“How are you feeling?”
“Horny.”

Not exactly an interaction one expects to find in a neuroscience blog, is it? But, prudish social norms aside, sexuality is a very normal part of human life, with the same […]

It’s nearly mid-October here at Tufts, and the lazy days of summer seem to drift further into memory as us students find ourselves increasingly bombarded with exams, interviews, projects—you name it. As someone prone to worry and obsess, I find myself often in a high state of arousal. Arousing stimuli constantly factor into our lives, influencing and shaping not just our affective states, but also cognitive processes like memory. With specific regard to memory, research suggests that arousing events alter both what we remember, as well as how we remember. Neuroscience research has explored and shed light on the brain regions and neural pathways that may explain the modulatory effects of arousal on memory.

Arousal has been shown to affect what aspects of stimulus information we remember, although much remains equivocal. Some research points to arousal heightening memory for central details at the cost of memory for peripheral details. Christianson & Loftus (1991) conducted a study in which participants viewed a series of slides. One critical slide in the middle of the series differed by group in that it was either arousal-provoking (a woman injured near a bicycle), or emotionally neutral (a woman riding a bicycle). The researchers found that subjects who viewed the series that contained the arousal-provoking slide were more likely to remember central details (i.e. details about the injured woman, such as the color of her clothing) of the image than peripheral details (i.e. details about the surrounding scene the woman was in), while subjects who viewed the series with the neutral slide were more likely to remember peripheral details than central details.

However, as Laney et al. (2004) point out, the scientific community must take caution when generalizing such findings. They argue that the arousing stimuli used in laboratory experiments often are strong negative visual stimuli, which may not accurately reflect the arousing stimuli people face in their everyday lives. They draw a distinction between the aforementioned visual stimuli, which may have served as “attention magnets”, and a different kind of arousal—thematically induced arousal. In this latter kind of arousal, the arousing stimuli are not necessarily singularly arousing visual images, but rather events that may be more subtle, less abrupt, and perhaps more sustainable. The researchers performed an experiment where participants were exposed to one of two narratives. The first was emotionally neutral and involved a story about an average day in the life of a college student, while the other was an analogous story that contained the same subject, but in this case the subject suffered from depression, failing grades, and suicidal thoughts. The researchers found no evidence of memory narrowing for central details in the arousing stimuli group, as they were able to recall peripheral information just as well as the control group. This result is as odds with the one previously suggested by Christianson & Loftus (1991), and suggests researchers must be careful in the ways they characterize and define arousal.

How does arousal act on memory consolidation on a neural level? Experts agree that the medial temporal lobe—which houses important structures implicated in memory consolidation, including the hippocampus and amygdala—is critical specifically for arousal-mediated memory consolidation. Rather than act as a “permanent site” of plastic changes resulting from memory consolidation, which Packard et al. (1994) showed is not the case in nonhuman subjects, research supports the idea that the amygdala plays a selective role in memory consolidation within the hippocampus through both direct and indirect pathways. In one study that sought to examine the importance of interactive amygdalo-hippocampal processes in memory consolidation, researchers compared memory for arousal-inducing vs. neutral words in unilateral temporal lobectomy patients and control subjects (LaBar & Phelps, 1998). Both control subjects and lobectomy subjects demonstrated heightened arousal at the time of encoding (as measured by skin conductance responses). However, with regard to recall of arousing words at the time of encoding (immediately following the experiment) as compared to recall one hour later, only control subjects showed increased memory of words. Both groups showed decreased memory for neutral words. These results seem to suggest that arousal acts on consolidation, and further, that the medial temporal lobe is critical for this consolidation process.

Arousal may mediate memory consolidation not just through direct neural pathways, but also through indirect hormonal connections. Cahill et al. (1994) suggested the important role of arousal-related hormones such as epinephrine and norepinephrine (as well as the role of their receptors) in remembering arousing information. In subjects who received a β-adrenergic receptor antagonist, propranolol hydrochloride, memory for an emotionally arousing narrative was significantly impaired, while memory for an emotionally neutral narrative was not impaired. This implies that activation of β-adrenergic systems is critical specifically for the encoding of arousing information and not essential for encoding of emotionally neutral information.

While neuroscience and cognitive psychology has made great headway in the study of arousal and its modulatory relationship on memory, it’s important to bear in mind that there are different ways of characterizing arousal, which in turn may have different implications on memory. In addition, on a neural level, there are different mechanisms, from synaptic connections of critical brain regions to hormonal regulation that play a role in the effect of arousal on memory formation and consolidation. All of these relationships and nuances are important to consider as more research is done.

References: 

Cahill, L., Prins, B., Weber, M., McGaugh, J. L. (1994). β-Adrenergic activation and memory for emotional events. Nature, 371, 702-704. 

Christianson, S., Loftus, E.F. (1991). Remembering emotional events: the fate of detailed information. Cognition and Emotion, 5, 81-108.

LaBar, K.S., Phelps, E.A. (1998). Arousal-mediated memory consolidation: role of the medial temporal lobe in humans. Psychological Science, 9, 409-413.

