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The ability to adaptively regulate responses to the proximity of potential danger is critical to survival and imbalance in this system may contribute to psychopathology. The bed nucleus of the stria terminalis (BNST) is implicated in defensive responding during uncertain threat anticipation whereas the amygdala may drive responding upon more acute danger. This functional dissociation between the BNST and amygdala is however controversial, and human evidence scarce. Here we used data from two independent functional magnetic resonance imaging studies [n = 108 males and n = 70 (45 females)] to probe how coordination between the BNST and amygdala may regulate responses during shock anticipation and actual shock confrontation. In a subset of participants from Sample 2 (n = 48) we demonstrate that anticipation and confrontation evoke bradycardic and tachycardic responses, respectively. Further, we show that in each sample when going from shock anticipation to the moment of shock confrontation neural activity shifted from a region anatomically consistent with the BNST toward the amygdala. Comparisons of functional connectivity during threat processing showed overlapping yet also consistently divergent functional connectivity profiles for the BNST and amygdala. Finally, childhood maltreatment levels predicted amygdala, but not BNST, hyperactivity during shock anticipation. Our results support an evolutionary conserved, defensive distancedependent dynamic balance between BNST and amygdala activity. Shifts in this balance may enable shifts in defensive reactions via the demonstrated differential functional connectivity. Our results indicate that early life stress may tip the neural balance toward acute threat responding and via that route predispose for affective disorder. [ABSTRACT FROM AUTHOR]

Experimental psychopathology is the application of experimental methods to the study of psychopathology and its underlying processes. The study of individual differences in the development, maintenance and/or relapse of psychopathology is currently at the forefront of research. Stressful events are known to exert a substantial impact on our lives. Why however, do some people react in an extremely adaptive way, while others develop pathology in the aftermath of a trauma? One particularly interesting individual differences factor is genetic makeup and the aim of this paper is to review the current state of the art of genetics in experimental psychopathology which is illustrated by using fear conditioning as an exemplary model in the study of mechanisms underlying anxiety. We identify and discuss current challenges of the field and provide recommendations on how these can be met. In addition, criteria for experimental models of psychopathology as well as future directions are discussed. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) of the ventral internal capsule is effective in treating therapy refractory obsessive-compulsive disorder (OCD). Given the close proximity of the stimulation site to the stria terminalis (BNST), we hypothesized that the striking decrease in anxiety symptoms following DBS could be the result of the modulation of contextual anxiety. However, the effect of DBS in this region on contextual anxiety is as of yet unknown. Thus, the current study investigated the effect of DBS on contextual anxiety in an experimental threat of shock paradigm. Eight patients with DBS treatment for severe OCD were tested in a double-blind crossover design with randomly assigned 2-week periods of active and sham stimulation. DBS resulted in significant decrease of obsessive-compulsive symptoms, anxiety, and depression. However, even though the threat manipulation resulted in a clear context-potentiated startle effect, none of the parameters derived from the startle recordings was modulated by the DBS. This suggests that DBS in the ventral internal capsule is effective in treating anxiety symptoms of OCD without modulating the startle circuitry.We hypothesize that the anxiety symptoms present in OCD are likely distinct from the pathological brain circuits in defensive states of other anxiety disorders. [ABSTRACT FROM AUTHOR]

Preclinical evidence implicates several neurotransmitter systems in the extinction of conditioned fear. These results are of great interest, because the reduction of acquired fear associations is critical in therapies for anxiety disorders. We tested whether findings with respect to the N-methyl-D-aspartate (NMDA) and cannabinoid receptor (CB) systems in animals carry over to healthy human subjects. To that end, we administered selected doses of D-cycloserine (partial NMDA receptor agonist, 250 mg), delta-9-tetrahydrocannabinol (THC, CB(1) receptor agonist, 10 mg), or placebo prior to the extinction session of a 3-day conditioning protocol. D-cycloserine did not affect within-session extinction, or the retention of extinction in healthy human participants, in contrast with patient data but in line with previous reports in healthy volunteers. During extinction training, Δ9-THC reduced conditioned skin conductance responses, but not fear-potentiated startle. This effect was not retained at the retention test 2 days later, suggesting it was dependent on acute effects of the drug. Our findings implicate that facilitation of the CB(1) or NMDA system with the substances used in this study does not affect conditioned fear extinction lastingly in healthy humans. The apparent discrepancy between these findings and the results from (pre-)clinical trials is discussed in terms of room for improvement in these systems in healthy volunteers, and the lack of specificity of THC as a CB(1) agonist. [ABSTRACT FROM AUTHOR]

