Specific Phobias

Specific Phobias

• A specific phobia is an intense, irrational fear of a specific object, situation, or stimulus, characterized by a consistent and excessive anxiety response.

Diagnostic Criteria

• A. The individual experiences a clear anxiety or concern about a specific object or situation.
• B. The phobic object or situation almost always provokes an immediate anxiety response.
• C. The individual actively avoids or endures the phobic object or situation with intense anxiety.
• D. The anxiety or fear is not proportional to the actual danger posed by the specific object or situation.
• E. The anxiety or fear is persistent, lasting at least 6 months.
• F. The anxiety or fear causes significant distress or impairment in social, occupational, or other areas of functioning.
• G. The disorder is not better explained by the symptoms of another mental disorder.

Epidemiology, Comorbidity, and Specific Course of Phobias

• Specific phobias are relatively common, with 41-50% of the general population experiencing specific phobias at some point in their lives.
• The total prevalence of specific phobias is around 12%, with a 12-month point prevalence of around 9%.
• Of those with a specific phobia, 22% experience severe symptoms, 30% experience moderate symptoms, and 48% experience mild symptoms.
• Situation phobias are the most common, followed by phobias of natural environments, animals, and blood-injury-injection (BII).
• Acrophobia (fear of heights) is the most common specific phobia.
• Specific phobias are more common in adolescents and less common in older adults.
• The diagnosis of specific phobia in adulthood is associated with a diagnosis of specific phobia in childhood or adolescence.
• Percentages of specific phobias are also higher in women than in men.

Natural Course of Phobias

• Many phobias begin in childhood or adolescence, with a early onset.
• Phobias related to animals and BII tend to begin earlier than phobias related to natural environments and situation phobias.
• Although phobias can begin early, specific fears appear even earlier.
• Phobias are usually chronic and rarely disappear without intervention.

Impairment and Comorbidity

• Impairment grows significantly with the number of (specific) fears.
• All subtypes of specific phobias are associated with greater interference in daily and social functioning compared to the general population.
• Situation phobias, in general, and the fear of being alone, were associated with the most interference, the greatest likelihood of seeking professional help, and the highest use of medication.
• Persons with a BII phobia are less likely to pursue certain medical treatments, which can have a negative impact on their overall health.

Etiology

• Genetic risk factors contribute to the development of specific phobias.
• Environmental risk factors, such as parental control, overprotection, and parental involvement, can also contribute to the development of specific phobias.
• Cognitive perspectives, such as maladaptive cognitions or schemas, can also contribute to the development of specific phobias.

Cognitive Models

• The process of anxiety consists of three components: motor escape and avoidance, physiological activation of the sympathetic nervous system, and cognitive evaluations of threat and danger.
• In specific phobias, physiological activation is the pre-potent response domain that serves to stimulate escape and motivate avoidance in the presence of the feared object.
• The cognitive component is tertiary and focuses on overestimating threat and danger.

Types of Phobias

• There are several subtypes of phobias, including:
  • Animal type (e.g. snakes, rodents, insects)
  • Natural environment type (e.g. thunderstorms, tornadoes, heights, darkness)
  • Blood-injection-injury (BII) type (e.g. needles, blood draws, open wounds)
  • Situational type (e.g. driving, flying, enclosed spaces)

Blood-Injection-Injury (BII) Phobia

• Unique characteristics of BII phobia:
  • Typically accompanied by a vasovagal syncope response, leading to fainting
  • 80% of individuals with BII phobia have a history of fainting or near-fainting
  • Often characterized by feelings of disgust or revulsion instead of anxiety
  • BII phobia is a common and unique phobia, with a lifetime prevalence of 3.5% (men and women) and 4.9% for women

Fainting Response in BII Phobia

• The fainting response is characterized by a 2-phase or bifasic response:
  • Initial phase: increased heart rate and blood pressure, typical of a fight-flight response
  • Second phase: bradycardia (decreased heart rate) and hypotension (low blood pressure), leading to decreased cerebral blood flow and eventual fainting

