Motivation and emotion/Book/2019/Ventral tegmental area and motivation and emotion

The Ventral Tegmental Area and motivation and emotion:
What role does the VTA play in motivation and emotion?

Multimedia presentation (3 min)

Overview

Our motivational and emotional lives are processed by underlying neurophysiological processes, which activate specific neural pathways, largely involving the brain's reward circuit (Trutti et al., 2019). It is imperative that we describe the human connectome in a comprehensive manner, in order to understand how we can willingly make changes to the way we generate behavioural action, and improve our regulatory capacities. For example, the Ventral Tegmental Area (VTA) is a complex neuroanatomical region which is involved in the production and release of a few neurotransmitters, including the neuro-excitatory dopamine, which is involved in associative learning of reward and aversion predictive errors (Holly & Miczek, 2016). Associative learning theories, such as conditioning, may explain the rise of motives and internal states, such as emotions, that shape our interpretation of the environment and adjust our external behaviour accordingly.

But, how does specific neural action facilitate motivated action? How is behaviour reinforced by it? Can we regulate our emotions? How can we improve our motivational and emotional lives using insights from neuroscience and psychology? This book chapter will explore themes related to the VTA, in an effort to offer empirically gathered answers, which contribute to our understanding of motivational and emotional processes.

Focus questions What is the Ventral Tegmental Area? What is the role of dopamine in the neurophysiological reward circuit? What role does the VTA play in motivational and emotional processes? How can use neuroscientific findings to improve our motivational and emotional lives?

Neuroscientific background

Developing a comprehensive delineation of the brain’s anatomical structures and connections is crucial for understanding brain function, and evaluating cognitive processing and behaviour (Beier et al., 2019).  Researchers have been mapping out defined connections using many tracing techniques and approaches from molecular biology (Beier et al., 2019), in order to contribute to the database of the Human Connectome Project (Coenen et al., 2018). The classic techniques employed for studying brain connectivity, usually involve injection of different traceable molecules into anatomical areas which are clearly defined (Beier et al., 2019). The term ‘clearly defined anatomical area’ refers to a specific region of the brain, that is comprised of only one type of neuronal cells, which have a closely related function (Holly & Miczek, 2016), meaning that that specific area is homogenous, and the connections are easily traced.

Figure 1. Image depicting the hemispheres in the human brain

However, the human brain is comprised of many heterogenous areas, such as the VTA (Holly & Miczek, 2016), in which a few different cell types are involved. This specific region has sparked neuroscientific interest since its discovery, especially since it requires innovative techniques to be explored molecularly (Beier et al., 2019). In fact, the first topological map of the VTA, which uses genetic tracing techniques, was revealed only revealed in 2019. Beier et al. (2019) used a novel monosynaptic input-tracing technique to examine the connectivity between the different cell types in the VTA. This technique had never been used in such a manner before, but its functionality paves the way for further exploration of brain function. Nevertheless, even before this development, researchers had accurately described the location and general function of the VTA, as a key component involved in many cognitive functions, such as, reward-based and associative learning, motivation, memory, emotion and cognitive control in decision-making, as well as in motor function (Trutti et al., 2019). Clearly, vast research has been conducted in order to implicate this structure in human behaviour, which demonstrates that it is important to consider the basic physiological mechanisms involved in our daily functioning. This could provide a framework for developing self-guided regulatory techniques, which can increase our motivation and emotional regulation.

Ventral Tegmental Area

Figure 2. Cross-section of the human brain showing the dopamine-based reward system

The brain has a dopaminergic system that is involved in processing information related to cognitive and motor functioning, and executes these functions by transmitting messages using the neurotransmitter dopamine (Trutti et al., 2019).  There are two pathways implicated in this system; the nigrostriatal and mesocorticolimbic pathways (Trutti et al., 2019). The nigrostriatal pathway is comprised of dopamine-based neurons spanning from the substantia nigra pars compacta (SNc) to the dorsal striatum, and it is part of the basal ganglia loop (Trutti et al., 2019). The mesocorticolimbic pathway covers both mesolimbic and mesocortical structures, in which projections from the VTA communicate with the nucleus accumbens (NAcc) in the ventral striatum, and the prefrontal cortex (PFC) (Trutti et al., 2019). When investigating the mesocorticolimbic pathway, neuroscientists infer implications concerning cognition and motivation, as this pathway has been identified as having the most associated behavioural heterogeneity (Trutti et al., 2019).