The endocannabinoid system is a promising candidate for anxiolytic therapy, but translation to the clinic has been lagging. We meta-analyzed the evidence for anxiety-reduction by compounds that facilitate endocannabinoid signaling in humans and animals. To identify areas of specific potential, effects of moderators were assessed. Literature was searched in Pubmed and Embase up to May 2021. A placebo/vehicle-control group was required and in human studies, randomization. We excluded studies that co-administered other substances. Risk of bias was assessed with SYRCLE's RoB tool and Cochrane RoB 2.0. We conducted three-level random effects meta-analyses and explored sources of heterogeneity using Bayesian regularized meta-regression (BRMA). The systematic review yielded 134 studies. We analyzed 120 studies (114 animal, 6 human) that investigated cannabidiol (CBD, 61), URB597 (39), PF-3845 (6) and AM404 (14). Pooled effects on conditioned and unconditioned anxiety in animals (with the exception of URB597 on unconditioned anxiety) and on experimentally induced anxiety in humans favored the investigational drugs over placebo/vehicle. Publication year was negatively associated with effects of CBD on unconditioned anxiety. Compared to approach avoidance tests, tests of repetitive-compulsive behavior were associated with larger effects of CBD and URB597, and the social interaction test with smaller effects of URB597. Larger effects of CBD on unconditioned anxiety were observed when anxiety pre-existed. Studies reported few side effects at therapeutic doses. The evidence quality was low with indications of publication bias. More clinical trials are needed to translate the overall positive results to clinical applications., Competing Interests: Conflict of interest The authors have no conflicting interests to declare., (Copyright © 2023. Published by Elsevier B.V.)

