive impairments in PTSD and to develop more targeted therapeutic approaches.
... 38 cognitive tasks in the presence of negative distractors, cognitive conflict, or attentional demands, abnormalities in functional activation of vmPFC emerge. 78,[83][84][85][86][87][88][89][90][91][92] Most notably, the vmPFC is overactive in PTSD during fear conditioning 93 yet under-active during fear conditioned extinction. 94 Increased functional connectivity between the amygdala and the vmPFC has been observed in the resting state in PTSD. ...
... 57,60,62,105,108,110 Functionally, altered activation of the dACC and insular cortex in PTSD occurs during exposure to negative imagery. 40,71,75,76,[79][80][81][82] During executive task performance, participants with PTSD exhibit abnormal activity in the dACC, 85,88,89,94,111 as well as in the insula. 90,112 In the resting state, increased connectivity of the dACC and the insula with the amygdala has been observed in PTSD, 95,96 perhaps indicating an increased relay of emotionally valenced information to frontal nodes of the salience circuit. ...
... With regard to mood circuitry, the sgACC is implicated in PTSD pathology by findings of decreased volume of the sgACC 56,62 and altered activation of the sgACC during exposure to negative imagery. 68,70,71 During performance of cognitive tasks that include emotionally valenced stimuli, decreased activity has been observed in the sgACC in PTSD participants 84,85,89 ; in contrast, increased sgACC activity has been found during fear conditioning in PTSD. 93 When PTSD participants listen to personal trauma scripts, increased functional connectivity between the amygdala and the sgACC has been described. ...
Symptoms of posttraumatic stress disorder include hyperarousal, avoidance of trauma-related stimuli, re-experiencing of trauma, and mood changes. This review focuses on the frontal cortical areas that form crucial links in circuitry pertinent to posttraumatic stress disorder symptomatology: (1) the conditioned fear extinction circuit, (2) the salience circuit, and (3) the mood circuit. These frontal areas include the ventromedial prefrontal cortex (conditioned fear extinction), the dorsal anterior cingulate and insular cortices (salience), and the lateral orbitofrontal and subgenual cingulate cortices (mood). Frontal lobe structural abnormalities in posttraumatic stress disorder, including volumetric reductions in the cingulate cortices, impact all three circuits. Functional analyses of frontal cortices in posttraumatic stress disorder show abnormal activation in all three according to task demand and emotional valence. Network analyses reveal altered amygdalo-frontal connectivity and failure to suppress the default mode network during cognitive engagement. Spine shape alterations also have been detected in the medial orbitofrontal cortex in posttraumatic stress disorder postmortem brains, suggesting reduced synaptic plasticity. Importantly, frontal lobe abnormalities in posttraumatic stress disorder extend beyond emotion-related circuits to include the lateral prefrontal cortices that mediate executive functions. In conclusion, widespread frontal lobe dysfunction in posttraumatic stress disorder provides a neurobiologic basis for the core symptomatology of the disorder, as well as for executive function impairment.
... Allgemein wird angenommen, dass dem (v)mPFC eine inhibierende Rolle auf eine Aktivierung der Amygdala zukommt (Etkin & Wager, 2007;Jovanovic & Ressler, 2010;Koenigs & Grafman, 2009;Shin et al., 2006). Außerdem wird angenommen, dass dieses Areal, gemeinsam mit dem Hippocampus, für eine Aufrechterhaltung von Furchtextinktion verantwortlich ist (Lebrón, Milad & Quirk, 2004;Milad & Quirk, 2002;Milad, Rauch, Pitman & Quirk, 2006 (Bush, Luu & Posner, 2000), aber in den vergangenen Jahren rücken auch immer mehr kognitive Prozesse wie Salienzprozesse oder exekutive Funktionen (Felmingham et al., 2009;Menon, 2011;Seeley et al., 2007;Shin et al., 2011) (Driessen et al., 2004;Pissiota et al., 2002;Rauch et al., 1996). ...
... Lanius et al. (2005Lanius et al. ( , 2007 (Bremner, Narayan, et al., 1999;Britton et al., 2005;Hou et al., 2007;Lanius et al., 2001Lanius et al., , 2003Yang et al., 2004), allerdings in Einklang mit den Studien 1 und 2, eine Hyperaktivierung dieser Region während einer ASD als bedeutsam für die Vorhersage der PTSD-Symptome. Es lässt sich vermuten, dass dieses Aktivierungsmuster das Korrelat von Aufmerksamkeitsprozessen hinsichtlich salienten, traumarelevanten Stimuli darstellt (Felmingham et al., 2009;Menon, 2011;Seeley et al., 2007;Shin et al., 2011 (Brewin, 2001;Lanius et al., 2006;Rauch et al., 1998Shin et al., 2006) (Buhle et al., 2014;Etkin et al., 2011;Falquez et al., 2014;McRae et al., 2010;Ochsner et al., 2012). Im Rahmen der PTSD postulierten bereits Ehlers und Clark (2000), dass negative Bewertungsprozesse zur Chronifizierung der PTSD beitragen (siehe Kapitel 2.9.2). ...
... Möglich wäre, dass dieses Aktivierungsmuster mit der Regulierung emotionaler Reaktionen im Allgemeinen zu begründen ist(Bush et al., 2000). Weiter könnte dieses Aktivierungsmuster das Korrelat erhöhter Aufmerksamkeitsprozesse hinsichtlich traumarelevanter Stimuli(Felmingham et al., 2009;Menon, 2011; Seeley et al., 2007;Shin et al., 2011) oder kognitiver, emotionsregulierender Prozesse darstellen(Etkin, Egner & Kalisch, 2011;McRae et al., 2010;Ochsner, Silvers & Buhle, 2012). Auch konnten in dieser Studie die in dem Modell postulierten dysfunktionalen Aktivierungsmuster des Hippocampus weder im Within-noch im Between-Group-Vergleich für PTSD-Patienten bei der Präsentation von traumaassoziierten gegenüber neutralen Stimuli beobachtet werden. ...
Die Akute Belastungsstörung (ASD) ist eine Traumafolgestörung, die durch Dissoziations-, Wiedererlebens-, Vermeidungs- und Übererregungssymptome innerhalb des ersten Monats nach einem traumatischen Ereignisses gekennzeichnet ist. Persistieren diese Symptome länger als einen Monat, spricht man von einer Posttraumatischen Belastungsstörung (PTSD).
Für die Entstehung und Aufrechterhaltung der PTSD wurde ein neuronales Schaltkreismodell einer Hyperaktivierung der Amygdala, Hypoaktivierungen im Cortex praefrontalis medialis und Cortex cingularis anterior (ACC) und Dysfunktionen des Hippocampus postuliert.
In der ersten Untersuchung wurden die Gemeinsamkeiten neuronaler Aktivierung der teilweise heterogenen Ergebnisse von 19 bildgebenden Sympromprovokationsstudien bei PTSD meta-analytisch untersucht. In der folgenden eigenen Symptomprovokationsstudie wurde mittels funktioneller Magnetresonanztomographie die Anwendbarkeit des Schaltkreismodells auf die ASD überprüft, indem die neuronalen Aktivierungsmuster von jeweils 19 ASD-Patienten und gesunden Kontrollprobanden während Symptomprovokation verglichen wurden. Die abschließende dritte Untersuchung sollte schlussendlich Hinweise darauf liefern, ob die in dem Schaltkreismodell angenommenen Aktivierungsmuster prädiktiv für die Entstehung der PTSD-Symptomschwere von 19 ASD-Patienten sind.
Insgesamt zeigen die Ergebnisse der vorliegenden Arbeit, dass das bisher angenommene Schaltkreismodell im Rahmen von Symptomprovokation weder für die Entstehung noch die Aufrechterhaltung der PTSD geeinget ist. Stattdessen zeigen die eigenen Studien, dass Hyperaktivierungen in posterior-parietalen Regionen und dem ACC sowie Hypoaktivierungen in lateralen präfrontalen Regionen bedeutsam sind.
... There are fewer studies implicating the DAN in PTSD during non-affective attention tasks. Bryant et al. (2005) reported that PTSD subjects had decreased right dorsal middle frontal gyrus activation during an auditory oddball task, while the same group (Felmingham et al., 2009) later found increased activity in a similar, but more posterior area. Both studies consisted of relatively small sample sizes, requiring further replication. ...
... More research has implicated abnormalities of the SN in PTSD, a network involved in conflict monitoring (Fan et al., 2005) (Table 5). The dACC (Bryant et al., 2005;Felmingham et al., 2009;Shin et al., 2007;, AI , and amygdala (Bryant et al., 2005;Semple et al., 2000) have been shown to be hyperactive across a variety of attention paradigms including the Stroop (Shin et al., 2007;, multisource interference task (VanElzakker, 2015), auditory oddball tasks (Bryant et al., 2005;Felmingham et al., 2009) and CPTs (Semple et al., 2000), which may intrude upon other neural network's ability to carry-out task-related goals. VanElzakker (2015), however, found that dACC hyperactivity was also present in non-traumatized twins of those with PTSD, suggesting that dACC hyperactivity may be a risk factor for developing PTSD. ...
... More research has implicated abnormalities of the SN in PTSD, a network involved in conflict monitoring (Fan et al., 2005) (Table 5). The dACC (Bryant et al., 2005;Felmingham et al., 2009;Shin et al., 2007;, AI , and amygdala (Bryant et al., 2005;Semple et al., 2000) have been shown to be hyperactive across a variety of attention paradigms including the Stroop (Shin et al., 2007;, multisource interference task (VanElzakker, 2015), auditory oddball tasks (Bryant et al., 2005;Felmingham et al., 2009) and CPTs (Semple et al., 2000), which may intrude upon other neural network's ability to carry-out task-related goals. VanElzakker (2015), however, found that dACC hyperactivity was also present in non-traumatized twins of those with PTSD, suggesting that dACC hyperactivity may be a risk factor for developing PTSD. ...
Posttraumatic Stress Disorder (PTSD) is associated with alterations in attention at the behavioral and neural levels. However, there are conflicting findings regarding the specific type of attention impairments present in PTSD, as the commonly used tests of attention do not isolate the mechanisms behind attention abnormalities, and the constructs measured do not map onto the neurocircuits governing attention. Here we review the literature on attention processing in PTSD and offer directions for future research to clarify these unanswered questions. First, using instruments that allow assessment of behavioral and neurophysiological attention components will be necessary to understand attention deficits in PTSD. Second, focus on intra-individual variability in addition to assessment of central tendency may help clarify some of the mixed findings. Third, longitudinal studies on attentional processes are warranted to determine how attention contributes to the development and maintenance of PTSD. Integration of behavioral and neural measures of attention will be useful in understanding the pathophysiology of PTSD.
... For instance, whereas a number of studies report lower hippocampal activation in PTSD relative to controls (e.g., Bremner et al., 2003;Hayes et al., 2011), others report greater hippocampal activation in response to both threat-related (Shin et al., 2001;Thomaes et al., 2009) and non-threat-related stimuli (Werner et al., 2009). Likewise, some studies report less activation (e.g., Britton et al., 2005;Shin et al., 2001) while others report greater activation in the rostral ACC (e.g., Bryant et al., 2005;Felmingham et al., 2009). Inconsistent findings also extend beyond the traditional model to other areas implicated in PTSD such as the insular cortex (e.g., Chen et al., 2009;Fonzo et al., 2010). ...
... Studies failing to report activation foci as 3D coordinates in stereotaxic space (n = 1; Bremner et al., 1997) were also excluded because these studies could not be meaningfully analyzed with ALE. For studies that reported results for multiple tasks using the same group of patients (e.g., Hou et al., 2007;Felmingham et al., 2009), the contrast with the greatest number of foci for only one task was selected in order to limit the contribution of any one set of participants to the pool of foci. In cases where multiple studies were performed by the same group, we contacted first authors to determine if there was any sample overlap between studies. ...
... Further studies investigating automatic trauma-related stimulus processing in PTSD have found decreased activation in ventral/pregenual parts of anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) ( Bremner et al., 1999;Shin et al., 2001;Sakamoto et al., 2005;Hou et al., 2007). Dorsal parts of these regions have been found to be hyperactivated at least during unspecific threat processing in PTSD ( Bryant et al., 2005;Felmingham et al., 2009;Shin and Liberzon, 2010). Due to different roles of ventral/pregenual and dorsal parts of ACC and mPFC, it is necessary to distinguish these regions in order to gain a better understanding of fear processing in PTSD. ...
... As expected, dorsal ACC/mPFC regions were hyperactivated in response to trauma-related pictures in IPV-PTSD patients in this study. This result is in line with previous PTSD studies reporting hyperactivity in dorsal parts of ACC/mPFC regions during general ( Bryant et al., 2005;Felmingham et al., 2009;Shin and Liberzon, 2010) and trauma-related threat processing ( Moser et al., 2015). It appears that dorsal parts of the ACC/mPFC are rather involved in emotion generation or processing, whereas ventral/pregenual parts are associated with emotion regulation processes ( Devinsky et al., 1995;Viviani, 2014;Duval et al., 2015;Etkin et al., 2015). ...
Interpersonal violence (IPV) is one of the most frequent causes for the development of posttraumatic stress disorder (PTSD) in women. Trauma-related triggers have been proposed to evoke automatic emotional responses in PTSD. The present functional magnetic resonance study investigated the neural basis of trauma-related picture processing in women with IPV-PTSD (n = 18) relative to healthy controls (n = 18) using a new standardized trauma-related picture set and a nonemotional vigilance task. We aimed to identify brain activation and connectivity evoked by trauma-related pictures, and associations with PTSD symptom severity.We found hyperactivation during trauma-related vs. neutral pictures processing in both subcortical (basolateral amygdala (BLA), thalamus, brainstem) and cortical (anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), insula, occipital cortex) regions in IPV-PTSD. In patients, brain activation in amygdala, ACC, insula, occipital cortex and brainstem correlated positively with symptom severity. Furthermore, connectivity analyses revealed hyperconnectivity between BLA and dorsal ACC/mPFC.Results show symptom severity dependent brain activation and hyperconnectivity in response to trauma-related pictures in brain regions related to fear and visual processing in women suffering from IPV-PTSD. These brain mechanisms appear to be associated with immediate responses to trauma-related triggers presented in a non-emotional context in this PTSD subgroup.
