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Browsing by Author "Oberlin, Brandon"
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Item De-Mixing Decision Representations in Rodent dmPFC to Investigate Strategy Change During Delay Discounting(2023-05) White, Shelby M.; Lapish, Christopher; Czachowski, Cristine; Oberlin, Brandon; Seamans, JeremySeveral pathological disorders are characterized by maladaptive decision-making (Dalley & Robbins, 2017). Decision-making tasks, such as Delay Discounting (DD), are used to assess the behavioral manifestations of maladaptive decision-making in both clinical and preclinical settings (de Wit, Flory, Acheson, Mccloskey, & Manuck, 2007). DD measures cognitive impulsivity and broadly refers to the inability to delay gratification (Hamilton et al., 2015). How decisions are made in tasks that measure DD can be understood by assessing patterns of behavior that are observable in the sequences of choices or the statistics that accompany each choice (e.g. response latency). These measures have led to insights that suggest strategies that are used by the agent to facilitate the decision (Linsenbardt, Smoker, Janetsian-Fritz, & Lapish, 2016). The current set of analyses aims to use individual trial data to identify the neural underpinnings associated with strategy transition during DD. A greater understanding of how strategy change occurs at a neural level will be useful for developing cognitive and behavioral strategies aimed at reducing impulsive choice. The rat dorso-medial prefrontal cortex (dmPFC) has been implicated as an important brain region for recognizing the need to change strategy during DD (Powell & Redish, 2016). Using advanced statistical techniques, such as demixed principal component analysis (dPCA), we can then begin to understand how decision representations evolve over the decision- making process to impact behaviors such as strategy change. This study was the first known attempt at using dPCA applied to individual sessions to accurately model how decision representations evolve across individual trials. Evidence exists that representations follow a breakdown and remapping at the individual trial level (Karlsson, Tervo, & Karpova, 2012; Powell & Redish, 2016). Furthermore, these representational changes across individual trials have previously been proposed to act as a signal to change strategies (Powell & Redish, 2016). This study aimed to test the hypothesis that a ‘breakdown’ followed by a ‘remapping’ of the decision representation would act as a signal to change strategy that is observable in the behavior of the animal. To investigate the relationship between trials surrounding the breakdown and/or subsequent remapping of the decision representation and trials surrounding strategy changes, sequences of trials surrounding the breakdown and/or remapping were compared to sequences of 9 trials surrounding the strategy-change trial. Strategy types consisted of either exploiting the immediate lever (IM-Exploit), delay lever (DEL-Exploit), or exploring between the two lever options (Explore). Contrary to the hypothesis, an overall relationship between breakdown and remapping trial sequences were not associated with change-trial sequences. In partial support of the hypothesis however, at the 4-sec delay when the subjective value of the immediate reward was high, a relationship between breakdown sequence and strategy change sequence was detected for when the animal was exploiting the delay lever (e.g. DEL-Exploit strategy). This result suggests that a breakdown in decision representation may act as a signal to prompt strategy change under certain contexts. One notable finding of this study was that the decision representation was much more robust at the 4-sec delay compared to the 8-sec delay, suggesting that decisions at the 4-sec delay contain more context that differentiate the two choice options (immediate or delay). In other words, the encoding of the two choice options was more dissociable at the 4-sec delay compared to the 8-sec delay, which was quantified by measuring the average distance between the two representations (immediate and delay) on a given trial. Given that Wistar rats are equally likely to choose between the immediate and delay choice alternatives at the 8-sec delay (Linsenbardt et al., 2016), this finding provides further support for current prevalent theories of how animals use a cognitive search process to mentally imagine choice alternatives during deliberation. If context which differentiates choice options at the 8-sec delay is less dissociable, it is likely that the cognitive search process would be equally likely to find either choice option. If the choice options are equally likely to be found, it would be assumed that the choice alternatives would also be equally likely to be chosen, which is what has been observed in Wistar rats at the 8-sec delay.Item Delay discounting and alcohol consumption correlate with dorsal anterior insula activation during choice in non‐treatment‐seeking heavy drinkers(Wiley, 2022) Halcomb, Meredith; Dzemidzic, Mario; Shen, Yitong I.; Lin, Zikai; Butcher, Tarah J.; Yoder, Karmen K.; Oberlin, Brandon; Radiology and Imaging Sciences, School of MedicineBackground The anterior insular cortex (AIC), a prominent salience network node, integrates interoceptive information and emotional states into decision-making. While AIC activation during delay discounting (DD) in alcohol use disorder (AUD) has been previously reported, the associations between AIC activation, impulsive choice, alcohol consumption, and connectivity remain unknown. We therefore tested AIC brain responses during DD in heavy drinkers and their association with DD performance, alcohol drinking, and task-based connectivity. Methods Twenty-nine heavy drinkers (12 females; 31.5±6.1 years; 40.8±23.4 drinks/week) completed a DD task during functional MRI. Regions activated during delay discounting decision-making were tested for correlations with DD behavior and alcohol drinking. Psychophysiological interaction (PPI) models assessed task-dependent functional connectivity (FC) of activation during choice. Results DD choice activated bilateral anterior insular cortex, anterior cingulate cortex, and left precentral gyrus. Right dorsal (d) AIC activation during choice negatively correlated with discounting of delayed rewards and alcohol consumption. PPI analysis revealed FC of right dAIC to both anterior and posterior cingulate cortex (PCC)—key nodes in the midline default mode network. Conclusions Greater dAIC involvement in intertemporal choice may confer more adaptive behavior (lower impulsivity and alcohol consumption). Moreover, salience network processes governing discounting may require midline default mode (precuneus/PCC) recruitment. These findings support