Fear Processing Research Articles

Potential of microRNAs as novel targets in the alleviation of pathological fear.

The current treatment of post-traumatic stress disorder (PTSD), phobias and other anxiety disorders, remains insufficient particularly in producing long-lasting full symptom control. Dysfunctional fear processing is common in these disorders, including a deficiency in fear-inhibitory mechanisms and impairment in the ability to discriminate between safety and danger cues. Research has aimed to elucidate brain circuitries, neurotransmitters and downstream signaling pathways important in the alleviation of aberrant fear, with a specific focus on mechanisms modulating fear memory and its behavioral expression. MicroRNAs (miRNA) as "fine tuners" of gene expression at the post-transcriptional level have emerged as critical regulators of such mechanisms important in both, the generation and the inhibition of fear memories. Along these lines, abnormal expression of miRNAs has been associated with different fear-related disorders. After providing an updated overview on the involvement of miRNAs in fear learning mechanisms, we summarize and discuss in particular those studies in which the implication of miRNAs in successful inhibition of fear has been explored. For a better overview, we dissociate the different modes of fear alleviation investigated in this regard and present studies in rodents demonstrating that specific miRNAs are involved in the destabilization of fear by interfering with consolidation/reconsolidation mechanisms or that they are associated with the generation of fear extinction or safety learning. Finally, we discuss the potential of miRNAs as biomarkers and novel therapeutic targets, as well as the challenges involved in applying the discovered mechanisms in the development of improved treatments of fear- and trauma-related disorders.

The Neurodevelopmental Basis of Early Childhood Disruptive Behavior: Irritable and Callous Phenotypes as Exemplars.

The arrival of the Journal's 175th anniversary occurs at a time of recent advances in research, providing an ideal opportunity to present a neurodevelopmental roadmap for understanding, preventing, and treating psychiatric disorders. Such a roadmap is particularly relevant for early-childhood-onset neurodevelopmental conditions, which emerge when experience-dependent neuroplasticity is at its peak. Employing a novel developmental specification approach, this review places recent neurodevelopmental research on early childhood disruptive behavior within the historical context of the Journal. The authors highlight irritability and callous behavior as two core exemplars of early disruptive behavior. Both phenotypes can be reliably differentiated from normative variation as early as the first years of life. Both link to discrete pathophysiology: irritability with disruptions in prefrontal regulation of emotion, and callous behavior with abnormal fear processing. Each phenotype also possesses clinical and predictive utility. Based on a nomologic net of evidence, the authors conclude that early disruptive behavior is neurodevelopmental in nature and should be reclassified as an early-childhood-onset neurodevelopmental condition in DSM-5. Rapid translation from neurodevelopmental discovery to clinical application has transformative potential for psychiatric approaches of the millennium. [AJP at 175: Remembering Our Past As We Envision Our Future November 1938: Electroencephalographic Analyses of Behavior Problem Children Herbert Jasper and colleagues found that brain abnormalities revealed by EEG are a potential causal factor in childhood behavioral disorders. (Am J Psychiatry 1938; 95:641-658 )].

Neural activity during traumatic film viewing is linked to endogenous estradiol and hormonal contraception

Women are at higher risk for Posttraumatic Stress Disorder (PTSD) and recent research has highlighted a modulating role of female sex hormones for cognitive and emotional processes potentially underlying PTSD symptoms. However, studies combining fMRI recordings of brain activity during trauma film viewing with assessment of female sex hormones are missing. The trauma film paradigm – a widely used experimental analogue for trauma exposure – confronts healthy participants with traumatic film clips and thus allows studying peritraumatic processing under laboratory conditions. Following this paradigm, the current fMRI study examined the role of endogenous estradiol and synthetic sex hormones for the neural processing of traumatic (i.e., depicting interpersonal violence) vs. neutral films in 53 healthy women (mean age 22.3 years; 23 using hormonal contraception, HC). As predicted, traumatic films strongly activated areas of the fear processing network, such as amygdala, insula, and dorsal anterior cingulate cortex. Estradiol levels in women not using HC were positively correlated with ventromedial prefrontal activity. Furthermore, women using HC as compared to women without HC demonstrated heightened insula and dorsal anterior cingulate cortex activity during traumatic film viewing. These experimental results highlight the effects of both gonadal hormone status and HC intake on peritraumatic processing in neural regions relevant for emotion generation and regulation that have been found to be abnormal in PTSD.

