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Scholarly Works (5 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2016)

Rationale. Individuals prenatally exposed to alcohol often have impaired working memory. Neuropsychological studies have further suggested that spatial working memory (SWM) may be significantly affected in this group. Studies of the neural correlates of working memory have consistently shown the involvement of a fronto-parietal network. Despite evidence for microstructural and functional abnormalities in frontal and parietal regions in individuals prenatally exposed to alcohol, the relation and contribution of these

abnormalities to SWM deficits remain unclear. The main goal of this study was to expand on previous research by using a multimodal imaging approach to examine brain structure and function associated with SWM deficits in children prenatally exposed to alcohol.

Design. Children ages 10 to 16 with histories of heavy prenatal alcohol exposure (AE group; n = 18) and non-exposed controls (CON group; n = 19) underwent functional magnetic resonance imaging while performing a SWM task and diffusion tensor imaging. Whole-brain blood oxygen level dependent (BOLD) response to SWM relative to vigilance trials (SWM – vigilance contrast) was computed for each participant. Whole brain task-related functional connectivity of bilateral dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) seed regions were estimated for each participant using a psychophysiological interaction approach. Fractional anisotropy and mean diffusivity were used as indices of white matter integrity. Independent samples t-tests were used to examine group differences in BOLD response contrast, task-based functional connectivity, and white matter integrity of the superior longitudinal fasciculus (SLF) and genu of the corpus callosum (GCC).

Results. Children in the AE group were less accurate than children in the CON group when performing the SWM task (p = .008). Group differences in neural activity to the SWM – vigilance contrast were found primarily in frontal, parietal, and cingulate regions. In all regions, the CON group showed greater BOLD response contrast compared to the AE group. Results from the functional connectivity analyses revealed positive coupling between bilateral DLPFC seeds and regions within the fronto-parietal network in the CON group, whereas the AE group showed negative connectivity. In contrast to the CON group, the AE group showed positive connectivity between PPC seeds and frontal lobe regions. Across seeds, weaker negative coupling with regions outside the fronto-parietal network (e.g., left middle occipital gyrus) were observed in the AE group relative to the CON group. Functional data clusters were considered significant at p < .05 (with an uncorrected voxelwise threshold: p < .05; minimum cluster volume: 63 voxels). No significant groups differences were noted with respect to white matter integrity in the SLF and GCC.

Conclusions. Overall findings suggest that localized alterations in neural activity, aberrant fronto-parietal network synchrony, and poor coordination of neural responses with regions outside of this network may help explain SWM deficits in individuals with a history of heavy prenatal alcohol exposure. Greater understanding of the neural mechanism underlying cognitive deficits in children prenatally exposed to alcohol may contribute to the development of targeted interventions, and may serve as a potential neurobiological marker of treatment outcomes.

    Cover page: Spatial Working Memory in Children with FASD: A Multimodal Imaging Approach
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2020)

    Background

    Altered brain activation during response inhibition has been linked to a greater risk for alcohol and other substance use behaviors in late adolescence. However, the ability of neural markers of response inhibition, acquired during adolescence, to temporally predict the transition from less frequent and lower quantity alcohol use to high-risk, frequent (≥ weekly) binge drinking behavior remains unclear.

    Methods

    Adolescents (N = 29; 9 females) were selected from a larger ongoing longitudinal study to include those who transitioned to at least weekly binge drinking (≥5/4 alcoholic drinks for males/females per occasion) over a 15-year follow-up period. Prior to the onset of weekly binge drinking (mean age = 18.0), participants underwent a functional MRI including a go/no-go task. Whole-brain activation from the no-go correct rejection versus no-go false alarm contrast was used to predict time to transition to frequent binge drinking.

    Results

    Less no-go correct rejection versus no-go false alarm activation in a cluster including the precentral gyri, insula, and inferior frontal gyri predicted a more rapid transition into frequent binge drinking (voxel-wise alpha < 0.001, cluster-wise alpha < 0.05, cluster threshold ≥ 18 voxels).

    Conclusions

    Results from this study are supported by literature suggesting that frontoinsular involvement is important for successful inhibition and cognitive control. Altered brain activation during response inhibition may thus represent neural antecedents of impulse regulation difficulties related to alcohol consumption. The magnitude of this activation provides temporal information that may be used to inform and optimize timing of interventions aimed at preventing the escalation and transition to problematic drinking for youth who have already begun to engage in drinking behaviors.
      Cover page: Prospective Associations between BOLD Markers of Response Inhibition and the Transition to Frequent Binge Drinking
      • Article
      • Peer Reviewed
      UC Santa Barbara Previously Published Works (2020)

      Background

      Youth whose parents have alcohol use disorder (AUD) are at higher risk for earlier initiation and greater magnitude of alcohol use, and have a higher likelihood of developing an AUD than their peers without parental history of AUD. This increased risk may be partly attributable to altered development of inhibitory control and related neural circuitry. This study examined neural activation during a motor response inhibition Stop Signal Task (SST) in substance-naïve youth aged 9 to 10 years with and without parental family history of AUD.

