scholarly journals Face processing in adolescents with positive and negative threat bias

2016 ◽  
Vol 47 (5) ◽  
pp. 800-809 ◽  
Author(s):  
C. M. Sylvester ◽  
S. E. Petersen ◽  
J. L. Luby ◽  
D. M. Barch
Keyword(s):  
Anxiety Disorders ◽  
Neural Mechanisms ◽  
Lower Activity ◽  
Prior History ◽  
Neural Processing ◽  
Brain Response ◽  
Threat Bias ◽  
Novel Treatments ◽  
Fearful Faces ◽  
Threat Avoidance

BackgroundIndividuals with anxiety disorders exhibit a ‘vigilance-avoidance’ pattern of attention to threatening stimuli when threatening and neutral stimuli are presented simultaneously, a phenomenon referred to as ‘threat bias’. Modifying threat bias through cognitive retraining during adolescence reduces symptoms of anxiety, and so elucidating neural mechanisms of threat bias during adolescence is of high importance. We explored neural mechanisms by testing whether threat bias in adolescents is associated with generalized or threat-specific differences in the neural processing of faces.MethodSubjects were categorized into those with (n = 25) and without (n = 27) threat avoidance based on a dot-probe task at average age 12.9 years. Threat avoidance in this cohort has previously been shown to index threat bias. Brain response to individually presented angry and neutral faces was assessed in a separate session using functional magnetic resonance imaging.ResultsAdolescents with threat avoidance exhibited lower activity for both angry and neutral faces relative to controls in several regions in the occipital, parietal, and temporal lobes involved in early visual and facial processing. Results generalized to happy, sad, and fearful faces. Adolescents with a prior history of depression and/or an anxiety disorder had lower activity for all faces in these same regions. A subset of results replicated in an independent dataset.ConclusionsThreat bias is associated with generalized, rather than threat-specific, differences in the neural processing of faces in adolescents. Findings may aid in the development of novel treatments for anxiety disorders that use attention training to modify threat bias.

scholarly journals Neurocognitive mechanisms of d-cycloserine augmented single-session exposure therapy for anxiety

2019 ◽  
Author(s):  
Andrea Reinecke ◽  
Alecia Nickless ◽  
Michael Browning ◽  
Catherine J. Harmer
Keyword(s):  
Panic Disorder ◽  
Anxiety Disorders ◽  
Exposure Therapy ◽  
Psychological Treatment ◽  
Self Report ◽  
Clinical Effects ◽  
Single Session ◽  
Threat Bias ◽  
Fearful Faces

AbstractObjectiveDrugs targeting the N-Methyl-D-aspartic acid (NMDA) system and the ability to learn new associations have been proposed as potential adjunct treatments to boost the success of exposure therapy for anxiety disorders. However, the effects of the NMDA partial agonist d-cycloserine on psychological treatment have been mixed. We investigated potential neurocognitive mechanisms underlying the clinical effects of d-cycloserine-augmented exposure, to inform the optimal combination of this and similar agents with psychological treatment.MethodsUnmedicated patients with panic disorder were randomised to single-dose d-cycloserine (250mg; N=17) or matching placebo (N=16) 2hrs before one session of exposure therapy. Neurocognitive markers were assessed one day after treatment, including reaction-time based threat bias for fearful faces and amygdala response to threat. Clinical symptom severity was measured using self-report and clinician-rated scales the day before and after treatment, and at 1- and 6-months follow-up. Analysis was by intention-to-treat.ResultsOne day after treatment, threat bias for fearful faces and amygdala threat response were attenuated in the drug compared to the placebo group. Lower amygdala magnitude predicted greater clinical improvement during follow-up across groups. D-cycloserine led to greater clinical recovery at 1-month follow-up (d-cycloserine 71% versus placebo 25%).DiscussionD-cycloserine-augmented single-session exposure therapy reduces amygdala threat response, and this effect predicts later clinical response. These findings highlight a neurocognitive mechanism by which d-cycloserine may exert its augmentative effects on psychological treatment and bring forward a marker that may help understand and facilitate future development of adjunct treatments with CBT for anxiety disorders. (D-cycloserine Augmented CBT for Panic Disorder; clinicaltrials.gov;NCT01680107)

A neurobehavioral account for individual differences in resilience to chronic military stress