Influence of catechol-O-methyltransferase Val158Met on fear of pain and placebo analgesia.

Higher levels of fear have been shown to partly explain individual differences in placebo analgesic responding. The catechol-O-methyltransferase (COMT) rs4680 Val158Met polymorphism has been associated with both increased placebo analgesia and increased fear-related behavior, in what appears to be inconsistent findings in the literature. The aim of the study was therefore to investigate placebo analgesia and fear-related processes with regard to the COMT genotype, to sort out whether the Met-allele is associated with increased placebo analgesia or increased fear of pain (FOP). A 3 Group (Emla, placebo and natural history) by 5 Test (2 pretest, 3 posttests) mixed design was used (N = 223). A contact heat-evoked stimulator was used to induce pain, and FOP was quantified with the Fear of Pain Questionnaire-III. Saliva was obtained for genotyping. As expected, we observed a significant interaction of test by group (P < 0.01), with lower pain report in the placebo group compared with the natural history group (P < 0.01). There was a main effect of the COMT genotype on fear of medical pain (P = 0.032), and Met-allele carriers reported significantly higher fear of medical pain compared with the Val-allele (P = 0.044). We observed no effect of the COMT genotype on mean pain-level report or placebo analgesia. Thus, we conclude that the Met-allele seems to be associated with the negative emotional process of fear, but not with placebo analgesia.

The spider anxiety and disgust screening for children: Reliability and validity of a screening for children

ObjectivesSpecific fears, such as fear of spiders, are often used as a model for studying the development of other fears because several studies suggest that the underlying processes of fear are similar. For the screening of spider fear in children, a good, fast, and reliable screening instrument is needed. Unfortunately, however, such an instrument does not appear to exist yet. Therefore, the purpose of this article was to develop a short, reliable, and valid questionnaire to assess spider fear and spider disgust in children, the Spider Anxiety and Disgust Screening for Children (SADS‐C).MethodsIn Study 1, we tested the items of the SADS‐C. In Study 2, we tested the psychometric properties related to the validity and reliability of the SADS‐C. In Study 3, we administered the SADS‐C in a large sample in order to provide normative data.ResultsThe results indicate good validity and reliability of the SADS‐C; it was able to predict Spider Phobia Questionnaire for Children‐C, Screen for Child Anxiety‐Related Emotional Disorders‐animal, and Behavioural Assessment Test Scores. The studies were all community‐based samples; none of the children were actually seeking help for their spider fear.ConclusionsThe SADS‐C is a suitable questionnaire for assessing spider fear and disgust in children and is very suitable for epidemiological studies or for the screening of children in experimental research for which there is currently no appropriate instrument.

Dynamic causal modeling in PTSD and its dissociative subtype: Bottom-up versus top-down processing within fear and emotion regulation circuitry.

