scholarly journals Acute alcohol administration dampens threat-related activation in the central extended amygdala

2018 ◽  
Author(s):  
Juyoen Hur ◽  
Claire M. Kaplan ◽  
Jason F. Smith ◽  
Daniel E. Bradford ◽  
Andrew S. Fox ◽  
...  
Keyword(s):  
Alcohol Abuse ◽  
Negative Reinforcement ◽  
Functional Organization ◽  
Treatment Strategies ◽  
Central Nucleus ◽  
Imaging Data ◽  
Bed Nucleus ◽  
Emotional Faces ◽  
Extended Amygdala ◽  
Activation Data

ABSTRACTAlcohol abuse is common, imposes a staggering burden on public health, and is challenging to treat, underscoring the need to develop a deeper understanding of the underlying neurobiology. When administered acutely, ethyl alcohol reduces threat reactivity in humans and other animals, and there is growing evidence that threat-dampening and related negative reinforcement mechanisms support the etiology and recurrence of alcohol and other kinds of substance misuse. Converging lines of evidence motivate the hypothesis that these effects are mediated by the central extended amygdala (EAc)—including the central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST)—but the relevance of this circuitry to acute alcohol effects in humans remains poorly understood. Using a single-blind, randomized-groups design, multiband imaging data were acquired from 49 social drinkers while they performed an fMRI-optimized emotional-faces/places paradigm after consuming alcohol or placebo. Relative to placebo, alcohol significantly dampened reactivity to threat-related emotional faces in the BST. To rigorously assess potential regional differences in activation, data were extracted from anatomically defined Ce and BST regions-of-interest. Analyses revealed a similar pattern of dampening across the two regions. In short, alcohol acutely dampens reactivity to threat-related faces in humans and it does so similarly across the two major divisions of the EAc. These observations provide a framework for understanding the translational relevance of addiction models derived from work in rodents, inform on-going debates about the functional organization of the EAc, and set the stage for bi-directional translational models aimed at developing improved treatment strategies for alcohol abuse and other addictions.

scholarly journals Neurobiological mechanisms for opponent motivational processes in addiction

2008 ◽  
Vol 363 (1507) ◽  
pp. 3113-3123 ◽  
Author(s):  
George F Koob ◽  
Michel Le Moal
Keyword(s):  
Ventral Striatum ◽  
Drugs Of Abuse ◽  
Negative Reinforcement ◽  
Drug Intake ◽  
Central Nucleus ◽  
Compulsive Disorder ◽  
Extended Amygdala ◽  
Reward Function ◽  
Opponent Process ◽  
Stress Response System

The conceptualization of drug addiction as a compulsive disorder with excessive drug intake and loss of control over intake requires motivational mechanisms. Opponent process as a motivational theory for the negative reinforcement of drug dependence has long required a neurobiological explanation. Key neurochemical elements involved in reward and stress within basal forebrain structures involving the ventral striatum and extended amygdala are hypothesized to be dysregulated in addiction to convey the opponent motivational processes that drive dependence. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission such as dopamine and opioid peptides in the ventral striatum, but also recruitment of brain stress systems such as corticotropin-releasing factor (CRF), noradrenaline and dynorphin in the extended amygdala. Acute withdrawal from all major drugs of abuse produces increases in reward thresholds, anxiety-like responses and extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence and to contribute to stress-induced relapse. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for the long hypothesized opponent motivational processes responsible for the negative reinforcement driving addiction.

scholarly journals Intrinsic functional connectivity of the central extended amygdala

2017 ◽  
Author(s):  
Rachael M. Tillman ◽  
Melissa D. Stockbridge ◽  
Brendon M. Nacewicz ◽  
Salvatore Torrisi ◽  
Andrew S. Fox ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
High Precision ◽  
Community Dwelling ◽  
Central Nucleus ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Extended Amygdala ◽  
Intrinsic Functional Connectivity ◽  
Multiband Imaging ◽  
Fear And Anxiety

