scholarly journals Altered Task-Evoked Corticolimbic Responsivity in Generalized Anxiety Disorder

2021 ◽  
Vol 22 (7) ◽  
pp. 3630
Author(s):  
Nayoung Kim ◽  
M. Justin Kim
Keyword(s):  
Anxiety Disorder ◽  
Generalized Anxiety Disorder ◽  
Functional Neuroimaging ◽  
A Priori ◽  
Blood Oxygen Level Dependent ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Generalized Anxiety ◽  
Blood Oxygen Level ◽  
Size Limits

Generalized anxiety disorder (GAD) is marked by uncontrollable, persistent worry and exaggerated response to uncertainty. Here, we review and summarize the findings from the GAD literature that employs functional neuroimaging methods. In particular, the present review focuses on task-based blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. We find that select brain regions often regarded as a part of a corticolimbic circuit (e.g., amygdala, anterior cingulate cortex, prefrontal cortex) are consistently targeted for a priori hypothesis-driven analyses, which, in turn, shows varying degrees of abnormal BOLD responsivity in GAD. Data-driven whole-brain analyses show the insula and the hippocampus, among other regions, to be affected by GAD, depending on the task used in each individual study. Overall, while the heterogeneity of the tasks and sample size limits the generalizability of the findings thus far, some promising convergence can be observed in the form of the altered BOLD responsivity of the corticolimbic circuitry in GAD.

scholarly journals Functional dissection of neural connectivity in generalized anxiety disorder

2022 ◽  
Author(s):  
Jonas L Steinhäuser ◽  
Adam R Teed ◽  
Obada Al-Zoubi ◽  
René Hurlemann ◽  
Gang Chen ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Anxiety Disorder ◽  
Generalized Anxiety Disorder ◽  
Resting State ◽  
A Priori ◽  
Resting State Fmri ◽  
Brain Regions ◽  
Generalized Anxiety ◽  
Correlated Activity ◽  
Dorsolateral Prefrontal

Differences in the correlated activity of networked brain regions have been reported in individuals with generalized anxiety disorder (GAD) but an overreliance on the null-hypothesis significance testing (NHST) framework limits the identification and characterization of disorder-relevant relationships. In this preregistered study, we applied a Bayesian statistical framework as well as NHST to the analysis of resting-state fMRI scans from females with GAD and demographically matched healthy comparison females. Eleven a-priori hypotheses about functional correlativity (FC) were evaluated using Bayesian (multilevel model) and frequentist (t-test) inference. Reduced FC between the ventromedial prefrontal cortex (vmPFC) and the posterior-mid insula (PMI) was confirmed by both statistical approaches. FC between the vmPFC-anterior insula, the amygdala-PMI, and the amygdala-dorsolateral prefrontal cortex (dlPFC) region pairs did not survive multiple comparison correction using the frequentist approach. However, the Bayesian model provided evidence for these region pairs having decreased FC in the GAD group. Leveraging Bayesian modeling, we demonstrate decreased FC of the vmPFC, insula, amygdala, and dlPFC in females with GAD. Exploiting the Bayesian framework revealed FC abnormalities between region pairs excluded by the frequentist analysis, as well as other previously undescribed regions, demonstrating the benefits of applying this statistical approach to resting state FC data.

Neural correlates of worry in generalized anxiety disorder and in normal controls: a functional MRI study

2009 ◽  
Vol 40 (1) ◽  
pp. 117-124 ◽  
Author(s):  
E. Paulesu ◽  
E. Sambugaro ◽  
T. Torti ◽  
L. Danelli ◽  
F. Ferri ◽  
...  
Keyword(s):  
Anxiety Disorder ◽  
Generalized Anxiety Disorder ◽  
Mood Induction ◽  
Normal Subjects ◽  
Neural Correlates ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Generalized Anxiety ◽  
State Worry ◽  
Normal Controls

BackgroundWorry is considered a key feature of generalized anxiety disorder (GAD), whose neural correlates are poorly understood. It is not known whether the brain regions involved in pathological worry are similar to those involved in worry-like mental activity in normal subjects or whether brain areas associated with worry are the same for different triggers such as verbal stimuli or faces. This study was designed to clarify these issues.MethodEight subjects with GAD and 12 normal controls underwent functional magnetic resonance imaging (fMRI) mood induction paradigms based on spoken sentences or faces. Sentences were either neutral or designed to induce worry. Faces conveyed a sad or a neutral mood and subjects were instructed to empathize with those moods.ResultsWe found that the anterior cingulate and dorsal medial prefrontal cortex [Brodmann area (BA) 32/23 and BA 10/11] were associated with worry triggered by sentences in both subjects with GAD and normal controls. However, GAD subjects showed a persistent activation of these areas even during resting state scans that followed the worrying phase, activation that correlated with scores on the Penn State Worry Questionnaire (PSWQ). This region was activated during the empathy experiment for sad faces.ConclusionsThe results show that worry in normal subjects and in subjects with GAD is based on activation of the medial prefrontal and anterior cingulate regions, known to be involved in mentalization and introspective thinking. A dysregulation of the activity of this region and its circuitry may underpin the inability of GAD patients to stop worrying.

