Effects of Prenatal Drug Exposure on Adolescent Brain Activation During a Visuospatial Working Memory Task

Abstract

Background: Previous research examining effects of prenatal drug exposure (PDE) has yielded mixed results regarding cognitive performance during school age years. Associations between PDE and tests of global functioning (IQ and academic achievement) tend to be minimal and are typically attenuated by environmental variables (e.g., caregiving environment). On the other hand, significant negative associations have been reported in tests of executive functioning (sustained attention, inhibitory control, and behavioral regulation), even with covariate control. These findings are consistent with animal models of PDE that report developmental abnormalities in brain regions associated with strong dopaminergic innervation including the striatum, anterior cingulate cortex, and prefrontal cortex. In humans, these regions are putatively involved in executive functions that coordinate the basic cognitive processes required for goal-directed action (e.g., attention inhibitory control, planning, working memory). The objective of the present study was to assess the effects of PDE on brain functioning during adolescence. Methods: fMRI was used to examine visuospatial working memory (VSWM) in 35 adolescents (mean: 14.3 years); 20 with intrauterine exposure to cocaine, heroin, or both and 15 unexposed children from the same community. All participants performed a 2-back VSWM paradigm that required dynamic storage and manipulation of spatial information. Whole-brain functional EPI scans were acquired using a 3T Siemens Scanner with standard parameters. Participants completed one 6-minute block-design run that alternated between a 30 second control condition (which required observation of visual stimuli, sustained attention, and a motor response) and 30 seconds of the VSWM condition. Brain responses were analyzed using the AFNI software package with appropriate contrasts and p < 0.05 corrected for multiple comparisons. Results: Across all participants, the VSWM task activated the frontal-parietal attention network including bilateral superior parietal lobules, precuneus, middle frontal gyri, superior frontal gyri, and insular cortex. Significant deactivations were observed in regions of the “default network,” including the left anterior cingulate gyrus, medial frontal gyrus, posterior cingulate, and bilateral parahippocampal cortices. Whole-brain between group comparisons with both age and gender entered as covariates revealed 3 regions that were differentially activated in the drug-exposed compared to the non-exposed group. These regions included right inferior parietal lobe, right precentral gryus, and left cuneus. The drug-exposed group showed deactivation of the right inferior parietal lobule compared to no change in the non-exposed group. The non-exposed group showed activations in both the right precentral gyrus and left cuneus compared to no change in the drug-exposed group. These differences in activations were detected despite equivalent behavioral performance on the task (i.e., accuracy and response time) and after statistically controlling environmental variables that differed between the groups, including placement in nonmaternal care, maternal age at time of birth and prenatal exposure to cigarettes. Discussion: Despite similar task performance, adolescents with a history of PDE showed different neural activations than the comparison group. Regions that were differentially activated are implicated in sequencing task information (i.e., right parietal lobe), working memory performance in healthy control children (i.e., right precentral gyrus), and visual attention (i.e., left cuneus). These results suggest regions and components of working memory processing that may be differentially affected by PDE in adolescence.