FC18-04 - Cue-induced brain activation mediates subsequent relapse in abstinent alcohol-dependent patients

IntroductionIn alcoholism, one relevant mechanism contributing to relapse is the exposure to stimuli that are associated with alcohol intake. Such conditioned cues can elicit conditioned responses like alcohol craving and consumption. In the last decade, considerable progress has been made in identifying basic neuronal mechanisms that underlie cue-induced alcohol craving.Objectives/ aimsWe explored whether functional brain activation during exposure to alcohol-associated stimuli is related to the prospective relapse risk in detoxified alcohol-dependent patients.Methods46 alcohol-dependent and 46 healthy volunteers participated in a fMRI study using a cue reactivity paradigm, in which visual alcohol-related and control stimuli were presented. Patients were followed for 3 months. Afterwards data was analysed regarding the subsequent relapse, resulting in 16 abstainers and 30 relapsers.ResultsAlcohol-related versus neutral stimuli activated a frontocortical-limbic network including inferior, medial and middle frontal gyrus as well as putamen in the group of patients relative to healthy controls. Moreover, abstainers showed a stronger activation in orbitofrontal cortex as well as midbrain during the presentation of alcohol-related cues whereas relapsers revealed a stronger activation of cingulate gyrus.ConclusionsThis study suggests that cue-induced activation of orbitofrontal cortex and dopaminergic innervated midbrain is negatively associated with the prospective relapse risk in alcohol-dependent patients. This could indicate a more pronounced and conscious processing of alcohol cues which might serve as a warning signal and a behavioural controlling function. In contrast, prospective relapsers showed a stronger activation of cingulate gyrus, a region involved in the attribution of motivational value.

Download Full-text

Plasma calcium concentration during detoxification predicts neural cue-reactivity and craving during early abstinence in alcohol-dependent patients

European Archives of Psychiatry and Clinical Neuroscience ◽

10.1007/s00406-021-01240-4 ◽

2021 ◽

Author(s):

Patrick Bach ◽

Rilana Schuster ◽

Anne Koopmann ◽

Sabine Vollstaedt-Klein ◽

Rainer Spanagel ◽

...

Keyword(s):

Prefrontal Cortex ◽

Calcium Concentration ◽

Cue Reactivity ◽

Brain Activation ◽

Plasma Calcium ◽

Brain Areas ◽

Alcohol Craving ◽

Frontal Brain ◽

Plasma Calcium Concentration ◽

Alcohol Dependent

AbstractRecent studies on the pathophysiology of alcohol dependence suggest a link between peripheral calcium concentrations and alcohol craving. Here, we investigated the association between plasma calcium concentration, cue-induced brain activation, and alcohol craving. Plasma calcium concentrations were measured at the onset of inpatient detoxification in a sample of N = 115 alcohol-dependent patients. Alcohol cue-reactivity was assessed during early abstinence (mean 11.1 days) using a functional magnetic resonance imaging (fMRI) alcohol cue-reactivity task. Multiple regression analyses and bivariate correlations between plasma calcium concentrations, clinical craving measures and neural alcohol cue-reactivity (CR) were tested. Results show a significant negative correlation between plasma calcium concentrations and compulsive alcohol craving. Higher calcium levels predicted higher alcohol cue-induced brain response in a cluster of frontal brain areas, including the dorsolateral prefrontal cortex (dlPFC), the anterior prefrontal cortex (alPFC), and the inferior (IFG) and middle frontal gyri (MFG). In addition, functional brain activation in those areas correlated negatively with craving for alcohol during fMRI. Higher peripheral calcium concentrations during withdrawal predicted increased alcohol cue-induced brain activation in frontal brain areas, which are associated with craving inhibition and cognitive control functions. This might indicate that higher plasma calcium concentrations at onset of detoxification could modulate craving inhibition during early abstinence.Trial registration number: DRKS00003388; date of registration: 14.12.2011.

Download Full-text

Disrupted Ventromedial Prefrontal Function, Alcohol Craving, and Subsequent Relapse Risk

JAMA Psychiatry ◽

10.1001/jamapsychiatry.2013.762 ◽

2013 ◽

Vol 70 (7) ◽

pp. 727 ◽

Cited By ~ 145

Author(s):

Dongju Seo ◽

Cheryl M. Lacadie ◽

Keri Tuit ◽

Kwang-Ik Hong ◽

R. Todd Constable ◽

...

