Functional Connectivity and Metabolic Alterations in Medial Prefrontal Cortex in a Rat Model of Fetal Alcohol Spectrum Disorder: A Resting-State Functional Magnetic Resonance Imaging and in Vivo Proton Magnetic Resonance Spectroscopy Study

Dev Neurosci. 2019;41(1-2):67-78. doi: 10.1159/000499183. Epub 2019 Apr 18.

Abstract

Prenatal ethanol exposure alters brain structure, functional connectivity, and behavior in humans and rats. Behavioral changes include deficits in executive function, which requires cooperative activity between the frontal cortices and other brain regions. In this study, we analyzed the functional connectivity and neurochemical levels of the prefrontal cortex (PFC) using resting-state functional magnetic resonance imaging (rsfMRI) and proton magnetic resonance spectroscopy (1H-MRS) in ethanol-exposed (Eth) and control (Ctr) rats. Pregnant Long-Evans rats were fed a liquid diet containing ethanol (2.1-6.46% v/v ethanol) from gestational days 6 to 21 (Eth). Ctr animals received an isocaloric, isonutritive liquid diet. In young adulthood, male and female offspring underwent in vivo MRI using a 7.0-Tesla system. 1H-MRS from the PFC and whole brain rsfMRI were obtained on the animals. Seed-based functional connectivity analysis was performed with seeds placed in the PFC, matching the voxel of MRS. Male, but not female, Eth rats showed less functional connectivity between PFC and dorsal striatum than Ctr animals. In Eth males glucose levels were significantly lower, and in Eth females lower levels of phosphorylcholine but an increased gamma-aminobutyric acid/glutamate ratio were observed in the PFC compared with Ctr animals. Prenatal ethanol alters brain metabolism and functional connectivity of the PFC in a sex-dependent manner.

Keywords: Blood oxygen level-dependent signal; Cognition; Fetal alcohol spectrum disorder; Neurochemistry; Sex differences.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Central Nervous System Depressants / toxicity
  • Disease Models, Animal
  • Ethanol / toxicity
  • Female
  • Fetal Alcohol Spectrum Disorders / metabolism*
  • Fetal Alcohol Spectrum Disorders / physiopathology*
  • Magnetic Resonance Imaging
  • Male
  • Neural Pathways / drug effects*
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / physiopathology
  • Proton Magnetic Resonance Spectroscopy
  • Rats
  • Rats, Long-Evans
  • Rest

Substances

  • Central Nervous System Depressants
  • Ethanol