Disrupted Amygdalar Subregion Functional Connectivity and Evidence of a Compensatory Network in Generalized Anxiety Disorder

Etkin, Amit; Prater, Katherine E.; Schatzberg, Alan F.; Menon, Vinod; Greicius, Michael D.

doi:10.1001/archgenpsychiatry.2009.104

Cited by 589 publications

(528 citation statements)

References 77 publications

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“…Further echoing earlier animal work, these iFC profiles were shown to undergo extensive age‐dependent changes, with BLA and CMA connectivity becoming increasingly segregated and specialized during the transition from adolescence to adulthood [Qin et al, 2012]. Importantly, and pertinent to the current study, these subregional iFC profiles seem relatively disorganized in psychiatric patients with emotion regulation deficits, suggesting impairments in various amygdala‐mediated functions [Aghajani et al, 2016; Etkin et al, 2009; Roy et al, 2013]. Despite the reputed amygdala dysfunction in psychopathy, though, little is known of how distinct traits of psychopathy might map onto BLA and CMA intrinsic connectivity, in people with clinical antisociality.…”

Section: Introductionsupporting

confidence: 80%

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct‐disordered juvenile offenders

Aghajani

Colins

Klapwijk

et al. 2016

Human Brain Mapping

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Psychopathy is a serious psychiatric phenomenon characterized by a pathological constellation of affective (e.g., callous, unemotional), interpersonal (e.g., manipulative, egocentric), and behavioral (e.g., impulsive, irresponsible) personality traits. Though amygdala subregional defects are suggested in psychopathy, the functionality and connectivity of different amygdala subnuclei is typically disregarded in neurocircuit‐level analyses of psychopathic personality. Hence, little is known of how amygdala subregional networks may contribute to psychopathy and its underlying trait assemblies in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral (BLA) and centromedial (CMA) amygdala networks in relation to affective, interpersonal, and behavioral traits of psychopathy, in conduct‐disordered juveniles with a history of serious delinquency (N = 50, mean age = 16.83 ± 1.32). As predicted, amygdalar connectivity profiles exhibited dissociable relations with different traits of psychopathy. Interpersonal psychopathic traits not only related to increased connectivity of BLA and CMA with a corticostriatal network formation accommodating reward processing, but also predicted stronger CMA connectivity with a network of cortical midline structures supporting sociocognitive processes. In contrast, affective psychopathic traits related to diminished CMA connectivity with a frontolimbic network serving salience processing and affective responding. Finally, behavioral psychopathic traits related to heightened BLA connectivity with a frontoparietal cluster implicated in regulatory executive functioning. We suggest that these trait‐specific shifts in amygdalar connectivity could be particularly relevant to the psychopathic phenotype, as they may fuel a self‐centered, emotionally cold, and behaviorally disinhibited profile. Hum Brain Mapp 37:4017–4033, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

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Section: Introductionsupporting

confidence: 80%

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct‐disordered juvenile offenders

Aghajani

Colins

Klapwijk

et al. 2016

Human Brain Mapping

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“…Roy et al, 2009 revealed that the CMA preferentially connects to subcortical brain regions, whereas the BLA preferentially connects to cortical regions in healthy adults. A study in social anxiety disorder patients showed increased gray matter volume in the CMA and less distinct connectivity patterns of the subregions (Etkin et al, 2009) compared with healthy controls. Stress-by-MR-blockade interaction on the connectivity between the centromedial amygdala and the caudate nucleus.…”

Section: Effects Of Mineralocorticoid Receptor Blocking In Humans S Vmentioning

confidence: 99%

Blocking the Mineralocorticoid Receptor in Humans Prevents the Stress-Induced Enhancement of Centromedial Amygdala Connectivity with the Dorsal Striatum

Vogel

Klumpers

Krugers

et al. 2014

Neuropsychopharmacol

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Two research lines argue for rapid stress-induced reallocations of neural network activity involving the amygdala. One focuses on the role of norepinephrine (NE) in mediating a shift towards the salience network and improving vigilance processing, whereas the other focuses on the role of cortisol in enhancing automatic, habitual responses. It has been suggested that the mineralocorticoid receptor (MR) is critical in shifting towards habitual responses, which are supported by the dorsal striatum. However, until now it remained unclear whether these two reallocations of neural recourses might be part of the same phenomenon and develop immediately after stress onset. We combined methods used in both approaches and hypothesized specifically that stress would lead to rapidly enhanced involvement of the striatum as assessed by amygala-striatal connectivity. Furthermore, we tested the hypothesis that this shift depends on cortisol interacting with the MR, by using a randomized, placebo-controlled, full-factorial, between-subjects design with the factors stress and MRblockade (spironolactone). We investigated 101 young, healthy men using functional magnetic resonance imaging after stress induction, which led to increased negative mood, heart rate, and cortisol levels. We confirmed our hypothesis by revealing a stress-by-MR-blockade interaction on the functional connectivity between the centromedial amygdala (CMA) and the dorsal striatum. Stress rapidly enhanced CMA-striatal connectivity and this effect was correlated with the stress-induced cortisol response, but required MR availability. This finding might suggest that the stress-induced shift described by distinct research lines might capture different aspects of the same phenomenon, ie, a reallocation of neural resources coordinated by both NE and cortisol. Neuropsychopharmacology (2015) 40, 947-956;