Mechanisms of Specific Phobias

• The role of disgust in BII and spider phobias:
  • Disgust sensitivity is a robust predictor of spider and BII phobias
  • Disgust mediates the severity of anxiety and distress
  • Disgust towards a stimulus predicts avoidance of spider and injection/ injury stimuli, beyond anxiety and concern
• Armfield's cognitive vulnerability model of specific phobias:
  • The general tendency to evaluate harmful stimuli as disgusting
  • The specific tendency to evaluate a phobic stimulus as disgusting
  • The tendency to react negatively to one's own feelings of disgust (disgust sensitivity) can all contribute to the etiology, maintenance, and expression of spider and BII phobias

Treatment of Specific Phobias

• The recommended treatment for Blood-Injection-Injury (BII) phobia is Applied Tension (AT), which involves tension techniques and in vivo exposure.
• AT has a significant effect on reducing self-reported levels of anxiety, avoidance during sessions, and fainting.
• However, when considering the effect sizes before and after treatment, E (exposure alone) performed better than all other treatments.

Individual Treatment Techniques for BII

• Exposure (E): Involves exposing patients to a customized hierarchy of feared situations, which is a natural choice for treating BII phobia.
• Applied Relaxation (AR): Based on the principle of progressive relaxation, involving repeated sequences of short tensing and relaxing of different skeletal muscle groups.
• Applied Tension (AT): Combines a muscle tension technique with in vivo exposure to prevent fainting responses.
• Tension (T): Involves exercising tension in arms, legs, and torso to increase blood pressure at will.

Exposure-Based Therapies

• In vivo exposure therapy involves three phases: instruction, direct exposure, and maintenance of treatment results.
• Systematic desensitization involves two crucial modifications: using a variant of Jacobson's progressive muscle relaxation to elicit a hunger response antagonistic to anxiety, and instructing patients to imagine the feared situation and gradually increase its intensity.
• Geconditioned inhibition involves eliciting a relaxation response antagonistic to the anxiety response during the feared cue, reducing the anxiety response.

Virtual Reality Exposure Therapy

• Involves using computer-generated interactive virtual realities, including visual displays, other sensory inputs, and body tracking devices, to conduct exposure therapy.
• Patients visit these virtual realities over a longer period during multiple sessions.
• Virtual reality exposure therapy (VRET) is particularly useful when it is difficult to realize the exposure environment in reality.

Effectiveness of Exposure-Based Therapies

• Specific phobias respond particularly well to exposure-based therapies, making them the preferred treatment for these disorders.
• Exposure-based therapies result in significantly better outcomes after treatment, regardless of whether they are evaluated by verbal report measures or behavioral avoidance tests.
• These therapies are highly effective and provide a stable improvement in self-reported anxiety and behavioral avoidance.

Active Ingredients of Exposure-Based Therapies

• In vivo exposure is more effective than systematic desensitization.
• Massed exposure training in one session is highly effective for treating specific phobias.
• The degree of therapist involvement during exposure is crucial, particularly in reducing avoidance behavior and increasing the frequency and duration of exposure practice.

Mechanisms of Change

• The central mechanisms of change during exposure therapy involve extinction, habituation, and contraconditioning.
• Extinction learning is a key mechanism of change, where the feared stimulus is no longer associated with aversive consequences.
• The neural correlates of extinction involve the activation of the amygdala and the prefrontal cortex.

Principles of Learning Theory

• Equipotentiality: any predictor can form an association with any outcome, leading to the development of phobias.
• Extinction: the well-documented effect that a conditioned stimulus (CS) alone, without the unconditioned stimulus (UCS), can lead to a decrease in response strength over time.

Aspects of Conditioning

• Conditioning is guided by CS-UCS associations, which form during conditioning and mediate the conditioned response (CR).
• Conditioning depends on past experiences: organisms bring information from past experiences and relationships between CS's and UCS's to conditioning episodes.
• Conditioning is not dependent on contiguity: the potential phobogenic stimulus does not need to occur simultaneously with a traumatic event.

Characteristics of Conditioning

• Conditioning can occur after a single trial: geconditioneerde reacties can be rapidly acquired.
• Associations formed after one trial are persistent: CS-UCS associations can be formed quickly and remain intact even with random presentations of CS and UCS.
• The CR and UR are not necessarily the same: the CS can elicit different responses related to the UCS, but not identical to the response elicited by the UCS.
• The CS does not always produce a CR after conditioning: feature modulation/occasion setting and overshadowing can influence the CR.