ABSTRACTThe central extended amygdala (EAc)—including the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)—plays a key role in orchestrating states of fear and anxiety and is implicated in the development and maintenance of anxiety disorders, depression, and substance abuse. Although it is widely thought that these disorders reflect the coordinated actions of large-scale functional circuits in the brain, the architecture of the EAc functional network, and the degree to which the BST and the Ce show distinct patterns of intrinsic functional connectivity, remains incompletely understood. Here, we leveraged a combination of approaches to trace the connectivity of the BST and the Ce in 130 psychiatrically healthy, racially diverse, community-dwelling adults with enhanced power and precision. Multiband imaging, high-precision data registration techniques, and spatially unsmoothed data were used to maximize anatomical specificity. Using newly developed seed regions, whole-brain regression analyses revealed robust functional connectivity between the BST and Ce via the sublenticular extended amygdala (‘substantia innominata’), the ribbon of subcortical gray matter encompassing the ventral amygdalofugal pathway. Both regions displayed significant coupling with the ventromedial prefrontal cortex (vmPFC), midcingulate cortex (MCC), insula, and anterior hippocampus. The BST showed significantly stronger connectivity with prefrontal territories—including the vmPFC, anterior MCC and pregenual anterior cingulate cortex—as well as the thalamus, striatum, and the periaqueductal gray. The only regions showing stronger functional connectivity with the Ce were located in the anterior hippocampus and dorsal amygdala. These observations provide a baseline against which to compare a range of special populations, inform our understanding of the role of the EAc in normal and pathological fear and anxiety, and highlight the value of several new approaches to image registration which may be particularly useful for researchers working with ‘de-identified’ neuroimaging data.GRAPHICAL ABSTRACTIntrinsic functional connectivity of bed nucleus of the stria terminalis (BST) and the central nucleus of the amygdala (Ce) in 130 psychiatrically healthy adults.HIGHLIGHTSBST and Ce implicated in normal and pathological fear and anxietyTraced the intrinsic functional connectivity of the BST and the Ce in 130 adultsMultiband imaging, high-precision registration, unsmoothed data, newly developed seedsBST and Ce show robust coupling with one another, hippocampus, insula, MCC, and vmPFCBST shows stronger coupling with prefrontal/cingulate territories and brainstem/PAG

scholarly journals The value of extended amygdala structures in emotive effects of narcogenic with diverse chemical structure

2019 ◽  
Vol 5 (3) ◽  
pp. 11-19
Author(s):  
Roman O. Roik ◽  
Andrei A. Lebedev ◽  
Petr D. Shabanov
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Receptors ◽  
Conditioned Reinforcement ◽  
Gaba Receptors ◽  
Sch 23390 ◽  
Central Nucleus ◽  
D1 Receptors ◽  
Nucleus Accumbens Shell ◽  
Bed Nucleus ◽  
Extended Amygdala

Introduction: Studies on the mechanisms of the reinforcing action of opioid and non-opioid narcotics confirmed the existence in the brain of a specialized system named the extended amygdala. Materials and methods: To clarify the value of the extended amygdala structures (bed nucleus, central nucleus of the amygdala and nucleus accumbens shell) in the mechanisms of unconditioned and conditioned reinforcement activated by various narcogenic, this paper carried out a neuropharmacological analysis of these effects, using blockade of dopamine receptors, GABA, opioids and CRF receptors within these brain structures, as well as an analysis of behavioral responses by self-stimulation (unconditioned reinforcement) and conditioned place preference (CPP) (conditioned reinforcement). Results and discussion: The central amygdala and the bed nucleus have a controlling influence on the hypothalamus, which is predominantly of CRF-, GABA- and dopaminergic nature. Through D1 dopamine receptors,, a direct positive (activating) effect on the lateral hypothalamus is made. The D2 receptor blockade of the nucleus accumbens prevents narcogenic from exerting the reinforcing properties, which are primarily stimulating. The blockade of the D1 receptors of the nucleus accumbens by SCH-23390 prevents the expression of unconditioned and conditioned reinforcing properties of predominantly opiates and opioids. The blockade of GABAA receptors in the nucleus accumbens with bicuculline prevents the manifestation of the primary and secondary reinforcing properties (CPP) of psychostimulant drugs (amphetamine), without affecting the effects of opiates and opioids (fentanyl and leu-enkephalin). Conclusion: The pharmacological analysis proves that CRF, dopamine and GABA receptors are most important for the correction of reinforcement activated by various narcogenic.

scholarly journals The unbalanced reorganization of weaker functional connections induces the altered brain network topology in schizophrenia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rossana Mastrandrea ◽  
Fabrizio Piras ◽  
Andrea Gabrielli ◽  
Nerisa Banaj ◽  
Guido Caldarelli ◽  
...  
Keyword(s):  
Resting State ◽  
Functional Organization ◽  
Functional Integration ◽  
Brain Network ◽  
Modular Organization ◽  
Node Degree ◽  
Imaging Data ◽  
Brain Disorder ◽  
Functional Connections ◽  
The Brain

AbstractNetwork neuroscience shed some light on the functional and structural modifications occurring to the brain associated with the phenomenology of schizophrenia. In particular, resting-state functional networks have helped our understanding of the illness by highlighting the global and local alterations within the cerebral organization. We investigated the robustness of the brain functional architecture in 44 medicated schizophrenic patients and 40 healthy comparators through an advanced network analysis of resting-state functional magnetic resonance imaging data. The networks in patients showed more resistance to disconnection than in healthy controls, with an evident discrepancy between the two groups in the node degree distribution computed along a percolation process. Despite a substantial similarity of the basal functional organization between the two groups, the expected hierarchy of healthy brains' modular organization is crumbled in schizophrenia, showing a peculiar arrangement of the functional connections, characterized by several topologically equivalent backbones. Thus, the manifold nature of the functional organization’s basal scheme, together with its altered hierarchical modularity, may be crucial in the pathogenesis of schizophrenia. This result fits the disconnection hypothesis that describes schizophrenia as a brain disorder characterized by an abnormal functional integration among brain regions.