... and education level and PTSD symptom severity (r = -0. 25 was significantly correlated with segmentation agreement (r = 0.12 and -0.03, respectively). ...
... For example, in studies very similar to the ERP studies discussed earlier, Bryant et al. [24] found hyperactivity in the dorsal ACC of people with PTSD in an auditory oddball task that was unrelated to trauma and emotional processing. Felmingham et al. [25] used the same auditory oddball task but also measured skin conductance response to target tones to determine autonomic arousal. They found that during target trials in which participants displayed a skin conductance response, participants with PTSD displayed greater dorsal ACC activation than controls. ...
People with Posttraumatic Stress Disorder (PTSD) often report difficulties with attention and memory on tasks that are unrelated to their trauma. One important component of everyday event comprehension is the segmentation of ongoing activity into meaningful events. The present study asked whether PTSD symptom severity was associated with impaired segmentation and memory for neutral, ongoing activity. A sample of 137 participants, ages 21–79, completed event segmentation and memory tasks, general cognitive functioning tasks, and questionnaires assessing PTSD symptom severity. People with higher levels of PTSD symptoms had poorer event segmentation and event memory performance. Hierarchical multiple regression analyses demonstrated that PTSD symptom severity explained unique variance in event segmentation performance, even after controlling for general cognitive function. These results suggest that interventions aimed at improving event comprehension may help compensate for memory disruptions in PTSD.
... Kogler et al. (2015) conducted a meta-analysis of neuroimaging studies and identified the SMG as a key brain region activated during physiological stress. Patients with PTSD were shown to have alterations in neural activity and functional connectivity of the SMG as compared to healthy controls (Bastos et al., 2022;Dossi et al., 2020;Felmingham et al., 2009;Rabellino et al., 2018). In addition, preliminary evidence has suggested that the associations of ICM with cognitive function may be through its importance for the integrity of neural connections and neural synchrony of cerebral cortex, particularly the facilitation of local brain synchrony (Grydeland et al., 2016;Vandewouw et al., 2021;Yang et al., 2020). ...
Perceived stress, which refers to people's evaluation of a stressful event and their ability to cope with it, has emerged as a stable predictor for physical and mental health outcomes. Increasing evidence has suggested the buffering effect of social support on perceived stress. Although previous studies have investigated the brain structural features (e.g., gray matter volume) associated with perceived stress, less is known about the association between perceived chronic stress and intra-cortical myelin (ICM), which is an important microstructure of brain and is essential for healthy brain functions, and the role of social support in this association. Using a sample of 1076 healthy young adults drawn from the Human Connectome Project, we quantified the ICMby the contrast of T1w and T2w images and examined its association with perceived chronic stress during the last month and social support. Behavioral results showed that perceived chronic stress was negatively associated with both emotional support and instrumental support. Vertex-wise multiple regression analyses revealed that higher level of perceived chronic stress was significantly associated with lower ICM content of a cluster in the right supramarginal gyrus (rSMG). Interestingly, the emotional support, but not the instrumental support, significantly mediated the association of perceived chronic stress with ICM in the rSMG. Overall, the present study provides novel evidence for the cortical myelination of perceived chronic stress in humans and highlights the essential role of the rSMG in perceived chronic stress and emotional support.
... The dorsal ACC (dACC, Brodmann's Area 24) is involved in emotional and physical stress response through threatening social and physical pain stimuli detection and response [123]. Hyperactivation of the dACC is associated with PTSD [137,[149][150][151][152] and has been shown to mediate hyperarousal symptoms of PTSD [153]. Neuroimaging studies also demonstrated activation in response to inflammation. ...
Posttraumatic stress disorder (PTSD) develops in a subset of individuals upon exposure to traumatic stress. In addition to well-defined psychological and behavioral symptoms, some individuals with PTSD also exhibit elevated concentrations of inflammatory markers, including C-reactive protein, interleukin-6, and tumor necrosis factor-α. Moreover, PTSD is often co-morbid with immune-related conditions, such as cardiometabolic and autoimmune disorders. Numerous factors, including lifetime trauma burden, biological sex, genetic background, metabolic conditions, and gut microbiota, may contribute to inflammation in PTSD. Importantly, inflammation can influence neural circuits and neurotransmitter signaling in regions of the brain relevant to fear, anxiety, and emotion regulation. Given the link between PTSD and the immune system, current studies are underway to evaluate the efficacy of anti-inflammatory treatments in those with PTSD. Understanding the complex interactions between PTSD and the immune system is essential for future discovery of diagnostic and therapeutic tools.
... Application of tcVNS in PTSD patients exposed to traumatic scripts resulted in increased brain activity within the anterior cingulate, including the subgenual (sgACC), anterior dorsal (adACC), and posterior dorsal (pdACC) subdivisions. Prior studies have observed a relative decrease in sgACC activity, located primarily within left BA 24, in PTSD patients exposed to traumatic reminders, including traumatic scripts (23,43,44), and cognitive challenges such as oddball paradigms (45,46). Downregulated activity of the sgACC in PTSD is thought to reflect deficient emotional regulation associated with traumatic remembrance (23) possibly via reduced inhibition of the amygdala by the anterior cingulate/medial prefrontal cortex as these areas have shown an inverse relationship during an emotional conflict task (47). ...
Objective:
Posttraumatic stress disorder (PTSD) is a disabling condition affecting a large segment of the population, however current treatment options have limitations. New interventions that target the neurobiological alterations underlying symptoms of PTSD could be highly beneficial. Transcutaneous cervical (neck) vagal nerve stimulation (tcVNS) has the potential to represent such an intervention. The goal of this study is to determine the effects of tcVNS on neural responses to reminders of traumatic stress in PTSD.
Methods:
Twenty-two participants were randomized to receive either sham (n = 11) or active (n = 11) tcVNS stimulation in conjunction with exposure to neutral and personalized traumatic stress scripts with High-Resolution Positron Emission Tomography scanning with radiolabeled water for brain blood flow measurements.
Results:
Compared to sham, tcVNS increased brain activations during trauma scripts (p < 0.005) within the bilateral frontal and temporal lobes, left hippocampus, posterior cingulate, and anterior cingulate (dorsal and pregenual), and right postcentral gyrus. Greater deactivations (p < 0.005) with tcVNS were observed within the bilateral frontal and parietal lobes and left thalamus. Compared to tcVNS, sham elicited greater activations (p < 0.005) in the bilateral frontal lobe, left precentral gyrus, precuneus, and thalamus, and right temporal and parietal lobes, hippocampus, insula, and posterior cingulate. Greater (p < 0.005) deactivations were observed with sham in the right temporal lobe, posterior cingulate, hippocampus, left anterior cingulate, and bilateral cerebellum.
Conclusion:
tcVNS increased anterior cingulate and hippocampus activation during trauma scripts, potentially indicating a reversal of neurobiological changes with PTSD consistent with improved autonomic control.Trial Registration#NCT02992899.
... In relation to complex behaviors, the OFC is integral to functional states related to homeostasis and allostasis, such as mood and emotion (Bechara, Damasio, & Damasio, 2000;Zhang, Harris, Split, Troiani, & Olson, 2016), hypothalamic-pituitary-adrenal-axis (HPA) activity (Sinclair, Webster, Fullerton, & Weickert, 2012), reward (Howard, Gottfried, Tobler, & Kahnt, 2015), and decision-making (Bechara & Damasio, 2005). Our observation of diminished OFC strength and functional connectivity in the PTSD group is highly consistent with many prior studies of posttraumatic stress in non-substance dependent individuals, who show reduced orbitofrontal or ventromedial prefrontal cortex (VMPFC) metabolism across a variety of task-demands, including trauma-related (Daigre et al., 2015;Moser et al., 2015) and trauma-unrelated task contexts (Felmingham et al., 2009;Herz et al., 2016;Rougemont-Bücking et al., 2011;Sripada et al., 2012;van Rooij et al., 2016). Confirming the association of PTSD with OFC/VMPFC function, a meta-analysis of 79 neuroimaging studies of PTSD also concluded that PTSD is associated with hypoactivity of ventromedial prefrontal regions, as well as of the inferior frontal gyrus (Hayes, VanElzakker, & Shin, 2012). ...
Interoception concerns the afferent vagal and spinothalamic lamina I systems, and their projection to regions of the brain comprising the central autonomic network (CAN). At the level of the cortex, the CAN includes regions such as the insula, medial prefrontal and cingulate
cortices, which interact with subcortical and brainstem networks to regulate autonomic, neuroendocrine, immune, and other visceral functions of the body. Interoception is an important
concept linking ‘primitive’ homeostatic functions of the brain to its ‘high-order’ cognitive functions. This view is supported by an increasing body of experimental evidence indicating the
relevance of interoceptive neural systems to motivational drives, mood, emotion, self-awareness, body-ownership, somatic disorders and psychopathology. However, constructs, paradigms and
other methodology for investigating neural interoception in humans require additional development and validation. Additionally, neural interoceptive processing in psychopathology has not been thoroughly characterized, hence limiting the translational relevance of findings
from this field. Given the emerging role of interoception in many psychological functions, a key question would be whether we could access and modulate neural interoceptive systems in
humans. Hence, the first aim of this thesis was to investigate whether interoceptive neural processing can be modulated through non-invasive stimulation of the cortex or through peripheral nerve stimulation. To accomplish these aims, transcranial magnetic stimulation (TMS) and transcutaneous vagus nerve stimulation (tVNS) were used to modulate heart-brain interactions. A second aim of this thesis was to determine whether traumatic stress exposure in
female psychiatric patients alters the degree to which neural interoceptive systems are engaged when asked to attend to somatic and visceral feelings during mindful breathing.
**STUDY 1** is a randomized, sham-controlled investigation to determine whether tVNS affects cardiovagal responses and neurocardiac integration in interoceptive cortices. The ability of tVNS to evoke cardiovagal responses was mixed. tVNS was found to increase baroreceptor sensitivity, but not heart rate variability, whereas both sham and tVNS elicited reductions in heart rate. At the level of the brain, tVNS increased electroencephalographic (EEG) functional
connectivity between regions of the CAN. In particular, stronger functional connectivity was obtained for the right somatosensory and anterior insula in the beta frequency band. The effect of
tVNS on an evoked potential reflecting neural cardiac interoceptive processing (the heart-evoked potential or ‘HEP’) was also assessed. At the sensor-levels, tVNS was associated with greater HEP negativity in left-lateralized frontal, temporal, parietal and central electrodes. Source localized functional connectivity between regions where HEPs have been observed intracranially revealed patterns of greater and lesser connectivity in several frequency bands. Insula-prefrontal
connectivity features correlated with heart rate during tVNS. Altogether, the results indicate that tVNS modulates neural systems relevant to cardiac interoceptive processing, which may be
relevant to the mechanisms of action by which tVNS improves cardiovascular autonomic function in somatic and psychiatric conditions.
**STUDY 2** applied transcranial magnetic stimulation to the right frontotemporal cortex to test whether modulating cortical excitability within regions putatively accessing the CAN alters cardiovascular autonomic responses. Intermittent theta-burst stimulation increased vagally mediated heart rate variability, but this effect appears to have been confounded by stimulation induced state anxiety. However, continuous theta-burst stimulation increased pulse-transit time
latency, an effect that was not explained by stimulation-induced anxiety. This study supports the use of TMS for modulating ‘top-down’ neurocardiac integration, and discusses approaches for optimizing TMS for investigating neural interoceptive and visceromotor processing, and its translational relevance.
**STUDY 3** investigated the functional MRI correlates of respiratory interoception in women in residential treatment for stimulant dependence (SUD) who have varying histories of physical,
psychological and/or sexual trauma. A subset of patients had a concurrent diagnosis of posttraumatic stress disorder (PTSD). Reduced functional connectivity of an interoception-linked
network was found in women with SUD-PTSD comorbidity. Specifically, an orbitofrontal network showed diminished strength of correlation with the insular, somatosensory and cognitive control regions during a mindfulness-based breathing task. Additionally, orbitofrontal network
strength was negatively associated with sexual violence exposure beyond the contribution of PTSD diagnosis alone. This study contributes to scientific understanding concerning interoceptive dysfunction in psychopathology and potential mechanisms through which psychobehavioral techniques such as mindfulness may improve mental health.
OVERALL, these results of this dissertation support the utility of non-invasive cortical or peripheral nerve stimulation in accessing and modulating neural interoceptive systems related to cardiovascular autonomic regulation. The results also support the utility of using certain psychobehavioral techniques, such as mindfulness, to engage interoceptive brain systems, and they highlight how different psychopathological conditions may respond differently to treatment
modalities involving interoceptive manipulations. Altogether, this work enhances basic understanding of brain-body interactions, and advances the translational value that can be derived from interoceptive theoretical frameworks.
... Fig. 2.B shows a high frequency of findings regarding increased activity for the cingulate cortex. From Table 2 it can be observed that the majority of the studies reporting increased activation or a positive correlation in the cingulate (Kanaan et al., 2007;Lanius et al., 2005, 2012Weniger et al., 2013) and anterior cingulate (Bryant and Das, 2012;Burke et al., 2014;Felmingham et al., 2009;Ketay et al., 2014;Lanius et al., 2005Lanius et al., , 2002Marshall et al., 1997) involved a symptom provocation paradigm of some kind. A resting-state study also reported an increase in activation (Schlumpf et al., 2014). ...