Laney, C., Campbell, H.V., Heuer, F., Reisberg, D. (2004). Memory for thematically arousing events. Memory & Cognition, 32, 1149-1159.

Packard, M.G., Cahill, L., McGaugh, J.L. (1994). Amygdala modulation of hippocampal-dependent and caudate nucleus-dependent memory processes, Proceedings of the National Academy of the Sciences, 91, 8477-8491.

Obsessive-compulsive disorder (OCD) is characterized by anxiety from intrusive thoughts (obsessions), repetitive behaviors to reduce anxiety (compulsions), or both.  While OCD is a relatively rare disorder, affecting only 1.6% of the population (Kessler et al., 2005b) at some point in their life, roughly half of the cases are severe and may be linked to suicide attempts, substantial work disability, or substance dependence (Kessler et al., 2005a).  This blog post focuses on the compulsive behaviors associated with OCD and evidence for an influence of the dopaminergic reward system.  I will discuss a couple of studies relating dopamine to a variety of compulsive behaviors and the effect of rewards on these compulsions.  I will then relate these findings to OCD.

Dopamine is related to reward processing in the brain, and it is too often linked to only the receipt of rewards.  This misconception is easy to make.  Increases in dopamine levels may increase rewards, and diminished dopamine definitely leads to less rewards.  However, it is often missed that dopamine actually creates the anticipation for reward.  If there is greater anticipation for reward, then more rewards can be received.  Similarly, if no rewards are anticipated, then any rewards received are not processed.  This distinction between anticipation and receipt of rewards is key to understanding the influence of the dopaminergic pathways on compulsive behaviors.

An early study of the reward system looked at the effect of self-stimulation in rats.  Olds (1958) reported that when rats with electrodes implanted in the hypothalamus self-stimulated for 26 straight hours at a continuous rate of more than 2000 responses an hour, then slept, and then resumed self-stimulation at the same rate.  This self-stimulation by the rats is an example of how a compulsive behavior can be maintained beyond the point of any health benefits and to the point where it is detrimental.  Similar patterns of compulsive behavior in humans can be found in drug addiction as people transition from casual usage to compulsive, and deterrents have little to no effect on behavior.  Not surprisingly, the dopamine system is also implicated in drug addiction in humans (Wise, 2002).

Another more recent study also uses self-stimulation of the hypothalamus in rats.  When rats are provided with a continuous supply of a palatable high-fat diet, they eat for extended periods and become obese (Johnson & Kenny, 2010).  Measurements of brain stimulation reward  threshold in the hypothalamus significantly increased in the obese rats, indicating that more stimulation was necessary for them to gain reward.  Additionally, the obese rats exhibited a reduced striatal dopamine D2 receptor (D2R) density and were resistant to changes in dietary behavior when the high-fat food became less available.

I propose that the striatum has become hyposensitive to dopamine as a homeostatic response to continuous activation, creating a need to resist the high rate of influx of dopamine to the striatum.  When the striatum releases an abnormal amount of dopamine into the synaptic cleft – more than can be degraded – the synaptic cleft becomes flooded with dopamine.  Some of the dopamine is brought back into the presynaptic cell by reuptake, but some continues to activate the postsynaptic cell.  The abundance of dopamine may then trigger the cell to be less receptive to new dopamine via the D2R.

Since the presynaptic cell can remove dopamine by reuptake, if the dopamine transporter (DAT) responsible for this process is not effective, synaptic activation will persist.  Another study shows that a particular DAT genotype is associated with activation of the ventral striatum during periods of reward anticipation (Dreher et al., 2009).  Using fMRI they investigated the activation of the striatum and prefrontal cortex (PFC) during reward anticipation and receipt.  Greater activation of the striatum was seen in people with DAT1 9-repeat genotypes, suggesting that uptake by the DAT was inhibited and activation persisted.

It is important to note that Dreher et al. report that reward anticipation is most robustly found in activation of the ventral striatum and reward receipt activates parts of the PFC.  Between these two studies we can see that reward anticipation is focused in the ventral striatum and that this anticipation drives compulsive behaviors.  This is evidence that compulsive behaviors, whether overeating or substance abuse, is linked to an imbalance in the dopaminergic reward system.  It appears that activation of the striatum is creating an expectation for reward, driving the animal to seek the reward.  When the reward is found, it does not satiate the expectation, and continued seeking for that reward ensues.

Panksepp (1998) points out that this seeking behavior is distinctly different than the receipt of reward.  Activation of the dopamine system through electrical stimulation or pharmacology causes rats to exhibit increased arousal and excited sniffing behavior, characteristic of the rat seeking for food.  When an animal finds food, it does not get more excited.  Instead it relaxes and becomes less excited.  This is the receipt of the reward and correlates with reduced activation of the subcortcial dopamine system.  An animal who has the striatum continuously activated will persistently seek the reward, even though the anticipation and expectation cannot be met.  I expect a similar outcome if there is anticipation of reward and either no reward is available or the reward processing is insufficient to satisfy the expectation.  In all of these cases there is an imbalance in the reward anticipation and receipt leading to a compulsive behavior.

