Although it is well-established that animals will self-stimulate electric current to various diverse brain structures, the neural substrate of brain stimulation reward (BSR) has eluded identification since its discovery more than a half-century ago. We show that GABA neurons in the midbrain, hypothalamus and thalamus express connexin-36 (Cx36) gap junctions and couple electrically with dopamine application or by stimulation of the internal capsule (IC), which also supports self-stimulation. The threshold for responding for self-stimulation of the IC is the threshold for coupling between these GABA neurons, the degree of responding for IC ICSS is proportional to the magnitude of electrical coupling between these GABA neurons, and GJ blockers, including the Cx36 blocker mefloquine, increase the threshold for IC self-stimulation without affecting performance. Thus, electrical coupling between this network of GABA neurons fits the prevailing model for the elusive integrator of BSR.

The purpose of this thesis project was to examine the function of connexin-36 (Cx36) gap junctions (GJs) in producing alcohol's intoxicating and rewarding effects. GABA neurons are thought to inhibit dopamine (DA) neurotransmission in the mesocorticolimbic system, which originates in the midbrain ventral tegmental area (VTA) and projects to limbic structures such as the nucleus accumbens (NAcc). The mesolimbic DA system is believed to be the neural substrate of alcohol intoxication and addiction (Tepper, Paladini, & Celada, 1998). Alcohol suppresses the firing rate of GABA neurons in the VTA (Gallegos, Criado, Lee, Henriksen, & Steffensen, 1999) and presumably disinhibits DA neurons thereby resulting in enhanced release of DA in the NAcc. Interestingly, VTA GABA neurons appear to form part of a larger syncytium of GABA neurons in the reticular formation that are linked by electrical synapses via Cx36 GJs (Allison, et al., 2006; Stobbs, et al., 2004; Lassen, et al., 2007). Gap junction blockers, including the Cx36-selective antagonist mefloquine, also suppress the excitability and electrical coupling of VTA GABA neurons (Stobbs, et al., 2004). Thus, I hypothesized that Cx36 GJs cause synchrony in VTA GABA neurons which alcohol blocks to cause intoxication and reward. To accomplish these studies I compared the effects of intoxicating doses of ethanol in Cx36 knockout (KO) mice and mefloquine-treated mice and their wild-type (WT) controls with two tests that index ataxia, an open field activity system and the fixed-speed rotarod apparatus, as well as with ethanol self-administration. I found that Cx36 KO and mefloquine-treated mice exhibit significantly more ethanol-induced loss of movement in the open field test, a paradigm which indexes gross motor activity and tremor, but less ataxia than their WT controls in the rotarod paradigm, a paradigm which indexes balance and coordination. Most importantly, both Cx36 KO and mefloquine-treated mice consumed less ethanol than their controls. These findings provide evidence in support of the hypothesis that Cx36 GJs are important targets for ethanol effects in the mesolimbic system.

Although the cerebellum has been traditionally thought of as a motor processing brain region, recent evidence suggests that the cerebellum is functionally diverse. The posterior cerebellum in particular has been shown to play a role in social cognitive processes, and recent work has proposed that this region helps fine tune mental models of social cognition to, for example, to ensure accurate selection of actions in a social scenario. Social interactions with strangers are difficult, in part because we are constantly trying to gauge whether the other person likes or dislikes us without much information for our mental models to help us. From a reward processing standpoint, this requires tracking the value (positive or negative) of people’s valence to us and ensuring that our predictions about people’s affect towards us are correct. The aim of this project was to specify how the posterior cerebellum uniquely contributes to social reward processing, and to distinguish this contribution from regions that are canonically part of the reward and social brain regions. Participants, ages 12-36, completed a well-matched social and monetary reward task in the scanner. In the monetary condition, participants were asked to select which of two doors would result in winning money, and in other trials losing money. In the social condition, participants were asked to select which of two faces representing people would like or dislike them. Representational similarity analysis was used to compare the responses of reward and social brain regions to conditions in which participants either won or lost money and were either liked or disliked by others. We found that portions of the posterior cerebellum were sensitive to social reward, and treated positive social rewards more similarly to negative social rewards than the striatum. These results suggest that these regions in the posterior cerebellum has a dissociable contribution to social reward processing compared to other brain regions. / Psychology

This research delves into the intricate dynamics of customer incentivization in company outreach, exploring the impact of incentives on consumer behavior. The study reveals a compelling connection between consumer opinions on monetary incentives and their actual responsiveness, emphasizing the need for strategic incentive-based programs. Theoretical frameworks, including regression analysis and Spearman's rank coefficient, are introduced for statistical analysis. Hypotheses posit a correlation between incentives and customer response, and the superior influence of altruistic motivations. The study employs a cross-sectional design utilizing Amazon MTurk workers,  Results indicate positive responses to company outreach, supporting the positive impact of incentives. Altruistic motivations significantly correlate with consistent engagement, but so does extrinsic motivations.

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Executive functioning (EF) deficits may be associated with depressed states, although limited research has examined components of EF as endophenotypes of depression. This study assessed whether affective updating predicted depressive symptoms in a sample pre-selected for varying levels of depression via the affective n-back. In this task, participants determine whether the valence of a stimulus matches the valence of the stimulus presented two stimuli prior. Results suggested affective updating ability did not significantly predict depressive symptoms approximately over time, although higher accuracy in updating negative information was associated with more depressive symptoms approximately twelve weeks later. Moreover, accuracy in updating positive and negative information did not differ between groups. However, a trend emerged for depressed participants to be more accurate in updating negative information in the face of interfering positive information, compared to updating positive information with interfering negative information. The latter results are considered within the reward devaluation framework.

A primary symptom of depression is anhedonia, or the loss of interest or pleasure. Anhedonic individuals can have deficits in anticipatory pleasure (‘wanting’ things) or consummatory pleasure (‘liking’ things). Depressed individuals generally have deficits in anticipatory but not consummatory pleasure. A possible buffer against anticipatory anhedonia is action orientation, or the ability to upregulate positive affect in pursuit of goals when stressed. To examine the relationship between stress, action/state orientation, and anhedonia, highly anhedonic individuals who were either action- or state-oriented underwent a demanding mood induction, and completed the Effort-Expenditure for Reward Task, a measure of motivation for reward. Evidence did not support action orientation as a buffer; however, individuals who showed fluctuation in self-reported motivation were less motivated to work for reward. Evidence emerged suggesting that fluctuation in motivation over time may predict less willingness to work. Future research can examine the relationship between variability in motivation and depression.

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