Recent meta-analyses indicated differences in fear acquisition and extinction between patients with anxiety-related disorders and comparison subjects. However, these effects are small and may hold for only a subsample of patients. To investigate individual trajectories in fear acquisition and extinction across patients with anxiety-related disorders (N = 104; before treatment) and comparison subjects (N = 93), data from a previous study (Duits et al., 2017) were re-analyzed using data-driven latent class growth analyses. In this explorative study, subjective fear ratings, shock expectancy ratings and startle responses were used as outcome measures. Fear and expectancy ratings, but not startle data, yielded distinct fear conditioning trajectories across participants. Patients were, compared to controls, overrepresented in two distinct dysfunctional fear conditioning trajectories: impaired safety learning and poor fear extinction to danger cues. The profiling of individual patterns allowed to determine that whereas a subset of patients showed trajectories of dysfunctional fear conditioning, a significant proportion of patients (≥50 %) did not. The strength of trajectory analyses as opposed to group analyses is that it allows the identification of individuals with dysfunctional fear conditioning. Results suggested that dysfunctional fear learning may also be associated with poor treatment outcome, but further research in larger samples is needed to address this question., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Eye movement desensitization and reprocessing (EMDR) is an effective treatment for posttraumatic stress disorder. During EMDR, patients make horizontal eye movements (EMs) while simultaneously recalling a traumatic memory, which renders the memory less vivid and emotional when it is later recalled again. Recalling highly emotional autobiographical memories enhances noradrenergic neurotransmission. Noradrenaline (NA) strengthens memory (re)consolidation. However, memories become less vivid after recall+EMs. Therefore, NA might either play no significant role or serve to strengthen memories that are degraded by EMs. The present study was designed to test the latter hypothesis. We predicted that blocking NA would abolish the memory degrading effects of EMs., Methods: Fifty-six healthy participants selected three negative autobiographical memories. One was then recalled while making EMs, one was recalled without EMs, and one was not recalled. Vividness and emotionality of the memories as well as heart rate and skin conductance level during memory retrieval were measured before, directly after, and 24 hours after the EM task. Before the task, participants received a placebo or the noradrenergic β-receptor blocker propranolol (40 mg)., Results: There were no effects of EMs on memory emotionality or psychophysiological measures in the propranolol and placebo groups. However, in the placebo group, but not in the propranolol group, memory vividness significantly decreased from pretest to posttest and follow-up after recall+EMs relative to the control conditions., Conclusions: Blocking NA abolished the effects of EMs on the vividness of emotional memories, indicating that NA is crucial for EMDR effectiveness and possibly strengthens the reconsolidation of the degraded memory., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The so-called 'replicability crisis' has sparked methodological discussions in many areas of science in general, and in psychology in particular. This has led to recent endeavours to promote the transparency, rigour, and ultimately, replicability of research. Originating from this zeitgeist, the challenge to discuss critical issues on terminology, design, methods, and analysis considerations in fear conditioning research is taken up by this work, which involved representatives from fourteen of the major human fear conditioning laboratories in Europe. This compendium is intended to provide a basis for the development of a common procedural and terminology framework for the field of human fear conditioning. Whenever possible, we give general recommendations. When this is not feasible, we provide evidence-based guidance for methodological decisions on study design, outcome measures, and analyses. Importantly, this work is also intended to raise awareness and initiate discussions on crucial questions with respect to data collection, processing, statistical analyses, the impact of subtle procedural changes, and data reporting specifically tailored to the research on fear conditioning., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Previous studies suggest that patients with panic disorder and agoraphobia (PD/A) tend to overestimate the associations between fear-relevant stimuli and threat. This so-called threat expectancy bias is thought to play a role in the development and treatment of anxiety disorders. The current study tested 1) whether patients with PD/A (N = 71) show increased threat expectancy ratings to fear-relevant and fear-irrelevant stimuli relative to a comparison group without an axis I disorder (N=65), and 2) whether threat expectancy bias before treatment predicts treatment outcome in a subset of these patients (n = 51)., Methods: In a computerized task, participants saw a series of panic-related and neutral words and rated for each word the likelihood that it would be followed by a loud, aversive sound., Results: Results showed higher threat expectancy ratings to both panic-related and neutral words in patients with PD/A compared to the comparison group. Threat expectancy ratings did not predict treatment outcome., Limitations: This study only used expectancy ratings and did not include physiological measures. Furthermore, no post-treatment expectancy bias task was added to shed further light on the possibility that expectancy bias might be attenuated by treatment., Conclusions: Patients show higher expectancies of aversive outcome following both fear-relevant and fear-irrelevant stimuli relative to the comparison group, but this does not predict treatment outcome., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In everyday life, aversive events are usually associated with certain predictive cues. Normally, the acquisition of these contingencies enables organisms to appropriately respond to threat. Presence of a threat cue clearly signals 'danger', whereas absence of such cues signals a period of 'safety'. Failure to identify threat cues may lead to chronic states of anxious apprehension in the context in which the threat has been imminent, which may be instrumental in the pathogenesis of anxiety disorders. In this study, existing data from 150 healthy volunteers in a cue and context virtual reality fear conditioning paradigm were reanalyzed. The aim was to further characterize the impact of cue acquisition and trait anxiety, and of a single nucleotide polymorphism in the serotonin 1A receptor gene (5-HTR1A, rs6295), on cued fear and contextual anxiety before and after fear contingencies were explicitly introduced. Fear conditioned responding was quantified with fear potentiation of the eyeblink startle reflex and subjective fear ratings. First, we replicated previous findings that the inability to identify danger cues during acquisition leads to heightened anxious apprehension in the threat context. Second, in subjects who did not identify the danger cue initially, contextual fear was associated with trait anxiety after the contingencies were explicitly instructed. Third, genetic variability within 5-HTR1A (rs6295) was associated with contextual fear independent of awareness or trait anxiety. These findings confirm that failure to acquire cue contingencies impacts contextual fear responding, in association with trait anxiety. The observed 5-HTR1A effect is in line with models of anxiety, but needs further replication., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Excessive anticipatory reactions to potential future adversity are observed across a range of anxiety disorders, but the neurogenetic mechanisms driving interindividual differences are largely unknown. We aimed to discover and validate a gene-brain-behavior pathway by linking presumed genetic risk for anxiety-related psychopathology, key neural activity involved in anxious anticipation, and resulting aversive emotional states., Methods: The functional neuroanatomy of aversive anticipation was probed through functional magnetic resonance imaging in two independent samples of healthy subjects (n = 99 and n = 69), and we studied the influence of genetic variance in the serotonin transporter linked polymorphic region (5-HTTLPR). Skin conductance and startle data served as objective psychophysiological indices of the intensity of individuals' anticipatory responses to potential threat., Results: Threat cues signaling risk of future electrical shock activated the dorsomedial prefrontal cortex (dmPFC), anterior insula, bed nucleus of the stria terminalis, thalamus, and midbrain consistently across both samples. Threat-related dmPFC activation was enhanced in 5-HTTLPR short allele carriers in sample 1 and this effect was validated in sample 2. Critically, we show that this region mediates the increase in anticipatory psychophysiological reactions in short allele carriers indexed by skin conductance (experiment 1) and startle reactions (experiment 2)., Conclusions: The converging results from these experiments demonstrate that innate 5-HTTLPR linked variation in dmPFC activity predicts psychophysiological responsivity to pending threats. Our results reveal a neurogenetic pathway mediating interindividual variability in anticipatory responses to threat and yield a novel mechanistic account for previously reported associations between genetic variability in serotonin transporter function and stress-related psychopathology., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Recent cross-sectional studies have shown that the inability to suppress fear under safe conditions is a key problem in people with posttraumatic stress disorder (PTSD). The current longitudinal study examined whether individual differences in fear inhibition predict the persistence of PTSD symptoms. Approximately 2 months after deployment to Afghanistan, 144 trauma-exposed Dutch soldiers were administered a conditional discrimination task (AX+/BX-). In this paradigm, A, B, and X are neutral stimuli. X combined with A is paired with a shock (AX+ trials); X combined with B is not (BX- trials). Fear inhibition was measured (AB trials). Startle electromyogram responses and shock expectancy ratings were recorded. PTSD symptoms were measured at 2 months and at 9 months after deployment. Results showed that greater startle responses during AB trials in individuals who discriminated between danger (AX+) and safety (BX-) during conditioning, predicted higher PTSD symptoms at 2 months and 9 months post-deployment. The predictive effect at 9 months remained significant after controlling for critical incidents during previous deployments and PTSD symptoms at 2 months. Responses to AX+ or BX- trials, or discrimination learning (AX+ minus BX-) did not predict PTSD symptoms. It is concluded that impaired fear inhibition learning seems to be involved in the persistence of PTSD symptoms., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Deficient fear conditioning leads to maladaptive contextual anxiety as predicting danger is a key factor in regulating anxiety. A virtual reality conditioning task was used to evaluate cue learning and contextual anxiety with fear-potentiated startle and subjective fear in two experiments. In Experiment 1, failure to condition to a cue resulted in a constant state of context anxiety (subjective fearfulness and startle). Trait anxiety was unrelated to learning cue contingencies but the participants who failed to learn scored lower on a self-report measure of attentional control. Part of the group that learned the cue contingency failed to deduce safety of the context and hence did not reduce their contextual anxiety. Experiment 2 specifically focused on isolating this process and demonstrated an inverse association between trait anxiety and adaptive modulation of contextual anxiety. In conclusion, predicting threat aids in but not automatically implies successful regulation of contextual anxiety. High trait anxiety may increase risk of deficient modulation of contextual anxiety., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The serotonin transporter (SERT) plays a crucial role in anxiety. Accordingly, variance in SERT functioning appears to constitute an important pathway to individual differences in anxiety. The current study tested the hypothesis that genetic variation in SERT function is associated with variability in the basic reflex physiology of defense. Healthy subjects (N=82) were presented with clearly instructed cues of shock threat and safety to induce robust anxiety reactions. Subjects carrying at least one short allele for the 5-HTTLPR polymorphism showed stronger fear-potentiated startle compared to long allele homozygotes. However, short allele carriers showed no deficit in the downregulation of fear after the offset of threat. These results suggest that natural variation in SERT function affects the magnitude of defensive reactions while not affecting the capacity for fear regulation., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Introduction: Reducing fear when a threat has disappeared protects against a continuously elevated anxiety state. In this study, we investigated the brain mechanism involved in this process., Methods: The threat paradigm consisted of discrete cues that signaled either threat of shock or safety. Healthy participants were tested in two sessions in which eyeblink startle (n = 26) and blood oxygen level dependence (n = 23) were measured to index subjects' defensive state and brain responses respectively., Results: Startle results indicated that subjects could rapidly decrease their defensive state after the offset of shock threat. Functional magnetic resonance imaging data indicated that the termination of threat was associated with the recruitment of lateral and ventromedial prefrontal cortices. An exploratory connectivity analysis showed that activity in these prefrontal regions was linked and was also associated with activity in brain regions typically responding to threat, the right anterior insula and amygdala., Conclusions: These results provide first evidence for a prefrontal mechanism that functions to control anxiety after threat offset, which may be dysfunctional in patients who suffer from excessive sustained anxiety. Moreover, the results support a model in which the lateral prefrontal cortex controls anxiety related limbic activity through connections with ventromedial prefrontal cortex., (Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Effects of predictability of threat on potentiation of the startle reflex were investigated by presenting participants with predictable and unpredictable electric shocks. Shocks were presented either paired with a visual cue (paired condition) or unrelated to the presentation of the visual cues (unpaired condition). In contrast to previous slower-paced studies, conditions alternated at a rapid rate: each context lasted 8.5 s and within these contexts the visual cues had a duration of 1.5 s. Results replicated previous findings: in the predictable condition, startle responses were augmented by a threat-signaling stimulus, and startle responses in the unpredictable condition were larger than in a neutral condition in which no shocks were presented. In all three conditions, visual stimuli that did not carry information about when a shock could be presented augmented startle reactivity. A control experiment showed that the effects of threat on the startle response could not be ascribed to attention and that the effects of the lead stimuli that did not signal threat are likely to be unrelated to the effects of threat. These results show that the fear system is modulated dynamically as a function of rapidly changing information about threat and emphasize the role of predictability of an aversive stimulus in the distinction between cue-specific and contextual fear.