Posttraumatic stress disorder (PTSD) is associated with decreased top-down emotion modulation from medial prefrontal cortex (mPFC) regions, a pathophysiology accompanied by hyperarousal and hyperactivation of the amygdala. By contrast, PTSD patients with the dissociative subtype (PTSD + DS) often exhibit increased mPFC top-down modulation and decreased amygdala activation associated with emotional detachment and hypoarousal. Crucially, PTSD and PTSD + DS display distinct functional connectivity within the PFC, amygdala complexes, and the periaqueductal gray (PAG), a region related to defensive responses/emotional coping. However, differences in directed connectivity between these regions have not been established in PTSD, PTSD + DS, or controls. To examine directed (effective) connectivity among these nodes, as well as group differences, we conducted resting-state stochastic dynamic causal modeling (sDCM) pairwise analyses of coupling between the ventromedial (vm)PFC, the bilateral basolateral and centromedial (CMA) amygdala complexes, and the PAG, in 155 participants (PTSD [n = 62]; PTSD + DS [n = 41]; age-matched healthy trauma-unexposed controls [n = 52]). PTSD was characterized by a pattern of predominant bottom-up connectivity from the amygdala to the vmPFC and from the PAG to the vmPFC and amygdala. Conversely, PTSD + DS exhibited predominant top-down connectivity between all node pairs (from the vmPFC to the amygdala and PAG, and from the amygdala to the PAG). Interestingly, the PTSD + DS group displayed the strongest intrinsic inhibitory connections within the vmPFC. These results suggest the contrasting symptom profiles of PTSD and its dissociative subtype (hyper- vs. hypo-emotionality, respectively) may be driven by complementary changes in directed connectivity corresponding to bottom-up defensive fear processing versus enhanced top-down regulation. Hum Brain Mapp 38:5551-5561, 2017. © 2017 Wiley Periodicals, Inc.

Evolutionary and Modern Image Content Differentially Influence the Processing of Emotional Pictures.

From an evolutionary perspective, environmental threats relevant for survival constantly challenged human beings. Current research suggests the evolution of a fear processing module in the brain to cope with these threats. Recently, humans increasingly encountered modern threats (e.g., guns or car accidents) in addition to evolutionary threats (e.g., snakes or predators) which presumably required an adaptation of perception and behavior. However, the neural processes underlying the perception of these different threats remain to be elucidated. We investigated the effect of image content (i.e., evolutionary vs. modern threats) on the activation of neural networks of emotion processing. During functional magnetic resonance imaging (fMRI) 41 participants watched affective pictures displaying evolutionary-threatening, modern-threatening, evolutionary-neutral and modern-neutral content. Evolutionary-threatening stimuli evoked stronger activations than modern-threatening stimuli in left inferior frontal gyrus and thalamus, right middle frontal gyrus and parietal regions as well as bilaterally in parietal regions, fusiform gyrus and bilateral amygdala. We observed the opposite effect, i.e., higher activity for modern-threatening than for evolutionary-threatening stimuli, bilaterally in the posterior cingulate and the parahippocampal gyrus. We found no differences in subjective arousal ratings between the two threatening conditions. On the valence scale though, subjects rated modern-threatening pictures significantly more negative than evolutionary-threatening pictures, indicating a higher level of perceived threat. The majority of previous studies show a positive relationship between arousal rating and amygdala activity. However, comparing fMRI results with behavioral findings we provide evidence that neural activity in fear processing areas is not only driven by arousal or valence, but presumably also by the evolutionary content of the stimulus. This has also fundamental methodological implications, in the sense to suggest a more elaborate classification of stimulus content to improve the validity of experimental designs.

COMT val158met polymorphism links to altered fear conditioning and extinction are modulated by PTSD and childhood trauma.

Risk for posttraumatic stress disorder (PTSD) is thought to be mediated by gene × environment (G × E) interactions that affect core cognitive processes such as fear learning. The catechol-O-methyltransferase (COMT) val158met polymorphism has been associated with risk for PTSD and impaired fear inhibition. We used a large, relatively homogenous population to (1) replicate previous findings of poor fear inhibition in COMT Met/Met carriers with PTSD; (2) determine if COMT association with fear inhibition is moderated by childhood trauma (CT), an environmental risk factor for PTSD; and (3) determine if COMT is associated with altered fear processes after recent exposure to combat trauma. Male Marines and Navy Corpsmen of European-American ancestry were assessed prior to (n = 714) and 4-6 months after deployment to Afghanistan (n = 452). Acquisition and extinction of fear-potentiated startle, childhood and combat trauma history, and PTSD diagnosis were assessed at both time points. Before deployment, Met/Met genotype was associated with fear inhibition deficits in participants with current PTSD; however, this association was dependent on CT exposure. After deployment, combat trauma was associated with a modest reduction in fear extinction in Met/Met compared with Val/Val carriers. There were no associations of COMT genotype with fear extinction within healthy and non-traumatized individuals. These findings support the hypothesis that G × E interactions underlie associations of COMT val158met with fear inhibition deficits. These studies confirm that Met/Met carriers with PTSD have poor fear inhibition, and support further research in understanding how this polymorphism might impact response to extinction-based therapies.

