Browsing by Author "Finn, Peter"

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    Alterations in White Matter Microstructure and Connectivity in Young Adults with Alcohol Use Disorder
    (Wiley, 2019) Chumin, Evgeny J.; Grecco, Gregory G.; Dzemidzic, Mario; Cheng, Hu; Finn, Peter; Sporns, Olaf; Newman, Sharlene D.; Yoder, Karmen K.; Radiology and Imaging Sciences, School of Medicine
    Background Magnetic resonance imaging (MRI) studies have shown differences in volume and structure in the brains of individuals with alcohol use disorder (AUD). Most research has focused on neuropathological effects of alcohol that appear after years of chronic alcohol misuse. However, few studies have investigated white matter (WM) microstructure and diffusion MRI‐based (DWI) connectivity during early stages of AUD. Therefore, the goal of this work was to investigate WM integrity and structural connectivity in emerging adulthood AUD subjects using both conventional DWI metrics and a novel connectomics approach. Methods Twenty‐two AUD and eighteen controls (CON) underwent anatomical and diffusion MRI. Outcome measures were scalar diffusion metrics and structural network connectomes. Tract Based Spatial Statistics was used to investigate group differences in diffusion measures. Structural connectomes were used as input into a community structure procedure to obtain a co‐classification index matrix (an indicator of community association strength) for each subject. Differences in co‐classification and structural connectivity (indexed by streamline density) were assessed via the Network Based Statistics Toolbox. Results AUD had higher FA values throughout the major WM tracts, but also had lower FA values in WM tracts in the cerebellum and right insula (pTFCE < 0.05). Mean diffusivity was generally lower in the AUD group (pTFCE < 0.05). AUD had lower co‐classification of nodes between ventral attention and default mode networks, and higher co‐classification between nodes of visual, default mode, and somatomotor networks. Additionally, AUD had higher fiber density between an adjacent pair of nodes within the default mode network. Conclusion Our results indicate that emerging adulthood AUD subjects may have differential patterns of FA and distinct differences in structural connectomes compared to CON. These data suggest that such alterations in microstructure and structural connectivity may uniquely characterize early stages of AUD and/or a predisposition for development of AUD.
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    Anterior Cingulate Cortex Metabolites and White Matter Microstructure: A Multimodal Study of Emergent Alcohol Use Disorder
    (Springer, 2021) Grecco, Gregory G.; Chumin, Evgeny J.; Dzemidzic, Mario; Cheng, Hu; Finn, Peter; Newman, Sharlene; Dydak, Ulrike; Yoder, Karmen K.; Radiology and Imaging Sciences, School of Medicine
    Multimodal imaging is increasingly used to address neuropathology associated with alcohol use disorder (AUD). Few studies have investigated relationships between metabolite concentrations and white matter (WM) integrity; currently, there are no such data in AUD. In this preliminary study, we used complementary neuroimaging techniques, magnetic resonance spectroscopy (MRS), and diffusion weighted imaging (DWI), to study AUD neurophysiology. We tested for relationships between metabolites in the dorsal anterior cingulate cortex (dACC) and adjacent WM microstructure in young adult AUD and control (CON) subjects. Sixteen AUD and fourteen CON underwent whole-brain DWI and MRS of the dACC. Outcomes were dACC metabolites, and diffusion tensor metrics of dACC-adjacent WM. Multiple linear regression terms included WM region, group, and region × group for prediction of dACC metabolites. dACC myo-inositol was positively correlated with axial diffusivity in the left anterior corona radiata (p < 0.0001) in CON but not AUD (group effect: p < 0.001; region × group: p < 0.001; Bonferroni-corrected). In the bilateral anterior corona radiata and right genu of the corpus callosum, glutamate was negatively related to mean diffusivity in AUD, but not CON subjects (all model terms: p < 0.05, uncorrected). In AUD subjects, dACC glutamate was negatively correlated with AUD symptom severity. This is likely the first integrative study of cortical metabolites and WM integrity in young individuals with AUD. Differential relationships between dACC metabolites and adjacent WM tract integrity in AUD could represent early consequences of hazardous drinking, and/or novel biomarkers of early-stage AUD. Additional studies are required to replicate these findings, and to determine the behavioral relevance of these results.
