Browsing by Author "Kareken, David"
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Item THE EFFECT OF ETHANOL ON IMPULSIVITY IN HIGH ALCOHOL PREFERRING MICE(2010-07-21T20:19:33Z) Oberlin, Brandon G.; Grahame, Nicholas; Fetterman, J. Gregor; Kareken, David; McBride, William J.Impulsivity is associated with addiction in many human studies. Delay discounting (DD) is often used to measure impulsive choice in humans and animals. In DD testing, a small immediate reward is pitted against a larger delayed reward, and relative preference is assessed. The relative contribution of ethanol to impulsivity in alcoholism is not well-understood, therefore I will test the hypothesis that ethanol exposure will increase impulsivity in High Alcohol Preferring (HAP) mice as measured in an adjusting amount DD task. Selectively bred HAP mice were exposed to ethanol and tested in DD in 3 different experiments. Experiment 1: ad lib homecage ethanol drinking for 21 days and 17 days were used to expose mice to ethanol. Additionally, mice were tested in DD while “currently drinking” vs. “abstinent”. In experiment 2, to achieve higher blood alcohol concentrations, mice were injected with 3.5 g/kg ethanol 8 times and tested before and after in DD. In both experiments 1 and 2, mice were tested at only 2 delays (0.5 sec and 10 sec), to maximize sensitivity to detect shifts in choice behavior. In experiment 3, mice responded for 8% ethanol or 0.01% saccharin at a full range of delays: 0, 1, 2, 4, and 8 sec. Experiment 1 did not reveal any impact of ethanol drinking on impulsivity. Experiment 2 revealed a strong trend of reduced impulsivity in the 10 sec delay group after ethanol injections. Experiment 3 revealed reduced impulsivity at the 8 sec delay in the group responding for ethanol, and also revealed a significant correlation between higher ethanol drinking and reduced impulsivity. These data were unexpected, and imply that the a priori hypothesis not only should be rejected, but that the opposite hypothesis may be true: ethanol decreases impulsivity, at least with high dose exposure and in responding for it as a reinforcer. This effect was similar to the effect observed in other studies with amphetamine, which consistently decreases impulsivity. Ethanol may have been exerting an amphetamine-like effect on impulsivity at the doses tested here. There is no evidence in the data generated in these studies that ethanol increases impulsivity.Item A morphospace of functional configuration to assess configural breadth based on brain functional networks(MIT Press, 2021-09) Duong-Tran, Duy; Abbas, Kausar; Amico, Enrico; Corominas-Murtra, Bernat; Dzemidzic, Mario; Kareken, David; Ventresca, Mario; Goñi, Joaquín; Neurology, School of MedicineThe quantification of human brain functional (re)configurations across varying cognitive demands remains an unresolved topic. We propose that such functional configurations may be categorized into three different types: (a) network configural breadth, (b) task-to task transitional reconfiguration, and (c) within-task reconfiguration. Such functional reconfigurations are rather subtle at the whole-brain level. Hence, we propose a mesoscopic framework focused on functional networks (FNs) or communities to quantify functional (re)configurations. To do so, we introduce a 2D network morphospace that relies on two novel mesoscopic metrics, trapping efficiency (TE) and exit entropy (EE), which capture topology and integration of information within and between a reference set of FNs. We use this framework to quantify the network configural breadth across different tasks. We show that the metrics defining this morphospace can differentiate FNs, cognitive tasks, and subjects. We also show that network configural breadth significantly predicts behavioral measures, such as episodic memory, verbal episodic memory, fluid intelligence, and general intelligence. In essence, we put forth a framework to explore the cognitive space in a comprehensive manner, for each individual separately, and at different levels of granularity. This tool that can also quantify the FN reconfigurations that result from the brain switching between mental states.Item The relationship between trait impulsivity and alcohol related attentional biases(2015-05-08) Coskunpinar, Ayca; Cyders, Melissa A.; Stewart, Jesse; Kareken, David; Rand, KevinHarmful alcohol use is a global concern, which has made