The ventral tegmental area (VTA) represents a pair of small circular nuclei-looking structures comprised of tightly clustered neurons, located close to the midline of the mesencephalon, or simply put, sitting on the floor of the ventral midbrain region (Zhang et al., 2018). The VTA is a heterogenic structure, comprised of 50-80% dopaminergic neurons, 30% GABAergic, 5% glutamatergic and some combinatorial neurons (Trutti et al., 2019). Dopaminergic neurons produce and release the chemical neurotransmitter dopamine, GABAergic ones produce GABA which stimulates or inhibits neurotransmission, and glutamatergic produce the excitatory neurotransmitter glutamate (Holly & Miczek, 2016). These neurons are interconnected but heterogeneously distributed in the VTA (Zhang et al., 2018), which is why the boundaries of this area are still a matter of debate (Trutti et al., 2019). Neurobiologists refer to the VTA as a region rather than a nucleus with clearly defined boundaries, because the transition in distribution from one type of cells to another is gradual (Trutti et al., 2019). This indicates that the VTA has substantial functional complexity. Furthermore, the delineation of the VTA is hindered by the lack of consensus regarding the region’s nomenclature, namely whether the whole region is one localized structure called the VTA, or the region ‘VTA’ is comprised of individual distinct subsections with unique locations (Trutti et al., 2019). Naturally, this would imply that there are many different published definitions regarding the exact size and shape of the VTA, as well as that it is difficult to compare and replicate studies, and pinpoint exact functional neuronal properties and their respective implications in behaviour and cognition. Moreover, historically functional live-brain VTA examinations have been done using animals (Trutti et al., 2019). Only recently have neuroimaging and genetic techniques advanced sufficiently to be able to examine the live human VTA (Trutti et al., 2019). Regardless of numerous conflicting contingencies surrounding the VTA, many studies have outlined its general function and psychosocial associations. Apropos that, the VTA is currently considered to be a key element in the dopaminergic mesocorticolimbic pathway, a critical part of the brain’s reward circuitry responsible for associative learning (Holly & Miczek, 2016).The majority of VTA activity is associated with the dopaminergic neurons which produce and release dopamine to other areas of the reward circuitry (Beier et al., 2019).

Role of the VTA in motivation

Psychology of motivation

Figure 3. Table outlining some motivation related processes.

Psychology broadly describes motivational processes as those which drive human behaviour to the external world (Albertos & Barberá, 1996). Motivational science examines the antecedents or actuators of any motivated action, in terms of underlying internal processes, such as, cognitions, emotions, goal achievement and need satisfaction, which energize, command and sustain behaviour (Reeve, 2018). Several theoretical approaches explain these concepts and the underlying mechanisms which give rise to motives for external action. One crucial behavioural theory describes the rise and sustainability of behaviour as conditioned processes, or learned responses due to rewards or punishments (Cohen, Haesler, Vong, Lowell & Uchida, 2012). Several types of conditioning have been described and researched, such as, classical, operant and differential conditioning, however, all postulate that learning of behaviours occurs due to mind-based associations between antecedents, behavioural action and consequences of said action (Cohen, Haesler, Vong, Lowell & Uchida, 2012). Associative learning then implies that some kind of neurophysiological process occurs and encodes the aforementioned contingencies, which results in motivated action. Various human neuroimaging and animal studies have found that mesolimbic and cortical structures are involved in reward and aversion processing (Beier et al., 2019), so it is important to consider some mechanisms by which our neurophysiology modulates our decisions and motivated actions.

