Neil C Dodge1, Kevin G F Thomas2, Ernesta M Meintjes3, Christopher D Molteno4, Joseph L Jacobson1,3,4, Sandra W Jacobson1,3,4. 1. From the Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, United States. 2. ACSENT Laboratory, Department of Psychology, University of Cape Town, Cape Town, South Africa. 3. Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. 4. Department of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Abstract
BACKGROUND: Prenatal alcohol exposure (PAE) has been linked to poorer performance on the Morris water maze (MWM), a test of spatial navigation in rodents that is dependent on hippocampal functioning. We recently confirmed these findings in children with PAE on a human analog of the MWM, the virtual water maze (VWM). Previous studies have shown that the hippocampus is particularly sensitive to PAE. Our aim was to determine whether hippocampal volume mediates the relation between PAE and virtual navigation. METHODS: VWM and MRI hippocampal data were collected from 50 right-handed 10-year-old children in a heavily exposed Cape Town, South African sample. PAE data had been collected from their mothers during pregnancy, and the children were examined by expert fetal alcohol spectrum disorder (FASD) dysmorphologists. In the VWM, the participant attempts to learn the location of a hidden platform in a virtual pool of water across a series of learning trials using only distal room cues. Hippocampal volumes were derived using FreeSurfer from MRI scans administered within 1 week of completing the VWM task. RESULTS: Both the fetal alcohol syndrome (FAS)/partial FAS and nonsyndromal heavy-exposed (HE) groups had smaller hippocampal volumes than controls. PAE was associated with reduced right hippocampal volumes even after control for total intracranial volume (ICV). Hippocampal volume was also positively associated with VWM performance. The relation between PAE and VWM performance was partially mediated by right hippocampal volume but not by total ICV. CONCLUSIONS: These data confirm previous reports linking PAE to poorer spatial navigation on the VWM and are the first to provide direct evidence that volume reductions in this region partially mediate the relation of FASD diagnosis to place learning, suggesting that PAE specifically impairs the ability to encode the spatial information necessary for successful location of the hidden platform on a navigation task.
BACKGROUND: Prenatal alcohol exposure (PAE) has been linked to poorer performance on the Morris water maze (MWM), a test of spatial navigation in rodents that is dependent on hippocampal functioning. We recently confirmed these findings in children with PAE on a human analog of the MWM, the virtual water maze (VWM). Previous studies have shown that the hippocampus is particularly sensitive to PAE. Our aim was to determine whether hippocampal volume mediates the relation between PAE and virtual navigation. METHODS: VWM and MRI hippocampal data were collected from 50 right-handed 10-year-old children in a heavily exposed Cape Town, South African sample. PAE data had been collected from their mothers during pregnancy, and the children were examined by expert fetal alcohol spectrum disorder (FASD) dysmorphologists. In the VWM, the participant attempts to learn the location of a hidden platform in a virtual pool of water across a series of learning trials using only distal room cues. Hippocampal volumes were derived using FreeSurfer from MRI scans administered within 1 week of completing the VWM task. RESULTS: Both the fetal alcohol syndrome (FAS)/partial FAS and nonsyndromal heavy-exposed (HE) groups had smaller hippocampal volumes than controls. PAE was associated with reduced right hippocampal volumes even after control for total intracranial volume (ICV). Hippocampal volume was also positively associated with VWM performance. The relation between PAE and VWM performance was partially mediated by right hippocampal volume but not by total ICV. CONCLUSIONS: These data confirm previous reports linking PAE to poorer spatial navigation on the VWM and are the first to provide direct evidence that volume reductions in this region partially mediate the relation of FASD diagnosis to place learning, suggesting that PAE specifically impairs the ability to encode the spatial information necessary for successful location of the hidden platform on a navigation task.
Authors: Sandra W Jacobson; Mark E Stanton; Neil C Dodge; Mariska Pienaar; Douglas S Fuller; Christopher D Molteno; Ernesta M Meintjes; H Eugene Hoyme; Luther K Robinson; Nathaniel Khaole; Joseph L Jacobson Journal: Alcohol Clin Exp Res Date: 2010-11-12 Impact factor: 3.455
Authors: Jesuchristopher Joseph; Christopher Warton; Sandra W Jacobson; Joseph L Jacobson; Chris D Molteno; Anton Eicher; Patrick Marais; Owen R Phillips; Katherine L Narr; Ernesta M Meintjes Journal: Hum Brain Mapp Date: 2012-11-05 Impact factor: 5.038
Authors: Kinga Iglói; Christian F Doeller; Alain Berthoz; Laure Rondi-Reig; Neil Burgess Journal: Proc Natl Acad Sci U S A Date: 2010-07-26 Impact factor: 11.205
Authors: Cynthia F Bearer; Joseph L Jacobson; Sandra W Jacobson; Dana Barr; Julie Croxford; Christopher D Molteno; Denis L Viljoen; Anna-Susan Marais; Lisa M Chiodo; Andrew S Cwik Journal: J Pediatr Date: 2003-10 Impact factor: 4.406
Authors: François De Guio; Jean-François Mangin; Denis Rivière; Matthieu Perrot; Christopher D Molteno; Sandra W Jacobson; Ernesta M Meintjes; Joseph L Jacobson Journal: Hum Brain Mapp Date: 2013-08-14 Impact factor: 5.038
Authors: Johnny A Kenton; Victoria K Castillo; Penelope E Kehrer; Jonathan L Brigman Journal: Alcohol Clin Exp Res Date: 2020-09-06 Impact factor: 3.455
Authors: Donovan J Roediger; Alyssa M Krueger; Erik de Water; Bryon A Mueller; Christopher A Boys; Timothy J Hendrickson; Mariah J Schumacher; Sarah N Mattson; Kenneth L Jones; Kelvin O Lim; Jeffrey R Wozniak Journal: Neurotoxicol Teratol Date: 2020-11-21 Impact factor: 3.763
Authors: Victoria M Niedzwiedz-Massey; James C Douglas; Tonya Rafferty; Patricia A Wight; Cynthia J M Kane; Paul D Drew Journal: Neurotoxicol Teratol Date: 2021-07-10 Impact factor: 4.071