research in this area a prime public health interest. Previous research has identified alcohol-related attentional biases (Cox et al., 2002, 2007; Marissen et al., 2006; Streeter et al., 2008) and impulsivity (see Acton, 2003; Dick et al., 2010; Mulder, 2002) as two important predictors that affect alcohol use, seeking, and relapse (Cox et al., 2002; Robbins & Ehrman, 2004). Recent review of the literature has also revealed that there is a significant relationship between these two constructs (Coskunpinar & Cyders, 2013). The current study used college undergraduate social drinkers (at least 3 drinks per week) (n = 42, mean age = 23.27 (SD = 5.21), female: 69.2%) to examine the relationship between specific trait impulsivity facets and alcohol-related attentional biases and to examine how this relationship is affected by measurement type (eye movement, reaction time measures), attentional bias constructs (initial orientation, delayed disengagement), and environmental cues (specifically mood and alcohol olfactory cues). Participants had alcohol-related attentional bias as measured by reaction time (areas of interest: p < .05) and eye-movement data (areas of interest: p < .05), which was not affected by mood, odor, or urgency.Item Tangent functional connectomes uncover more unique phenotypic traits(Elsevier, 2023-08-12) Abbas, Kausar; Liu, Mintao; Wang, Michael; Duong-Tran, Duy; Tipnis, Uttara; Amico, Enrico; Kaplan, Alan D.; Dzemidzic, Mario; Kareken, David; Ances, Beau M.; Harezlak, Jaroslaw; Goñi, Joaquín; Neurology, School of MedicineFunctional connectomes (FCs) containing pairwise estimations of functional couplings between pairs of brain regions are commonly represented by correlation matrices. As symmetric positive definite matrices, FCs can be transformed via tangent space projections, resulting into tangent-FCs. Tangent-FCs have led to more accurate models predicting brain conditions or aging. Motivated by the fact that tangent-FCs seem to be better biomarkers than FCs, we hypothesized that tangent-FCs have also a higher fingerprint. We explored the effects of six factors: fMRI condition, scan length, parcellation granularity, reference matrix, main-diagonal regularization, and distance metric. Our results showed that identification rates are systematically higher when using tangent-FCs across the “fingerprint gradient” (here including test-retest, monozygotic and dizygotic twins). Highest identification rates were achieved when minimally (0.01) regularizing FCs while performing tangent space projection using Riemann reference matrix and using correlation distance to compare the resulting tangent-FCs. Such configuration was validated in a second dataset (resting-state).Item Tangent space functional reconfigurations in individuals at risk for alcohol use disorder(ArXiv, 2024-05-24) Moghaddam, Mahdi; Dzemidzic, Mario; Guerrero, Daniel; Liu, Mintao; Alessi, Jonathan; Plawecki, Martin H.; Harezlak, Jaroslaw; Kareken, David; Goñi, Joaquín; Neurology, School of MedicineHuman brain function dynamically adjusts to ever-changing stimuli from the external environment. Studies characterizing brain functional reconfiguration are nevertheless scarce. Here we present a principled mathematical framework to quantify brain functional reconfiguration when engaging and disengaging from a stop signal task (SST). We apply tangent space projection (a Riemannian geometry mapping technique) to transform functional connectomes (FCs) and quantify functional reconfiguration using the correlation distance of the resulting tangent-FCs. Our goal was to compare functional reconfigurations in individuals at risk for alcohol use disorder (AUD). We hypothesized that functional reconfigurations when transitioning in/from a task would be influenced by family history of alcohol use disorder (FHA) and other AUD risk factors. Multilinear regression model results showed that engaging and disengaging functional reconfiguration were driven by different AUD risk factors. Functional reconfiguration when engaging in the SST was negatively associated with recent drinking. When disengaging from the SST, however, functional reconfiguration was negatively associated with FHA. In both models, several other factors contributed to the explanation of functional reconfiguration. This study demonstrates that tangent-FCs can characterize task-induced functional reconfiguration, and that it is related to AUD risk.