Neurobiology of fear and specific phobias.

Fear, which can be expressed innately or after conditioning, is triggered when a danger or a stimulus predicting immediate danger is perceived. Its role is to prepare the body to face this danger. However, dysfunction in fear processing can lead to psychiatric disorders in which fear outweighs the danger or possibility of harm. Although recognized as highly debilitating, pathological fear remains insufficiently treated, indicating the importance of research on fear processing. The neurobiological basis of normal and pathological fear reactions is reviewed in this article. Innate and learned fear mechanisms, particularly those involving the amygdala, are considered. These fear mechanisms are also distinguished in specific phobias, which can indeed be nonexperiential (implicating innate, learning-independent mechanisms) or experiential (implicating learning-dependent mechanisms). Poor habituation and poor extinction are presented as dysfunctional mechanisms contributing to persistence of nonexperiential and experiential phobias, respectively.

CART neuropeptide modulates the extended amygdalar CeA-vBNST circuit to gate expression of innate fear

Innate fear is critical for the survival of animals and is under tight homeostatic control. Deregulation of innate fear processing is thought to underlie pathological phenotypes including, phobias and panic disorders. Although central processing of conditioned fear has been extensively studied, the circuitry and regulatory mechanisms subserving innate fear remain relatively poorly defined.In this study, we identify cocaine- and amphetamine-regulated transcript (CART) neuropeptide signaling in the central amygdala (CeA) – ventral bed nucleus of stria terminalis (vBNST) axis as a key modulator of innate fear expression. 2,4,5-trimethyl-3-thiazoline (TMT), a component of fox faeces, induces a freezing response whose intensity is regulated by the extent of CART-signaling in the CeA neurons. Abrogation of CART activity in the CeA attenuates the freezing response and reduces activation of vBNST neurons. Conversely, ectopically elevated CART signaling in the CeA potentiates the fear response concomitant with enhanced vBNST activation. We show that local levels of CART signaling modulate the activation of CeA neurons by NMDA receptor-mediated glutamatergic inputs, in turn, regulating activity in the vBNST.This study identifies the extended amygdalar CeA-vBNST circuit as a CART modulated axis encoding innate fear. CART signaling regulates the glutamatergic excitatory drive in the CeA-vBNST circuit, in turn, gating the expression of the freezing response to TMT.

Directed threat imagery in generalized anxiety disorder.

Worrying has been suggested to prevent emotional and elaborative processing of fears. In cognitive-behavioral therapy (CBT), generalized anxiety disorder (GAD) patients are exposed to their fears during the method of directed threat imagery by inducing emotional reactivity. However, studies investigating neural correlates of directed threat imagery and emotional reactivity in GAD patients are lacking. The present functional magnetic resonance imaging (fMRI) study aimed at delineating neural correlates of directed threat imagery in GAD patients. Nineteen GAD patients and 19 healthy controls (HC) were exposed to narrative scripts of either disorder-related or neutral content and were encouraged to imagine it as vividly as possible. Rating results showed that GAD patients experienced disorder-related scripts as more anxiety inducing and arousing than HC. These results were also reflected in fMRI data: Disorder-related v. neutral scripts elicited elevated activity in the amygdala, dorsomedial prefrontal cortex, ventrolateral prefrontal cortex and the thalamus as well as reduced activity in the ventromedial prefrontal cortex/subgenual anterior cingulate cortex in GAD patients relative to HC. The present study presents the first behavioral and neural evidence for emotional reactivity during directed threat imagery in GAD. The brain activity pattern suggests an involvement of a fear processing network as a neural correlate of initial exposure during directed imagery in CBT in GAD.

