The neurocircuitry of fear, stress, and anxiety disorders

Annals of The New York Academy of Sciences, 2006

Abstract: Neuroimaging research has helped to advance neurobiological models of anxiety disorders. The amygdala is known to play an important role in normal fear conditioning and is implicated in the pathophysiology of anxiety disorders. The amygdala may also be a target for the beneficial effects of cognitive-behavioral and medication treatments for anxiety disorders. In the current paper, we review neuroimaging research pertaining to the role of the amygdala in anxiety disorders and their treatment. Moreover, we discuss the development of new neuroimaging paradigms for measuring aspects of amygdala function, as well as the function of related brain regions. We conclude that such tools hold great promise for facilitating progress in relevant basic neuroscience as well as clinical research domains.

Therapeutics and Clinical Risk Management, 2015

Anxiety and stress disorders are among the most prevalent neuropsychiatric disorders. In recent years, multiple studies have examined brain regions and networks involved in anxiety symptomatology in an effort to better understand the mechanisms involved and to develop more effective treatments. However, much remains unknown regarding the specific abnormalities and interactions between networks of regions underlying anxiety disorder presentations. We examined recent neuroimaging literature that aims to identify neural mechanisms underlying anxiety, searching for patterns of neural dysfunction that might be specific to different anxiety disorder categories. Across different anxiety and stress disorders, patterns of hyperactivation in emotion-generating regions and hypoactivation in prefrontal/regulatory regions are common in the literature. Interestingly, evidence of differential patterns is also emerging, such that within a spectrum of disorders ranging from more fear-based to more anxiety-based, greater involvement of emotion-generating regions is reported in panic disorder and specific phobia, and greater involvement of prefrontal regions is reported in generalized anxiety disorder and posttraumatic stress disorder. We summarize the pertinent literature and suggest areas for continued investigation. submit your manuscript | www.dovepress.com

Human brain …, 2008

Biological Psychiatry, 2007

The amygdala is implicated as a key brain structure in fear processing. Studies exploring this process using the paradigm of fear conditioning have implicated the amygdala in fear acquisition and in generating behavioral fear responses. As such, fear extinction could be expected to induce a reduction in amygdala activity. However, exposure in specific phobia has never been shown persistently to reduce amygdala activity.By means of event-related functional magnetic resonance imaging, responses to phobia-related, general threat, and neutral pictures were measured before and 2 weeks after an intensive exposure session in 20 subjects with specific phobia for spiders and compared with healthy control subjects.Phobic subjects showed increased amygdala activity at baseline. This hyperactivity was significantly reduced 2 weeks after exposure therapy. Furthermore, a significant reduction of hyperactivity in anterior cingulate cortex and insula was found postexposure.To our knowledge, this is the first study demonstrating the effect of exposure on the amygdala in specific phobia. Our findings suggest that exposure therapy can have an effect on subcortical structures.

Asian Journal of Pharmaceutical and Clinical Research, 2016

ABSTRACTAnxiety disorders are among the most common mental, emotional, and behavioral problems. These affect one-eighth of the total population worldwide.Anxiety disorders are a group of mental disorders characterized by irritability, fear, insomnia, nervousness, tachycardia, inability to concentrate,poor coping skills, palpitation, sweating, agoraphobia, and social withdrawal. Brain regions and networks involved in anxiety symptomatology isan effort to better understand the mechanism involved and to develop more effective treatments for the anxiety disorders. Thus, neuroanatomicaland neuroimaging research in anxiety disorders has centered on the role of the amygdala, reciprocal connections between the amygdala and theprefrontal cortex, and, most recently, alterations in interoceptive processing by the anterior insula. Anxiety disorders are characterized by alterationsin a diverse range of neurochemical systems, suggesting ample novel targets for drug therapies. The neurotransmitter...