a key adaptive role for right dAIC in decision-making involving future rewards and risky drinking.Item Delay Discounting in At-Risk Preadolescents: Brain Mechanisms and Behavior(2021-12) Butcher, Tarah J; Oberlin, Brandon; Lapish, Christopher; Hulvershorn, LeslieIt is well documented that adolescent substance use is associated with deficits in brain function and behavior. However, possible deficits that predate substance use initiation remain poorly characterized in preadolescents at-risk for developing substance use disorder (SUD). To characterize potential brain and behavioral differences that predate substance use, substance naïve preadolescents, ages 11–12, were recruited into three groups to complete functional magnetic resonance imaging delay discounting: (1) High-risk youth (n=35) with a family history of SUD and externalizing psychiatric disorders, (2) psychiatric controls (n=35) with no family history of SUD, but equivalent externalizing psychiatric disorders as high-risk youth, and (3) healthy controls (n=29) with no family history of SUD and minimal psychopathology. While no behavioral differences between groups were identified, there were group differences in posterior cingulate cortex (PCC) function during decision making. Specifically, the high-risk group showed stronger deactivation of the PCC than healthy controls. These results suggest that high-risk preadolescents may need to suppress activity of key nodes of the default mode network (a task negative network) to a greater extent to properly allocate attention to the task.Item Effects of Abstinence in Early Addiction Recovery on Functional Brain Networks and Behaviors(2024-05) Shen, Yitong; Oberlin, Brandon; Cyders, Melissa; Dzemidzic, MarioBackground: Alcohol use disorder (AUD) poses negative health and social consequences, and is costly to affected individuals, loved ones, and society (Whiteford et al., 2013). It is a chronic neuropsychiatric disorder, associated with impaired decision making and altered functional connectivity patterns in the brain. Many studies have shown changes in the brain and behaviors after sustained abstinence using within-participant design or between-participant design comparing participants in recovery versus healthy controls (Muller & Meyerhoff, 2021; Wilcox et al., 2019). The purpose of this study was to investigate brain differences between participants in recovery and participants who are actively drinking. Specifically, this study evaluated within- and between-network resting-state functional connectivity (rsFC) strengths in the context of the triple network model, which focuses on three key networks for complex perceptual, emotional and behavior processing as well as introspection, theory of mind and self-awareness; the salience network (SN), the central executive network (CEN), and the default mode network (DMN) (Menon, 2019). Moreover, this study assessed the relationship between impulsive choices in temporal decision-making and changes in resting-state functional connectivity patterns in these networks. Methods: This study included two groups: the Recovery Group and the Drinking Group. The Recovery Group included participants who were starting recovery (within one year), met AUD diagnosis criteria or showed lifetime heavy drinking behaviors during a 12-month period, received treatment for substance use disorder for alcohol and/or illicit drugs, and showed ongoing intentions and efforts to maintain recovery (n=18, 6 females, mean age=32.4±7.4, 17 White, mean years of education=14.5±3.1, average days of abstinence prior to interview days=78.2±45.7). The Drinking Group included participants who were currently drinking that met diagnosis criteria for AUD or showed heavy drinking behaviors (n=49, 24 females, mean age=31.7±6.4, 29 White, mean years of education=13.6±2.3). Participants underwent an initial screen day where structured interviews were conducted to evaluate the number of lifetime AUD criteria and prior drinking patterns. On the study day, participants completed computer tasks and questionnaires prior to their functional Magnetic Resonance Imaging (fMRI) sessions. Participants in the Recovery Group received a virtual reality (VR) intervention targeting future self-continuity where they interacted with avatars that are versions of themselves (present self and future selves in recovery and relapsed) prior to MRI sessions. All participants completed baseline Delay Discounting (DD) to measure intertemporal choice preferences prior to the fMRI sessions and prior to the VR intervention for the Recovery Group. Results: This study did not find any significant differences in within- and between-network rsFC strength of regions of interest of this study within the triple networks between participants in recovery and those who were actively drinking. The study found that participants in recovery showed a greater preference for delayed rewards (measured by DD task) compared to participants who are actively drinking. Additionally, measures of self-reported impulsivity and impulsive decision-making were associated with resting state functional connectivity (rsFC) strength between regions within the Salience Network (SN), and between the SN and Central Executive Network (CEN). Specifically, baseline delayed reward preference was positively associated with the rsFC between two SN hubs: left dorsal anterior insula (dAIC) and dorsal anterior cingulate cortex (dACC). The rsFC between the left dACC (SN) and dorsolateral prefrontal cortex (dlPFC; CEN) negatively associated with subscales (including negative urgency, lack of perseverance, and lack of premeditation) of self-reported impulsivity measured by the Urgency-Premeditation-Perseverance-Sensation Seeking-Positive Urgency (UPPS-P) impulsive behavior scale. Together, these results suggested that there was an emerging pattern where enhanced the rsFC strength in these regions associated with higher impulsive tendencies. The exploratory analysis showed that the rsFC strength between the right precuneus and ventromedial prefrontal cortex (vmPFC) was related to abstinence length in participants in recovery. Conclusions: These findings indicated that participants in recovery exhibited higher delayed reward preference compared to participants who were actively drinking, alongside a significant relationship between measures of impulsivity and the rsFC within the SN and between the SN and CEN. These results highlighted the importance of the SN and its dynamic interaction with the CEN in self-reported impulsivity and impulsive decision making in addiction. Additionally, this study found that within-network functional connectivity strength in the DMN was related to abstinence length, suggesting that repairment in the rsFC strength within DMN might be integral to the process of addiction recovery.