Pattern Analyses Reveal Separate Experience-Based Fear Memories in the Human Right Amygdala.

Learning fear via the experience of contingencies between a conditioned stimulus (CS) and an aversive unconditioned stimulus (US) is often assumed to be fundamentally different from learning fear via instructions. An open question is whether fear-related brain areas respond differently to experienced CS-US contingencies than to merely instructed CS-US contingencies. Here, we contrasted two experimental conditions where subjects were instructed to expect the same CS-US contingencies while only one condition was characterized by prior experience with the CS-US contingency. Using multivoxel pattern analysis of fMRI data, we found CS-related neural activation patterns in the right amygdala (but not in other fear-related regions) that dissociated between whether a CS-US contingency had been instructed and experienced versus merely instructed. A second experiment further corroborated this finding by showing a category-independent neural response to instructed and experienced, but not merely instructed, CS presentations in the human right amygdala. Together, these findings are in line with previous studies showing that verbal fear instructions have a strong impact on both brain and behavior. However, even in the face of fear instructions, the human right amygdala still shows a separable neural pattern response to experience-based fear contingencies.SIGNIFICANCE STATEMENT In our study, we addressed a fundamental problem of the science of human fear learning and memory, namely whether fear learning via experience in humans relies on a neural pathway that can be separated from fear learning via verbal information. Using two new procedures and recent advances in the analysis of brain imaging data, we localized purely experience-based fear processing and memory in the right amygdala, thereby making a direct link between human and animal research.

Fear processing is differentially affected by lateralized stimulation of carotid baroreceptors

Information processing, particularly of salient emotional stimuli, is influenced by cardiovascular afferent signals. Carotid baroreceptors signal the state of cardiovascular arousal to the brain, controlling blood pressure and heart rate via the baroreflex. Animal studies suggest a lateralization of this effect: Experimental stimulation of the right carotid sinus has a greater impact on heart rate when compared to left-sided stimulation. We tested, in humans, whether the processing of emotional information from faces was differentially affected by right versus left carotid afferents. To achieve so, we used an automated neck suction device to stimulate the carotid mechanoreceptors in the carotid sinus (parasympathetic pathway) synchronously with functional magnetic resonance imaging (fMRI) acquisition whilst participants were engaged in an emotional rating task of fearful and neutral faces. We showed that both right and left carotid stimulation (CS) influenced brain activity within opercular regions, although a stronger activation was observed within left insula during right stimulation compared to left stimulation. As regards the processing of fearful faces, right, but not left carotid stimulation attenuated the perceived intensity of fear, and (albeit to a lesser extent) enhanced intensity ratings of neutral faces. Mirroring the behavioural effects, there was a significant expression-by-stimulation interaction for right carotid stimulation only, when bilateral amygdala responses were attenuated to fear faces and amplified to neutral faces. Individual differences in basal heart rate variability (HRV) predicted the extent to which right carotid stimulation attenuated amygdala responses during fear processing. Our study provides unique evidence for lateralized viscerosensory effects on brain systems supporting emotional processing.

Neuroimaging in cockroach phobia: An experimental study

Background/ObjectiveIn this study we explored the neuroimaging characteristics of persons with specific small animal (cockroach) phobia to determine whether there are differences in cerebral activity between persons with and without cockroach phobia under conditions of phobic and non-phobic stimulation. Method: 24 adult persons (12 with phobia) were studied. The diagnosis of phobia was obtained with a structured interview and questionnaires. All participants were exposed to a 3D video presentation during an fMRI session. Results: The phobic group showed significant differential activations that were congruent with a dual route model of fear processing through the thalamus-amygdala (route I) and the thalamus-sensory and association cortex-entorhinal cortex-hippocampus-subiculum-amygdala (route II). Apart from this dual route, we also found differential activations in the globus pallidum, parahippocampal gyrus, insula, pars orbitalis, triangularis and opercularis of the frontal cortex, and cerebellum. Respect to non-phobic group, no activations were found in the insula or the anterior cingulate cortex. Conclusions: There seems to be a dual route depending on how persons with phobia to cockroaches process phobic stimuli. This double processing can have implications for the psychological treatment of specific phobias.