Stimulus novelty or deviance may be especially salient in anxiety-related states due to sensitization to environmental change, a key symptom of anxiety disorders such as posttraumatic stress disorder (PTSD). We aimed to identify human brain regions that show potentiated responses to stimulus deviance during anticipatory anxiety. Twenty participants (14 men) were presented a passive oddball auditory task in which they were exposed to uniform auditory stimulation of tones with occasional deviations in tone frequency, a procedure that elicits the mismatch negativity (MMN) and its magnetic counterpart (MMNm). These stimuli were presented during threat periods when participants anticipated unpleasant electric shocks, and safe periods when no shocks were anticipated. Neuromagnetic data were collected with a 275-channel whole-head MEG system and event-related beamformer analyses were conducted to estimate source power across the brain in response to stimulus deviance. Source analyses revealed greater right auditory and inferior parietal activity to stimulus deviance under threat relative to safe conditions, consistent with locations of MMN and MMNm sources identified in other studies. Structures related to evaluation of threat, left amygdala and right insula, also showed increased activity to stimulus deviance under threat. As anxiety level increased across participants, right and left auditory cortical as well as right amygdala activity increased to stimulus deviance. These findings fit with evidence of a potentiated MMN in PTSD relative to healthy controls, and warrant closer evaluation of how these structures might form a functional network mediating sensitization to stimulus deviance during anticipatory anxiety.