Pathological dissociation is a severe, debilitating and transdiagnostic psychiatric symptom. This review identifies biomarkers of pathological dissociation in a transdiagnostic manner to recommend the most promising research and treatment pathways in support of the precision medicine framework. A total of 205 unique studies that met inclusion criteria were included. Studies were divided into four biomarker categories, namely neuroimaging, psychobiological, psychophysiological, and genetic biomarkers. The dorsomedial and dorsolateral prefrontal cortex, bilateral superior frontal regions, (anterior) cingulate, posterior association areas, and basal ganglia were identified as neurofunctional biomarkers of pathological dissociation and decreased hippocampal, basal ganglia, and thalamic volumes as neurostructural biomarkers. Increased oxytocin and prolactin and decreased tumor necrosis factor alpha (TNF-α) were identified as psychobiological markers. Psychophysiological biomarkers, including blood pressure, heart rate and skin conductance, were inconclusive. For the genetic biomarker category studies related to dissociation were limited and no clear directionality of effect was found to warrant identification of a genetic biomarker. Recommendations for future research pathways and possible clinical applicability are provided.
... Brain imaging studies have implicated the medial prefrontal cortex/anterior cingulate in PTSD [200][201][202][203][204][205][206][207][208][209][210][211][212][213][214][215] and depression [216][217][218]. An increase in function in PTSD is observed in insula [205,209,219] and increased amygdala function is associated with both PTSD [204,205,213,215,[220][221][222][223][224][225][226][227][228][229][230][231][232][233][234][235][236][237] and depression [238][239][240][241]. Treatment is associated with changes in these brain regions for both PTSD [34, [242][243][244][245][246][247] and depression [240,241,[248][249][250][251][252]. As reviewed below, similar studies have been performed looking at neural circuits and systems response in depression [253][254][255][256][257][258][259], and our group has initiated studies using High-Resolution Positron Emission Tomography (HRPET) to assess neural correlates of treatment response in PTSD [260]. ...
Background:
Vagal Nerve Stimulation (VNS) has been shown to be efficacious for the treatment of depression, but to date, VNS devices have required surgical implantation, which has limited widespread implementation.
Methods:
New noninvasive VNS (nVNS) devices have been developed which allow external stimulation of the vagus nerve, and their effects on physiology in patients with stress-related psychiatric disorders can be measured with brain imaging, blood biomarkers, and wearable sensing devices. Advantages in terms of cost and convenience may lead to more widespread implementation in psychiatry, as well as facilitate research of the physiology of the vagus nerve in humans. nVNS has effects on autonomic tone, cardiovascular function, inflammatory responses, and central brain areas involved in modulation of emotion, all of which make it particularly applicable to patients with stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD) and depression, since dysregulation of these circuits and systems underlies the symptomatology of these disorders.
Results:
This paper reviewed the physiology of the vagus nerve and its relevance to modulating the stress response in the context of application of nVNS to stress-related psychiatric disorders.
Conclusions:
nVNS has a favorable effect on stress physiology that is measurable using brain imaging, blood biomarkers of inflammation, and wearable sensing devices, and shows promise in the prevention and treatment of stress-related psychiatric disorders.
... The neural correlates of the emotional dysregulation in PTSD likely involve the fronto-limbic system, given the corresponding symptoms of anger, nervousness, fear, intrusive, recurrent recollections, flashbacks, and nightmares. However, only a few publications have utilized cognitive tasks that probe the poor concentration and other related executive function difficulties that are commonly noted in PTSD (Moores et al. 2008;Sailer et al. 2008;Felmingham et al. 2009;Cisler et al. 2015;Shaw et al. 2009;Elman et al. 2009;Astur et al. 2006;Strigo et al. 2010;Geuze et al. 2008;Bryant et al. 2005;Falconer et al. 2008;Jovanovic et al. 2013). Given that emotions influence cognition, it is hypothesized that there would be whole-brain involvement, with combined emotional and cognitive domain dysfunction and corresponding network abnormalities in both the cognitive and emotional brain networks. ...
Post-traumatic stress disorder (PTSD) manifests as emotional suffering and problem-solving impairments under extreme stress. This meta-analysis aimed to pool the findings from all the studies examining emotion and cognition in individuals with PTSD to develop a robust mechanistic understanding of the related brain dysfunction. We identified primary studies through a comprehensive literature search of the MEDLINE and PsychINFO databases. The GingerALE software (version 2.3.6) from the BrainMap Project was used to conduct activation likelihood estimation meta-analyses of the eligible 1,2 1 1✉ 1 2 2020. 6. 25. e.Proofing https://eproofing.springer.com/journals_v2/printpage.php?token=aF_v5_IYYg7SyY2S0QpbwX_RPueCNgnkPlDIILDR63P-A4zL_yy0OzAOmCpX… 2/36 studies for cognition, emotion and interface of both. Relative to the non-clinical (NC) group, the PTSD group showed greater activation during emotional tasks in the amygdala and parahippocampal gyrus. In contrast, the NC group showed significantly greater activation in the bilateral anterior cingulate cortex (ACC) than did the PTSD group in the emotional tasks. When both emotional and cognitive processing were evaluated, the PTSD group showed significantly greater activation in the striatum than did the NC group. No differences in activation between the PTSD and NC groups were noted when only the cognitive systems were examined. Individuals with PTSD exhibited overactivity in the subcortical regions, i.e., amygdala and striatum, when processing emotions. Underactivity in the emotional and cognitive processing intermediary cortex, i.e., the ACC, was especially prominent in individuals with PTSD relative to the NC population following exposure to emotional stimuli. These findings may explain the trauma-related fear, irritability, and negative effects as well as the concentration difficulties during cognitive distress associated with emotional arousal, that are commonly observed in individuals with PTSD.
... RACC hyperactivity related to intrusion frequency is in line with results of Bourne et al. (26), demonstrating heightened rACC activity to intrusion-eliciting versus non-intrusion-eliciting film scenes. Relatedly, rACC hyperactivity has been reported in PTSD (53,54) and might be associated with increased attention to salient information (49,55,56). Although VMPFC hyporesponsiveness in PTSD (57) has been linked to deficient emotion regulation, the current study indicates a positive correlation between VMPFC activity and subsequent intrusion frequency, which could in combination with rACC reflect unsuccessful regulation (58). ...
Background:
Deficient extinction learning has been suggested as an important mechanism involved in the etiology of posttraumatic stress disorder (PTSD). A key feature of PTSD, re-experiencing the trauma in form of intrusions, may be linked to deficient extinction learning. This link is investigated in a novel, fMRI-compatible fear conditioning procedure that uses trauma-films. Based on previous results, we expected deficient fear extinction indexed by exaggerated responding in anterior insula and dorsal anterior cingulate cortex (dACC) to predict subsequent intrusions.
Methods:
Fifty-eight healthy participants underwent acquisition and extinction learning with faces as conditioned stimuli (CS) and highly aversive 16-sec films depicting interpersonal violence as unconditioned stimuli (US). During three subsequent days, participants reported intrusive memories on their smartphone.
Results:
Successful fear acquisition was evidenced by differential (CS+>CS-) activity of a widespread network including anterior insula and dACC whereas extinction was characterized exclusively by differential anterior insula activity. Differential conditioned responding during late extinction in anterior insula and dACC was positively related to intrusive memory frequency independently of US responding. Exploratory analysis additionally revealed intrusion sensitivity of hippocampus, rostral anterior cingulate cortex and ventromedial prefrontal cortex amongst others.
Conclusions:
Results support the role of extinction learning in intrusive memory formation: a failure to uncouple conditioned emotional responding from external threat cues was associated with subsequent intrusive memories, representing a potential risk marker for developing PTSD-symptomatology after trauma.
... Those findings are well in line with findings by Bourne et al. (9) that show stronger rACC activity to intrusion-eliciting versus nonintrusion-eliciting aversive film scenes, though a history of lifetime adversity was not taken into account. Although some clinical PTSD studies reported rACC hypoactivity in association with amygdala inhibition (13), others reported hyperactivity (71)(72)(73). Moreover, as rACC hyperactivity has been linked to increased attention to salient information (66,74,75), those findings could further be in line with increased salience mapping as a mechanism explaining increased intrusion load; however, rACC hyperactivity could also implicate unsuccessful emotional regulation (76), particularly in participants reporting several lifetime adversities. ...
Background:
Pathological peritraumatic encoding is proposed as a proximal risk factor for the development of posttraumatic stress disorder (PTSD), with trauma-analog studies linking increased neural processing of trauma films to intrusive trauma recollections, a core symptom of PTSD. Cumulative lifetime adversity is proposed as a more distal risk factor, with research indicating a tipping point at about five events with regard to PTSD development following re-exposure to trauma. Thus, within a diathesis × stress framework, increased peritraumatic neural processing may constitute a specific risk factor for PTSD, particularly in individuals with several lifetime adversities.
Methods:
Fifty-three healthy women watched highly aversive films depicting severe interpersonal violence versus neutral films during functional magnetic resonance imaging, and they reported involuntary recollections during subsequent days. Moderation analyses tested the interactive relationship between peritraumatic neural processing and lifetime adversity in predicting intrusion load, i.e., the total number of intrusions weighted for their average distress.
Results:
Increased processing of aversive versus neutral films in the amygdala, anterior insula, dorsal and rostral anterior cingulate cortices, and hippocampus predicted increased intrusion load only in participants reporting above five lifetime adversities; for participants reporting few to none, no such relationship was found. This interactive relationship explained ≤59% of variance. Conditioned stimuli preceding film viewing mirrored this pattern.
Conclusions:
Peritraumatic neural processing in multiple salience network regions and cumulative lifetime adversity interactively predicted PTSD-like symptomatology, representing a diathesis × stress framework that might guide identification of at-risk individuals and potential targets for symptom prevention after traumatic incidents.
... As the SCR response is one of the putative biomarkers of anxiety (Orr et al., 2002;Pole et al., 2003Pole et al., , 2009, smaller caudal ACC volume may reffect general ACC hypofunction, which may be associated with a greater threat sensitivity and a stronger threat response. There is some evidence that suggests ACC dysfunction in individuals with PTSD is linked to a compromised arousal network (Felmingham et al., 2009). Thus, smaller ACC volume may interact with trauma exposure to inffuence resting arousal, which could in turn lead to greater threat sensitivity (e.g. ...
Posttraumatic stress disorder (PTSD) is associated with fear response system dysregulation. Research has shown that the anterior cingulate cortex (ACC) may modulate the fear response and that individuals with PTSD have abnormalities in ACC structure and functioning. Our objective was to assess whether ACC volume moderates the relationship between PTSD and fear-potentiated psychophysiological response in a sample of Gulf War Veterans. 142 Veteran participants who were associated with a larger study associated with Gulf War Illness were exposed to no threat, ambiguous threat, and high threat conditions in a fear conditioned startle response paradigm and also provided MRI imaging data. PTSD was assessed using the Clinician Administered PTSD Scale (CAPS). Decreased caudal ACC volume predicted greater psychophysiological responses with a slower habituation of psychophysiological magnitudes across trials (p < 0.001). PTSD diagnosis interacted significantly with both caudal and rostral ACC volumes on psychophysiological response magnitudes, where participants with PTSD and smaller rostral and caudal ACC volumes had greater psychophysiological magnitudes across trials (p < 0.05 and p < 0.001, respectively) and threat conditions (p < 0.05 and p < 0.005). Our results suggest that ACC volume may moderate both threat sensitivity and threat response via impaired habituation in individuals who have been exposed to traumatic events. More research is needed to assess whether ACC size and these associated response patterns are due to neurological processes resulting from trauma exposure or if they are indicative of a premorbid risk for PTSD subsequent to trauma exposure.
... The dlPFC is also involved in selective attention processes in PTSD in combination with the ventrolateral PFC, ACC, and amygdala (Bremner et al., 2004;El Khoury-Malhame et al., 2011;Felmingham et al., 2009). In PTSD, greater dlPFC activation is associated with lower symptoms in an emotional anticipation task (Aupperle et al., 2012), and smaller dlPFC activation was found in response to threat cue trials (Fani et al., 2012). ...
Objective
Posttraumatic stress disorder (PTSD) is a trouble that arises in the aftermath of a traumatic event. The overwhelming resulting stressful memory can be desensitized by a brief therapy, Eye Movement Desensitization and Reprocessing (EMDR). The aim of the present study is to explore the functional brain correlate of such an effective treatment (EMDR) in PTSD.
Method
Sixteen PTSD patients underwent fMRI during negative emotional face recognition task, before and after EMDR treatment. Brain activity changes at test and retest (P < 0.005) were compared to those of 16 healthy controls matched for age, gender, and education.
Results
In PTSD patients, EMDR therapy elicited significant functional decreases in deep gray matter (including the amygdala, thalamus, and caudate nucleus) and cortical activities (including notably the precuneus, and the ventromedial and dorsolateral prefrontal cortex), as compared to healthy controls (P < 0.005). The right thalamic activity decrease was positively correlated with PTSD symptom reduction as assessed by PCL-S (r = 0.62, n = 16, P < 0.01).
Conclusions
The healing process of traumatic memory desensitization by EMDR would act through a functional decrease in brain regions shown to be disrupted in PTSD. Given the role of these structures in memory, self-perception, fear extinction, REM sleep, reward, and attention, we discuss possible explanations of EMDR mechanisms of action in PTSD that may help further improve this therapy.
... Hence, the dorsal ACC is suggested to be important in the detection of and response to threatening social and physical stimuli (Eisenberger and Lieberman, 2004). Furthermore, increased dorsal ACC activation has been widely reported in patients with PTSD (Felmingham et al., 2009;Milad et al., 2009;Shin et al., 2007) and has been suggested as the mediator of hyperarousal symptoms of PTSD (Hamner et al., 1999). The dorsal ACC is also a region known to be greatly influenced by cytokine action. ...