2014 ◽  
Vol 45 (5) ◽  
pp. 1011-1023 ◽  
Author(s):  
T. Lin ◽  
S. Vaisvaser ◽  
E. Fruchter ◽  
R. Admon ◽  
I. Wald ◽  
...  
Keyword(s):  
Trait Anxiety ◽  
Military Training ◽  
Anterior Cingulate ◽  
Trauma Symptoms ◽  
Brain Response ◽  
Threat Bias ◽  
Dorsal Anterior Cingulate Cortex ◽  
High Anxious ◽  
Hippocampal Activity ◽  
Military Stress

Background.Military training is a chronic stressful period that often induces stress-related psychopathology. Stress vulnerability and resilience depend on personality trait anxiety, attentional threat bias and prefrontal–limbic dysfunction. However, how these neurobehavioral elements interact with regard to the development of symptoms following stress remains unclear.Method.Fifty-five healthy combat soldiers undergoing intensive military training completed functional magnetic resonance imaging (fMRI) testing while performing the dot-probe task (DPT) composed of angry (threat) and neutral faces. Participants were then stratified according to their bias tendency to avoidance (n = 25) or vigilance (n = 30) groups, categorized as high or low trait anxiety and assessed for post-stress symptom severity.Results.Avoidance compared to vigilance tendency was associated with fewer post-trauma symptoms and increased hippocampal response to threat among high anxious but not low anxious individuals. Importantly, mediation analysis revealed that only among high anxious individuals did hippocampal activity lead to lower levels of symptoms through avoidance bias tendency. However, in the whole group, avoidance bias was modulated by the interplay between the hippocampus and the dorsal anterior cingulate cortex (dACC).Conclusions.Our results provide a neurobehavioral model to explain the resilience to post-trauma symptoms following chronic exposure. The model points to the importance of considering threat bias tendency in addition to personality traits when investigating the brain response and symptoms of trauma. Such a multi-parametric approach that accounts for individual behavioral sensitivities may also improve brain-driven treatments of anxiety, possibly by targeting the interplay between the hippocampus and the dACC.

scholarly journals Acute Ketamine Modulated Functional Brain Coupling and Dissociative and Affective States in Human Subjects: Interim Analyses

2021 ◽  
Author(s):  
Laura M Hack ◽  
Katherine G Warthen ◽  
Xue Zhang ◽  
Boris D Heifets ◽  
Trisha Suppes ◽  
...  
Keyword(s):  
Functional Neuroimaging ◽  
Therapeutic Potential ◽  
Neural Mechanisms ◽  
Self Report ◽  
Affective States ◽  
Brain Response ◽  
Functional Brain ◽  
Functional Connections ◽  
Reward Responsiveness ◽  
Acute Responses

Ketamine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor that is both a drug of abuse and an FDA-approved anesthetic used off-label for treatment-resistant depression. Despite its growing clinical use for depression and pain, the relationships between the acute dissociative and affective effects of ketamine that contribute to its abuse liability and therapeutic potential, along with the neural mechanisms underlying these effects, are not well established. To address this need, we have implemented a randomized, double-blinded, placebo-controlled, within-subjects mechanistic trial. Healthy adult subjects undergo infusion with two fixed doses of subanesthetic racemic intravenous (IV) ketamine and placebo and their acute responses are assessed with self-report questionnaires, behavioral measures, hormone levels, and neuroimaging. As planned in our analysis strategy, we present interim results for the first 7 subjects of our study, focusing on dissociative and affective states and resting functional brain coupling signatures of these states. The first key finding was that ketamine induced dose-dependent increases in dissociation and related intoxication. Ketamine also altered affective states, reducing emotional insensitivity but increasing stress assessed by cortisol. Second, ketamine had an effect on altering brain connectivity, particularly for specific connections between regions of the reward and negative affect circuits and involving thalamic sub-regions. Third, regarding brain-response associations, ketamine-induced increases in amygdala-anteroventral thalamus coupling were correlated with greater dissociation and intoxication, whereas decreases in the coupling of the anteromedial thalamus and posterior parietal thalamus were correlated with increased sensory aspects of reward responsiveness. Additional specific correlations were observed between affective measures relevant to reward responsiveness or its absence and drug-altered changes in localized functional connections involving the nucleus accumbens (NAcc), amygdala, and thalamic sub-regions. We also discovered a consistent profile of negative associations between ketamine altered connectivity involving the NAcc and specific thalamic sub-regions and effects of anxiety. Further, drug-altered increases in the coupling of the amygdala and anteroventral thalamus were associated with increases in cortisol, an indicator of biochemical stress. The findings highlight the utility of integrating self-reports, objective measures, and functional neuroimaging to disentangle the brain states underlying specific acute responses induced by ketamine. With the likely continued expansion of FDA indications for ketamine, understanding acute responses and underlying neural mechanisms is important for maximizing the therapeutic potential of ketamine while minimizing the risk of promoting misuse or abuse of this substance. Clinical Trial Registration ID #: NCT03475277