Other Aspects of Conditioning

• Conditioning can occur without a real CS and UCS: mental representations of stimuli can suffice for learning.
• Second-order conditioning: a CS1 is paired with a CS2, which becomes a predictor of the outcome, evoking a CR.
• The UCS does not need to be biologically significant: associations can be formed without an unconditioned response.

Extinction and Renewal

• Extinction does not break the CS-UCS association: extinction can be context-dependent, and renewal can occur in certain contexts.
• Spontaneous recovery: extinguished CR's can reappear over time, even in a different context.

Traumatic Incidents

• Traumatic incidents may not be traumatic at the time: the reevaluation of the UCS can make a stimulus traumatic, leading to the development of phobias.

Classical Conditioning and Anxiety

• Unconditioned Stimulus (UCS): a stimulus that elicits a natural response, such as food, pain, or sex, resulting in an Unconditioned Response (UCR), a reflex that is not under a person's voluntary control.
• Conditioned Stimulus (CS): a neutral stimulus that can predict the occurrence of a UCS, leading to a Conditioned Response (CR), a learned response associated with the CS.

Anxiety and the Body's Response

• Anxiety Response: a natural response to a perceived threat, characterized by:
  • Increased heart rate and blood pressure
  • Rapid breathing
  • Sweating
  • Tense muscles
  • Pupils dilating
• Parasympathetic Activation: a response that counters the anxiety response, characterized by:
  • Decreased heart rate and blood pressure
  • Increased digestion
  • Relaxed muscles

Classical Conditioning Process

• Learning: the association between a CS and a UCS, leading to a CR
• Extinction: the process of eliminating the CR by repeatedly presenting the CS without the UCS
• Spontaneous Recovery: the reappearance of a CR after extinction, which can be triggered by an external stimulus
• Counterconditioning: a procedure that trains the CS to predict a response opposite to the UCR, such as relaxation

Higher-Order Conditioning and Complex Phenomena

• Second-Order Conditioning: the association between a CS and a UCS, where the CS is already associated with another UCS
• Equipotentiality: the idea that any stimulus can be associated with any outcome, making it possible for two stimuli to be associated with each other
• Contextual Dependence: the influence of context on the expression of a CR
• Blocking: the phenomenon where a CS is overshadowed by a more salient stimulus

Glossary of Terms

• Latent Inhibition: the observation that multiple experiences with a CS without a UCS can make it harder to learn a CS-UCS association
• Learned Irrelevance: a phenomenon where a stimulus is repeatedly presented with multiple UCSs, making it harder to learn a new CS-UCS association
• Superlearning: the rapid learning of a new CS-UCS association due to prior learning with a different stimulus
• Overshadowing: the phenomenon where a more salient stimulus overshadows a less salient stimulus, making it harder to learn a CS-UCS association

Operant Conditioning and Anxiety/Fear

• Operant conditioning explains anxiety/fear through positive reinforcement, negative reinforcement, and punishment.

Positive Reinforcement

• Positive reinforcement occurs when a behavior is followed by a positive consequence (+Cpos), increasing the likelihood of the behavior.
• In the context of anxiety, positive reinforcement can strengthen avoidance behaviors, even if the original fear stimulus is not present.

Negative Reinforcement

• Negative reinforcement occurs when a behavior is followed by the removal of an aversive stimulus (-Cneg), increasing the likelihood of the behavior.
• There are two types of negative reinforcement: escape and avoidance.
• Escape: a behavior that removes an aversive stimulus, such as a shock.
• Avoidance: a behavior that prevents an aversive stimulus from occurring, such as not going to a place where a feared stimulus is present.

Discriminative Stimulus (Sd) and S-Delta (SΔ)

• A discriminative stimulus (Sd) is a stimulus that increases the likelihood of a response.
• S-Delta (SΔ) is a stimulus that decreases the likelihood of a response.
• In anxiety, Sd can be a stimulus that triggers a fear response, while SΔ is a stimulus that does not trigger a fear response.