It is widely thought that phasic and sustained responses to threat reflect dissociable circuits centered on the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST), the two major subdivisions of the central extended amygdala. Early versions of this hypothesis remain highly influential and have been incorporated into the National Institute of Mental Health Research Research Domain Criteria framework. However, new observations encourage a different perspective. Anatomical studies show that the Ce and BST form a tightly interconnected unit, where different kinds of threat-relevant information can be integrated and used to assemble states of fear and anxiety. Imaging studies in humans and monkeys show that the Ce and BST exhibit similar functional profiles. Both regions are sensitive to a range of aversive challenges, including uncertain or temporally remote threat; both covary with concurrent signs and symptoms of fear and anxiety; both show phasic responses to short-lived threat; and both show heightened activity during sustained exposure to diffusely threatening contexts. Mechanistic studies demonstrate that both regions can control the expression of fear and anxiety during sustained exposure to diffuse threat. These observations compel a reconsideration of the central extended amygdala's contributions to fear and anxiety and its role in neuropsychiatric disease.

2011

Specific anxiety disorders are characterized by altered emotion processing of phobia-specific stimuli at the neurobiological level. Recent work has concentrated on specific anxietyprovoking stimuli; focusing on arousal-or fear-related brain areas such as the amygdala. We analyzed brain activation during the cued anticipation of unpleasant or uncertain emotional stimuli as a means of modeling an unspecific anxiety-laden situation. Sixteen patients with social anxiety disorder (SAD) and eighteen healthy control subjects completed a task during functional magnetic resonance imaging involving the anticipation of cued visual stimuli with prior known emotional valence (positive, negative, and neutral) or prior unknown/ambiguous emotional content. The anticipated stimuli had no social phobia specific content. During the anticipation of emotional stimuli of prior known negative and prior ambiguous emotional valence, brain activity in patients with SAD was increased in the upper midbrain/dorsal thalamus, the amygdala, and in temporo-occipital and parietal regions as compared to control subjects. Activity was decreased in SAD in left orbitofrontal cortex. Activations in the amygdala and in occipital regions correlated with trait anxiety and social anxiety measures. In conclusion, SAD was associated with enhanced activation in brain regions involved in emotional arousal as well as in attention and perception processing during the anticipation of non-specific, general emotional stimuli. Hence, our results suggest that patients with SAD not only have an altered processing of specific feared stimuli, but also a more generally disturbed emotion processing in basic neural pathways. These findings have implications for diagnostic models and the treatment of SAD.

The American Journal of Psychiatry, 2009

Psychological Medicine, 2010

BackgroundFear conditioning involves the amygdala as the main neural structure for learning fear responses whereas fear extinction mainly activates the inhibitory prefrontal cortex (PFC). In this study we investigated whether individual differences in trait anxiety affect amygdala and dorsal anterior cingulate cortex (dACC) activation during fear conditioning and extinction.MethodThirty-two healthy subjects were investigated by functional magnetic resonance imaging (fMRI) at 3 T while performing a cued fear-conditioning task. All participants completed the trait version of the State-Trait Anxiety Inventory (STAI-T). Activations of the amygdala and the dACC were examined with respect to the effects of trait anxiety.ResultsAnalysis of the fMRI data demonstrated enhanced activation in fear-related brain areas, such as the insula and the ACC, during both fear conditioning and extinction. Activation of the amygdala appeared only during the late acquisition phase whereas deactivation was ...

Behavioural Brain Research, 2011

The dynamic interactions between the amygdala and the medial prefrontal cortex (mPFC) are usefully conceptualized as a circuit that both allows us to react automatically to biologically relevant predictive stimuli as well as regulate these reactions when the situation calls for it. In this review, we will begin by discussing the role of this amygdala-mPFC circuitry in the conditioning and extinction of aversive learning in animals. We will then relate these data to emotional regulation paradigms in humans. Finally, we will consider how these processes are compromised in normal and pathological anxiety. We conclude that the capacity for efficient crosstalk between the amygdala and the mPFC, which is represented as the strength of the amygdala-mPFC circuitry, is crucial to beneficial outcomes in terms of reported anxiety.