Background: The startle reflex is potentiated by aversive states. It has been proposed that phasic startle potentiation to a threat cue and sustained startle potentiation to contextual stimuli reflect distinct processes mediated by different brain structures. The present study tested the hypothesis that alprazolam would reduce the sustained startle potentiation to contextual threats but not the startle potentiation to a threat cue., Methods: Sixteen healthy subjects received each of four treatments: placebo, .5 mg of alprazolam, 1 mg of alprazolam, and 50 mg of diphenhydramine (Benadryl) in a crossover design. Participants were exposed to three conditions, including one in which predictable aversive shocks were signaled by a cue, a second in which shocks were administered unpredictably, and a third condition in which no shocks were anticipated. Acoustic startle were delivered regularly across conditions., Results: Phasic startle potentiation to the threat cue in the predictable condition was not affected by alprazolam. In contrast, the sustained increase in startle in the predictable and unpredictable conditions was reduced significantly by the high dose of alprazolam., Conclusions: Startle responses to an explicit threat cue and to an aversive context are psychopharmacologically distinct, suggesting that they may represent functionally dissociable aversive states.

Background: Sustained anxiety can be modeled using context conditioning, which can be studied in a virtual reality environment. Unpredictable stressors increase context conditioning in animals. This study examined context conditioning to predictable and unpredictable shocks in humans using behavioral avoidance, potentiated startle, and subjective reports of anxiety., Methods: Subjects were guided through three virtual rooms (no-shock, predictable, unpredictable contexts). Eight-sec duration colored lights served as conditioned stimuli (CS). During acquisition, no shock was administered in the no-shock context. Shocks were paired with the CS in the predictable context and were administered randomly in the unpredictable context. No shock was administered during extinction. Startle stimuli were delivered during CS and between CS to assess cued and context conditioning, respectively. To assess avoidance, subjects freely navigated into two of the three contexts to retrieve money., Results: Startle between CS was potentiated in the unpredictable context compared to the two other contexts. Following acquisition, subjects showed a strong preference for the no-shock context and avoidance of the unpredictable context., Conclusions: Consistent with animal data, context conditioning is increased by unpredictability. These data support virtual reality as a tool to extend research on physiological and behavioral signs of fear and anxiety in humans.