Anxiety and Fear

• Anxiety and fear can be reduced through escape and avoidance behaviors.
• However, these behaviors can also be negatively reinforced, making it difficult to overcome anxiety and fear.

Avoidance Behaviors

• Avoidance behaviors can be subtle, such as not going to a place where a feared stimulus is present.
• These behaviors can provide temporary relief but can also maintain anxiety and fear in the long run.
• Avoidance behaviors can be reinforced by the removal of an aversive stimulus, but they can also lead to a lack of exposure to the feared stimulus, making it difficult to overcome anxiety and fear.

Safety Behaviors

• Safety behaviors are subtle avoidance behaviors that aim to prevent a catastrophic event.
• These behaviors can provide temporary relief but can also maintain anxiety and fear in the long run.

Punishment of Avoidance Behaviors

• Avoidance behaviors can be punished in the long run, leading to difficulties in daily life.
• Punishment can take three forms: removal of something positive, addition of something negative, or blocking of something positive.

Conflict in Anxiety

• The short-term consequences of avoidance behaviors can be rewarding, but the long-term consequences can be negative.
• This conflict can lead individuals to seek treatment.

Criticisms of the Learning Theory

• Retrospective memory: individuals with a specific phobia may not remember the associative learning event.
• Not all individuals who experience trauma or anxiety develop a phobia.
• Incubation: the fear response can increase over time, even if the conditioned stimulus is not present.
• Unequal distribution of anxieties: certain stimuli are more likely to be associated with anxiety and fear.
• Indirect ways to acquire anxiety: anxiety can be acquired through verbal information and observational learning.

Operant Conditioning and Anxiety/Fear

• Operant conditioning explains anxiety/fear through positive reinforcement, negative reinforcement, and punishment.

Positive Reinforcement

• Positive reinforcement occurs when a behavior is followed by a positive consequence (+Cpos), increasing the likelihood of the behavior.
• In the context of anxiety, positive reinforcement can strengthen avoidance behaviors, even if the original fear stimulus is not present.

Negative Reinforcement

• Negative reinforcement occurs when a behavior is followed by the removal of an aversive stimulus (-Cneg), increasing the likelihood of the behavior.
• There are two types of negative reinforcement: escape and avoidance.
• Escape: a behavior that removes an aversive stimulus, such as a shock.
• Avoidance: a behavior that prevents an aversive stimulus from occurring, such as not going to a place where a feared stimulus is present.

Discriminative Stimulus (Sd) and S-Delta (SΔ)

• A discriminative stimulus (Sd) is a stimulus that increases the likelihood of a response.
• S-Delta (SΔ) is a stimulus that decreases the likelihood of a response.
• In anxiety, Sd can be a stimulus that triggers a fear response, while SΔ is a stimulus that does not trigger a fear response.

Anxiety and Fear

• Anxiety and fear can be reduced through escape and avoidance behaviors.
• However, these behaviors can also be negatively reinforced, making it difficult to overcome anxiety and fear.

Avoidance Behaviors

• Avoidance behaviors can be subtle, such as not going to a place where a feared stimulus is present.
• These behaviors can provide temporary relief but can also maintain anxiety and fear in the long run.
• Avoidance behaviors can be reinforced by the removal of an aversive stimulus, but they can also lead to a lack of exposure to the feared stimulus, making it difficult to overcome anxiety and fear.

Safety Behaviors

• Safety behaviors are subtle avoidance behaviors that aim to prevent a catastrophic event.
• These behaviors can provide temporary relief but can also maintain anxiety and fear in the long run.

Punishment of Avoidance Behaviors

• Avoidance behaviors can be punished in the long run, leading to difficulties in daily life.
• Punishment can take three forms: removal of something positive, addition of something negative, or blocking of something positive.

Conflict in Anxiety

• The short-term consequences of avoidance behaviors can be rewarding, but the long-term consequences can be negative.
• This conflict can lead individuals to seek treatment.

Criticisms of the Learning Theory

• Retrospective memory: individuals with a specific phobia may not remember the associative learning event.
• Not all individuals who experience trauma or anxiety develop a phobia.
• Incubation: the fear response can increase over time, even if the conditioned stimulus is not present.
• Unequal distribution of anxieties: certain stimuli are more likely to be associated with anxiety and fear.
• Indirect ways to acquire anxiety: anxiety can be acquired through verbal information and observational learning.

