Dataset Information

Dynamic frontostriatal functional peak connectivity (in alcohol use disorder).

ABSTRACT: Alcohol use disorder (AUD) is associated with changes in frontostriatal connectivity, but functional magnetic resonance imaging (fMRI) functional connectivity (FC) approaches are usually not adapted to these circuits. We developed a circuit-specific fMRI analysis approach to detect dynamic changes in frontostriatal FC inspired by medial-ventral-rostral to lateral-dorsal-caudal frontostriatal gradients originally identified in nonhuman primate tract-tracing data. In our PeaCoG ("peak connectivity on a gradient") approach we use information about the location of strongest FC on empirical frontostriatal connectivity gradients. We have recently described a basic PeaCoG version with conventional FC, and now developed a dynamic PeaCoG approach with sliding-window FC. In resting state data of n = 66 AUD participants and n = 40 healthy controls we continue here the analyses that we began with the basic version. Our former result of an AUD-associated ventral shift in right orbitofrontal cortex PeaCoG is consistently detected in the dynamic approach. Temporospatial variability of dynamic PeaCoG in the left dorsolateral prefrontal cortex is reduced in AUD and associated with self-efficacy to abstain and days of abstinence. Our method has the potential to provide insight into the dynamics of frontostriatal circuits, which has so far been relatively unexplored, and into their role in mental disorders and normal cognition.

SUBMITTER: Gerchen MF

PROVIDER: S-EPMC7721230 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Dynamic frontostriatal functional peak connectivity (in alcohol use disorder).

Gerchen Martin Fungisai MF Weiss Franziska F Kirsch Martina M Rentsch Alena A Halli Patrick P Kiefer Falk F Kirsch Peter P

Human brain mapping 20200904 1

Alcohol use disorder (AUD) is associated with changes in frontostriatal connectivity, but functional magnetic resonance imaging (fMRI) functional connectivity (FC) approaches are usually not adapted to these circuits. We developed a circuit-specific fMRI analysis approach to detect dynamic changes in frontostriatal FC inspired by medial-ventral-rostral to lateral-dorsal-caudal frontostriatal gradients originally identified in nonhuman primate tract-tracing data. In our PeaCoG ("peak connectivity ...[more]

PMID: 32885886

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Project description:Although altered function in neural reward circuitry is widely proposed in models of addiction, more recent conceptual views have emphasized the role of disrupted response in prefrontal regions. Changes in regions such as the orbitofrontal cortex, medial prefrontal cortex, and dorsolateral prefrontal cortex are postulated to contribute to the compulsivity, impulsivity, and altered executive function that are central to addiction. In addition, few studies have examined function in these regions during young adulthood, when exposure is less chronic than in typical samples of alcohol-dependent adults. To address these issues, we examined neural response and functional connectivity during monetary reward in 24 adults with alcohol dependence and 24 psychiatrically healthy adults. Adults with alcohol dependence exhibited less response to the receipt of monetary reward in a set of prefrontal regions including the medial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex. Adults with alcohol dependence also exhibited greater negative correlation between function in each of these regions and that in the nucleus accumbens. Within the alcohol-dependent group, those with family history of alcohol dependence exhibited lower mPFC response, and those with more frequent drinking exhibited greater negative functional connectivity between the mPFC and the nucleus accumbens. These findings indicate that alcohol dependence is associated with less engagement of prefrontal cortical regions, suggesting weak or disrupted regulation of ventral striatal response. This pattern of prefrontal response and frontostriatal connectivity has consequences for the behavior patterns typical of addiction. Furthermore, brain-behavior findings indicate that the potential mechanisms of disruption in frontostriatal circuitry in alcohol dependence include family liability to alcohol use problems and more frequent use of alcohol. In all, these findings build on the extant literature on reward-circuit function in addiction and suggest mechanisms for disrupted function in alcohol dependence.

