Alterations in Amygdala-Prefrontal Functional Connectivity Account for Excessive Worry and Autonomic Dysregulation in Generalized Anxiety Disorder

Makovac, Elena; Meeten, Frances; Watson, David; Herman, Aleksandra M.; Garfinkel, Sarah N.; Critchley, Hugo; Ottaviani, Cristina

doi:10.1016/j.biopsych.2015.10.013

Cited by 160 publications

(153 citation statements)

References 59 publications

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“…There were no significant group differences for any of the assessed socio-demographic and lifestyle variables (see Makovac et al, 2016). …”

Section: Resultsmentioning

confidence: 87%

“…The GAD group also had significantly higher scores on the PSWQ, the STAI, and the RRS and significantly lower HRV than the HC group (see Makovac et al, 2016). …”

Section: Resultsmentioning

confidence: 95%

“…The perseverative cognition induction has established efficacy in eliciting worrisome thoughts that were reproduced in this group (described Makovac et al, 2016). …”

Section: Methodsmentioning

confidence: 99%

“…Based on the finding that a perseverative cognition induction resulted in increased connectivity between the amygdala and PFC in GAD participants (Makovac et al, 2016), we predicted that trait AMA stop-rule adoption is associated with a shift towards increased connectivity between the amygdala and PFC following the perseverative cognition induction.…”

Section: Introductionmentioning

confidence: 99%

“…The relationship between autonomic and neurobiological signatures of pathological worry has recently been examined by Makovac et al (2016) where resting state functional magnetic resonance imaging (fMRI) techniques and physiological recordings were combined to characterize the interplay between psychological and physiological symptoms of worry. This study reinforced earlier findings of lower connectivity between the right amygdala and pre-frontal areas (namely right superior frontal gyrus, right paracingulate/anterior cingulate cortex (ACC) and right supramarginal gyrus) in individuals with GAD.…”

Section: Introductionmentioning

confidence: 99%

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Goal Directed Worry Rules Are Associated with Distinct Patterns of Amygdala Functional Connectivity and Vagal Modulation during Perseverative Cognition

Meeten

Davey

Makovac

et al. 2016

Front. Hum. Neurosci.

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Excessive and uncontrollable worry is a defining feature of Generalized Anxiety Disorder (GAD). An important endeavor in the treatment of pathological worry is to understand why some people are unable to stop worrying once they have started. Worry perseveration is associated with a tendency to deploy goal-directed worry rules (known as “as many as can” worry rules; AMA). These require attention to the goal of the worry task and continuation of worry until the aims of the “worry bout” are achieved. This study examined the association between the tendency to use AMA worry rules and neural and autonomic responses to a perseverative cognition induction. To differentiate processes underlying the AMA worry rule use from trait worry, we also examined the relationship between scores on the Penn State Worry Questionnaire (PSWQ) and neural and autonomic responses following the same induction. We used resting-state functional magnetic resonance brain imaging (fMRI) while measuring emotional bodily arousal from heart rate variability (where decreased HRV indicates stress-related parasympathetic withdrawal) in 19 patients with GAD and 21 control participants. Seed-based analyses were conducted to quantify brain changes in functional connectivity (FC) with the amygdala. The tendency to adopt an AMA worry rule was associated with validated measures of worry, anxiety, depression and rumination. AMA worry rule endorsement predicted a stronger decrease in HRV and was positively associated with increased connectivity between right amygdala and locus coeruleus (LC), a brainstem noradrenergic projection nucleus. Higher AMA scores were also associated with increased connectivity between amygdala and rostral superior frontal gyrus. Higher PSWQ scores amplified decreases in FC between right amygdala and subcallosal cortex, bilateral inferior frontal gyrus, middle frontal gyrus, and areas of parietal cortex. Our results identify neural mechanisms underlying the deployment of AMA worry rules. We propose that the relationship between AMA worry rules and increased connectivity between the amygdala and prefrontal cortex (PFC) represents attempts by high worriers to maintain arousal and distress levels in order to feel prepared for future threats. Furthermore, we suggest that neural mechanisms associated with the PSWQ represent effortful inhibitory control during worry. These findings provide unique information about the neurobiological processes that underpin worry perseveration.

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“…There were no significant group differences for any of the assessed socio-demographic and lifestyle variables (see Makovac et al, 2016). …”

Section: Resultsmentioning

confidence: 87%

“…The GAD group also had significantly higher scores on the PSWQ, the STAI, and the RRS and significantly lower HRV than the HC group (see Makovac et al, 2016). …”

Section: Resultsmentioning

confidence: 95%

“…The perseverative cognition induction has established efficacy in eliciting worrisome thoughts that were reproduced in this group (described Makovac et al, 2016). …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Goal Directed Worry Rules Are Associated with Distinct Patterns of Amygdala Functional Connectivity and Vagal Modulation during Perseverative Cognition

Meeten

Davey

Makovac

et al. 2016

Front. Hum. Neurosci.

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Association of Generalized Anxiety Disorder With Autonomic Hypersensitivity and Blunted Ventromedial Prefrontal Cortex Activity During Peripheral Adrenergic Stimulation

et al. 2022

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IMPORTANCE β-Adrenergic stimulation elicits heart palpitations and dyspnea, key features of acute anxiety and sympathetic arousal, yet no neuroimaging studies have examined how the pharmacologic modulation of interoceptive signals is associated with fear-related neurocircuitry in individuals with generalized anxiety disorder (GAD).OBJECTIVE To examine the neural circuitry underlying autonomic arousal induced via isoproterenol, a rapidly acting, peripheral β-adrenergic agonist akin to adrenaline.

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Structural and Functional Neuroanatomy of Generalized Anxiety Disorder

Schienle

Wabnegger

2020

Generalized Anxiety Disorder and Worrying

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Alterations in Amygdala-Prefrontal Functional Connectivity Account for Excessive Worry and Autonomic Dysregulation in Generalized Anxiety Disorder

Cited by 160 publications

References 59 publications

Goal Directed Worry Rules Are Associated with Distinct Patterns of Amygdala Functional Connectivity and Vagal Modulation during Perseverative Cognition

Goal Directed Worry Rules Are Associated with Distinct Patterns of Amygdala Functional Connectivity and Vagal Modulation during Perseverative Cognition

Association of Generalized Anxiety Disorder With Autonomic Hypersensitivity and Blunted Ventromedial Prefrontal Cortex Activity During Peripheral Adrenergic Stimulation

Structural and Functional Neuroanatomy of Generalized Anxiety Disorder

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