Keyword(s):

Alcohol Craving ◽

Relapse Risk ◽

Prefrontal Function ◽

Subsequent Relapse

Download Full-text

Faculty Opinions recommendation of Enhanced negative emotion and alcohol craving, and altered physiological responses following stress and cue exposure in alcohol dependent individuals.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1159802.621218 ◽

2009 ◽

Author(s):

George Breese ◽

Mary Katherine Kelm

Keyword(s):

Negative Emotion ◽

Physiological Responses ◽

Cue Exposure ◽

Alcohol Craving ◽

Alcohol Dependent

Download Full-text

Reward-Related Learning in Alcoholism

European Psychiatry ◽

10.1016/s0924-9338(11)73717-8 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 2014-2014

Author(s):

A. Heinz ◽

A. Beck ◽

S.Q. Park ◽

L. Deserno ◽

F. Schlagenhauf

Keyword(s):

Reversal Learning ◽

Ventral Striatum ◽

Imaging Study ◽

Brain Activation ◽

Dopamine Synthesis ◽

Healthy Controls ◽

Reward Seeking ◽

Positron Emission ◽

Dorsolateral Prefrontal ◽

Alcohol Dependent

The disposition and maintenance of alcohol addiction has been associated with dysfunctional learning, particularly with increased salience attribution to alcohol-associated stimuli and Pavlovian-to-instrumental transfer, which establishes an effect of alcohol-associated cues on operant alcohol seeking and consumption. Previous imaging studies showed that dopamine dysfunction in the ventral striatum is associated with increased brain activation elicited by alcohol-associated cues in brain areas associated with attention. Furthermore, brain activation elicited by non-alcohol (e.g. monetary) reward was decreased in detoxified alcohol-dependent patients. Neuroadaptation following addiction therefore seems to augment neuronal responses to well-established, drug-associated stimuli while interfering with the learning of new, reward-seeking behaviour patterns. Using functional magnetic resonance imaging (fMRI) we showed that in detoxified alcoholics, reward-dependent reversal learning is impaired compared to healthy controls, and that this impairment correlates with reduced functional connectivity between the ventral striatum and the dorsolateral prefrontal cortex. Furthermore, we will present first data from a multimodal imaging study combining fMRI and positron-emission-tomography (PET) to measure the association between dopamine synthesis reduction and impaired functional brain activation during reversal learning in detoxified alcohol-dependent patients compared with healthy controls.

Download Full-text

I know that I don’t know: Structural and functional connectivity underlying meta-ignorance in pre-schoolers

10.1101/450346 ◽

2018 ◽

Cited By ~ 1

Author(s):

Elisa Filevich ◽

Caroline Garcia Forlim ◽

Carmen Fehrman ◽

Carina Forster ◽

Markus Paulus ◽

...

Keyword(s):

Functional Connectivity ◽

Default Mode Network ◽

Orbitofrontal Cortex ◽

Cingulate Gyrus ◽

Partial Knowledge ◽

Metacognitive Monitoring ◽

Default Mode ◽

Posterior Cingulate Gyrus ◽

Knowledge Condition ◽

The Brain

Research Highlights[1] Children develop the ability to report that they do not know something at around five years of age.[2] Children who could correctly report their own ignorance in a partial-knowledge task showed thicker cortices within medial orbitofrontal cortex.[3] This region was functionally connected to parts of the default-mode network.[4] The default-mode network might support the development of correct metacognitive monitoring.AbstractMetacognition plays a pivotal role in human development. The ability to realize that we do not know something, or meta-ignorance, emerges after approximately five years of age. We aimed at identifying the brain systems that underlie the developmental emergence of this ability in a preschool sample.Twenty-four children aged between five and six years answered questions under three conditions of a meta-ignorance task twice. In the critical partial knowledge condition, an experimenter first showed two toys to a child, then announced that she would place one of them in a box behind a screen, out of sight from the child. The experimenter then asked the child whether or not she knew which toy was in the box.Children who answered correctly both times to the metacognitive question in the partial knowledge condition (n=9) showed greater cortical thickness in a cluster within left medial orbitofrontal cortex than children who did not (n=15). Further, seed-based functional connectivity analyses of the brain during resting state revealed that this region is functionally connected to the medial orbitofrontal gyrus, posterior cingulate gyrus and precuneus, and mid- and inferior temporal gyri.This finding suggests that the default mode network, critically through its prefrontal regions, supports introspective processing. It leads to the emergence of metacognitive monitoring allowing children to explicitly report their own ignorance.

Download Full-text