A Pilot Study of Anterior Cingulate Cortex Neurochemistry in Adolescents with Generalized Anxiety Disorder

2013 ◽  
Vol 67 (4) ◽  
pp. 224-229 ◽  
Author(s):  
Jeffrey R. Strawn ◽  
Wen-Jang Chu ◽  
Rachel M. Whitsel ◽  
Wade A. Weber ◽  
Matthew M. Norris ◽  
...  
Keyword(s):  
Anxiety Disorder ◽  
Pilot Study ◽  
Anterior Cingulate Cortex ◽  
Generalized Anxiety Disorder ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Generalized Anxiety

scholarly journals Illness Severity Moderated Association Between Trait Anxiety and Amygdala-Based Functional Connectivity in Generalized Anxiety Disorder

2021 ◽  
Vol 15 ◽  
Author(s):  
Yang Du ◽  
Hailong Li ◽  
Hongqi Xiao ◽  
Mei Wang ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Anxiety Disorder ◽  
Functional Connectivity ◽  
Generalized Anxiety Disorder ◽  
Trait Anxiety ◽  
Symptom Severity ◽  
Inferior Frontal Gyrus ◽  
Illness Severity ◽  
Anterior Cingulate ◽  
Generalized Anxiety ◽  
Significant Group

Trait anxiety is considered a vulnerability factor for the development of generalized anxiety disorder (GAD). The amygdala is related to both trait anxiety and GAD. Thus, we investigated amygdala-based functional connectivity (FC) in drug-naive non-comorbid GAD patients and explored its associations with personality, symptoms, and illness severity. FC analyses using the bilateral amygdala as seeds were performed with resting-state functional MRI data from 38 GAD patients and 20 matched healthy controls (HCs). Clinical characteristics were correlated with FC Z-scores from regions showing significant group differences. Furthermore, moderation analyses were used to explore the conditional effect of illness severity measured by the Clinical Global Impression–Severity (CGI-S) scale on the relationship between FC and trait anxiety. Relative to HCs, GAD patients showed hypoconnectivity between the amygdala and the rostral anterior cingulate cortex (rACC), inferior frontal gyrus (IFG), parahippocampal gyrus, and cerebellum and hyperconnectivity between the amygdala and the superior temporal gyrus (STG), insula, and postcentral gyrus. In GAD patients, amygdala–rACC connectivity was negatively associated with symptom severity and trait anxiety, and amygdala–IFG connectivity was positively associated with symptom severity. Moreover, CGI-S scores moderated the negative correlation between trait anxiety and amygdala–rACC FC. We demonstrate that there is extensive amygdala-based network dysfunction in patients with GAD. More importantly, amygdala–rACC connectivity plays a key role in the neural pathology of trait anxiety. Finally, the more severe the illness, the stronger the negative association between trait anxiety and amygdala–rACC FC. Our results emphasize the importance of personalized intervention in GAD.

Attenuated responses to emotional expressions in women with generalized anxiety disorder

2010 ◽  
Vol 41 (5) ◽  
pp. 1009-1018 ◽  
Author(s):  
M. E. Palm ◽  
R. Elliott ◽  
S. McKie ◽  
J. F. W. Deakin ◽  
I. M. Anderson
Keyword(s):  
Prefrontal Cortex ◽  
Anxiety Disorder ◽  
Anterior Cingulate Cortex ◽  
Facial Expressions ◽  
Generalized Anxiety Disorder ◽  
Recognition Task ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Generalized Anxiety ◽  
Bold Signal

BackgroundGeneralized anxiety disorder (GAD) is under-researched despite its high prevalence and large impact on the healthcare system. There is a paucity of functional magnetic resonance imaging (fMRI) studies that explore the neural correlates of emotional processing in GAD. The present study investigated the blood oxygen level dependent (BOLD) response to processing positive and negative facial emotions in patients with GAD.MethodA total of 15 female GAD patients and 16 female controls undertook an implicit face emotion task during fMRI scanning. They also performed a face emotion recognition task outside the scanner.ResultsThe only behavioural difference observed in GAD patients was less accurate detection of sad facial expressions compared with control participants. However, GAD patients showed an attenuated BOLD signal in the prefrontal cortex to fearful, sad, angry and happy facial expressions and an attenuated signal in the anterior cingulate cortex to happy and fearful facial expressions. No differences were found in amygdala response.ConclusionsIn contrast with previous research, this study found BOLD signal attenuation in the ventrolateral and medial prefrontal cortex and the anterior cingulate cortex during face emotion processing, consistent with a hypothesis of hypo-responsivity to external emotional stimuli in GAD. These decreases were in areas that have been implicated in emotion and cognition and may reflect an altered balance between internally and externally directed attentional processes.