Background: Brainstem auditory evoked potentials (BAEP) reflect the activation of brainstem nuclei in the first milliseconds after presentation of an auditory stimulus. These electrophysiological correlates of neural processing are highly automatic and not influenced by cognitive factors or task demands; however, data from patients with anxiety disorders suggest deviations in the BAEP. It has been hypothesized that these differences reflect heightened activation of structures involved in defensive states, such as the amygdala and locus coeruleus, projecting to the inferior colliculus, one of the brainstem generators of wave V of the BAEP. The present study investigated this possibility by testing BAEP during experimentally induced anxiety in healthy volunteers., Methods: In this study, BAEP were recorded from healthy normal volunteers under threat of shock, compared with safe conditions., Results: The first experiment (n = 12) showed that shock anticipation increased the amplitude of wave V. A replication experiment (n = 13) confirmed this finding., Conclusions: Although BAEP are highly robust with respect to attentional manipulations, they are affected by transient activation of the fear system due to threat of shock. This finding indicates that some of the electrophysiological brainstem abnormalities observed in anxiety disorders can be replicated in healthy control subjects by inducing a transient state of anxiety.

Fear-potentiated startle (FPS) is an increasingly popular psychophysiological method for the objective assessment of fear and anxiety. Studies applying this method often elicit the startle reflex with loud white-noise stimuli. Such intense stimuli may, however, alter psychological processes of interest by creating unintended emotional or attentional artifacts. Additionally, loud acoustic probes may be unsuitable for use with infants, children, the elderly, and those with hearing damage. Past studies have noted robust and reliable startle reflexes elicited by low intensity airpuffs. The current study compares the aversiveness of white-noise (102 dB) and airpuff (3 psi) probes and examines the sensitivity of each probe for the assessment of fear-potentiated startle. Results point to less physiological arousal and self-reported reactivity to airpuff versus white-noise probes. Additionally, both probes elicited equal startle magnitudes, response probabilities, and levels of fear-potentiated startle. Such results support the use of low intensity airpuffs as efficacious and relatively non-aversive startle probes.

This study investigated whether attentional processes contribute to fear-potentiated startle. Ten subjects participated in a threat of shock experiment and an attentional control condition. In the threat of shock experiment, visual cues indicated whether or not an aversive shock might occur. In the attentional control, the shocks were replaced by faint vibrotactile stimuli that had to be counted. The P300 amplitudes of the ERP evoked by the visual cues did not differ under threat and counting, which suggested that both conditions engaged attention to the same extent. In contrast, startle potentiation in the threat condition was an order of magnitude larger than the marginally significant attentional startle facilitation in the counting condition. These results indicate that an attentional contribution to fear-potentiated startle under the present experimental conditions is small. In addition, contextual effects of threat of shock became manifest as baseline startle was facilitated relative to the attention condition. This may reflect a more sustained state of anxiety on which cue-specific fear responses are superimposed.

Objectives: Physiological correlates of visual selective attention have been observed by recording ERPs to attended versus ignored target stimuli. Over many such studies, spatial attention has been observed to modulate early sensory components beginning 70 ms after stimulus onset, while effects of selection based on other stimulus features such as color and spatial frequency occur at longer latencies. Together, these findings argue for a primacy of location in early attentional selection. However, there have been some reports suggesting attention effects on short latency sensory-evoked potentials during selection of spatial frequency. The prime objective of the present study was to assess whether or not spatial frequency-dependent potentials are modulated by attention at a latency as early as 70-100 ms., Methods: Checkerboard patterns were flashed to the subject, one being the target requiring a response. We investigated attentional effects using high-density scalp mapping and inverse dipole modeling., Results: The earliest robust signs of selective attention to spatial frequencies consisted of an occipital selection negativity (OSN) and a frontal selection positivity (FSP). The OSN started at a latency of 140 ms, the FSP somewhat earlier at 120 ms. These attention effects were readily modeled by sources in cortical areas ventrally and laterally to the more primary areas generating the shorter-latency sensory components., Conclusions: This pattern of results has been found for non-spatial stimulus features in several studies, and is clearly different from the ERP correlates of spatial selection.