VTA and dopamine

Figure 4. Diagram depicting dopamine pathways in the brain

Dopamine is an important neurotransmitter which has a central role in motivation and reward cognition (Cohen, Haesler, Vong, Lowell & Uchida, 2012). The VTA’s neurotransmitter release is mostly dopaminergic, and subsequently has an excitatory function on the mesocorticolimbic pathway, which stimulates subjective rewarding feelings (Beier et al., 2019). Several studies have outlined the general implications of the VTA’s dopaminergic activity. For example, Arsenault, Rima, Stemmann and Vanduffel (2014) have described how the VTA regulates stimulus-specific reinforcement and motivation, and how this output modulates the whole brain-based reward circuitry in primates. The researchers conducted three experiments using MRI-based chronic electrical microstimulation of the VTA. They designed a free-choice task based on the operant conditioning paradigm, in which monkeys responded to visual cues by choosing one preference. 50% of the responses were rewarded positively with juice, which was expected to induce positive reinforcement of the visual-cue-choosing behaviour. After establishing a baseline for preference indexes and cue selection, they employed electrical micro-stimulation of the VTA, using directly placed electrodes, during every rewarded trial of cue selection. They found that the cue preference indexes were higher after stimulating more dopamine release from the VTA, with correlation coefficients p < 0.05 for both test subjects, and subsequently that the preferences remained consistent once the reward was removed or altered, which indicated that reinforcement, or associative learning, had occurred. The second experiment was similarly designed using classical conditioning. The overall results suggest that the monkeys were motivated to choose a specific cue because they expected a reward. Using fMRI, it was also observed that the VTA’s dopamine release affected the activity of further structures in the dopaminergic system. The findings suggest a mechanism by which the VTA modulates the reward circuit by broadcasting signals of prediction errors. Prediction errors refer to the discrepancy between actual and expected rewards (Cohen, Haesler, Vong, Lowell & Uchida, 2012). This means that when motivational value was assigned to specific visual cues, the behavioural preference for those cues was modulated by activity of the dopaminergic neurons in the VTA. Comparable results were obtained in another similarly-designed conditioning study using rodents and motivation for seeking out pleasurable odours (Cohen, Haesler, Vong, Lowell & Uchida, 2012). Using neuroimaging techniques it was observed that all the dopaminergic neurons from the rodent VTA engaged in phasic excitatory activity after conditioning, consistent with reward prediction error coding.

Although electro-stimulating studies cannot provide causal relationships between neuronal activity and external behavioural action, because they require artificial alterations of neuronal activity, correlational and observational examination of data suggests that the reward-based properties arise from the VTA. That being said, the two aforementioned studies provide a causal framework which should be examined further, considering that the rewards and electrostimulation were completely independent from the choice of cue, and the reward circuit was observed after establishing a conditioned response. Nevertheless, implications can be drawn regarding human neuronal activity. By activating the mesocorticolimbic pathway, the brain might process actual or perceived rewards with the release of dopamine, and stimulate behavioural action which aims to satisfy that motive. This notion would indicate that we are motivated to engage in certain behaviours driven by actual or expected rewards. For example, we might be motivated to put effort into completing an assignment because we expect a good mark in that unit. In terms of self-help strategies, understanding this physiological process can help us improve our motivation towards everyday productive behaviours, simply by intentionally adding some rewarding consequence to them. Once the associations have been learned by the brain, we can then expect to engage in that specific behaviour simply because the motivation has become innate to the brain. But, this raises an important question; how does reward anticipation generate a sustainable motive over time which ensures prolonged engagement in a behaviour?

Encoding of pleasure

One explanation is that the reward generates feelings of pleasure, which in turn motivate us to engage in the behaviour which first produced the hedonic sensation, in order to replicate the effects over and over again (Salamone & Correa, 2012). This is a neurophysiologically plausible explanation, as the effects of dopamine have been noted to modulate hedonic experiences (Salamone & Correa, 2012). Subsequently, research involving the VTA supports the involvement of the mesocorticolimbic reward-based pathway in the subjective experience of pleasure (Salamone & Correa, 2012). A review of the literature on the neurological representations of pleasure and displeasure, as well as the causation of pleasure or ‘liking’ in the brain, outlines the mechanisms involving the VTA (Berridge & Kringelbach, 2012). The hedonic quality of pleasure has been observed to involve the activation of a few cortical and subcortical regions from the brain-based reward system, most notably the nucleus accumbens (NAcc) (Berridge & Kringelbach, 2012). Studies have shown that dopaminergic projections from the VTA are released into the NAcc, which is in turn activated when pleasure or liking is experienced (Beier et al., 2019). The NAcc is considered to be the ‘pleasure hotspot’ (Salamone & Correa, 2012), so the VTA has an important function in modulating its activity by producing and releasing excitatory dopamine.