The heterogeneity of post-traumatic stress disorder (PTSD) symptoms indicates that multiple neurobiological mechanisms underlie the pathophysiology of the condition. However, no generally accepted PTSD biomarkers in clinical practice currently exist. The sequential responses to recurrent and chronic stress by the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) system are considered to play a significant role in the onset and progression of PTSD. Decreased activity of the HPA axis and parasympathetic nervous system, along with increased activity of the sympathetic nervous system, have been observed in PTSD, which may lead to increased levels of proinflammatory cytokines. Such heightened activity of the immune system may cause alterations in the structure and function of brain regions-for example, the amygdala, hippocampus, medial prefrontal cortex, anterior cingulate cortex, and insula-through changes in levels of serotonin and kynurenine pathway metabolites, and direct neurotoxic effects of cytokines. Although chronic inflammation-induced alterations in brain regions critical in controlling emotional behavior and fear regulation may represent a strong candidate biomarker of PTSD, future studies are necessary to further elucidate inflammation-associated neural biomarkers of PTSD. Continued research on therapeutic methods that involve the normalization of the HPA axis, ANS, and immune system is expected to contribute to the development of novel ways to treat PTSD.
... En fait, il existe une atteinte très disparate des flux informationnels dont il est le siège.Plus précisément, il existe une hyperactivité du Cortex Cingulaire Antérieur dorsal et une hypoactivité du Cortex Cingulaire Antérieur ventral, retrouvée en IRMf notamment par K.FELMINGHAM en 2009(86) . Le CCA dorsal joue un rôle dans la détection des conflits tandis que le CCA ventral oriente vers la résolution de ceux-ci.Cela expliquerait le défaut d'extinction du conditionnement aversif, et donc des symptômes selon certains auteurs, comme BRUNET. ...
Si les phénomènes de transe sont connus depuis l'Antiquité, le débat sur la nature de l'hypnose entre étatistes et non-étatistes, vieux de plusieurs siècles, est aujourd'hui clos notamment grâce aux progrès apportés par la neuro-imagerie fonctionnelle. En effet, celle-ci permet d'objectiver l'existence d'un fonctionnement neurologique propre en hypnose, corroborant donc l'hypothèse de l'existence d'un état hypnotique, différent de l'état vigil. Cela vient appuyer les thèses psychodynamiques d'Hilgard et Janet, expliquant l'hypnose par un état de conscience modifié et une dissociation dans les fonctions du Moi. Un certain nombre de caractéristiques propres à l'hypnothérapie en font un traitement de choix du psychotraumatisme, qui reste un enjeu majeur de santé publique du fait notamment de sa forte prévalence et de l'importance de ses conséquences sur la santé psychique des sujets. Or, si les études réalisées à ce jour sont encourageantes, elles sont encore trop peu nombreuses pour valider l'hypnothérapie comme traitement de première intention des états de stress post-traumatiques. Certains obstacles propres à l'évaluation d'une thérapie qui se plie difficilement aux protocoles de la recherche en médecine constituent un élément de réponse quant à cette carence d'études sur le sujet. Il reste donc nécessaire d'approfondir la recherche en ce domaine, l'hypnose étant en mesure de constituer un atout thérapeutique majeur dans la prise en charge du psychotraumatisme.
... They argue that distraction by meaningless perceptual changes reduces one's ability to identify meaningful event boundaries within the environment and, thus, interfere with comprehending the larger unfolding event. They suggest a link between PTSD symptoms and diminished segmentation may be rooted in hyperactivation in the dorsal anterior cingulate context (dACC), which has been linked to PTSD symptoms Felmingham et al., 2009) and cognitive processes that support segmentation (Cohen, Botvinick, & Carter, 2000). They posit PTSD or dACC hyperactivation could potentially affect several segmentation processes including making perceptual predictions, monitoring prediction errors, orienting, and updating memory. ...
... For instance, PTSD patients were shown to have a reduced ACC volume in comparison to the healthy controls (Abe et al., 2006;Karl, Malta, & Maercker, 2006). Furthermore, studies showed greater ventral ACC activation Werner et al., 2009) and dorsal ACC activation in PTSD (Felmingham et al., 2009;Shin et al., 2011). It is possible that trauma-related alterations in the ACC functioning may lead to the reduced cognitive control in PTSD patients observed in the current study, which is consistent with previous studies (Johnsen, Kanagaratnam, & Asbjornsen, 2011). ...
Background:
Attentional bias to affective information and reduced cognitive control may maintain the symptoms of post-traumatic stress disorder (PTSD) and impair cognitive functioning. However, the role of content specificity of affective stimuli (e.g., trauma-related, emotional trauma-unrelated) in the observed attentional bias and cognitive control is less clear, as this has not been tested simultaneously before. Therefore, we examined the content specificity of attentional bias to threat in PTSD.
Methods:
PTSD participants (survivors of a multistory factory collapse, n=30) and matched controls (n=30) performed an Eriksen Flanker task. They identified the direction of a centrally presented target arrow, which was flanked by several task-irrelevant distractor arrows pointed to the same (congruent) or opposite direction (incongruent). Additionally, participants were presented with a picture of a face (neutral, emotional) or building (neutral=normal, emotional=collapsed multistory factory) as a task-irrelevant background image.
Results:
We found that PTSD participants produced overall larger conflict effects and longer reaction times (RT) to emotional than to neutral stimuli relative to their healthy counterparts. Moreover, PTSD, but not healthy participants showed a stimulus specific dissociation in processing emotional stimuli. Emotional faces elicited longer RTs compared to neutral faces, while emotional buildings elicited faster responses, compared to neutral buildings.
Conclusions:
PTSD patients show a content-sensitive attentional bias to emotional information and impaired cognitive control.
... 71 studies suggest that PTSD is associated with a reduction in activity of the ventral anterior cingulate gyrus that is specifically linked to engagement of arousal networks as assessed by increases in skin conduction in response to neuropsychological challenge. 73 ...
Stress in mammals triggers a neuroendocrine response mediated by the hypothalamic–pituitary–adrenal (HPA) axis and the autonomic nervous system (ANS). Increased activity of these two systems induces behavioral, cardiovascular, endo-crine, and metabolic cascades that enable the individual to fight or flee and cope with stress. Our understanding of stress and stress response mechanisms is generally robust. However, several themes remain uncertain/controversial and perhaps deserve further scrutiny before they achieve canonical status. These themes include perinatal exposure effects on the health of the adult, genetic susceptibility to stress, the neurochemis-try of posttraumatic stress disorder (ANS versus the HPA), significance of hippocampal volume for major depressive disorder and other mental disorders, and the role of stress in the etiology of gastroduodenal ulcers. All five themes are of clinical and therapeutic significance, pose fundamental questions about stress mechanisms and offer important areas for future research.
... We also detected initial and sustained hyperactivations in MCC and PCC in PTSD patients in contrast to HC. Cingulate cortex activation was also found in HC during anticipation of aversive stimuli [Alvarez et al., 2011;Chua et al., 1999;Drabant et al., 2011;Kalisch et al., 2006;Nitschke et al., 2006] and patients with panic disorder expecting a panic attack [Boshuisen et al., 2002] or disorder-related pictures [Wittmann et al., 2014]. In PTSD, hyperactivations in MCC have been found during fear conditioning [Rougemont-Bucking et al., 2011], recall of extinction learning [Milad et al., 2009], and auditory oddball paradigms [Bryant et al., 2005;Felmingham et al., 2009;Pannu Hayes et al., 2009]. Additionally, a metaanalysis of neuroimaging studies in PTSD provided evidence for MCC hyperresponsiveness in PTSD [Shin and Herrmann et al., 2016]. ...
Feelings of uncontrollability and anxiety regarding possibly harmful events are key features of post-traumatic stress disorder (PTSD) symptomatology. Due to a lack of studies, the neural correlates of anticipatory anxiety in PTSD are still poorly understood. During functional magnetic resonance imaging, female PTSD patients with interpersonal violence trauma and healthy controls (HC) anticipated the temporally unpredictable presentation of aversive (human scream) or neutral sounds. Based on separate analysis models, we investigated phasic and sustained brain activations. PTSD patients reported increased anxiety during anticipation of aversive versus neutral sounds. Furthermore, we found both increased initial, phasic amygdala activation and increased sustained activation of the bed nucleus of the stria terminalis (BNST) during anticipation of aversive versus neutral sounds in PTSD patients in comparison to HC. PTSD patients as compared with HC also showed increased phasic responses in mid-cingulate cortex (MCC), posterior cingulate cortex (PCC), mid-insula and lateral prefrontal cortex (PFC) as well as increased sustained responses in MCC, PCC, anterior insula and lateral and medial PFC. Our results demonstrate a relationship between anticipatory anxiety in PTSD patients and hyperresponsiveness of brain regions that have previously been associated with PTSD symptomatology. Additionally, the dissociation between amygdala and BNST indicates distinct temporal and functional characteristics and suggests that phasic fear and sustained anxiety responses are enhanced during unpredictable anticipation of aversive stimuli in PTSD. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.
... 71 studies suggest that PTSD is associated with a reduction in activity of the ventral anterior cingulate gyrus that is specifically linked to engagement of arousal networks as assessed by increases in skin conduction in response to neuropsychological challenge. 73 ...
Stress in mammals triggers a neuroendocrine response mediated by the hypothalamic–pituitary–adrenal (HPA) axis and the autonomic nervous system (ANS). Increased activity of these two systems induces behavioral, cardiovascular, endocrine, and metabolic cascades that enable the individual to fight or flee and cope with stress. Our understanding of stress and stress response mechanisms is generally robust. However, several themes remain uncertain/controversial and perhaps deserve further scrutiny before they achieve canonical status. These themes include perinatal exposure effects on the health of the adult, genetic susceptibility to stress, the neurochemistry of posttraumatic stress disorder (ANS versus the HPA), significance of hippocampal volume for major depressive disorder and other mental disorders, and the role of stress in the etiology of gastroduodenal ulcers. All five themes are of clinical and therapeutic significance, pose fundamental questions about stress mechanisms and offer important areas for future research.
... tion, where they demonstrated that increased connectivity between the mid-dorsal ACC and the midbrain during imminent danger is associated with automatic or 'hard-wired' defensive behaviors (also see Panksepp, 1998). Aberrant ACC activity is strongly associated with PTSD and is thought to contribute to reexperiencing, avoidance, and hyperarousal symptoms (Felmingham et al., 2009;Rougemont-Bücking et al., 2011;Shin et al., 2001). Given that the PAG failed to show connectivity with the dACC in healthy participants, the increased VL-PAG and DL-PAG connectivity with the dACC in PTSD patients observed here suggests inadequate control of fear, which in turn may contribute to a predisposition to engage in reflexive defensive behaviors. ...
Background
Posttraumatic stress disorder (PTSD) is associated with hyperarousal and active fight or flight defensive responses. By contrast, the dissociative subtype of PTSD, characterized by depersonalization and derealization symptoms, is frequently accompanied by additional passive or submissive defensive responses associated with autonomic blunting. Here, the periaqueductal gray (PAG) plays a central role in defensive responses, where the dorsolateral (DL‐PAG) and ventrolateral PAG (VL‐PAG) are thought to mediate active and passive defensive responses, respectively.
Methods
We examined PAG subregion (dorsolateral and ventrolateral) resting‐state functional connectivity in three groups: PTSD patients without the dissociative subtype (n = 60); PTSD patients with the dissociative subtype (n = 37); and healthy controls (n = 40) using a seed‐based approach via PickAtlas and SPM12.
Results
All PTSD patients showed extensive DL‐ and VL‐PAG functional connectivity at rest with areas associated with emotional reactivity and defensive action as compared to controls (n = 40). Although all PTSD patients demonstrated DL‐PAG functional connectivity with areas associated with initiation of active coping strategies and hyperarousal (e.g., dorsal anterior cingulate; anterior insula), only dissociative PTSD patients exhibited greater VL‐PAG functional connectivity with brain regions linked to passive coping strategies and increased levels of depersonalization (e.g., temporoparietal junction; rolandic operculum).
Conclusions
These findings suggest greater defensive posturing in PTSD patients even at rest and demonstrate that those with the dissociative subtype show unique patterns of PAG functional connectivity when compared to those without the subtype. Taken together, these findings represent an important first step toward identifying neural and behavioral targets for therapeutic interventions that address defensive strategies in trauma‐related disorders.
... Exaggerated activation of the dACC has been well described in individuals with PTSD (Felmingham et al, 2009;Milad et al, 2009;Pannu Hayes et al, 2009;Shin et al, 2007;Shin et al, 2001) and is associated with increased attention bias to threat (Fani et al, 2012a). Women with PTSD due to interpersonal trauma also show increased dACC activity in response to viewing threatening facing (Eisenberger et al, 2005). ...
The study of inflammation in fear- and anxiety- disorders has gained interest as a growing literature indicates that pro-inflammatory markers can directly modulate affective behavior. Indeed, heightened concentrations of inflammatory signals, including cytokines and C-reactive protein (CRP), have been described in posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), and phobias (agoraphobia, social phobia, etc.). However, not all reports indicate a positive association between inflammation and fear- and anxiety- symptoms, suggesting that other factors are important in future assessments of inflammation's role in the maintenance of these disorders (ie sex, comorbid conditions, types of trauma exposure, behavioral sources of inflammation). The most parsimonious explanation of increased inflammation in PTSD, GAD, PD, and phobias is via the activation of the stress response and central and peripheral immune cells to release cytokines. Dysregulation of the stress axis in the face of increased sympathetic tone and decreased parasympathetic activity characteristic of anxiety disorders could further augment inflammation and contribute to increased symptoms by having direct effects on brain regions critical for the regulation of fear and anxiety (such as the prefrontal cortex, insula, amygdala and hippocampus). Taken together, the available data suggest that targeting inflammation may serve as a potential therapeutic target for treating these fear- and anxiety- disorders in the future. However, the field must continue to characterize the specific role pro-inflammatory signaling in the maintenance of these unique psychiatric conditions.Neuropsychopharmacology accepted article preview online, 11 August 2016. doi:10.1038/npp.2016.146.