scholarly journals Finding the P3 in the P600: Decoding shared neural mechanisms of responses to syntactic violations and oddball target detection

2018 ◽  
Author(s):  
Jona Sassenhagen ◽  
Christian J. Fiebach
Keyword(s):  
Direct Evidence ◽  
Pattern Analysis ◽  
Neural Mechanisms ◽  
Multivariate Pattern Analysis ◽  
Brain Response ◽  
Alternative Account ◽  
Brain Responses ◽  
Multivariate Pattern ◽  
Visual Oddball ◽  
Substantial Degree

AbstractThe P600 Event-Related Brain Potential, elicited by syntactic violations in sentences, is generally interpreted as indicating language-specific structural/combinatorial processing, with far-reaching implications for models of language. P600 effects are also often taken as evidence for language-like grammars in non-linguistic domains like music or arithmetic. An alternative account, however, interprets the P600 as a P3, a domain-general brain response to salience. Using time-generalized multivariate pattern analysis, we demonstrate that P3 EEG patterns, elicited in a visual Oddball experiment, account for the P600 effect elicited in a syntactic violation experiment: P3 pattern-trained MVPA can classify P600 trials just as well as P600-trained ones. A second study replicates and generalizes this finding, and demonstrates its specificity by comparing it to face- and semantic mismatch-associated EEG responses. These results indicate that P3 and P600 share neural patterns to a substantial degree, calling into question the interpretation of P600 as a language-specific brain response and instead strengthening its association with the P3. More generally, our data indicate that observing P600-like brain responses provides no direct evidence for the presence of language-like grammars, in language or elsewhere.

Novel Approaches for Treating Anxiety Disorders

2017 ◽  
Author(s):  
David A. Sturman ◽  
Milissa L. Kaufman ◽  
Cara E. Bigony ◽  
Kerry J. Ressler
Keyword(s):  
Mental Health ◽  
Anxiety Disorders ◽  
Mental Health Treatment ◽  
Health Treatment ◽  
Novel Treatments ◽  
Incomplete Response ◽  
Novel Approaches ◽  
Anxiety And Fear

While multiple effective pharmacotherapies and psychotherapies exist for anxiety disorders, to many they lack efficacy, tolerability, and/or accessibility. Only one-third of those with anxiety disorders seek mental health treatment and, of those who do, nonadherence and nonresponse (or incomplete response) remain substantial problems. There is thus a great need for novel treatments. In this chapter, we discuss approaches for the development of new anxiety treatments based on an improved understanding of the neurobiology underlying anxiety and fear-related disorders. We define novel treatments as those that hold potential promise but are not yet fully proven or available, or those that are recently available but not widely implemented.

scholarly journals The Effect of Varenicline on the Neural Processing of Fearful Faces and the Subjective Effects of Alcohol in Heavy Drinkers

2016 ◽  
Vol 40 (5) ◽  
pp. 979-987 ◽  
Author(s):  
Joshua L. Gowin ◽  
Vatsalya Vatsalya ◽  
Jonathan G. Westman ◽  
Melanie L. Schwandt ◽  
Selena Bartlett ◽  
...  
Keyword(s):  
Subjective Effects ◽  
Neural Processing ◽  
Fearful Faces ◽  
Heavy Drinkers

Gabapentin and Lamotrigine: Novel Treatments for Mood and Anxiety Disorders

CNS Spectrums ◽  
1997 ◽  
Vol 2 (10) ◽  
pp. 56-61 ◽  
Author(s):  
Mark H. Pollack ◽  
Erin L. Scott
Keyword(s):  
Bipolar Disorder ◽  
Anxiety Disorders ◽  
Treatment Options ◽  
Mood Stabilizers ◽  
Generalized Anxiety ◽  
Research Attention ◽  
Novel Treatments ◽  
Mood And Anxiety Disorders ◽  
Systematic Inquiry ◽  
Psychiatric Conditions