Project description:Growing evidence suggests greater vulnerability of women than men to the adverse effects of alcohol on mood and sleep. However, the underlying neurobiological mechanisms are still poorly understood. Here, we examined sex difference in resting state functional connectivity in alcohol use disorder using a whole-brain data driven approach and tested for relationships with mood and self-reported sleep. To examine whether sex effects vary by severity of alcohol use disorder, we studied two cohorts: non-treatment seeking n = 141 participants with alcohol use disorder (low severity; 58 females) from the Human Connectome project and recently detoxified n = 102 treatment seeking participants with alcohol use disorder (high severity; 34 females) at the National Institute on Alcohol Abuse and Alcoholism. For both cohorts, participants with alcohol use disorder had greater sleep and mood problems than healthy control, whereas sex by alcohol use effect varied by severity. Non-treatment seeking females with alcohol use disorder showed significant greater impairments in sleep but not mood compared to non-treatment seeking males with alcohol use disorder, whereas treatment-seeking females with alcohol use disorder reported greater negative mood but not sleep than treatment-seeking males with alcohol use disorder. Greater sleep problems in non-treatment seeking females with alcohol use disorder were associated with lower cerebello-parahippocampal functional connectivity, while greater mood problems in treatment-seeking females with alcohol use disorder were associated with lower fronto-occipital functional connectivity during rest. The current study suggests that changes in resting state functional connectivity may account for sleep and mood impairments in females with alcohol use disorder. The effect of severity on sex differences might reflect neuroadaptive processes with progression of alcohol use disorder and needs to be tested with longitudinal data in the future.

Project description:: Individuals with alcohol use disorder (AUD) manifest a variety of impairments that can be attributed to alterations in specific brain networks. The current study aims to identify features of EEG-based functional connectivity, neuropsychological performance, and impulsivity that can classify individuals with AUD (N = 30) from unaffected controls (CTL, N = 30) using random forest classification. The features included were: (i) EEG source functional connectivity (FC) of the default mode network (DMN) derived using eLORETA algorithm, (ii) neuropsychological scores from the Tower of London test (TOLT) and the visual span test (VST), and (iii) impulsivity factors from the Barratt impulsiveness scale (BIS). The random forest model achieved a classification accuracy of 80% and identified 29 FC connections (among 66 connections per frequency band), 3 neuropsychological variables from VST (total number of correctly performed trials in forward and backward sequences and average time for correct trials in forward sequence) and all four impulsivity scores (motor, non-planning, attentional, and total) as significantly contributing to classifying individuals as either AUD or CTL. Although there was a significant age difference between the groups, most of the top variables that contributed to the classification were not significantly correlated with age. The AUD group showed a predominant pattern of hyperconnectivity among 25 of 29 significant connections, indicating aberrant network functioning during resting state suggestive of neural hyperexcitability and impulsivity. Further, parahippocampal hyperconnectivity with other DMN regions was identified as a major hub region dysregulated in AUD (13 connections overall), possibly due to neural damage from chronic drinking, which may give rise to cognitive impairments, including memory deficits and blackouts. Furthermore, hypoconnectivity observed in four connections (prefrontal nodes connecting posterior right-hemispheric regions) may indicate a weaker or fractured prefrontal connectivity with other regions, which may be related to impaired higher cognitive functions. The AUD group also showed poorer memory performance on the VST task and increased impulsivity in all factors compared to controls. Features from all three domains had significant associations with one another. These results indicate that dysregulated neural connectivity across the DMN regions, especially relating to hyperconnected parahippocampal hub as well as hypoconnected prefrontal hub, may potentially represent neurophysiological biomarkers of AUD, while poor visual memory performance and heightened impulsivity may serve as cognitive-behavioral indices of AUD.

Dataset Information

Dynamic frontostriatal functional peak connectivity (in alcohol use disorder).

Publications

Dynamic frontostriatal functional peak connectivity (in alcohol use disorder).

Similar Datasets

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