... The finding of greater rACC activation in nondrinkers as compared to drinkers absent a difference in SSRT may suggest an effect of alcohol use on altered saliency processing. The rACC is implicated in saliency responses in a variety of behavioral paradigms (Brazdil et al., 2007) and decreased activation in many clinical conditions including alcohol and substance use disorders (Felmingham et al., 2009;Heinz et al., 2007;Moeller et al., 2014). For instance, decreased rACC response to errors is associated with impaired emotional awareness in cocaine abusers (Moeller et al., 2014) and impaired error awareness in cannabis users (Hester et al., 2009). ...
Background:
Deficits in inhibitory control have been widely implicated in alcohol misuse. However, the literature does not readily distinguish the effects of drinking problems and chronic alcohol use. Here, we examined how years of drinking and the Alcohol Use Disorders Identification Test (AUDIT) score each influences the cerebral responses to inhibitory control in nondependent drinkers.
Methods:
Fifty-seven adult drinkers and 57 age- and gender-matched nondrinkers participated in one 40-minute functional magnetic resonance imaging scan of the stop signal task. Data were preprocessed and modeled using SPM8. In a regression model, we contrasted stop and go success trials for individuals and examined activities of response inhibition each in link with the AUDIT score and years of alcohol use in group analyses. We specified the effects of duration of use by contrasting regional activations of drinkers and age-related changes in nondrinkers. In mediation analyses, we investigated how regional activities mediate the relationship between drinking problems and response inhibition.
Results:
Higher AUDIT score but not years of drinking was positively correlated with prolonged stop signal reaction time (SSRT) and diminished responses in the cerebellum, thalamus, frontal and parietal regions, independent of years of alcohol use. Further, activity of the thalamus, anterior cingulate cortex, and presupplementary motor area significantly mediates the association, bidirectionally, between the AUDIT score and SSRT. The duration of alcohol use was associated with decreased activation in the right inferior frontal gyrus extending to superior temporal gyrus, which was not observed for age-related changes in nondrinkers.
Conclusions:
The results distinguished the association of drinking problems and years of alcohol use to inhibitory control in young adult nondependent drinkers. These new findings extend the imaging literature of alcohol misuse and may have implications for treatment to prevent the escalation from social to dependent drinking. More research is needed to confirm age-independent neural correlates of years of alcohol use.
... Previous studies have reported ACC volume reduction as well as diminished cingulate activity during identification of fearful facial affect in patients with PD (Asami et al., 2008;Pillay et al., 2006). Impaired ACC activity appears to be associated with engagement of arousal networks in anxiety-related disorders (Felmingham et al., 2009;Shin et al., 2001). The currently observed blunted ACC Glx response to a panicogenic challenge in T allele carriers could thus be hypothesized to be due to chronic hyperarousal in NPSR1 T risk allele carriers, while the rapid and dynamic increase of Glx/Cr concentration in AA homozygotes potentially reflects an adaptive and thus resilience-increasing stress-counteracting reaction. ...
An excitatory-inhibitory neurotransmitter dysbalance has been suggested in pathogenesis of panic disorder. The neuropeptide S (NPS) system has been implicated in modulating GABA and glutamate neurotransmission in animal models and to genetically drive altered fear circuit function and an increased risk of panic disorder in humans. Probing a multi-level imaging genetic risk model of panic, in the present magnetic resonance spectroscopy (MRS) study brain glutamate+glutamine (Glx) levels in the bilateral anterior cingulate cortex (ACC) during a pharmacological cholecystokinin tetrapeptide (CCK-4) panic challenge were assessed depending on the functional neuropeptide S receptor gene (NPSR1) rs324981 A/T variant in a final sample of 35 healthy male subjects. The subjective panic response (Panic Symptom Scale; PSS) as well as cortisol and ACTH levels were ascertained throughout the experiment. CCK-4 injection was followed by a strong panic response. A significant time×genotype interaction was detected (p=.008), with significantly lower ACC Glx/Cr levels in T allele carriers as compared to AA homozygotes 5min after injection (p=.003). CCK-4 induced significant HPA axis stimulation, but no effect of genotype was discerned. The present pilot data suggests NPSR1 gene variation to modulate Glx levels in the ACC during acute states of stress and anxiety, with blunted, i.e. possibly maladaptive ACC glutamatergic reactivity in T risk allele carriers. Our results underline the notion of a genetically driven rapid and dynamic response mechanism in the neural regulation of human anxiety and further strengthen the emerging role of the NPS system in anxiety.
Copyright © 2015. Published by Elsevier B.V.
... Activation likelihood estimation meta-analytic results for studies comparing PTSD to trauma-naïve controls using whole brain-based analysis and ROI analysis, excluding studies presenting trauma-related stimuli, at cluster level inference p < 0.05. (Astur et al., 2006;Aupperle et al., 2012;Bluhm et al., 2012;Bruce et al., 2013;Bryant et al., 2005Bryant et al., , 2008El Khoury-Malhame et al., 2011;Elman et al., 2009;Falconer et al., 2008;Felmingham et al., 2009Felmingham et al., , 2010Fonzo et al., 2010;Frewen et al., 2010Frewen et al., , 2012Jatzko et al., 2006;Kim et al., 2008;Landré et al., 2012;Mazza et al., 2012Mazza et al., , 2013Protopopescu et al., 2005;Sailer et al., 2008;Sakamoto et al., 2005;Schechter et al., 2012;Simmons et al., 2008Simmons et al., , 2009Steuwe et al., 2014;Strigo et al., 2010;Thomaes et al., 2009;van Rooij et al., 2014;Werner et al., 2009;Williams et al., 2006;Zhang et al., 2013). Due to overlap between participants used in multiple studies, one study was excluded from each group, leaving the final meta-analysis of trauma-exposed controls compared to individuals with PTSD comprised of 18 studies (577 participants, 145 foci) for whole-brain analyses; and 20 studies (609 participants, 93 foci) for ROI analyses. ...
... Investigations in animals have employed lesion methods [6], electrical stimulation [7], and pharmacologic [8] and optogenetic manipulation [9]. In humans, work has included psychophysical experiments on measures of arousal [10,11], functional neuroimaging studies [3,12,13], and even naturalistic lesion studies [14]. ...
Combat stress can be followed by persistent emotional consequences. It is thought that these emotional consequences are caused in part by increased amygdala reactivity. It is also thought that amygdala hyper-reactivity results from decreased inhibition from portions of the anterior cingulate cortex (ACC) in which activity is negatively correlated with activity in the amygdala. However, experimental support for these proposals has been inconsistent.
We showed movies of combat and civilian scenes during a functional magnetic resonance imaging (fMRI) session to 50 veterans of recent combat. We collected skin conductance responses (SCRs) as measures of emotional arousal. We examined the relation of blood oxygenation-level dependent (BOLD) signal in the amygdala and ACC to symptom measures and to SCRs.
Emotional arousal, as measured with SCR, was greater during the combat movie than during the civilian movie and did not depend on symptom severity. As expected, amygdala signal during the less-arousing movie increased with increasing symptom severity. Surprisingly, during the more-arousing movie amygdala signal decreased with increasing symptom severity. These differences led to the unexpected result that amygdala signal in highly symptomatic subjects was lower during the more-arousing movie than during the less-arousing movie. Also unexpectedly, we found no significant inverse correlation between any portions of the amygdala and ACC. Rather, signal throughout more than 80% of the ACC showed a strong positive correlation with signal throughout more than 90% of the amygdala.
Amygdala reactivity can be tuned bi-directionally, either up or down, in the same person depending on the stimulus and the degree of post-traumatic symptoms. The exclusively positive correlations in BOLD activity between the amygdala and ACC contrast with findings that have been cited as evidence for inhibitory control of the amygdala by the ACC. The conceptualization of post-traumatic changes in neural function should be reconsidered.
... VA Author Manuscript brain activation during symptom provocation which may help to define the mechanisms of treatment modality, pathophysiology of PTSD/AUD comorbidity [29,30], provide treatment targets [31,32], and predict response to empirical interventions [33,34]. This study is the largest neuroimaging study of comorbid PTSD/AUD and the first translational study to examine whether patterns of brain activation can predict differences in treatment response in individuals with PTSD/AUD. ...
There is increasing interest in including measures of biological mechanisms as mediators and moderators of treatment outcome in randomized controlled trials (RCT's) of psychotherapy efficacy. However, examining biological mechanisms is often expensive and budget caps of most major funding agencies have remained stable in recent years. The goal of this manuscript is to describe how a psychotherapy efficacy trial is using a model of collaborative, affiliated grants to maximize resources and the potential knowledge to be gained from a single site RCT. The trial is an ongoing RCT comparing two psychotherapies for the treatment of concurrent posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) with a sample of treatment seeking veterans. Through collaboration with a team of investigators with independently-funded but affiliated grants, measures of select sleep, neurobiological, and genetic biomarkers were integrated into this single site RCT. This model has allowed us to pose research questions regarding the role of biological mechanisms, maximize the utility of recruitment, and be efficient in maximizing knowledge to be gained in a way that would not be possible solely on the funding of a single site RCT. Challenges of this model include high participant burden in regard to assessment and complicated coordinating procedures among studies. Strategies to address these challenges are described.
Published by Elsevier Inc.
... Studies report hypoactivation of the rostral ACC in PTSD versus controls during symptom provocation using script-driven imagery [Britton et al., 2005;Lanius et al., 2001Lanius et al., , 2007, during the presentation of trauma-related stimuli [Hou et al., 2007;Yang et al., 2004], and the presentation of negative stimuli Lanius et al., 2003;Shin et al., 2001Shin et al., , 2005Williams et al., 2006]. Several studies have reported that nonthreatening salient stimuli induce dorsal ACC hyperactivity in PTSD versus controls [Bryant et al., 2005;Felmingham et al., 2009;Milad et al., 2009;Rougemont-B€ ucking et al., 2011;Shin et al., 2011]. Thus, depending on the tasks investigated in these studies, there seems to be a tendency that the rostral ACC is hypoactive in PTSD, while the dorsal ACC is hyperactive in PTSD. ...
Post-traumatic stress disorder (PTSD) is an anxiety disorder that is associated with structural and functional alterations in several brain areas, including the anterior cingulate cortex (ACC). Here, we examine resting state functional connectivity of ACC subdivisions in PTSD, using a seed-based approach. Resting state magnetic resonance images were obtained from male veterans with (n = 31) and without (n = 25) PTSD, and healthy male civilian controls (n = 25). Veterans with and without PTSD (combat controls) had reduced functional connectivity compared to healthy controls between the caudal ACC and the precentral gyrus, and between the perigenual ACC and the superior medial gyrus and middle temporal gyrus. Combat controls had increased connectivity between the rostral ACC and precentral/middle frontal gyrus compared to PTSD patients and healthy civilian controls. The resting state functional connectivity differences in the perigenual ACC network reported here indicate that veterans differ from healthy controls, potentially due to military training, deployment, and/or trauma exposure. In addition, specific alterations in the combat controls may potentially be related to resilience. These results underline the importance of distinguishing trauma-exposed (combat) controls from healthy civilian controls when studying PTSD. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
... The MEG gamma-band hyperactivity from dmPFC, including the dACC, in PTSD was also consistent with prior PET and fMRI findings (Bremner et al., 1999;Felmingham et al., 2009;Pannu et al., 2009;Shin et al., 2001Shin et al., , 2007Shin et al., , 2011. The dmPFC, including the dACC, is thought to play an important role in a variety of cognitive processes such as performance monitoring, response selection, error detection, and decision making . ...
Post-traumatic stress disorder (PTSD) is a leading cause of sustained impairment, distress, and poor quality of life in military personnel, veterans, and civilians. Indirect functional neuroimaging studies using PET or fMRI with fear-related stimuli support a PTSD neurocircuitry model that includes amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC). However, it is not clear if this model can fully account for PTSD abnormalities detected directly by electromagnetic-based source imaging techniques in resting-state. The present study examined resting-state magnetoencephalography (MEG) signals in 25 active-duty service members and veterans with PTSD and 30 healthy volunteers. In contrast to the healthy volunteers, individuals with PTSD showed: 1) hyperactivity from amygdala, hippocampus, posterolateral orbitofrontal cortex (OFC), dorsomedial prefrontal cortex (dmPFC), and insular cortex in high-frequency (i.e., beta, gamma, and high-gamma) bands; 2) hypoactivity from vmPFC, Frontal Pole (FP), and dorsolateral prefrontal cortex (dlPFC) in high-frequency bands; 3) extensive hypoactivity from dlPFC, FP, anterior temporal lobes, precuneous cortex, and sensorimotor cortex in alpha and low-frequency bands; and 4) in individuals with PTSD, MEG activity in the left amygdala and posterolateral OFC correlated positively with PTSD symptom scores, whereas MEG activity in vmPFC and precuneous correlated negatively with symptom score. The present study showed that MEG source imaging technique revealed new abnormalities in the resting-state electromagnetic signals from the PTSD neurocircuitry. Particularly, posterolateral OFC and precuneous may play important roles in the PTSD neurocircuitry model.
... fits with a general alteration of arousal-related networks in PTSD (Felmingham et al., 2009). Studies using personalized traumatic scripts as stimuli have found similar results to this study, particularly in relation to the association of PTSD with an altered pattern of ACC and mPFC activation (e.g. ...
Post-traumatic stress disorder (PTSD) is a disorder that involves impaired regulation of the fear response to traumatic reminders.