Corticotropin-Releasing Factor (CRF)

• CRF is a small neuropeptide that regulates neuro-endocrine, autonomic, and behavioral responses to stress.
• CRF induces the release of adrenocorticotropic hormone (ACTH) from the pituitary gland, leading to increased glucocorticoid release from the adrenal cortex.
• CRF acts as a neurotransmitter in neural circuits involved in stress response, including the amygdala.
• Intra-ventricular administration of CRF stimulates the sympathetic nervous system, increases plasma adrenaline, and raises heart rate and blood pressure.
• CRF has multiple effects on feeding, gastrointestinal activity, and energy balance.

Corticotropin-Releasing Factor (CRF) and Anxiety

• CRF induces anxiety-like behavior in conflict tests, social interpretation, and exploration in novel open fields.
• Direct neuronal administration of CRF produces strong stimulating effects in many brain regions, including the hippocampus, amygdala, locus coeruleus, cortex, and hypothalamus.
• The amygdala has many CRF-expressing neurons and receptors, and CRF release in the amygdala is associated with anxiety symptoms.
• Higher CRF levels increase the firing rate of cells in the locus coeruleus and increase the turnover of norepinephrine (NE).

Norepinephrine (NE) and Anxiety

• Reciprocal connections between the amygdala and locus coeruleus provide mechanisms for the stimulation of anxiety, orientation, and response to fear stimuli.
• The locus coeruleus is a large cluster of noradrenergic cell bodies in the dorsal pons, which send axons to various brain regions to increase arousal and attention to physiologically relevant stimuli.
• The corresponding hypervigilance is similar to that seen in post-traumatic stress disorder (PTSD) and other anxiety disorders.
• Electrical stimulation of the locus coeruleus induces warning and anxiety reactions.
• Norepinephrine release in the locus coeruleus is inhibited by GABA and serotonin.

Norepinephrine (NE) and Emotion

• Norepinephrine is released in response to emotional stimuli, including fear, and plays a role in the formation of emotional memories.
• Individuals with panic disorder and PTSD have more dramatic bodily responses to anxiety-provoking stimuli, and veterans with PTSD have higher circulating NE.
• Norepinephrine and epinephrine have a role in the formation of emotional memories that can contribute to anxiety disorders, including agoraphobia, panic, and PTSD.

GABA and Anxiety

• GABA (gamma-aminobutyric acid) has a calming effect on anxiety and is involved in the suppression of anxiety responses.
• The GABA receptor complex includes a chloride channel, which opens when GABA binds, allowing chloride ions to enter the cell and causing hyperpolarization.
• The reduction of action potential and the decrease of anxiety responses are a result of this hyperpolarization.
• Different sedative-hypnotics, such as benzodiazepines and barbiturates, enhance the function of GABA, leading to sedation, reduced anxiety, and anticonvulsive effects.

5-HT and Anxiety

• The anxiolytic effects of 5-HT are demonstrated by the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in the treatment of anxiety disorders.
• 5-HT agonists have anxiolytic effects in tasks that require active coping with a stressor, but increase anxiety in tasks that require passive behavior or withholding of a response to expected threat.
• This can be explained by the subtype of 5-HT receptor involved, differences in acute and chronic treatment, or the specific brain regions involved in anxiety versus fear (active coping versus passive response).

Anxiolytics

• Anxiolytics are drugs used to relieve anxiety, which belong to the class of sedativa-hypnotica, a subcategory of CNS-depressiva.
• This category includes barbiturates, benzodiazepines, and alcohol.

Mechanism of Action

• The primary mechanism of action of sedative-hypnotic drugs is to enhance GABA transmission.
• GABA is the major inhibitory neurotransmitter in the nervous system.
• GABA agonists produce local hyperpolarization or inhibitory postsynaptic potential and inhibit cell firing.