Converging Prefronto-Insula-Amygdala Pathways in Negative Emotion Regulation in Marmoset Monkeys

BackgroundImpaired regulation of emotional responses to potential threat is a core feature of affective disorders. However, while the subcortical circuitry responsible for processing and expression of fear has been well characterized, the top-down control of this circuitry is less well understood. Our recent studies demonstrated that heightened emotionality, as measured both physiologically and behaviorally, during conditioned fear and innate/social threat was induced, independently, by excitotoxic lesions of either the anterior orbitofrontal cortex (antOFC) or ventrolateral prefrontal cortex (vlPFC). An important outstanding question is whether the antOFC and vlPFC act on common or distinct downstream targets to regulate negative emotion. MethodsThe question was addressed by combining localized excitotoxic lesions in the PFC of a nonhuman primate and functional neuroimaging ([18F]fluorodeoxyglucose positron emission tomography) with a fear-regulating extinction paradigm. Marmoset monkeys with unilateral lesions of either the antOFC or vlPFC were scanned immediately following exposure to a fearful or safe context, and differences in [18F]fluorodeoxyglucose uptake were evaluated. Results[18F]fluorodeoxyglucose uptake in the insula and amygdala of the intact hemisphere was significantly increased in response to the fearful context compared with the safe context. Such discrimination between the two contexts was not reflected in the activity of the insula-amygdala of the antOFC or vlPFC-lesioned hemisphere. Instead, uptake was at an intermediate level in both contexts. ConclusionsThese findings demonstrate that the distinct control functions of the antOFC and vlPFC converge on the same downstream targets to promote emotion regulation, taking us closer to a mechanistic understanding of different forms of anxiety.

Associations of plasma leptin to clinical manifestations in reproductive aged female patients with panic disorder

Preclinical studies suggest the implication of the adipocyte hormone leptin in anxiety and fear processes. We explored for potential differences regarding plasma leptin, cortisol and the ratio leptin/Body Mass Index (BMI) between 27 medication-free female patients with Panic Disorder (PD) and 42 age-matched female controls, and for potential associations between plasma leptin and psychometric evaluations including number of panic attacks during last week, Clinical Global Impression-Severity of Illness (CGI-S) and Symptoms Checklist-90-Revised (SCL-90-R). Cortisol levels showed no differences between patients and controls, or correlations to leptin or to any clinical features. Both groups demonstrated a strong positive correlation between leptin and BMI and similar leptin and leptin/BMI, despite patients’ lower BMI. However, patients –but not controls- demonstrated significant negative correlations of leptin to the ‘somatization’, ‘anxiety’, and ‘phobic anxiety’ SCL-90-R subscales. Moreover, there was a significant negative correlation of leptin and of leptin/BMI ratio to the number of panic attacks during last week, while higher CGI-S was associated with lower leptin/BMI ratio. Our results, limited to PD female patients, suggest that lower leptin serum levels are significantly associated with greater severity of psychopathological manifestations, including number of panic attacks, symptoms of somatization, anxiety and phobic anxiety and overall clinical presentation.