This study tested how women with male-perpetrated interpersonal violence-related PTSD (IPV-PTSD) differed in their brain activation
from healthy controls (HC) when exposed to scenes of male–female interaction of differing emotional content. Sixteen women
with symptoms of IPV-PTSD and 19 HC participated in this study. During magnetic resonance imaging, participants watched a
stimulus protocol of 23 different 20 s silent epochs of male–female interactions taken from feature films, which were neutral,
menacing or prosocial. IPV-PTSD participants compared with HC showed (i) greater dorsomedial prefrontal cortex (dmPFC) and
dorsolateral prefrontal cortex (dlPFC) activation in response to menacing vs prosocial scenes and (ii) greater anterior cingulate cortex (ACC), right hippocampus activation and lower ventromedial prefrontal
cortex (vmPFC) activty in response to emotional vs neutral scenes. The fact that IPV-PTSD participants compared with HC showed lower activity of the ventral ACC during emotionally
charged scenes regardless of the valence of the scenes suggests that impaired social perception among IPV-PTSD patients transcends
menacing contexts and generalizes to a wider variety of emotionally charged male–female interactions.
... Increased insula was demonstrated in PTSD patients (Etkin & Wager, 2007;Fonzo et al. 2010;Aupperle et al. 2012). Furthermore, increased dACC activity in PTSD was found in several studies (Bryant et al. 2005;Felmingham et al. 2009;Milad et al. 2009;Rougemont-Bucking et al. 2011;Shin et al. 2011). In contrast, the sgACC is particularly associated with major depressive disorder (MDD) (Drevets et al. 1997;Mayberg et al. 1999). ...
Background:
Post-traumatic stress disorder (PTSD) is thought to be characterized by general heightened amygdala activation. However, this hypothesis is mainly based on specific studies presenting fear or trauma-related stimuli, hence, a thorough investigation of trauma-unrelated emotional processing in PTSD is needed.
Methods:
In this study, 31 male medication-naive veterans with PTSD, 28 male control veterans (combat controls; CC) and 25 non-military men (healthy controls; HC) were included. Participants underwent functional MRI while trauma-unrelated neutral, negative and positive emotional pictures were presented. In addition to the group analyses, PTSD patients with and without major depressive disorder (MDD) were compared.
Results:
All groups showed an increased amygdala response to negative and positive contrasts, but amygdala activation did not differ between groups. However, a heightened dorsal anterior cingulate cortex (dACC) response for negative contrasts was observed in PTSD patients compared to HC. The medial superior frontal gyrus was deactivated in the negative contrast in HC, but not in veterans. PTSD+MDD patients showed decreased subgenual ACC (sgACC) activation to all pictures compared to PTSD-MDD.
Conclusion:
Our findings do not support the hypothesis that increased amygdala activation in PTSD generalizes to trauma-unrelated emotional processing. Instead, the increased dACC response found in PTSD patients implicates an attentional bias that extends to trauma-unrelated negative stimuli. Only HC showed decreased medial superior frontal gyrus activation. Finally, decreased sgACC activation was related to MDD status within the PTSD group.
... Furthermore, neuroimaging studies demonstrated functional and morphological abnormalities in the ACC of patients with PTSD. Brain functional studies using positron emission tomography (PET) or functional magnetic resonance imaging (fMRI) showed altered function in the ACC (Yehuda et al., 2009;Bremner et al., 2005;Felmingham et al., 2009b;Thomaes et al., 2013), while morphometric MRI studies demonstrated reduced volume of the ACC (Woodward et al., 2008;Kitayama et al., 2006b;Cohen et al., 2006) in comparison to non-PTSD subjects. However, volumetric studies of ACC in PTSD using MRI have had conflicting findings; one study using the conventional manual tracing method found significant volume reduction in pregenual ACC, but not dorsal (Rauch et al., 2003). ...
... Further, in an auditory oddball task, targets that elicited arousal as measured by skin conductance responses, were associated with reduced activation in rACC as measured by fMRI, in PTSD subjects relative to controls. In contrast, non-arousing targets had no such rACC effects (209). Together, these findings support the amygdala's suppressive influence on rACC. ...
Posttraumatic stress disorder (PTSD) is a frequent and distressing mental disorder, about which much remains to be learned. It is a heterogeneous disorder; the hyperarousal subtype (about 70% of occurrences and simply termed PTSD in this paper) is the topic of this article, but the dissociative subtype (about 30% of occurrences and likely involving quite different brain mechanisms) is outside its scope. A theoretical model is presented that integrates neuroscience data on diverse brain regions known to be involved in PTSD, and extensive psychiatric findings on the disorder. Specifically, the amygdala is a multifunctional brain region that is crucial to PTSD, and processes peritraumatic hyperarousal on grounded cognition principles to produce hyperarousal symptoms. Amygdala activity also modulates hippocampal function, which is supported by a large body of evidence, and likewise amygdala activity modulates several brainstem regions, visual cortex, rostral anterior cingulate cortex (rACC), and medial orbitofrontal cortex (mOFC), to produce diverse startle, visual, memory, numbing, anger, and recklessness symptoms. Additional brain regions process other aspects of peritraumatic responses to produce further symptoms. These contentions are supported by neuroimaging, neuropsychological, neuroanatomical, physiological, cognitive, and behavioral evidence. Collectively, the model offers an account of how responses at the time of trauma are transformed into an extensive array of the 20 PTSD symptoms that are specified in the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition. It elucidates the neural mechanisms of a specific form of psychopathology, and accords with the Research Domain Criteria framework.
... For instance, Milad et al. (2009) report greater dACC activity during extinction recall in patients with PTSD, and Rougemont-Bucking et al. (2011) report exaggerated dACC activation in response to context presentation during late conditioning and early extinction. Other studies support that dmPFC/dACC hyperactivity in PTSD is also present during cognitive interference tasks such as oddball tasks (Bryant et al., 2005;Felmingham et al., 2009), Stroop tasks (Shin et al., 2007) and the Multi-Source Interference Task (Shin et al., 2011). The greater vmPFC activity found in highly avoidant patients, on the other hand, seemingly diverges from some previous reports of hypoactive vmPFC in PTSD (Bremner et al., 2005;Milad et al., 2009;Rougemont-Bucking et al., 2011). ...
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.
Post-traumatic stress disorder (PTSD) and related trauma spectrum psychiatric disorders, including major depression, borderline personality disorder, and the dissociative disorders, are associated with considerable morbidity and loss of function. Treatment of these disorders, which include medications and psychotherapy, have limitations. New neuromodulation approaches targeting the underlying neurobiology of these disorders—including elevated inflammation, impaired autonomic nervous system activity, and alterations in brain areas that mediate emotion and the stress response—could improve the treatment and management of these patients. Vagal nerve stimulation (VNS) blocks sympathetic and inflammatory responses, and modulates brain areas involved in stress. Implantable VNS devices are approved for treatment refractory depression. New generation transcutaneous VNS devices that stimulate branches of the vagus nerve via the neck (cervical) or ear (auricular) are potentially applicable to trauma spectrum psychiatric disorders. This chapter reviews the effects of VNS on neurobiology and applications to patients with these psychiatric disorders.
The rapidly growing field of immunopsychiatry combines expertise and insights from immunology, psychiatry and neuroscience to understand the role of inflammation and other immune processes in causing and treating mental illness. This represents a major shift in mental health science, traditionally focused on psychological and neuronal mechanisms of depression, psychosis and dementia. This book provides the first comprehensive overview of recent, inter-disciplinary research linking disordered function of the immune system to the brain and mental illness. It offers a broad and deep perspective on the implications of immune system involvement in psychiatric disorders, including a balanced focus on basic science and clinical applications. Chapters cover the scientific evidence linking immune processes to major mental illnesses such as schizophrenia, depression, anxiety and dementia. An invaluable guide for graduate students, doctors in training, scientific researchers and others interested in the link between the immune system and mental health.
Decades of research have revealed that the cingulate cortex is important in posttraumatic stress disorder (PTSD). Initially inspired by basic rodent research examining the mechanisms of fear learning, researchers have attempted to determine the respective roles of the anterior cingulate cortex (ACC), anterior midcingulate cortex (aMCC), and posterior cingulate cortex (PCC) in PTSD. Various neuroimaging techniques have shown the ACC is both functionally hypoactive and structurally diminished in PTSD, while the aMCC is functionally hyperactive and structurally diminished. Relatedly, chronic stress has been shown to be a significant vulnerability factor in the development of PTSD after a traumatic event, inspiring research into the effect of chronic stress on brain activation and structure. Similar to patterns in PTSD, perceived work-related stress, outgroup membership, and lower socioeconomic status appear to negatively affect cingulate function and morphology. While great strides have been made to understand better the ACC, aMCC, and PCC in both PTSD and chronic stress, additional studies are needed to determine the origin of these cingulate abnormalities and whether they can be used as biomarkers in assessing and predicting treatment response in PTSD.
Aim:
Substance use disorders (SUDs) are highly comorbid with post-traumatic stress disorder (PTSD). PTSD-SUD comorbidity is associated with greater functional impairments and relapse risk. Women with SUDs experience markedly higher rates of trauma and PTSD compared to men with SUDs, particularly due to sexual and domestic abuse. Despite the strong association between trauma exposure and SUDs, the neurobiological correlates are understudied, particularly among females with SUDs. However, there is indication of abnormal somatic and interoceptive processing in women with PTSD. The present study examines interoception-linked differences in intrinsic brain networks in a group of women with SUDs and varying histories of trauma exposure, some of whom have a current PTSD diagnosis.
Methods:
Pre-intervention data were analyzed from a subset (N = 43) of women in SUD residential treatment recruited for a mindfulness-based intervention efficacy clinical trial. Participants diagnosed with PTSD (n = 14) or not (n = 29) performed a task which involved attending to the somatic and visceral sensations of the breathing cycle (interoception) while undergoing a functional MRI (fMRI) scan. FMRI analysis employed independent components analysis and dual regression. First, we assessed differences in functional connectivity of interoception-modulated functional networks among those with and without PTSD. Second, we tested associations between network strength and lifetime sexual violence exposure across all participants on networks that showed significant group differences.
Results:
PTSD diagnosis was associated with reduced functional connectivity of an orbitofrontal network with the precuneus, mid-posterior insula, lateral prefrontal cortex and angular gyrus. OFC network strength was inversely associated with sexual violence exposure over-and-above the contribution of PTSD status alone.
Conclusions:
Our findings provide a novel network-level account of brain activity associated with PTSD among women with SUDs, which may inform treatment response in this subpopulation.
Background:
Survival requires effective shifting of attention from one stimulus to another as goals change. It has been consistently demonstrated that posttraumatic stress disorder (PTSD) is associated with both faster orienting of attention toward and slower disengagement of attention from affective stimuli. Prior work, however, suggests that attention abnormalities in PTSD may extend beyond the affective domain.
Methods:
We used the Attention Network Test-modified to include invalid spatial cues-in conjunction with functional magnetic resonance imaging to examine the neurocognitive underpinnings of visuospatial attention in participants with PTSD (n = 31) and control participants who were (n = 20) and were not (n = 21) exposed to trauma.
Results:
We observed deficits in the utilization of spatial information in the group with PTSD. Specifically, compared with the non-trauma-exposed group, participants with PTSD showed a smaller reaction time difference between invalidly and validly cued targets, demonstrating that they were less likely to use spatial cues to inform subsequent behavior. We also found that in both the PTSD and trauma-exposed control groups, utilization of spatial information was positively associated with activation of attentional control regions (e.g., right precentral gyrus, inferior and middle frontal gyri) and negatively associated with activation in salience processing regions (e.g., right insula).
Conclusions:
This pattern suggests that both trauma exposure and psychopathology may be associated with alterations of spatial attention. Overall, our findings suggest that both attention- and salience-network abnormalities may be related to altered attention in trauma-exposed populations. Treatments that target these neural networks could therefore be a new avenue for PTSD research.
Attention impairments are common symptoms of posttraumatic stress disorder (PTSD); however, the nature of these impairments remains elusive. Attention impairment may arise as the result of either excessive response to task-irrelevant stimuli or reduced response to task-relevant information. To test the association between PTSD and response to task-relevant and task-irrelevant stimuli, we used a 3-tone novelty auditory oddball task (AOD). We hypothesized that participants with PTSD relative to trauma controls would have less response during novelty processing in the dorsolateral prefrontal cortex (dlPFC) and the anterior cingulate cortex, as well as less response in the dlPFC and the orbitofrontal cortex during target detection. Thirty-one male veterans completed a 3-tone novelty AOD task during functional magnetic resonance imaging. Compared to trauma controls, the PTSD group had reduced response during novelty processing in ventromedial prefrontal cortex, superior/middle frontal gyrus (dlPFC), supplementary motor area/caudate, and in posterior regions including bilateral posterior cingulate cortex. The current results suggest PTSD is associated with a pattern of reduced response to novel stimuli. A disturbed orienting response in these brain regions could theoretically underlie PTSD attention-related symptoms.
Symptoms of posttraumatic stress disorder (PTSD) are thought to be the behavioral manifestation of stress-induced changes in brain structure and function. More specifically, stress results in acute and chronic changes in neurochemical systems and specific brain regions, which result in long-term changes in neural circuits involved in the stress response. Neuroimaging studies using magnetic resonance imaging (MRI) to measure hippocampal volume demonstrated that Vietnam veterans with PTSD have smaller right hippocampal volume, compared with controls, and that the decreases in hippocampal volume in the PTSD patients were associated with deficits in short-term memory. In addition to investigating changes in brain structure in patients with PTSD, numerous studies have examined changes in the neurohormonal systems that play a role in PTSD and stress responses, including the noradrenergic system and the hypothalamic-pituitary-adrenal (HPA)/cortisol system. In addition to showing deficits in cognitive functioning, PTSD patients have exhibited decreased sensitivity to pain.