scholarly journals Anticipatory Activation in the Amygdala and Anterior Cingulate in Generalized Anxiety Disorder and Prediction of Treatment Response

2009 ◽  
Vol 166 (3) ◽  
pp. 302-310 ◽  
Author(s):  
Jack B. Nitschke ◽  
Issidoros Sarinopoulos ◽  
Desmond J. Oathes ◽  
Tom Johnstone ◽  
Paul J. Whalen ◽  
...  
Keyword(s):  
Anxiety Disorder ◽  
Treatment Response ◽  
Generalized Anxiety Disorder ◽  
Anterior Cingulate ◽  
Generalized Anxiety ◽  
Anticipatory Activation

Directed threat imagery in generalized anxiety disorder

2017 ◽  
Vol 48 (4) ◽  
pp. 617-628 ◽  
Author(s):  
C. Buff ◽  
C. Schmidt ◽  
L. Brinkmann ◽  
B. Gathmann ◽  
S. Tupak ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Anxiety Disorder ◽  
Generalized Anxiety Disorder ◽  
Emotional Reactivity ◽  
Behavioral Therapy ◽  
Brain Activity ◽  
Neural Correlates ◽  
Anterior Cingulate ◽  
Generalized Anxiety ◽  
Initial Exposure

BackgroundWorrying has been suggested to prevent emotional and elaborative processing of fears. In cognitive-behavioral therapy (CBT), generalized anxiety disorder (GAD) patients are exposed to their fears during the method of directed threat imagery by inducing emotional reactivity. However, studies investigating neural correlates of directed threat imagery and emotional reactivity in GAD patients are lacking. The present functional magnetic resonance imaging (fMRI) study aimed at delineating neural correlates of directed threat imagery in GAD patients.MethodNineteen GAD patients and 19 healthy controls (HC) were exposed to narrative scripts of either disorder-related or neutral content and were encouraged to imagine it as vividly as possible.ResultsRating results showed that GAD patients experienced disorder-related scripts as more anxiety inducing and arousing than HC. These results were also reflected in fMRI data: Disorder-related v. neutral scripts elicited elevated activity in the amygdala, dorsomedial prefrontal cortex, ventrolateral prefrontal cortex and the thalamus as well as reduced activity in the ventromedial prefrontal cortex/subgenual anterior cingulate cortex in GAD patients relative to HC.ConclusionThe present study presents the first behavioral and neural evidence for emotional reactivity during directed threat imagery in GAD. The brain activity pattern suggests an involvement of a fear processing network as a neural correlate of initial exposure during directed imagery in CBT in GAD.

Effective Connectivity During an Avoidance-Based Pavlovian-to-Instrumental Transfer Task

2021 ◽  
Author(s):  
Daniel Petrie ◽  
Sy-Miin Chow ◽  
Charles Geier
Keyword(s):  
Effective Connectivity ◽  
A Priori ◽  
Transfer Task ◽  
Blood Oxygen Level Dependent ◽  
Brain Regions ◽  
Response Patterns ◽  
Multiple Model ◽  
Hemodynamic Response Function ◽  
Blood Oxygen Level ◽  
Psychological Phenomena

Pavlovian-to-instrumental transfer (PIT) refers to a phenomenon whereby a classically conditioned stimulus (CS) impacts the motivational salience of instrumental behavior. We examined behavioral response patterns and functional magnetic resonance imaging (fMRI) based effective connectivity during an avoidance-based PIT task. Eleven participants (8 females; Mage = 28.2, SD = 2.8, range = 25-32 years) completed the task. Effective connectivity between a priori brain regions engaged during the task was determined using hemodynamic response function group iterative multiple model estimation (HRF-GIMME). Behaviorally, participants exhibited specific PIT, a CS previously associated with a reinforcing outcome increased instrumental responding directed at the same outcome. We did not find evidence for general PIT; a CS did not significantly increase instrumental responding towards a different but related outcome. Using HRF-GIMME, we recovered effective connectivity maps among corticostriatal circuits engaged during the task. Group-level paths revealed directional effects from left putamen to right insula and from right putamen to right cingulate. Importantly, a direct effect of specific PIT stimuli on blood-oxygen-level-dependent (BOLD) activity in the left putamen was found. Results provide initial evidence of effective connectivity in key brain regions in an avoidance-based PIT task network. This study adds to the literature studying PIT effects in humans and employing GIMME models to understand how psychological phenomena are supported in the brain.

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