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    Effects of Alcohol Cues on MRS Glutamate Levels in the Anterior Cingulate
    (Oxford University Press, 2018-05-01) Cheng, Hu; Kellar, Derek; Lake, Allison; Finn, Peter; Rebec, George V.; Dharmadhikari, Shalmali; Dydak, Ulrike; Newman, Sharlene; Radiology and Imaging Sciences, School of Medicine
    Growing evidence suggests that glutamate neurotransmission plays a critical role in alcohol addiction. Cue-induced change of glutamate has been observed in animal studies but never been investigated in humans. This work investigates cue-induced change in forebrain glutamate in individuals with alcohol use disorder (AUD). A total of 35 subjects (17 individuals with AUD and 18 healthy controls) participated in this study. The glutamate concentration was measured with single-voxel 1H-MR spectroscopy at the dorsal anterior cingulate. Two MRS sessions were performed in succession, the first to establish basal glutamate levels and the second to measure the change in response to alcohol cues. The changes in glutamate were quantified for both AUD subjects and controls. A mixed model ANOVA and t-tests were performed for statistical analysis. ANOVA revealed a main effect of cue-induced decrease of glutamate level in the anterior cingulate cortex (ACC). A significant interaction revealed that only AUD subjects showed significant decrease of glutamate in the ACC. There were no significant group differences in the level of basal glutamate. However, a negative correlation was found between the basal glutamate level and the number of drinking days in the past 2 weeks for the AUD subjects. Collectively, our results indicate that glutamate in key areas of the forebrain reward circuit is modulated by alcohol cues in early alcohol dependence.
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    Family history of substance use disorder and parental impulsivity are differentially associated with neural responses during risky decision-making
    (Frontiers Media, 2023-06-21) Aloi, Joseph; Kwon, Elizabeth; Hummer, Tom A.; Crum, Kathleen I.; Shah, Nikhil; Pratt, Lauren; Aalsma, Matthew C.; Finn, Peter; Nurnberger, John; Hulvershorn, Leslie A.; Psychiatry, School of Medicine
    Background: Risky decision-making is associated with the development of substance use behaviors during adolescence. Although prior work has investigated risky decision-making in adolescents at familial high risk for developing substance use disorders (SUDs), little research has controlled for the presence of co-morbid externalizing disorders (EDs). Additionally, few studies have investigated the role of parental impulsivity in offspring neurobiology associated with risky decision-making. Methods: One-hundred twenty-five children (28 healthy controls, 47 psychiatric controls with EDs without a familial history of SUD, and 50 high-risk children with co-morbid EDs with a familial history of SUD) participated in the Balloon Analog Risk Task while undergoing functional magnetic resonance imaging. Impulsivity for parents and children was measured using the UPPS-P Impulsive Behavior Scale. Results: We found that individuals in the psychiatric control group showed greater activation, as chances of balloon explosion increased, while making choices, relative to the healthy control and high-risk groups in the rostral anterior cingulate cortex (rACC) and lateral orbitofrontal cortex (lOFC). We also found a positive association between greater activation and parental impulsivity in these regions. However, within rACC, this relationship was moderated by group, such that there was a positive relationship between activation and parental impulsivity in the HC group, but an inverse relationship in the HR group. Conclusions: These findings suggest that there are key differences in the neurobiology underlying risky decision-making in individuals with EDs with and without a familial history of SUD. The current findings build on existing models of neurobiological factors influencing addiction risk by integrating parental factors. This work paves the way for more precise risk models in which to test preventive interventions.