Hormonal cycle modulates arousal circuitry. Animal experiments suggested that progesterone enhanced fear-potentiated startle. At present, direct electrophysiological evidence of a gender difference in novel and unpredictive stimuli is still sparse. Ten men and 23 women at one of two different stages of the menstrual cycle (menses phase, WM, and luteal phase, WL) were examined for event-related potential evidence of attention allocation in the oddball task phase (OTP) and predictive task phase (PTP). We used two tones, 1 kHz 80% as standard stimuli and 2 kHz 20%, as novel stimuli presented randomly in OTP. In PTP, every novel stimuli fixed followed a white noise, but 1 kHz tones never followed white noise. The results showed: (1) In OTP, the P3 amplitude in the WL group during the 350–400-ms time window was higher than that of the other two groups. (2) In PTP, no difference was observed between the groups with respect to the amplitude of contingent negative variation during the 1080–1180 ms and 1320–1360 ms time windows. Thus, it is concluded that women in WL present modulated autonomic arousal, but no difference to predictive negative stimuli than women in WM and men.
Assessments of anterior cingulate cortex in experimental animals and humans have led to unifying theories of its structural organization and contributions to mammalian behaviour The anterior cingulate cortex forms a large region around the rostrum of the corpus callosum that is termed the anterior executive region. This region has numerous projections into motor systems, however since these projections originate from different parts of anterior cingulate cortex and because functional studies have shown that it does not have a uniform contribution to brain functions, the anterior executive region is further subdivided into 'affect' and 'cognition' components. The affect division includes areas 25, 33 and rostral area 24, and has extensive connections with the amygdala and periaqueductal grey, and parts of it project to autonomic brainstem motor nuclei. In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal-infant interactions. The cognition divi sion includes caudal areas 24' and 32', the cingulate motor areas in the cingulate sulcus and nociceptive cortex. The cingulate motor areas project to the spinal cord and red nucleus and have premotor functions, while the nociceptive area is engaged in both response selection and cognitively demanding information processing. The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulate cortex in movement affect and social behaviours. Excessive cingulate activity in cases with seizures confirmed in anterior cingulate cortex with subdural electrode recordings, can impair consciousness alter affective stare and expression, and influence skeletomotor and autonomic activity. Interictally, patients with anterior cingulate cortex epilepsy often display psychopathic or sociopathic behaviours. In other clinical examples of elevated anterior cingulate cortex activity it may contribute to ties, obsessive-compulsive behaviours, and aberrent social behaviour. Conversely, reduced cingulate activity following infarcts or surgery can contribute to behavioural disorders including akinetic mutism, diminished self-awareness and depression, motor neglect and impaired motor initiation, reduced responses to pain, and aberrent social behaviour. The role of anterior cingulate cortex in pain responsiveness is suggested by cingulumotomy results and functional imaging studies during noxious somatic stimulation. The affect division of anterior cingulate cortex modulates autonomic activity and internal emotional responses, while the cognition division is engaged in response selection associated with skeletomotor activity and responses to noxious stimuli. Over-all, anterior cingulate cortex appears to play a crucial role in initiation, motivation, and goal-directed behaviours. The anterior cingulate cortex is part of a larger matrix of structures that are engaged in similar functions. These structures from the rostral limbic system and include the amygdala, periaqueductal grey, ventral striatum, orbitofrontal and anterior insular cortices. The system formed by these interconnected areas assesses the motivational content of internal and external stimuli and regulates context-dependent behaviours.
Assessments of anterior cingulate cortex in experimental animals and humans have led to unifying theories of its structural organization and contributions to mammalian behaviour. The anterior cingulate cortex forms a large region around the rostrum of the corpus callosum that is termed the anterior executive region. This region has numerous projections into motor systems, however, since these projections originate from different parts of anterior cingulate cortex and because functional studies have shown that it does not have a uniform contribution to brain functions, the anterior executive region is further subdivided into 'affect' and 'cognition' components. The affect division includes areas 25, 33 and rostral area 24, and has extensive connections with the amygdala and periaqueductal grey, and parts of it project to autonomic brainstem motor nuclei. In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal-infant interactions. The cognition division includes caudal areas 24' and 32', the cingulate motor areas in the cingulate sulcus and nociceptive cortex. The cingulate motor areas project to the spinal cord and red nucleus and have premotor functions, while the nociceptive area is engaged in both response selection and cognitively demanding information processing. The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulate cortex in movement, affect and social behaviours. Excessive cingulate activity in cases with seizures confirmed in anterior cingulate cortex with subdural electrode recordings, can impair consciousness, alter affective state and expression, and influence skeletomotor and autonomic activity. Interictally, patients with anterior cingulate cortex epilepsy often display psychopathic or sociopathic behaviours. In other clinical examples of elevated anterior cingulate cortex activity it may contribute to tics, obsessive-compulsive behaviours, and aberrent social behaviour. Conversely, reduced cingulate activity following infarcts or surgery can contribute to behavioural disorders including akinetic mutism, diminished self-awareness and depression, motor neglect and impaired motor initiation, reduced responses to pain, and aberrent social behaviour. The role of anterior cingulate cortex in pain responsiveness is suggested by cingulumotomy results and functional imaging studies during noxious somatic stimulation. The affect division of anterior cingulate cortex modulates autonomic activity and internal emotional responses, while the cognition division is engaged in response selection associated with skeletomotor activity and responses to noxious stimuli. Overall, anterior cingulate cortex appears to play a crucial role in initiation, motivation, and goal-directed behaviours.(ABSTRACT TRUNCATED AT 400 WORDS)
Patients with posttraumatic stress disorder (PTSD) show a reliable increase in PTSD symptoms and physiological reactivity following exposure to traumatic pictures and sounds. In this study neural correlates of exposure to traumatic pictures and sounds were measured in PTSD.
Positron emission tomography and H2[15O] were used to measure cerebral blood flow during exposure to combat-related and neutral pictures and sounds in Vietnam combat veterans with and without PTSD.
Exposure to traumatic material in PTSD (but not non-PTSD) subjects resulted in a decrease in blood flow in medial prefrontal cortex (area 25), an area postulated to play a role in emotion through inhibition of amygdala responsiveness. Non-PTSD subjects activated anterior cingulate (area 24) to a greater degree than PTSD patients. There were also differences in cerebral blood flow response in areas involved in memory and visuospatial processing (and by extension response to threat), including posterior cingulate (area 23), precentral (motor) and inferior parietal cortex, and lingual gyrus. There was a pattern of increases in PTSD and decreases in non-PTSD subjects in these areas.
The findings suggest that functional alternations in specific cortical and subcortical brain areas involved in memory, visuospatial processing, and emotion underlie the symptoms of patients with PTSD.
The neuronal circuitry underlying posttraumatic stress disorder (PTSD) was studied in traumatized subjects with and without PTSD.
Traumatized subjects with (N=9) and without (N=9) PTSD were studied by using the script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging at a 4-T field strength.
PTSD subjects showed significantly less activation of the thalamus, the anterior cingulate gyrus (Brodmann's area 32), and the medial frontal gyrus (Brodmann's area 10/11) than did the comparison subjects.
The findings suggest anterior cingulate, frontal, and thalamic involvement in the neuronal circuitry underlying PTSD.
Previous functional neuroimaging studies have demonstrated exaggerated amygdala responses and diminished medial prefrontal cortex responses during the symptomatic state in posttraumatic stress disorder (PTSD).
To determine whether these abnormalities also occur in response to overtly presented affective stimuli unrelated to trauma; to examine the functional relationship between the amygdala and medial prefrontal cortex and their relationship to PTSD symptom severity in response to these stimuli; and to determine whether responsivity of these regions habituates normally across repeated stimulus presentations in PTSD.
Case-control study.
Academic medical center.
Volunteer sample of 13 men with PTSD (PTSD group) and 13 trauma-exposed men without PTSD (control group).
We used functional magnetic resonance imaging (fMRI) to study blood oxygenation level-dependent signal during the presentation of emotional facial expressions.
The PTSD group exhibited exaggerated amygdala responses and diminished medial prefrontal cortex responses to fearful vs happy facial expressions. In addition, in the PTSD group, blood oxygenation level-dependent signal changes in the amygdala were negatively correlated with signal changes in the medial prefrontal cortex, and symptom severity was negatively related to blood oxygenation level-dependent signal changes in the medial prefrontal cortex. Finally, relative to the control group, the PTSD group tended to exhibit diminished habituation of fearful vs happy responses in the right amygdala across functional runs, although this effect did not exceed our a priori statistical threshold.
These results provide evidence for exaggerated amygdala responsivity, diminished medial prefrontal cortex responsivity, and a reciprocal relationship between these 2 regions during passive viewing of overtly presented affective stimuli unrelated to trauma in PTSD.
Anterior cingulate cortex (ACC) is a part of the brain's limbic system. Classically, this region has been related to affect, on the basis of lesion studies in humans and in animals. In the late 1980s, neuroimaging research indicated that ACC was active in many studies of cognition. The findings from EEG studies of a focal area of negativity in scalp electrodes following an error response led to the idea that ACC might be the brain's error detection and correction device. In this article, these various findings are reviewed in relation to the idea that ACC is a part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing. Neuroimaging studies showing that separate areas of ACC are involved in cognition and emotion are discussed and related to results showing that the error negativity is influenced by affect and motivation. In addition, the development of the emotional and cognitive roles of ACC are discussed, and how the success of this regulation in controlling responses might be correlated with cingulate size. Finally, some theories are considered about how the different subdivisions of ACC might interact with other cortical structures as a part of the circuits involved in the regulation of mental and emotional activity.
TO seek neural sources of endogenous event-related potentials, brain activations related to rare target stimuli detection in auditory and visual oddball tasks were imaged using a high temporal resolution functional MRI technique. There were multiple modality specific and modality non-specific activations. Auditory specific activations were seen in the bilateral transverse temporal gyri and posterior superior temporal planes while visual specific activations were seen in the bilateral occipital lobes and their junctions with the temporal lobes. Modality non-specific activations were seen in multiple areas including the bilateral parietal and temporal association areas, bilateral prefrontal cortex, bilateral premotor areas, bilateral supplementary motor areas and anterior cingulate gyrus. Results were consistent with previous intracranial evoked potential recording studies, and supported the multiple generator theory of the endogenous event-related potentials.
Levinson and Edelberg's (1985) recent critique of scoring criteria for electrodermal studies pointed to the need to reduce the latency range used to define the electrodermal response. The present study examined the impact of such a narrowing of the latency window upon habituation and instructional effects in studies of the orienting response to low intensity innocuous stimuli. The first experiment found only a small effect of halving the latency window upon habituation to neutral stimuli, apparent as a strengthening of trends over trials. A second experiment showed somewhat larger effects with significant stimuli, apparent as slightly modified trial and group effects. These data support the view that nothing is to be lost by moving to a narrower latency range to define the electrodermal orienting response to stimulus presentation, and suggest that the advantages of such a change will become increasingly important as nonspecific electrodermal fluctuations increase with increasing electrodermal arousal. An analysis of habituation criteria within this context suggested that the choice of two rather than three no-response trials to define habituation adds to the benefits obtained by the selection of a narrow latency window to define the response.
Overlapping phasic skin conductance responses (SCRs) obtained using short interstimulus interval (ISI) paradigms such as those employed in cognitive research, confound measurement of each discrete phasic SCR as well as the tonic skin conductance level (SCL). We report a method of resolving this problem using a modelling technique that takes advantage of the stereotyped nature of the within-subject SCR waveform. A four-parameter sigmoid-exponential SCR model that describes the entire response, was developed and extended to five-, six- and eight-parameter skin conductance (SC) models. These SC models were successfully curve-fitted to more than 60 SC segments, each containing one SCR or two overlapping SCRs on a sloping baseline obtained from 20 normal subjects. The SC segments were consequently decomposed into their components: the tail of the previous response, one or two SCRs and the SCL. The SCRs free of the complication of overlap were then quantified. The raw SCRs of the same data set were also measured using a standard method. The standard measurement showed a significant reduction of 15% in amplitude and 140 ms in peak latency compared to our method. The basic four SCR model parameters--onset time, rise time, decay time constant and gain--showed increasing inter-subject variability in that order. These SCR model parameters may be studied as variables in normal and patient groups and as indices of treatment response. This quantitative method also provides a means to assess the relationships between central and autonomic psychophysiologic measures.
This study investigated attentional allocation in 39 Vietnam combat veterans, 25 with and 14 without posttraumatic stress disorder, assessing P300 amplitudes and latencies during both three-tone and novelty "oddball" tasks.
The three-tone oddball task consisted of three stimuli: frequent tones (85%), rare target tones (7.5%), and rare distractor tones (7.5%). The novelty oddball task was identical to the three-tone task except that the rare distractor tones were replaced with nonrepeating novel sounds (7.5%).
Combat veterans with posttraumatic stress disorder showed significant P300 amplitude enhancements at frontal sites in response to distracting stimuli during the novelty but not during the three-tone oddball tasks. There were no amplitude differences in target tones during either task.
The data suggest that combat veterans with posttraumatic stress disorder demonstrate P300 responses consistent with a heightened orientation response to novel, distracting stimuli. This finding is consistent both with the clinical presentation of the disorder and with theoretical notions that individuals with posttraumatic stress disorder demonstrate information-processing biases towards vague or potentially threatening stimuli.
Anterior cingulate cortex (ACC) is a part of the brain's limbic system. Classically, this region has been related to affect, on the basis of lesion studies in humans and in animals. In the late 1980s, neuroimaging research indicated that ACC was active in many studies of cognition. The findings from EEG studies of a focal area of negativity in scalp electrodes following an error response led to the idea that ACC might be the brain's error detection and correction device. In this article, these various findings are reviewed in relation to the idea that ACC is a part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing. Neuroimaging studies showing that separate areas of ACC are involved in cognition and emotion are discussed and related to results showing that the error negativity is influenced by affect and motivation. In addition, the development of the emotional and cognitive roles of ACC are discussed, and how the success of this regulation in controlling responses might be correlated with cingulate size. Finally, some theories are considered about how the different subdivisions of ACC might interact with other cortical structures as a part of the circuits involved in the regulation of mental and emotional activity.