      Methods

      Baseline cross-sectional survey and functional magnetic resonance imaging (fMRI) data were drawn from 6,898 youth in the US-based Adolescent Brain Cognitive Development Study. Generalized additive mixed models were conducted to examine the association between maternal, paternal, and parental (both mother and father) family history of AUD with neural activation during successful and failed response inhibition. Family history interactions with sex and stratification by ethnicity were explored.

      Results

      Of 6,898 participants, 951 (14%) were family history positive for any parental AUD. Paternal history of AUD was associated with greater activation for successful inhibition in the right medial orbital frontal gyrus, compared to youth with no family history. Maternal history of AUD was associated with greater activation for failed response inhibition among females in the cerebellum, compared to females with no such history. Parental history (both mother and father) of AUD was associated with greater activation during successful inhibition in the left paracentral gyri and left superior parietal lobule. Maternal history and parental history of AUD findings were accounted for by a family history of substance use disorder in general. All effect sizes were relatively small.

      Conclusions

      Substance-naïve children with a parental family history of AUD exhibit greater neural activation in some regions of the fronto-basal ganglia and cerebellar networks when they successfully or unsuccessfully inhibit a response as compared to children with no such family history. This unique neural response pattern could reflect a compensatory response and may represent an inherent neurobiological vulnerability to risk-related behaviors in these youth which will be examined in future longitudinal analyses of this cohort.
        Cover page: Parental Family History of Alcohol Use Disorder and Neural Correlates of Response Inhibition in Children From the Adolescent Brain Cognitive Development (ABCD) Study
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2019)

        Background

        Acute alcohol consumption is associated with temporarily increased regional cerebral blood flow (CBF). The extent of this increase appears to be moderated by individual differences in the level of response (LR) to alcohol's subjective effects. The low LR phenotype is a known risk factor for the development of alcohol problems. This study investigates how the low LR phenotype relates to the relationship between alcohol-related changes in CBF and alcohol problems 5 years later.

        Methods

        Young adults (ages 18 to 25) were selected based on their LR to alcohol and underwent a neuroimaging protocol including arterial spin labeling and functional scans. These participants were recontacted ~5 years later and assessed on alcohol outcomes. A final sample of 107 subjects (54 low and 53 high LR subjects) was included in the analyses. Whole-brain analysis revealed 5 clusters of significant alcohol-induced, versus placebo-induced, CBF changes that were consistent with a previous report. Peak alcohol-placebo CBF response was extracted from these regions and, along with the LR group, submitted to a hierarchical linear regression predicting alcohol problems. Analyses controlled for age, sex, and baseline alcohol problems.

        Results

        In the regression analysis, greater alcohol-placebo CBF difference in the right middle/superior/inferior frontal gyri and bilateral anterior cingulate gyri clusters predicted greater future alcohol problems for the low LR group, whereas this relationship was not found to be significant in the high LR group.

        Conclusions

        This study demonstrates a clinically important relationship between CBF and future alcohol problems, particularly in individuals with a low LR phenotype. These initial results help to elucidate the neurobiological pathways involved in the development of alcohol use disorders for individuals with low LR.
          Cover page: The Relationship Between Regional Cerebral Blood Flow Estimates and Alcohol Problems at 5‐Year Follow‐Up: The Role of Level of Response
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2020)

          Background

          Youth whose parents have alcohol use disorder (AUD) are at higher risk for earlier initiation and greater magnitude of alcohol use, and have a higher likelihood of developing an AUD than their peers without parental history of AUD. This increased risk may be partly attributable to altered development of inhibitory control and related neural circuitry. This study examined neural activation during a motor response inhibition Stop Signal Task (SST) in substance-naïve youth aged 9 to 10 years with and without parental family history of AUD.

          Methods

          Baseline cross-sectional survey and functional magnetic resonance imaging (fMRI) data were drawn from 6,898 youth in the US-based Adolescent Brain Cognitive Development Study. Generalized additive mixed models were conducted to examine the association between maternal, paternal, and parental (both mother and father) family history of AUD with neural activation during successful and failed response inhibition. Family history interactions with sex and stratification by ethnicity were explored.

          Results

          Of 6,898 participants, 951 (14%) were family history positive for any parental AUD. Paternal history of AUD was associated with greater activation for successful inhibition in the right medial orbital frontal gyrus, compared to youth with no family history. Maternal history of AUD was associated with greater activation for failed response inhibition among females in the cerebellum, compared to females with no such history. Parental history (both mother and father) of AUD was associated with greater activation during successful inhibition in the left paracentral gyri and left superior parietal lobule. Maternal history and parental history of AUD findings were accounted for by a family history of substance use disorder in general. All effect sizes were relatively small.

          Conclusions

          Substance-naïve children with a parental family history of AUD exhibit greater neural activation in some regions of the fronto-basal ganglia and cerebellar networks when they successfully or unsuccessfully inhibit a response as compared to children with no such family history. This unique neural response pattern could reflect a compensatory response and may represent an inherent neurobiological vulnerability to risk-related behaviors in these youth which will be examined in future longitudinal analyses of this cohort.
            Cover page: Parental Family History of Alcohol Use Disorder and Neural Correlates of Response Inhibition in Children From the Adolescent Brain Cognitive Development (ABCD) Study
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