Benzodiazepines (BDZ's)

• BDZ's bind to their modulatory sites on the GABAA complex, enhancing the effect of GABA by increasing the frequency of channel openings.
• BDZ's have no effect on Cl- channel opening in the absence of GABA.
• BDZ's are addictive, whereas SSRIs are not, making them a first-choice treatment.

Comparison with Barbiturates

• Barbiturates also increase the affinity of the GABAA receptor for GABA.
• However, they increase the duration of Cl- channel openings triggered by GABA, rather than the frequency.
• Barbiturates can be lethal, unlike BDZ's.

Therapeutic Effects

• BDZ's are commonly used for anxiety relief, reducing feelings of anxiety and anxiety symptoms.
• Mild sedation from BDZ use decreases after repeated use over a week to 10 days.

Misuse and Dependence

• Misuse of BDZ's can be divided into two patterns: intentional misuse and unintentional misuse.
• Dependence requires evidence of compulsive behavior in seeking drugs and loss of control.
• Physical dependence is typical of addiction, but it is not a required criterion.
• Long-term use of BDZ's can cause physical dependence, but it is not necessarily misuse or addiction.

Withdrawal Symptoms

• Withdrawal symptoms occur when the blood or tissue concentration of a dependence-forming substance decreases.
• Symptoms are often the opposite of the acute effects of the medication.
• Withdrawal symptoms are usually more severe and have a faster onset in patients using BDZ's with shorter half-lives.

Alternatives to Benzodiazepine Anxiolytics

• Beta-receptor blockers can control vegetative symptoms of anxiety and tension.
• SSRIs and SNRIs are effective in treating acute GAD symptoms and panic disorders.
• There are no pharmacological treatments available for specific phobias.

Emotional Learning and Memory

• Fear conditioning involves the thalamus, amygdala, and cortex, with the thalamus communicating with the amygdala to process fear-inducing stimuli.
• The emotional meaning of a stimulus is determined not only by the stimulus itself but also by the context in which it occurs.

The Role of the Amygdala and Hippocampus

• Lesions in the amygdala interfere with the response to tone and conditioning.
• Lesions in the hippocampus interfere with the response to context, but not tone.
• The hippocampus plays a crucial role in processing complex information, including spatial context.

The Auditory Cortex and Anger Conditioning

• The auditory cortex is involved in the establishment of fear responses, especially for simple auditory stimuli.
• Lesions in the auditory cortex disrupt fear conditioning for one of the two stimuli paired with shock.
• The cortex is not necessary for simple fear conditioning, and the thalamus and amygdala can process fear stimuli without cortical involvement.

Glutamate Transmission and LTP

• Glutamate transmission is involved in memory formation and long-term potentiation (LTP), a process that strengthens synaptic connections.
• LTP has been found in the fear-conditioning route, and studies have shown that the prefrontal regions regulate emotional responses through the amygdala.

Emotional Learning and Extinction

• Extinction is an active learning process that requires the same neural pathways as fear conditioning.
• The prefrontal cortex plays a critical role in regulating emotional responses, and damage to this region can make it difficult to extinguish emotional learning.
• Blocking NMDA receptors in the amygdala disrupts extinction, suggesting that extinction is an active learning process.

Two Routes for Emotional Learning

• There are two routes for emotional learning: the cortical "high-road" and the subcortical "low-road".
• The high-road involves the cortex and is involved in more complex emotional processing, while the low-road is a faster, more instinctual response.
• Therapy can improve the high-road, leading to better emotional regulation.

Emotional Memory and Trauma

• Emotional memories can be stored in the declarative memory, but they are stored as cold facts.
• Traumatic events can influence mental and behavioral functions later in life through processes that are inaccessible to conscious awareness.
• The emotional memory system, which develops earlier, forms and stores unconscious memories of traumatic events.

Neuroanatomy and Neuroimaging of Anxiety Disorders

Fear Network

• The amygdala is crucial for the perception and expression of emotion, specifically for anxiety-related negative affects and anxiety conditioning.
• The insula is involved in subjective feelings and emotional processing in general.
• The anterior cingulate cortex (ACC) is related to approach and avoidance behavior during anxiety learning.