Capillary Index Score Derived from Computed Tomography Angiography as An Indicator of Collateral Flow after Acute Ischemic Stroke

2019 ◽  
Author(s):  
Shang Kai ◽  
Xiaoxing Zhang ◽  
Yuehua Li
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Cerebral Artery ◽  
Treatment Strategies ◽  
Artery Occlusion ◽  
Index Score ◽  
Collateral Flow ◽  
Imaging Data ◽  
Flow Group ◽  
Cerebral Artery Occlusion

Abstract Background The capillary index score (CIS) determined from DSA is used to evaluate cerebral collateral flow in acute ischemic stroke (AIS) caused by cerebral artery occlusion. Our aim was to determine the reliability of CIS calculated from MIP-CTA images as an alternative to DSA-based CIS, as CTA is less invasive and less expensive. Methods Clinical and imaging data of 40 patients with AIS caused by cerebral artery occlusion within 6 h from symptom onset were collected. CIS was calculated from CTA and DSA images. Patients were classified into the favorable collateral flow group if CIS was ≥2 (fCIS), and into the poor collateral flow group if CIS was <2 (pCIS). Agreement between the methods was evaluated using the Kappa test. Logistic regression was performed to explore the relationship between CTA-based CIS and clinical outcomes. Results The two methods had high consistency (Kappa = 0.72), and the diagnostic accuracy of CTA for CIS classification was 87.5%. The decrease in the NIHSS score at discharge was not significantly different between the fCIS and pCIS groups according to CTA (p = 0.156), while the 90-day mRS was higher in the pCIS group (p = 0.04). High CTA-based CIS and low blood glucose at admission were significantly correlated with good outcome. Conclusion CIS calculated using CTA is as reliable as DSA-based CIS for assessing collateral flow in AIS, and is also a good predictor of clinical outcome. This index could be useful for guiding patient selection and treatment strategies for AIS.

scholarly journals Embryonic Origin of the Islet1 and Pax6 Neurons of the Chicken Central Extended Amygdala Using Cell Migration Assays and Relation to Different Neuropeptide-Containing Cells

2015 ◽  
Vol 85 (3) ◽  
pp. 139-169 ◽  
Author(s):  
Alba Vicario ◽  
Antonio Abellán ◽  
Loreta Medina
Keyword(s):  
Transcription Factors ◽  
Cell Migration ◽  
Published Data ◽  
Stria Terminalis ◽  
Dorsal Part ◽  
Medial Region ◽  
Bed Nucleus ◽  
Extended Amygdala ◽  
Embryonic Origin ◽  
Migration Assays

In a recent study, we tentatively identified different subdivisions of the central extended amygdala (EAce) in chicken based on the expression of region-specific transcription factors (including Pax6 and Islet1) and several phenotypic markers during embryonic development. Such a proposal was partially based on the suggestion that, similarly to the subdivisions of the EAce of mammals, the Pax6 and Islet1 neurons of the comparable chicken subdivisions derive from the dorsal (Std) or ventral striatal embryonic domains (Stv), respectively. To investigate whether this is true, in the present study, we carried out cell migration assays from chicken Std or Stv combined with immunofluorescence for Pax6 or Islet1. Our results showed that the cells of the proposed chicken EAce truly originate in either Std (expressing Pax6) or Stv (expressing Islet1). This includes lateral subdivisions previously compared to the intercalated amygdalar cells and the central amygdala of mammals, also rich in Std-derived Pax6 cells and/or Stv-derived Islet1 cells. In the medial region of the chicken EAce, the dorsal part of the lateral bed nucleus of the stria terminalis (BSTL) contains numerous cells expressing Nkx2.1 (mostly derived from the pallidal domain), but our migration assays showed that it also contains neuron subpopulations from the Stv (expressing Islet1) and Std (expressing Pax6), resembling the mouse BSTL. These findings, together with those previously published in different species of mammals, birds and reptiles, support the homology of the chicken EAce to that of other vertebrates, and reinforce the existence of several cell subcorridors inside the EAce. In addition, together with previously published data on neuropeptidergic cells, these results led us to propose the existence of at least seventeen neuron subtypes in the EAce in rodents and/or some birds (chicken and pigeon). The functional significance and the evolutionary origin of each subtype needs to be analyzed separately, and such studies are mandatory in order to understand the multifaceted modulation by the EAce of fear responses, ingestion, motivation and pain in different vertebrates.

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