An anatomical parcellation of the spatially normalized single-subject high-resolution T1 volume provided by the Montreal Neurological Institute (MNI) (D. L. Collins et al., 1998, Trans. Med. Imag. 17, 463-468) was performed. The MNI single-subject main sulci were first delineated and further used as landmarks for the 3D definition of 45 anatomical volumes of interest (AVOI) in each hemisphere. This procedure was performed using a dedicated software which allowed a 3D following of the sulci course on the edited brain. Regions of interest were then drawn manually with the same software every 2 mm on the axial slices of the high-resolution MNI single subject. The 90 AVOI were reconstructed and assigned a label. Using this parcellation method, three procedures to perform the automated anatomical labeling of functional studies are proposed: (1) labeling of an extremum defined by a set of coordinates, (2) percentage of voxels belonging to each of the AVOI intersected by a sphere centered by a set of coordinates, and (3) percentage of voxels belonging to each of the AVOI intersected by an activated cluster. An interface with the Statistical Parametric Mapping package (SPM, J. Ashburner and K. J. Friston, 1999, Hum. Brain Mapp. 7, 254-266) is provided as a freeware to researchers of the neuroimaging community. We believe that this tool is an improvement for the macroscopical labeling of activated area compared to labeling assessed using the Talairach atlas brain in which deformations are well known. However, this tool does not alleviate the need for more sophisticated labeling strategies based on anatomical or cytoarchitectonic probabilistic maps.
The goal of this study was to examine the neuronal circuitry underlying different emotional states (neutral, sad, anxious, and traumatic) in posttraumatic stress disorder (PTSD) in traumatized subjects versus traumatized subjects without PTSD.
Traumatized subjects with (n = 10) and without (n = 10) PTSD were studied using the script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging (fMRI) at a 4 Tesla field strength.
Compared to the trauma-exposed comparison group, PTSD subjects showed significantly less activation of the thalamus and the anterior cingulate gyrus (area 32) in all three emotional states (sad, anxious, and traumatic).
These findings suggest thalamic and anterior cingulate dysfunction in the recollection of traumatic as well as other negative events. Thalamic and anterior cingulate dysfunction may underlie emotion dysregulation often observed clinically in PTSD.
Understanding how fears are acquired is an important step in translating basic research to the treatment of fear-related disorders. However, understanding how learned fears are diminished may be even more valuable. We explored the neural mechanisms of fear extinction in humans. Studies of extinction in nonhuman animals have focused on two interconnected brain regions: the amygdala and the ventral medial prefrontal cortex (vmPFC). Consistent with animal models suggesting that the amygdala is important for both the acquisition and extinction of conditioned fear, amygdala activation was correlated across subjects with the conditioned response in both acquisition and early extinction. Activation in the vmPFC (subgenual anterior cingulate) was primarily linked to the expression of fear learning during a delayed test of extinction, as might have been expected from studies demonstrating this region is critical for the retention of extinction. These results provide evidence that the mechanisms of extinction learning may be preserved across species.
Neuroimaging studies report reduced medial prefrontal cortical (particularly anterior cingulate) but enhanced amygdala response to fear signals in posttraumatic Stress Disorder (PTSD). We investigated whether anterior cingulate-amygdala dysregulation in PTSD would generalize to salient, but nonthreat related signals.
Individuals with PTSD (n = 14) and age and sex-matched nontraumatized controls (n = 14) completed an auditory oddball paradigm adapted to functional magnetic resonance imaging at a 1.5-T field strength.
Controls displayed bilateral activation in ventral anterior cingulate and amygdala networks, and PTSD subjects showed bilateral dorsal anterior cingulate and amygdala activation to targets relative to nontargets. Compared to controls, PTSD subjects showed enhanced responses to targets in the dorsal and rostral anterior cingulate, and left amygdala. Whole-brain analyses confirmed the expected pattern of distributed prefrontal-parietal responses to targets in the oddball task. Greater activity in posterior parietal somatosensory regions was observed in PTSD.
Our findings of enhanced anterior cingulate responses in PTSD contrast with reports of reduced activity for threat stimuli, suggesting that the latter may be specific to processing of threat-related content. Activation in rostral and dorsal anterior cingulate, left amygdala and posterior parietal networks in response to salient, nonthreatening stimuli may reflect generalized hypervigilance.
Effective fear processing relies on the amygdala and medial prefrontal cortex (MPFC). Post-trauma reactions provide a compelling model for examining how the heightened experience of fear impacts these systems. Post-traumatic stress disorder (PTSD) has been associated with excessive amygdala and a lack of MPFC activity in response to nonconscious facial signals of fear, but responses to consciously processed facial fear stimuli have not been examined. We used functional MRI to elucidate the effect of trauma reactions on amygdala-MPFC function during an overt fear perception task. Subjects with PTSD (n = 13) and matched non-traumatized healthy subjects (n = 13) viewed 15 blocks of eight fearful face stimuli alternating pseudorandomly with 15 blocks of neutral faces (stimulus duration 500 ms; ISI 767 ms). We used random effects analyses in SPM2 to examine within- and between-group differences in the MPFC and amygdala search regions of interest. Time series data were used to examine amygdala-MPFC associations and changes across the first (Early) versus second (Late) phases of the experiment. Relative to non-traumatized subjects, PTSD subjects showed a marked bilateral reduction in MPFC activity (in particular, right anterior cingulate cortex, ACC), which showed a different Early-Late pattern to non-traumatized subjects and was more pronounced with greater trauma impact and symptomatology. PTSD subjects also showed a small but significant enhancement in left amygdala activity, most apparent during the Late phase, but reduction in Early right amygdala response. Over the time course, trauma was related to a distinct pattern of ACC and amygdala connections. The findings suggest that major life trauma may disrupt the normal pattern of medial prefrontal and amygdala regulation.
The Gordon [37-40] framework of Integrative Neuroscience is used to develop a continuum model for understanding the central role of motivationally-determined "significance" in organizing human information processing. Significance is defined as the property which gives a stimulus relevance to our core motivation to minimize danger and maximize pleasure. Within this framework, the areas of cognition and emotion, theories of motivational arousal and orienting, and the current understanding of neural systems are brought together. The basis of integration is a temporal continuum in which significance processing extends from the most rapid millisecond time scale of automatic, nonconscious mechanisms to the time scale of seconds, in which memory is shaped, to the controlled and conscious mechanisms unfolding over minutes. Over this continuum, significant stimuli are associated with a spectrum of defensive (or consumptive) behaviors through to volitional regulatory behaviors for danger (versus pleasure) and associated brainstem, limbic, medial forebrain bundle and prefrontal circuits, all of which reflect a balance of excitatory (predominant at rapid time scales) to inhibitory mechanisms. Across the lifespan, the negative and positive outcomes of significance processing, coupled with constitutional and genetic factors, will contribute to plasticity, shaping individual adaptations and maladaptions in the balance of excitatory-inhibitory mechanisms.
In this article we propose a psychobiological model that construes PTSD fundamentally as a disorder of affect arousal regulation. Neuroimaging studies of emotion regulation in psychologically healthy populations are initially reviewed as a framework for interpreting the results of previously published investigations of the neural correlates of PTSD reexperiencing and dissociation. We then apply the emotion regulation framework toward understanding other perturbed affective states in PTSD. We conclude by discussing the clinical significance of this framework for psychological assessment and treatment of posttrauma psychopathology.
The prevailing neurocircuitry models of anxiety disorders have been amygdalocentric in form. The bases for such models have progressed from theoretical considerations, extrapolated from research in animals, to in vivo human imaging data. For example, one current model of posttraumatic stress disorder (PTSD) has been highly influenced by knowledge from rodent fear conditioning research. Given the phenomenological parallels between fear conditioning and the pathogenesis of PTSD, we have proposed that PTSD is characterized by exaggerated amygdala responses (subserving exaggerated acquisition of fear associations and expression of fear responses) and deficient frontal cortical function (mediating deficits in extinction and the capacity to suppress attention/response to trauma-related stimuli), as well as deficient hippocampal function (mediating deficits in appreciation of safe contexts and explicit learning/memory). Neuroimaging studies have yielded convergent findings in support of this model. However, to date, neuroimaging investigations of PTSD have not principally employed conditioning and extinction paradigms per se. The recent development of such imaging probes now sets the stage for directly testing hypotheses regarding the neural substrates of fear conditioning and extinction abnormalities in PTSD.
Orienting responses are elicited by salient stimuli, and may be indexed by skin conductance responses. Concurrent functional magnetic resonance imaging and skin conductance response recording was used to identify neural correlates of orienting to abrupt sensory change (infrequent high pitch oddball 'target' tones embedded in frequent lower pitch 'standard' tones) in 16 healthy participants. 'With skin conductance response' responses to targets were distinguished by preferentially greater activity in the amygdala and ventral medial and lateral frontal cortical regions. By contrast, 'without skin conductance response' responses elicited distinctive activity in the dorsal lateral frontal cortex and supramarginal gyrus. These findings suggest that orienting to unexpected sensory change elicits a network for appraising salience and novelty, whereas, in the absence of orienting, a parallel network for sensory and context evaluation is preferentially engaged.
Biological models of posttraumatic stress disorder (PTSD) suggest that patients will display heightened amygdala but decreased medial prefrontal activity during processing of fear stimuli. However, a rapid and automatic alerting mechanism for responding to nonconscious signals of fear suggests that PTSD may display heightened rather than decreased MPFC under nonconscious processing of fear stimuli. This study used functional magnetic resonance imaging to examine blood oxygenation level-dependent signal changes during nonconscious presentation (16.7 ms, masked) of fearful and neutral faces in 15 participants with PTSD and 15 age and sex-matched healthy control participants. Results indicate that PTSD participants display increased amygdala and MPFC activity during nonconscious processing of fearful faces. These data extend existing models by suggesting that the impaired MPFC activation in PTSD may be limited to conscious fear processing. Hum Brain Mapp, 2008. (c) 2007 Wiley-Liss, Inc.
Previous neuroimaging research has shown diminished anterior cingulate cortex (ACC) function in posttraumatic stress disorder (PTSD), with most of these findings occurring in pregenual/subgenual ACC. This study investigates whether dorsal ACC (dACC) function is also diminished in PTSD. The authors used functional magnetic resonance imaging to study dACC function during the performance of the counting Stroop. Thirteen men with PTSD and 13 trauma-exposed men without PTSD participated. In the interference-neutral comparison, both groups showed response time increases and dACC activations. These results suggest that dACC function in PTSD is not diminished during the performance of this nonemotional task. In fact, there were statistical trends in the opposite direction. These findings will help to better characterize functional brain abnormalities in this disorder.
The anterior cingulate cortex (ACC) is critically involved not only in affective and anxiety processing, but also in error and conflict monitoring. To investigate how anxiety interacts with processing affective ambiguity, 15 anxious and 15 nonanxious individuals were scanned while performing a validated affective appraisal task, in which the fraction of faces of a particular affect or gender was parametrically controlled to provide various levels of ambiguity. The anxious group showed less ventral and greater dorsal ACC activation during ambiguous affective relative to ambiguous gender stimuli. For anxious individuals, dorsal ACC activation was related to a more biased response. Collectively, these data indicate that anxious individuals activate the dorsal and ventral components of the ACC differently during affective appraisal.
How the brain processes fear after trauma
- R A Bryant
- A H Kemp
- K L Felmingham
- B J Liddell
- G Olivieri
- A Peduto
- L M Williams
Bryant, R.A., Kemp, A.H., Felmingham, K.L., Liddell, B.J., Olivieri, G., Peduto, A., Williams, L.M.,
2007. How the brain processes fear after trauma. Human Brain Mapping 29, 517-523.
Manual for the Depression Anxiety Stress Scales. Psychology Foundation of Australia
- P Lovibond
- S Lovibond
Lovibond, P., Lovibond, S., 1995. Manual for the Depression Anxiety Stress Scales.
Psychology Foundation of Australia, Sydney Australia.
86, P b 0.01) in PTSD (n = 11) compared to controls (n = 11) in response to 'with-SCR' targets, and increased BOLD activity in bilateral dorsal anterior cingulate cortex (30 6 32, t = 3.26, P b 0.01; − 36 34 26, t = 3.2, P b 0.01) in PTSD to 'with-SCR' targets
- K L Felmingham
Reduced BOLD activity in right ventral anterior cingulate cortex (4 34 − 8, t = 2.86, P b 0.01) in PTSD (n = 11) compared to controls (n = 11) in response to 'with-SCR' targets, and increased BOLD activity in bilateral dorsal anterior cingulate cortex (30 6 32, t = 3.26, P b 0.01; − 36 34 26, t = 3.2, P b 0.01) in PTSD to 'with-SCR' targets. K.L. Felmingham et al. / Psychiatry Research: Neuroimaging 173 (2009) 59–62 Blake, D.D., Weathers, F.W., Nagy, L.M., Cantaloupe, D.G., Carney, D.S., Keane, T.M., 1990. A clinician rating scale for assessing current and lifetime PTSD: the CAPS-1. Behavior Therapy 13, 187–188.
86, P b 0.01) in PTSD (n = 11) compared to controls (n = 11) in response to 'with-SCR' targets, and increased BOLD activity in bilateral dorsal anterior cingulate cortex (30 6 32
Fig. 1. Reduced BOLD activity in right ventral anterior cingulate cortex (4 34 − 8, t = 2.86, P b 0.01) in PTSD (n = 11) compared to controls (n = 11) in response to 'with-SCR' targets,
and increased BOLD activity in bilateral dorsal anterior cingulate cortex (30 6 32, t = 3.26, P b 0.01; − 36 34 26, t = 3.2, P b 0.01) in PTSD to 'with-SCR' targets.
K.L. Felmingham et al. / Psychiatry Research: Neuroimaging 173 (2009) 59–62
How the brain processes fear after trauma
- Bryant