AbstractClinical experience and systematic inquiry demonstrate that many patients with mood and anxiety disorders remain symptomatic despite standard interventions. These observations have prompted the search for alternative pharmacotherapeutic treatment options. Anticonvulsants, including valproic acid and carbamazepine, have demonstrated benefit for a number of psychiatric conditions. Recently, clinical and research attention has focused on the use of the new anticonvulsants gabapentin and lamotrigine as alternatives to standard pharmacotherapies for the treatment of mood and anxiety disorders. This paper reviews the experience to date with these agents in the treatment of psychiatric conditions. Gabapentin demonstrates promise for the treatment of panic and generalized anxiety, while both gabapentin and lamotrigine appear useful as mood stabilizers in the treatment of bipolar disorder.

scholarly journals Cholinergic modulation of disorder-relevant human defensive behaviour in generalised anxiety disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adam Perkins ◽  
Fiona Patrick ◽  
Toby Wise ◽  
Nicholas Meyer ◽  
Ndaba Mazibuko ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Anxiety Disorder ◽  
State Anxiety ◽  
Repeated Measures ◽  
Avoidance Behaviour ◽  
Defensive Behaviour ◽  
Generalised Anxiety Disorder ◽  
Healthy Human ◽  
Fearful Faces ◽  
Threat Avoidance

AbstractDrugs that are clinically effective against anxiety disorders modulate the innate defensive behaviour of rodents, suggesting these illnesses reflect altered functioning in brain systems that process threat. This hypothesis is supported in humans by the discovery that the intensity of threat-avoidance behaviour is altered by the benzodiazepine anxiolytic lorazepam. However, these studies used healthy human participants, raising questions as to their validity in anxiety disorder patients, as well as their generalisability beyond GABAergic benzodiazepine drugs. BNC210 is a novel negative allosteric modulator of the alpha 7 nicotinic acetylcholine receptor and we recently used functional Magnetic Resonance Imaging to show it reduced amygdala responses to fearful faces in generalised anxiety disorder patients. Here we report the effect of BNC210 on the intensity of threat-avoidance behaviour in 21 female GAD patients from the same cohort. We used the Joystick Operated Runway Task as our behavioural measure, which is a computerised human translation of the Mouse Defense Test Battery, and the Spielberger state anxiety inventory as our measure of state affect. Using a repeated-measures, within-subjects design we assessed the effect of BNC210 at two dose levels versus placebo (300 mg and 2000 mg) upon two types of threat-avoidance behaviour (Flight Intensity and Risk Assessment Intensity). We also tested the effects of 1.5 mg of the benzodiazepine lorazepam as an active control. BNC210 significantly reduced Flight Intensity relative to placebo and the low dose of BNC210 also significantly reduced self-reported state anxiety. Risk Assessment Intensity was not significantly affected. Results show both human defensive behaviour and state anxiety are influenced by cholinergic neurotransmission and there provide converging evidence that this system has potential as a novel target for anxiolytic pharmacotherapy.

scholarly journals Attention expedites target selection by prioritizing the neural processing of distractor features

2020 ◽  
Author(s):  
Mandy V. Bartsch ◽  
Christian Merkel ◽  
Mircea A. Schoenfeld ◽  
Jens-Max Hopf
Keyword(s):  
Daily Life ◽  
Target Identification ◽  
Target Selection ◽  
Target Color ◽  
Neural Processing ◽  
Brain Response ◽  
Feature Representations ◽  
Feature Attention ◽  
Human Participants ◽  
Neural Gain

AbstractWhether doing the shopping, or driving the car – to navigate daily life, our brain has to rapidly identify relevant color signals among distracting ones. Despite a wealth of research, how color attention is dynamically adjusted is little understood. Previous studies suggest that the speed of feature attention depends on the time it takes to enhance the neural gain of cortical units tuned to the attended feature. To test this idea, we had human participants switch their attention on the fly between unpredicted target color alternatives, while recording the electroencephalographic brain response to probes matching the target, a non-target, or a distracting alternative target color. Paradoxically, we observed a temporally prioritized processing of distractor colors. A larger neural gain for the distractor followed by stronger attenuation expedited target identification. Our results suggest that dynamic adjustments of feature attention involve the temporally prioritized processing and elimination of distracting feature representations.

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