So if dopamine is the chemical culprit of pleasure, then what exactly is pleasure? Well, the reward circuit involves three key neuropsychological elements, which play a unique role in optimizing the brain’s resources required for evolutionary survival, including initiation, sustainability and alteration of behaviour in an adaptive way (Berridge & Kringelbach, 2012). Firstly, the hedonic affect of pleasure has to be present (‘liking’), followed by motivation or incentive to obtain a reward (‘wanting’), and lastly, reward-related associative learning (Berridge & Kringelbach, 2012), which has been described above. Therefore, experiencing pleasure is never merely just a sensation. For example, the pleasurable experience which arises when we eat something sweet, requires additional input from specialized neural mechanisms, in order to interpret the sweet taste as rewarding, and add to the hedonic impact, or elicit ‘liking’ and 'wanting' which then motivate us further to eat sweets.

Figure 5. Location of nucleus accumbens relative to the VTA

The aforementioned activation of the NAcc explains the initiation of ‘liking’. The second element in the reward circuit is ‘wanting’, or motivation. Well, recent examinations of mesolimbic dopamine indicate that it has an additional mechanism for initiating ‘wanting’, more specifically it is postulated that dopamine mediates the motivational process of incentive salience, or giving a motivational value to something (Berridge & Kringelbach, 2012). For instance, one fMRI study which examined the brain activity of 25 healthy women while viewing different pleasurable images, found that the excitatory function of the NAcc while viewing highly appetizing food, produced intense ‘wanting’ for individual food stuffs which the participants deem appetizing to themselves (Lawrence, Hinton, Parkinson & Lawrence, 2012). While substantial research has implicated activity in the VTA and NAcc in food motivation and hunger satisfaction (Berridge & Kringelbach, 2012; Skibicka, Hansson, Alvarez-Crespo, Friberg & Dickson, 2011), the current study showed that the activation of the mesolimbic areas initiated by the VTA, was not related to the level of hunger during completion of the viewing tasks. These findings suggest that indeed ‘wanting’ or motivational salience is produced and modulated by these structures and dopamine, while creating associations. Furthermore, the researchers asked the participants to complete sets of questions related to food cravings and to record their snack consumption after the task was completed. The responses indicated a significant positive correlation between higher activity in the NAcc during food related cues, and later food consumption. This implies that human brains might have a natural inclination to attribute higher motivational (incentive) salience, or generate ‘wanting’ as a motive, which precedes the seeking-out behaviour to satisfy it. This study uses correlational data which cannot imply causation, the sample size is small and restricted to women, and some measures were obtained from self-reports, which might be biased. Nevertheless, the results contribute novel ideas to research on food motivation and dopaminergic modulation of motive satisfaction.

By these mechanisms, all three components of pleasure are satisfied, and behaviour is motivated to achieve this pleasure. That would imply that the dopaminergic experience of pleasure is by default the reward received after performing a behaviour, which stimulated its release in the brain in the first place. Basically, your brain loves dopamine and wants to feel it constantly. When you engage in something which stimulates dopamine release, the presence of dopamine then motivates you to do the same thing as to keep feeling it’s effects. We could then improve our motivational lives by simulating pleasurable experiences of the activities that we perceive as productive for ourselves, perhaps through initiating a dopaminergic response by rewarding ourselves for engaging in the behaviour.

While on the topic of pleasure stimulated by dopamine, it is important to note that substantial research has focused on psychopathological implications related to its activity. For example, the reinforcing 'liking' and 'wanting' dopaminergic consequences have been researched in relation to addictions (Salamone & Correa, 2012), and subsequently the dysfunction of these mechanisms is being examined in the occurrence of anhedonic symptoms in depression (Small, Nunes, Hughley & Addy, 2016). Although extremely relevant, this book chapter omits the scope of psychopathological implications, in to outline the general motivation and emotional regulation mechanisms initiated by the VTA.

