Longitudinal changes of amygdala and default mode activation in adolescents prenatally exposed to cocaine

Abstract

Prenatal cocaine exposure (PCE) is associated with long-term and negative effect on arousal regulation. Recent neuroimaging studies have examined brain mechanisms related to arousal dysregulation with cross-sectional experimental designs; but longitudinal changes in the brain, reflecting group differences in neurodevelopment, have never been directly examined. To directly assess the interaction of PCE and neurodevelopment, the present study used a longitudinal design to analyze functional magnetic resonance imaging (fMRI) data collected from 33 adolescents (21 with PCE and 12 non-exposed controls) while they performed the same working memory task with emotional distracters at two points in time. The mean age of participants was 14.3 years at time_1 and 16.7 years at time_2. With confounding factors statistically controlled, the fMRI data revealed significant exposure-by-time interaction in the activations of the amygdala and default mode network (DMN). For the control adolescents, brain activations associated with emotional arousal (amygdala) and cognitive effort (DMN) were both reduced at time_2 as compared to that at time_1. However, these activation reductions were not observed in the PCE group, indicating persistently high levels of emotional arousal and cognitive effort. In addition, correlations between longitudinal changes in the brain and in behavior have shown that adolescents with persistently high emotional arousal were more likely in need of high cognitive effort; and their cognitive performance was more likely to be affected by distractive challenges. The present results complement and extend previous findings from cross-sectional studies with further evidence supporting the view of PCE associated long-term teratogenic effects on arousal regulation.

Thalamocortical functional connectivity and behavioral disruptions in neonates with prenatal cocaine exposure

“…hyper amygdalo-frontal connectivity (Salzwedel et al, 2015)] alterations in neonates with PCE. These findings parallel a growing body of work, which have demonstrated amygdala and/or frontal abnormalities in humans with PCE (Li et al, 2009; Li et al, 2016; Li et al, 2013; Liu et al, 2013; Rando et al, 2013; Rao et al, 2007; Roussotte et al, 2010; Sheinkopf et al, 2009), however no definitive brain-behavior relationships have been established. In this study, we have shown significant PCE-related disruptions and brain-behavioral relationships associated with the thalamus in exposed neonates, suggesting that thalamocortical pathways are also part of the PCE-effect cascade during early brain development.…”

“…Imbalanced gating between different processing streams, particularly between limbic and executive regions, has been put forth as a potential mechanism (Harvey, 2004; Mayes, 2002). Indeed, neuroimaging efforts have lent credence to this theory (Grewen et al, 2014; Li et al, 2009; Li et al, 2016; Li et al, 2013; Liu et al, 2013; Rando et al, 2013; Rao et al, 2007; Roussotte et al, 2010; Salzwedel et al, 2015; Sheinkopf et al, 2009) and shown PCE-related structural and functional alterations associated with the amygdalo-frontal pathway. However the thalamus, another region that is reportedly critical for this set of PCE-affected functions, has received relatively little attention.…”

Altered functional connectivity to stressful stimuli in prenatally cocaine-exposed adolescents

“…Consistent with these findings, data from two recent resting-state studies suggest that PCE adolescents’ functional connectivity is altered in the amygdala and DMN, compared to NDE counterparts (Li et al, 2016; Li et al, 2011). However, to our knowledge, no prior studies have assessed functional connectivity amongst PCE adolescents during the processing of appetitive, stressful and neutral-relaxing stimuli.…”

“…One study has shown that PCE adolescents have higher DMN activity and connectivity during rest and less DMN activity during task, relative to their NDE counterparts (Li et al, 2011), and these dysregulations may persist into early adulthood (Li et al, 2016). The PCC/precuneus brain region, also observed in the current study, is a major hub in the brain’s DMN.…”

“…Previous preclinical and clinical studies have implicated PCE in impacting corticolimbic brain regions including the anterior cingulate (ACC) (Harvey, 2004), prefrontal cortex (PFC) (Grewen et al, 2014; McCarthy and Bhide, 2012; McCarthy et al, 2014), amygdala (Li et al, 2016) and ventral striatum (Harvey et al; Wang et al, 2013). Dysregulation of corticolimbic pathways have been shown in response to reward-related and stressful cues among individuals with obesity and with cocaine addiction (Jasinska et al, 2014; Jastreboff et al, 2013; Potenza, 2012).…”