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    Functional connectivity in frontostriatal networks differentiate offspring of parents with substance use disorders from other high-risk youth
    (Elsevier, 2021) Kwon, Elizabeth; Hummer, Tom; Andrews, Katharine D.; Finn, Peter; Aalsma, Matthew; Bailey, Allen; Hanquier, Jocelyne; Wang, Ting; Hulvershorn, Leslie; Psychiatry, School of Medicine
    Background: Family history (FH) of substance use disorders (SUDs) is known to elevate SUD risk in offspring. However, the influence of FH SUDs has been confounded by the effect of externalizing psychopathologies in the addiction risk neuroimaging literature. Thus, the current study aimed to assess the association between parental SUDs and offspring functional connectivity in samples matched for psychopathology and demographics. Methods: Ninety 11-12-year-old participants with externalizing disorders were included in the study (48 FH+, 42 FH-). We conducted independent component analyses (ICA) and seed-based analyses (orbitofrontal cortex; OFC, nucleus accumbens (NAcc), dorsolateral prefrontal cortex) with resting state data. Results: FH+ adolescents showed stronger functional connectivity between the right lateral OFC seed and anterior cingulate cortex compared to FH- adolescents (p < 0.05, corrected). Compared to FH-, FH+ adolescents showed stronger negative functional connectivity between the left lateral OFC seed and right postcentral gyrus and between the left NAcc seed and right middle occipital gyrus (p < 0.05, corrected). Poorer emotion regulation was associated with more negative connectivity between right occipital/left NAcc among FH+ adolescents based on the seed-based analysis. FH- adolescents had stronger negative functional connectivity between ventral attention/salience networks and dorsal attention/visuospatial networks in the ICA. Conclusions: Both analytic methods found group differences in functional connectivity between brain regions associated with executive functioning and regions associated with sensory input (e.g., postcentral gyrus, occipital regions). We speculate that families densely loaded for SUD may confer risk by altered neurocircuitry that is associated with emotion regulation and valuation of external stimuli beyond what would be explained by externalizing psychopathology alone.
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    Global white matter microstructural abnormalities associated with addiction liability score in drug naïve youth
    (Springer Nature, 2018-02) Hulvershorn, Leslie; Hummer, Tom; Wu, Yu-Chien; Tarter, Ralph; Rea, Parker; Anand, Amit; Andrew Chambers, R.; Finn, Peter; Psychiatry, School of Medicine
    Abnormalities in brain white matter (WM) structure have been reported in youths having a family history of substance use disorders (SUDs). It was hypothesized that these abnormalities constitute features of the liability for SUDs transmitted across generations. The association between severity of intergenerational risk for SUD, measured by the Transmissible Liability Index (TLI), and white matter microstructure was examined. Diffusion tensor imaging (DTI) measured WM microstructure in forty-four drug-naïve 10-14 year-olds (N = 19 with parental SUD). Metrics of WM microstructure (i.e., fractional anisotropy, radial diffusivity, mean diffusivity and axial diffusivity) were quantified across the whole brain and in four tracts of interest: anterior corona radiata, superior and inferior longitudinal fasciculi and superior fronto-occipital fasciculi. The TLI was completed by the youths, their parents and, when available, their teachers. The relationship between WM structure and TLI score across the entire group was evaluated using linear multiple regression and between group comparisons were also examined. Fractional anisotropy and radial diffusivity in multiple tracts across the brain were significantly associated with TLI scores. Confirming and extending prior research, the findings indicate that global atypicality in WM tracts was linearly related to liability for eventual SUD development in drug naïve youths.
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    Neural activation during risky decision-making in youth at high risk for substance use disorders
    (Elsevier, 2015-08-30) Hulvershorn, Leslie A.; Hummer, Tom A.; Fukunaga, Rena; Leibenluft, Ellen; Finn, Peter; Cyders, Melissa A.; Anand, Amit; Overhage, Lauren; Dir, Allyson; Brown, Joshua; Department of Psychiatry, IU School of Medicine
    Risky decision-making, particularly in the context of reward-seeking behavior, is strongly associated with the presence of substance use disorders (SUDs). However, there has been little research on the neural substrates underlying reward-related decision-making in drug-naïve youth who are at elevated risk for SUDs. Participants comprised 23 high-risk (HR) youth with a well-established SUD risk phenotype and 27 low-risk healthy comparison (HC) youth, aged 10-14. Participants completed the balloon analog risk task (BART), a task designed to examine risky decision-making, during functional magnetic resonance imaging. The HR group had faster reaction times, but otherwise showed no behavioral differences from the HC group. HR youth experienced greater activation when processing outcome, as the chances of balloon explosion increased, relative to HC youth, in ventromedial prefrontal cortex (vmPFC). As explosion probability increased, group-by-condition interactions in the ventral striatum/anterior cingulate and the anterior insula showed increasing activation in HR youth, specifically on trials when explosions occurred. Thus, atypical activation increased with increasing risk of negative outcome (i.e., balloon explosion) in a cortico-striatal network in the HR group. These findings identify candidate neurobiological markers of addiction risk in youth at high familial and phenotypic risk for SUDs.