Role of the VTA in emotion

“ "It is worth pointing out that feeling things (which usually means feeling them painfully) is at some level linked to the acquisition of knowledge."
- Alain de Botton ”

Cognitive emotion regulation is an imperative survival feature which allows us to modulate our emotional responses (Mulej Bratec et al., 2015). For example, when you enter your car and surprisingly notice a big spider on the dashboard, this will induce fear, a flight tendency and elevated heart rate. However, when a few seconds later you realize that it is the fuzzy end of a key-chain which you mistakenly thought was a spider, and this is not dangerous for you, the fear will immediately decrease. Neurophysiological processes underlie this example of cognitive emotion processing. For example, the brain activity of areas necessary for experiencing emotions, such as the amygdala, insula and striatum, is significantly reduced, by signals projected from the prefrontal cortex, which are involved in cognitive functions (Mulej Bratec et al., 2015). However, due to the motivational importance of emotions, as motives which guide behaviour, they are able to modify the subjective value of certain stimuli as to promote the formation of associations between the emotion-provoking stimulus and external behaviour (Mulej Bratec et al., 2015). This would imply that mesolimbic brain areas, such as the VTA and NAcc, are involved in the associative learning process, as described previously. Given that associative learning occurs due to prediction errors, and both aversive and reward prediction errors have been observed to underlie activity in the VTA and NAcc (Holly & Miczek, 2016), it is plausible that cognitive emotion regulation is modulated by their dopaminergic activity.

One human neuroimaging research study, examining whether cognitive emotion regulation is response-mediated or learning-mediated, implicated the involvement of the mesocorticolimbic reward circuit involving the VTA (Mulej Bratec et al., 2015). The researchers designed a computer-based classical conditioning experiment, in which conditioned stimuli (coloured shapes) were paired with unconditioned stimuli (pictures depicting an aversive situation), or a blank screen in the unpaired trials, and the participants were instructed to predict when an aversive picture will show up on the screen. Moreover, some of the participants were instructed to use self-distancing techniques when they saw an aversive picture, in order to cognitively evaluate their emotions regarding that picture, or to passively observe the aversive picture. For example, some of the aversive pictures included situations depicting war, famine and natural disasters, for which the participants were instructed to internally tell themselves that those situations do not affect them or their families, the situation is far away from them etc. fMRI was used to observe brain activity during the tasks, while aversive prediction errors were calculated using the Rescorla–Wagner rule, and subsequent behavioural measures of emotion regulation success were recorded by a self-reported scale-rating of the participants’ emotional feeling following each trial. They found a significant interaction between the emotion intensity and self-regulation mechanism (F = 63.95, p < 0.001), and a significant reduction of emotion intensity after cognitive evaluation  (t = 10.779, p < 0.001), indicating that cognitive evaluation and regulation of emotion intensity had occurred. Furthermore, the measures of aversive prediction error indicated that associative learning had also taken place, and fMRI measures outlined the activity of the mesocorticolimbic pathway during task completion. During the cognitive regulation process, emotion-related brain activity was reduced, and aversive prediction error-related phasic firing of dopaminergic neurons in the VTA, hippocampus, insula and striatum increased. Furthermore, the functional activity between the VTA and the PFC substantially increased during the cognitive regulation process. The results suggest that the role of the VTA in the brain is even more heterogenic than previously mentioned, now including implications for cognitive regulation. A subsequent similar study by Mulej Bratec et al. (2017) further confirmed the findings, and added a neurophysiological mechanism by which inferior and superior cognitive regulators activate competing pathways associated with dopaminergic action in the VTA, NAcc and PFC.

Figure 6. Neuropsychological model of motivation processing as described by Mulej Bratec et al. (2017).

The implications provide us with information for understanding how our brains are evolutionarily designed to help us process our outside world. If we understand the mechanisms by which we regulate neurochemically how we experience aversive stress and emotional pressure, we can use that knowledge to increase our productivity and emotional stability. Therefore, it could be useful to employ cognitive self-help regulatory techniques to deal with stressors which impact our external behaviour, for example, using self-distancing regulatory language to reduce affective stress in the workplace. Future research could provide a basis for developing new inferior and superior regulatory tactics as to target specific activity in an appropriate manner according to the situation. The findings from the studies provide a framework for this future research into emotion-regulation processes involving the VTA, more specifically to determine the neurochemical nature between the VTA and phylogenetically older cortical structures, the cognitive regulation of aversive emotions as motivators of behaviour, as well as the implications for psychopathology.

