Neural Substrates of Anticipation and Interoception in Anxiety Disorders
Principal Investigator: M B Stein
Affiliation: University of California
Abstract: DESCRIPTION (provided by applicant): This proposal is the competing renewal of our ongoing work into the neural substrates of anxiety. In a natural progression of this work, we now propose to test key aspects of a neural circuit model for anxiety disorders. We will use BOLD fMRI in conjunction with emotion processing tasks to compare healthy controls subjects (HC) to patients with panic disorder (PD) and generalized anxiety disorder (GAD), who will be studied before and after cognitive behavioral treatment (CBT). This proposal brings together methods and approaches from behavioral and cognitive neuroscience, functional neuroimaging imaging, and psychological clinical therapeutics to outline a series of studies with the long-term objective of delineating the neural substrates of anxiety disorders. The principal objective of this competitive renewal is to build on the applicants'previously accomplished work in non-clinical individuals with anxiety proneness and apply this to patients with anxiety disorders with the following specific aims: (1) To develop a basic systems neuroscience endophenotype for anxiety disorders. Based on our prior work, we hypothesize that, compared to healthy controls (HC), patients with GAD or PD will show increased activation of the anterior insula during various types of emotion processing that engage interoceptive systems. Moreover, we hypothesize that there is less functional coupling between the insular cortex and both the amygdala and the medial prefrontal cortex (mPFC) in patients with anxiety disorders. (2) To evaluate effects of CBT on the neural systems hypothesized to be dysfunctional in patients with anxiety disorders. We expect that successful treatment will be associated with attenuation of insular cortex activity and increased coupling between insula and both amygdala and mPFC, respectively. In the case of GAD, we also expect to see a reduction in task-related dorsolateral prefrontal cortex (DLPFC) activity. Anxiety disorders are early onset, prevalent, serious conditions that impact adversely on individual and societal functioning. Improved understanding of the neural circuitry of anxiety disorders will inform diagnostic conceptualizations and enable the more directed development and testing of novel therapies that are based on a more thorough understanding of pathophysiology, thereby conveying new therapeutic options to the many patients with anxiety disorders for whom existing treatments are inadequate.
Funding Period: 2002-04-01 - 2012-05-31
more information: NIH RePORT
- Single-subject anxiety treatment outcome prediction using functional neuroimagingTali M Ball
1 Department of Psychiatry, University of California San Diego, La Jolla, CA, USA 2 San Diego State University University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA
Neuropsychopharmacology 39:1254-61. 2014..Moreover, activation patterns are consistent with the notion that greater activation in cortico-limbic circuitry predicts better CBT response in GAD and PD. ..
- Anxiety positive subjects show altered processing in the anterior insula during anticipation of negative stimuliAlan N Simmons
Department of Psychiatry, University of California San Diego, San Diego, California 92161, USA
Hum Brain Mapp 32:1836-46. 2011..These results are consistent with the hypothesis that anxiety is related to greater anticipatory reactivity in the brain and that there may be functional asymmetries in the brain that interact with psychiatric traits...
- Escitalopram attenuates posterior cingulate activity during self-evaluation in healthy volunteersScott C Matthews
Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA
Psychiatry Res 182:81-7. 2010..These results show that SSRIs change medial cortical activity and may alter self-evaluation...
- Initial evidence of a failure to activate right anterior insula during affective set shifting in posttraumatic stress disorderAlan Simmons
Department of Psychiatry, University of California San Diego, San Diego, CA, USA
Psychosom Med 71:373-7. 2009..An altered ability to monitor or modulate interoception as it relates to subjective experience may provide a mechanistic explanation for the development of some forms of psychiatric illness...
- Functioning of neural systems supporting emotion regulation in anxiety-prone individualsLaura Campbell-Sills
Department of Psychiatry, University of California, San Diego, La Jolla, CA 92037, USA
Neuroimage 54:689-96. 2011..Anxious participants required greater engagement of lateral and medial PFC in order to successfully reduce negative emotions...
- Functional activation and neural networks in women with posttraumatic stress disorder related to intimate partner violenceAlan N Simmons
Department of Psychiatry, University of California San Diego, and VA San Diego Healthcare System, San Diego, California 92037, USA
Biol Psychiatry 64:681-90. 2008..Victims of IPV are often preoccupied by the anticipation of impending harm. This investigation tested the hypothesis that IPV-related PTSD individuals show exaggerated insula reactivity to the anticipation of aversive stimuli...
- Association between individual differences in self-reported emotional resilience and the affective perception of neutral facesEstibaliz Arce
Department of Psychiatry, University of California San Diego, La Jolla, CA 92037 0985, United States
J Affect Disord 114:286-93. 2009..We used a novel experimental paradigm to test the hypothesis that highly resilient individuals show a judgment bias towards positive emotions...
- Influence of RGS2 on anxiety-related temperament, personality, and brain functionJordan W Smoller
Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Arch Gen Psychiatry 65:298-308. 2008..The gene encoding regulator of G protein signaling 2 (Rgs2) is a quantitative trait gene that influences mouse anxiety behavior, making its human ortholog (RGS2) a compelling candidate gene for human anxiety phenotypes...
- Intolerance of uncertainty correlates with insula activation during affective ambiguityAlan Simmons
Laboratory of Biological Dynamics and Theoretical Medicine, USA
Neurosci Lett 430:92-7. 2008..Previously observed insula hyperactivity in anxiety disorder individuals may therefore be directly linked to altered processes of uncertainty...
- Heritability of anterior cingulate response to conflict: an fMRI study in female twinsScott C Matthews
Laboratory of Biological Dynamics and Theoretical Medicine, CA, USA
Neuroimage 38:223-7. 2007..These results suggest an endophenotype that may be applied to various psychiatric disorders that are both highly heritable and associated with altered dACC function...
- Role of functional magnetic resonance imaging in drug discoveryMartin P Paulus
Department of Psychiatry, University of California, San Diego UCSD, 8950 Villa La Jolla Drive, Suite C 213, La Jolla, CA 92037, USA
Neuropsychol Rev 17:179-88. 2007....