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“…Studies in rodents (Carbo-Gas et al, 2014a, Ikai et al, 1992, monkeys (Melchitzky and Lewis, 2000), and humans (Anderson et al, 2006) are indicative of dopaminergic synaptic components and transmission in the cerebellum across species. This evidence is accompanied by the fact that the cerebellar vermis has demonstrated to be linked to limbic and reward-related structures, such as amygdala (Sang et al, 2012;Yu et al, 2016), hippocampus (Sang et al, 2012), as well as ventral tegmental area (Rogers et al, 2011;Etkin et al, 2009;Kline et al, 2016;Kwon et al, 2014) and both dorsal (Tomasi and Volkow, 2011) ventral striatal zones (Cauda et al, 2011;Koehler et al, 2013). Accordingly, this part of the cerebellum could be able to integrate the incoming information from all these brain areas, which would encode the primary emotional and motivational aspects of the cue, to guide the response.…”

Section: The Cerebellum's Role: Craving or Prediction?mentioning

confidence: 99%

“…Concretely, co-activations and functional connections between cerebellum and cortical structures, such as dorsolateral prefrontal cortex (Habas et al, 2009;Leutgeb et al, 2016;Moulton et al, 2011;Sang et al, 2012), orbitofrontal cortex (Addis et al, 2016;Habas et al, 2009;Leutgeb et al, 2016), anterior cingulate cortex (Addis et al, 2016;Moulton et al, 2011;Sang et al, 2012;Zeng et al, 2012), insula (Addis et al, 2016;Habas et al, 2009;Moulton et al, 2011;Sang et al, 2012), and inferior frontal gyrus (Addis et , 2016;Moulton et al, 2011;Tomasi and Volkow, 2011) have been reported. Other subcortical structures such as amygdala (Leutgeb et al, 2016;Sang et al, 2012;Zeng et al, 2012), hippocampus (Onuki et al, 2015;Sang et al, 2012;Zeng et al, 2012), ventral tegmental area (Carnell et al, 2014;Etkin et al, 2009;Kline et al, 2016;Kwon et al, 2014), dorsal striatum (Moulton et al, 2011;Sang et al, 2012;Tomasi and Volkow, 2011), and ventral striatum (Cauda et al, 2011;Cservenka et al, 2014;Koehler et al, 2013) also have demonstrated to be connected to the cerebellum.…”

Section: Introductionmentioning

confidence: 99%

The cerebellum in drug craving

Moreno-Rius

Miquel

2017

Drug and Alcohol Dependence

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Craving has been considered one of the core features of addiction. It can be defined as the urge or conscious desire to use a drug elicited by the drug itself, drug-associated cues or stressors. Craving plays a major role in relapse, even after prolonged periods of abstinence, as well as in the maintenance of drug seeking in non-abstinent addicts. The circuitry of craving includes medial parts of the prefrontal cortex, ventral striatal zones, ventral tegmental area, ventral pallidum, and limbic regions. Interestingly, the cerebellum shows reciprocal loops with many of these areas. The cerebellum has been linked traditionally to motor functions but increasing evidence indicates that this part of the brain is also involved in functions related to cognition, prediction, learning, and memory. Moreover, the functional neuroimaging studies that have addressed the study of craving in humans repeatedly demonstrate cerebellar activation when craving is elicited by the presentation of drug-related cues. However, the role of cerebellar activity in these craving episodes remains unknown. Therefore, the main goal of this review is to provide a brief update on craving studies and the traditional neural basis of this phenomenon, and then discuss and propose a hypothesis for the function of the cerebellum in craving episodes.

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Disrupted Amygdalar Subregion Functional Connectivity and Evidence of a Compensatory Network in Generalized Anxiety Disorder

Cited by 589 publications

References 77 publications

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct‐disordered juvenile offenders

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct‐disordered juvenile offenders

Blocking the Mineralocorticoid Receptor in Humans Prevents the Stress-Induced Enhancement of Centromedial Amygdala Connectivity with the Dorsal Striatum

The cerebellum in drug craving

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