Scenario: self-help regulatory strategy You are given an important task at your corporate workplace, and only two days to complete it. This induces anxious feelings and emotional pressure to complete the task, which keep you in a constant state of stress while you are actively trying to work on the task. You are aware that this is an aversive stimulus, as you keep getting distracted and unable to control your physical expressions of frustration. You must find a way to control your emotions and motivate yourself to focus on the task. Luckily, you recently read an online book chapter which can help you devise a plan. The book chapter suggested that engaging in a self-distancing technique from the task, might help you process your emotions in a regulatory manner. Subsequently, rewarding yourself for smaller task-achievements might motivate you to stay focused on the task. From previous experience, you know that solving a 'Candy Crush' puzzle on your phone helps you relax and distance yourself from the surroundings. It also makes you jittery with excitement when you complete a level on the first try. You decide that every time you complete a section of your work-task, you will complete one level on 'Candy Crush'. This way you get little regulatory breaks, which keep you cognitively active, and you get a reinforcing reward every time you complete a level on the first try, thus motivating you to get back to work and complete the next objective, so that you can beat the next level!

Quiz Time! 1 Which neurons constitute the largest portion of the VTA? GABAergic Dopaminergic Glutamatergic Combinatorial 2 Which anatomical structure is considered to be the pleasure 'hotspot'? Ventral striatum Prefrontal cortex Nucleus accumbens Hippocampus 3 The mesocorticolimbic reward-based pathway involves: substantia nigra pars compacta and dorsal striatum prefrontal cortex and basal ganglia loop the VTA, nucleus accumbens (in the ventral striatum) and prefrontal cortex the nucleus accumbens, amygdala and prefrontal cortex 4 The three components of experiencing pleasure are: liking, wanting and needing hedonic affect, incentive salience and reward-based associative learning pleasing sensation, motivation and emotion pleasurable feeling, motivational value and execution of behaviour

Conclusion

So, can be concluded about the general motivational and emotional processes involving the VTA? The research outlined provides a backbone for understanding our neurophysiological mechanisms which encode these processes. We can generalize that the dopamine based circuit, modulates subjective motives for behaviours, based on reinforcements or punishments. Simply put, the VTA's role in emotion and motivation is to activate a mesocorticolimbic network of neuroactivity (Beier et al., 2019), which responds to external, or possibly even internal, sources of reinforcers which motivate us to achieve or avoid them. By activating mesolimbic structures, the dopaminergic activity of the VTA is related to generating feelings of pleasure (Salamone & Correa, 2012), while during activation of cortical structures, the VTA's activity is related to cognitive regulation processes (Mulej Bratec et al., 2015). By understanding these functions, we can infer that we can choose to modify our emotional and motivated states to suit our predetermined desirable outcomes. Many studies have examined the role of the VTA in various connectome relations, thus this chapter only provides an overview. Researchers must reach a general consensus regarding opposing views of the VTA (Beier et al., 2019) which can subsequently lead to more specific research. Future research can then focus its attention more on psychopathological mechanisms involving the dysfunction of the VTA, the brain's reward-circuit, and impaired cognitive regulation. In general, new findings can help us create novel treatment options, and optimize the existing ones, as well as provide us with innovative self-help strategies which can energize our motivated and emotional brains to pursue their goals to the best of their abilities.