Generalized Anxiety Disorder (GAD)

• Functional neuroimaging studies have shown a higher response of the amygdala and insula to anxiety-related or aversive images in GAD compared to healthy controls.
• Hyperresponsivity of the medial prefrontal cortex (PFC), specifically dorsal and rostral ACC, was observed in adolescent GAD patients.

Social Anxiety Disorder (SAD)

• Higher amygdala and hippocampal responses to conditioned stimuli were found in SAD.
• Neutral faces used as conditioned stimuli evoked amygdala activation.
• Learned improved emotional response to social stimuli may be a key factor in SAD.

Specific Phobias

• Hyperreactivity in the amygdala, insula, hippocampus, and dorsal medial PFC was observed during anticipation and processing of phobia-related versus neutral stimuli.

Post-Traumatic Stress Disorder (PTSD)

• Amygdala hyperreactivity was found for symptom provocation or anxiety learning in PTSD.
• Reduced amygdala response was associated with higher resilience in PTSD.
• A negative association was found between medial PFC response and symptom severity.

Panic Disorder

• Hyperreactivity in the amygdala, thalamus, and hippocampus, together with hyporesponsivity of frontal cortical regions, is important in the pathophysiology of PD.

Obsessive-Compulsive Disorder (OCD)

• Dysfunctional thalamo-cortico-striatal circuits with higher responses in the striatum are associated with OCD.
• Hyperresponsivity in the PFC and ACC is related to anxiety and obsessive thoughts.

Connectivity Studies

• Deficient interaction between the amygdala and medial PFC was found in PTSD.
• A significant negative interaction between the amygdala and dorsolateral PFC was observed during conditioning.

Neuroimaging in Anxiety Disorders

• Functional neuroimaging studies have shown hyperactivty of the amygdala during symptom provocation in anxiety disorders.
• Ventral PFC and ACC are also involved in anxiety processing.
• CCK-4-induced panic attacks can serve as a useful model to study the pathophysiology and neurobiological basis of PD.

Imaging Neural Correlates of Treatment

• Changed patterns of neural function were observed after successful treatment of specific phobias.
• Amygdala activity decreased after successful exposure therapy in spinfobics.
• Changes in patterns of brain activity were observed after CBT in OCD patients.

Circuitry Underlying Regulation of Conditioned Fear

• The study examines the neural mechanisms underlying the regulation of conditioned fear using two approaches: extinction of conditioned fear and cognitive emotion regulation.
• The research aims to investigate the similarities and differences in the neural mechanisms underlying these two paradigms for reducing fear.

Neural Mechanisms of Extinction and Emotion Regulation

• Extinction learning involves the formation of new inhibitory associations that reduce the expression of conditioned fear responses.
• The ventromedial prefrontal cortex (vmPFC) plays a crucial role in extinction learning, and its cortical thickness predicts the speed of extinction.
• Cognitive emotion regulation strategies can also reduce fear responses, and the study examines the neural mechanisms underlying this process.

Cognitive Emotion Regulation Strategies

• The study uses a cognitive reappraisal strategy, where participants are instructed to reinterpret emotional stimuli in a less negative way.
• This strategy is associated with decreased activity in the amygdala and increased activity in the dorsolateral prefrontal cortex (dlPFC).
• The dlPFC is involved in working memory, decision-making, and emotion regulation.

Neural Correlates of Emotion Regulation

• The study uses functional magnetic resonance imaging (fMRI) to examine the neural correlates of emotion regulation.
• Blood oxygenation level-dependent (BOLD) signal is used to measure neural activity in different brain regions.
• The results show that cognitive emotion regulation is associated with increased activity in the dlPFC and decreased activity in the amygdala.

Overlap with Extinction Mechanisms

• The study finds that the neural mechanisms underlying cognitive emotion regulation overlap with those involved in extinction learning.
• Both processes involve the vmPFC and amygdala, suggesting that similar neural mechanisms are recruited to reduce fear responses.

Key Findings

• Emotion regulation strategies can reduce conditioned fear responses by decreasing activity in the amygdala and increasing activity in the dlPFC.
• The vmPFC plays a general regulatory role in diminishing fear across different paradigms.
• Cognitive emotion regulation strategies can be used to reduce fear responses, and the neural mechanisms underlying this process involve similar regions as extinction learning.