Aberrant development of post-movement beta rebound in adolescents and young adults with fetal alcohol spectrum disorders

Abstract

Dependent on maternal (e.g. genetic, age) and exposure (frequency, quantity, and timing) variables, the effects of prenatal alcohol exposure on the developing fetus are known to vary widely, producing a broad range of morphological anomalies and neurocognitive deficits in offspring, referred to as fetal alcohol spectrum disorders (FASD). Maternal drinking during pregnancy remains a leading risk factor for the development of intellectual disabilities in the US. While few functional findings exist today that shed light on the mechanisms responsible for the observed impairments in individuals with FASD, animal models consistently report deleterious effects of early alcohol exposure on GABA-ergic inhibitory pathways. The post-motor beta rebound (PMBR), a transient increase of 15-30 Hz beta power in the motor cortex that follows the termination of movement, has been implicated as a neural signature of GABA-ergic inhibitory activity. Further, PMBR has been shown to be a reliable predictor of age in adolescents. The present study sought to investigate any differences in the development of PMBR between FASD and control groups. Beta event-related de-synchronization (ERD) and movement-related gamma synchronization (MRGS), although not clearly linked to brain maturation, were also examined. Twenty-two participants with FASD and 22 age and sex-matched controls (12-22 years old) underwent magnetoencephalography scans while performing an auditory oddball task, which required a button press in response to select target stimuli. The data surrounding the button presses were localized to the participants' motor cortices, and the time courses from the locations of the maximally evoked PMBR were subjected to wavelet analyses. The subsequent analysis of PMBR, ERD, and MRGS revealed a significant interaction between group and age in their effects on PMBR. While age had a significant effect on PMBR in the controls, no simple effects of age were detected in the FASD group. The FASD group additionally displayed decreased overall ERD levels. No group or age effects on MRGS were detected. The described findings provide further evidence for broad impairments in inhibitory processes in adolescents with FASD, possibly related to aberrant development of GABA-ergic pathways.

Keywords: Adolescents; FASD; Fetal alcohol spectrum disorder; Magnetoencephalography; PMBR; Post-movement beta rebound.

Fig. 1

Post-movement beta rebound localization. Data from representative participants in the young adult healthy control (HC), young adult FASD, adolescent control, and adolescent FASD groups are presented in radiological convention on MNI-152 template volumes. The threshold for the activation maps is p = 0.05. The crosshairs are centered on the location of maximum evoked PMBR in each volume.

Fig. 2

Interactions and main effects on beta ERD. Main effects of age and group are presented in absolute values of evoked de-synchronization. The main effect of group was significant (p < 0.05), with controls displaying higher levels of de-synchronization than the FASD group. Additionally, a significant effect of age was also detected, revealing increased ERD power in the young adult cohort. The group by age interaction was not significant.

Fig. 3

Significant interactions and main effects on PMBR. Controls displayed significantly higher PMBR than the FASD group (p < 0.001). Main effect of age group (12–15 and 16–22 years old) was significant, with higher PMBR in controls than in the FASD group (p < 0.001). Relative to the [−1.5 −1 s] baseline period, late [1 1.5] PMBR power was statistically higher than the early [0.5 1 s] PMBR power levels (p < 0.001). Group-by-age interaction is presented in terms of simple effects of group (FASD and control) within each level of age (adolescents and young adults). While a significant effect of age was observed in the control group (p < 0.001), no such effect was detected in the FASD group (p = 0.7).

Fig. 4

Interactions and main effects on MRGS. Evoked MRGS values are summarized for each experimental group. No significant effects of age or group were detected on MRGS (p > 0.05). The interaction between age and group was also not significant (p > 0.05).

Fig. 5

Time–frequency MRGS representations. Averaged time–frequency maps are presented for the FASD and control groups, as well as the difference between them. Young adult and adolescent cohorts' time–frequency representations are also presented. The interaction between age and group was not significant (p > 0.05). Further, each variable's main effect on MRGS also failed to reach significance (p > 0.05).

Fig. 6

Time–frequency maps for main effects. Time–frequency maps are presented for the control and FASD groups, as well as the contrast between the two. The main effects of group are outlined (black = control > FASD; white = FASD > control; FDR-corrected p = 0.001). Average beta time courses are shown for both groups, with black bars on the bottom representing the significance of a between-group t-test at each time point (FDR-corrected p = 0.001). Time–frequency maps for the young adult and adolescent groups are also shown, with the main effects of age outlined on the comparison map (black = young adults > adolescents; white = adolescents > young adults; FDR-corrected p = 0.001). Beta time courses are presented for both groups, with black bars on the bottom representing the significance of a between-group t-test at each time point (FDR-corrected p = 0.001).

Fig. 7

Simple effects of group within different levels of age. Group (FASD, control) did not exhibit a statistically significant simple effect on PMBR within the adolescent cohort. A simple effect of group on PMBR within the young adult cohort was significant (FDR-corrected p = 0.001), with greater rebound power observed in controls than participants with FASDs. Contrast maps are presented, with statistically significant differences outlined (black = control > FASD). Beta time courses are presented as well, with black bars on the bottom representing the significance of a between-group t-test at each time point (FDR-corrected p = 0.001).