See also

• Motivation and emotion/Book/2017/Positive thinking as a cause of emotional problems
• Motivation and emotion/Book/2018/Anterior cingulate cortex and emotion
• Motivation and emotion/Book/2018/Cognitive dissonance and emotion

References

Albertos, P., & Barberá, E. (1996). Control Structures in Motivational Psychology. IFAC Proceedings Volumes, 29(1), 4527-4532. doi: 10.1016/s1474-6670(17)58395-0

Arsenault, J., Rima, S., Stemmann, H., & Vanduffel, W. (2014). Role of the Primate Ventral Tegmental Area in Reinforcement and Motivation. Current Biology, 24(12), 1347-1353. doi: 10.1016/j.cub.2014.04.044

Beier, K., Gao, X., Xie, S., DeLoach, K., Malenka, R., & Luo, L. (2019). Topological Organization of Ventral Tegmental Area Connectivity Revealed by Viral-Genetic Dissection of Input-Output Relations. Cell Reports, 26(1), 159-167.e6. doi: 10.1016/j.celrep.2018.12.040

Berridge, K., & Kringelbach, M. (2012). Neuroscience of affect: brain mechanisms of pleasure and displeasure. Current Opinion In Neurobiology, 23(3), 294-303. doi: 10.1016/j.conb.2013.01.017

Coenen, V., Schumacher, L., Kaller, C., Schlaepfer, T., Reinacher, P., & Egger, K. et al. (2018). The anatomy of the human medial forebrain bundle: Ventral tegmental area connections to reward-associated subcortical and frontal lobe regions. Neuroimage: Clinical, 18, 770-783. doi: 10.1016/j.nicl.2018.03.019

Cohen, J., Haesler, S., Vong, L., Lowell, B., & Uchida, N. (2012). Neuron-type-specific signals for reward and punishment in the ventral tegmental area. Nature, 482(7383), 85-88. doi: 10.1038/nature10754

Holly, E., & Miczek, K. (2016). Ventral tegmental area dopamine revisited: effects of acute and repeated stress. Psychopharmacology, 233(2), 163-186. doi: 10.1007/s00213-015-4151-3

Lawrence, N., Hinton, E., Parkinson, J., & Lawrence, A. (2012). Nucleus accumbens response to food cues predicts subsequent snack consumption in women and increased body mass index in those with reduced self-control. Neuroimage, 63(1), 415-422. doi: 10.1016/j.neuroimage.2012.06.070

Mulej Bratec, S., Xie, X., Schmid, G., Doll, A., Schilbach, L., & Zimmer, C. et al. (2015). Cognitive emotion regulation enhances aversive prediction error activity while reducing emotional responses. Neuroimage, 123, 138-148. doi: 10.1016/j.neuroimage.2015.08.038

Mulej Bratec, S., Xie, X., Wang, Y., Schilbach, L., Zimmer, C., & Wohlschläger, A. et al. (2017). Cognitive emotion regulation modulates the balance of competing influences on ventral striatal aversive prediction error signals. Neuroimage, 147, 650-657. doi: 10.1016/j.neuroimage.2016.12.078

Reeve, J. (2018). Understanding motivation and emotion (7th ed.). Hoboken, NJ: Wiley.

Salamone, J., & Correa, M. (2012). The Mysterious Motivational Functions of Mesolimbic Dopamine. Neuron, 76(3), 470-485. doi: 10.1016/j.neuron.2012.10.021

Skibicka, K., Hansson, C., Alvarez-Crespo, M., Friberg, P., & Dickson, S. (2011). Ghrelin directly targets the ventral tegmental area to increase food motivation. Neuroscience, 180, 129-137. doi: 10.1016/j.neuroscience.2011.02.016

Small, K., Nunes, E., Hughley, S., & Addy, N. (2016). Ventral tegmental area muscarinic receptors modulate depression and anxiety-related behaviors in rats. Neuroscience Letters, 616, 80-85. doi: 10.1016/j.neulet.2016.01.057

Trutti, A., Mulder, M., Hommel, B., & Forstmann, B. (2019). Functional neuroanatomical review of the ventral tegmental area. Neuroimage, 191, 258-268. doi: 10.1016/j.neuroimage.2019.01.062

Zhang, C., Liu, X., Zhou, P., Zhang, J., He, W., & Yuan, T. (2018). Cholinergic tone in ventral tegmental area: Functional organization and behavioral implications. Neurochemistry International, 114, 127-133. doi: 10.1016/j.neuint.2018.02.003

External links

• 2 Minute Neuroscience: Ventral Tegmental Area (VTA) (youtube.com)
• Ventral Tegmental Area: Overview of available ScienceDirect Topics (sciencedirect.com)