Functional connectivity abnormalities and associated cognitive deficits in fetal alcohol Spectrum disorders (FASD)

Abstract

Consistent with well-documented structural and microstructural abnormalities in prenatal alcohol exposure (PAE), recent studies suggest that functional connectivity (FC) may also be disrupted. We evaluated whole-brain FC in a large multi-site sample, examined its cognitive correlates, and explored its potential to objectively identify neurodevelopmental abnormality in individuals without definitive dysmorphic features. Included were 75 children with PAE and 68 controls from four sites. All participants had documented heavy prenatal alcohol exposure. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Resting-state FC was examined using whole-brain graph theory metrics to characterize each individual’s connectivity. Although whole-brain FC metrics did not discriminate prenatally-exposed from unexposed overall, atypical FC (> 1 standard deviation from the grand mean) was significantly more common (2.7 times) in the PAE group vs. controls. In a subset of 55 individuals (PAE and controls) whose dysmorphology examination could not definitively characterize them as either Fetal Alcohol Syndrome (FAS) or non-FAS, atypical FC was seen in 27 % of the PAE group, but 0 % of controls. Across participants, a 1 % difference in local network efficiency was associated with a 36 point difference in global cognitive functioning. Whole-brain FC metrics have potential to identify individuals with objective neurodevelopmental abnormalities from prenatal alcohol exposure. When applied to individuals unable to be classified as FAS or non-FAS from dysmorphology alone, these measures separate prenatally-exposed from non-exposed with high specificity.

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Acknowledgments

This work was performed in conjunction with the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), which is funded by grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Additional information about CIFASD can be found at www.cifasd.org.

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Correspondence to Jeffrey R. Wozniak.

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This study was funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The following support was utilized in this work: NIAAA U01AA017122 (PI: ERS); NIAAA U01AA14834 (PI: SNM); U24AA014811 (EPR); U24AA014815 (PI: KLJ); U24AA014818 (PI: Barnett); support from the Minnesota Supercomputing Institute.

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None of the authors has a relevant conflict of interest to disclose.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. All procedures were reviewed and approved by local human subject’s protection programs. This article does not contain any studies with animals performed by any of the authors.

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Wozniak, J.R., Mueller, B.A., Mattson, S.N. et al. Functional connectivity abnormalities and associated cognitive deficits in fetal alcohol Spectrum disorders (FASD). Brain Imaging and Behavior 11, 1432–1445 (2017). https://doi.org/10.1007/s11682-016-9624-4

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Keywords

  • Fetal alcohol (FAS, FASD)
  • Brain
  • Functional MRI (fMRI), resting-state, connectivity
  • Neuropsychology