Fear learning alterations after traumatic brain injury and their role in development of posttraumatic stress symptoms

It is unknown how traumatic brain injury (TBI) increases risk for posttraumatic stress disorder (PTSD). One potential mechanism is via alteration of fear-learning processes that could affect responses to trauma memories and cues. We utilized a prospective, longitudinal design to determine if TBI is associated with altered fear learning and extinction, and if fear processing mediates effects of TBI on PTSD symptom change. Eight hundred fifty two active-duty Marines and Navy Corpsmen were assessed before and after deployment. Assessments included TBI history, PTSD symptoms, combat trauma and deployment stress, and a fear-potentiated startle task of fear acquisition and extinction. Startle response and self-reported expectancy and anxiety served as measures of fear conditioning, and PTSD symptoms were measured with the Clinician-Administered PTSD Scale. Individuals endorsing "multiple hit" exposure (both deployment TBI and a prior TBI) showed the strongest fear acquisition and highest fear expression compared to groups without multiple hits. Extinction did not differ across groups. Endorsing a deployment TBI was associated with higher anxiety to the fear cue compared to those without deployment TBI. The association of deployment TBI with increased postdeployment PTSD symptoms was mediated by postdeployment fear expression when recent prior-TBI exposure was included as a moderator. TBI associations with increased response to threat cues and PTSD symptoms remained when controlling for deployment trauma and postdeployment PTSD diagnosis. Deployment TBI, and multiple-hit TBI in particular, are associated with increases in conditioned fear learning and expression that may contribute to risk for developing PTSD symptoms.

288. Δ-9-THC Modulates Fear Processing and Functional Connectivity in an Emotional Salience Task

288. Δ-9-THC Modulates Fear Processing and Functional Connectivity in an Emotional Salience Task

0732 NIGHTMARE DISTRESS IS NEGATIVELY CORRELATED WITH REGIONAL CEREBRAL BLOOD FLOW IN FRONTAL AREAS DURING AN IAPS PICTURE-VIEWING TASK

Research has shown that nightmare-related distress (NMD) may better explain the association between nightmares (NM) and psychopathology than NM frequency, but its neurophysiological correlates remain unknown. As part of a brain imaging project exploring the neural correlates of NM in frequent NM sufferers, we investigated if NMD is related to activity in regions hypothesized to be involved in NM production (Nielsen & Levin, 2007). We predicted NMD would correlate with reduced activity (i.e. regional cerebral blood flow) in bilateral prefrontal areas known to down-regulate fear processes governed by the amygdala, i.e., anterior cingulate and medial prefrontal cortices. We also expected NMD to be correlated with reduced activity in the hippocampus and increased activity in the amygdala. We used high resolution 99m-Tc-ECD SPECT imaging to assess regional cerebral blood flow (rCBF) in 21 frequent NM sufferers (NM: 24.9 ± 4.5 yrs (18 W)) during the viewing of negative pictures from the International Affective Picture System (IAPS). We correlated Nightmare Distress Questionnaire (NMDQ) scores with rCBF using a significance threshold of p < .005 (uncorrected) and a cluster threshold of k > 100. Significant negative correlations were observed between NMDQ scores and rCBF in bilateral insula (t = 4.1 and 4.37), bilateral anterior cingulate cortex (t = 4.49 and 5.42), left precentral gyrus (t = 3.54), left medial prefrontal cortex (t = 4.63), and bilateral putamen (t = 4.55 and 4.37). No correlations were observed with the amygdala or hippocampus and no positive correlations were found. Findings partially support our hypothesis. Reduced rCBF in these prefrontal regions involved in affect regulation could reflect a cross-state emotion regulation deficit, which also leads to more distress during dreaming. Our results also reveal reduced activity in regions for which a regulatory role in affective response during dreaming is unclear (insula, putamen), but for which research has demonstrated anatomical and/or functional alterations in PTSD. Supported by research grants from the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Fonds de recherche Québec-Santé (FRQS).

Panic attacks, a sequel of left temporal lobectomy in a patient with low-grade glioma

Medial temporal lobe and associated limbic areas have vital role in processing of emotions. Amygdala, an important brain structure in processing of fear and anxiety has been implicated in the pathogenesis of panic symptoms. Brain pathology involving medial temporal lobe and amygdala can present with features of panic attacks. We highlight here a case of low-grade glioma, who had panic attacks following temporal lobectomy and improved with antidepressant (escitalopram) treatment.