Compulsive behaviors related to OCD likely derive from a similar imbalance in the dopaminergic reward system.  Perhaps continuous activation of the ventral striatum creates an undirected expectation for reward.  The unfulfilled expectation causes an anxious feeling and an urge to satisfy the void.  As a result, learned rituals are practiced to generate this reward.  However, the reward is likely too little and the ritual needs to be repeated.  Ideally, it is not repeated to the point of physical exhaustion like the rats in the Olds experiment.

References

Dreher, J. C., Kohn, P., Kolachana, B., Weinberger, D. R., & Berman, K. F. (2009). Variation in dopamine genes influences responsivity of the human reward system. Proceedings of the National Academy of Sciences, 106(2), 617-622.

Johnson, P. M., & Kenny, P. J. (2010). Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nature neuroscience,13(5), 635-641.

Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005a). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of general psychiatry, 62(6), 593-602.

Kessler, R. C., Chiu, W. T., Demler, O., & Walters, E. E. (2005b). Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Archives of general psychiatry, 62(6), 617-627.

Olds, J. (1958). Self-stimulation of the brain its use to study local effects of hunger, sex, and drugs. Science, 127(3294), 315-324.

Panksepp, J. (1998). Affective neuroscience: The foundations of human and animal emotions. Oxford university press.

Wise, R. A. (2002). Brain reward circuitry: insights from unsensed incentives.Neuron, 36(2), 229-240.

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“We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the pursuit of Happiness.” (Jefferson, 1776)

What is the Key to Happiness?

American culture is predicated on the idea that everyone has the right to be happy. Of course, what “being happy” means tends to vary a great deal from person to person, and perhaps even from moment to moment. On a typical fall morning, for example, I tend to define happiness as a scalding-hot cup of coffee, a fluffy blanket, and seeing books stacked upon books stacked upon (surprise!) yet more books. Unsurprisingly, I tend to be very unhappy when I run out of coffee, am subjected to a chilly room, and don’t get time to read.

Happiness is having baristas memorize your drink order.

While some things that make me happy on fall mornings make me happy 24/7/365, there is certainly a lot of variability there. During summer mornings, for instance, air conditioning tends to make me happier than a fluffy blanket, and frozen lemonade tends to make me happier than warm espresso on summer nights. On a less superficial level, having dinner with my family, going out with my friends, scaling the Colorado Rocky Mountains, wading into the warm Atlantic waters on the southeastern Florida coastline, or driving north through the exquisite expanse of New England’s fall foliage tends to make me far happier than, say, drinking a cup of coffee ever could (…okay, maybe it doesn’t make me that much happier. I really, really, really like coffee. I’m sorry).

Happiness, then, is great, however it’s achieved; or so it would seem. When you really stop and think about it, though, happiness might not always be the best goal to strive for. Let’s say that I love my job (which I do!) but don’t quite love some of the more trying tasks that come with it, like giving presentations to large groups of people. It’s unrealistic to assume that I’m going to be happy, in any sense of the word, while I’m speaking to hundreds of my respected colleagues. In fact, I might not even want to feel happy while I’m speaking. If being slightly anxious makes me more aware of my talking points, maybe my goal should be to feel slightly anxious while I’m speaking so that I ensure I’m covering all of the relevant material. Given that contextual complexities can significantly alter your emotional goals, when should you strive to experience positive emotions in the first place?

Before we can get into when positive emotions can be generally bad, how positive emotions can arise at inopportune times, and what specific types of positive emotions are bad in specific contexts, however, it’s important to have a clear understanding of the neural bases of positive emotions and their regulation relative to the neural bases of negative emotions and their regulation. We’ll get into that in our next section.

The Neural Bases of Positive and Negative Emotions

Our ability to study the brain has increased dramatically over the past couple of decades. (For a nice introduction to the different structures of the brain, play around with the BBC’s Human Brain Map at http://www.bbc.co.uk/science/humanbody/body/interactives/organs/brainmap/). Techniques like functional magnetic resonance imaging (fMRI), positron emission topography (PET), and more have allowed us to peer at what’s underneath the skull in incredible ways. While these techniques are fascinating first steps on our way to understanding the brain, how it works, and how it affects people’s behavior, they still have many limitations, like suboptimal spatial and temporal resolution, that give us pause and make us stop short of declaring their findings the definitive “truth” on brain functionality. Nevertheless, even a rudimentary understanding of where emotions originate in the brain and how they might be related to certain behaviors have helped scientists realize how positive and negative emotions differ from one another.

Several research inquiries have been conducted which suggest that positive emotions are uniquely situated within the brain. For instance, a recent meta-analysis of 83 PET and fMRI studies demonstrated that happiness, relative to the emotions of sadness, anger, fear, and disgust, tended to activate the rostral anterior cingulate cortex (ACC) and right superior temporal gyrus (STG; Vytal & Hamman, 2010). Another study using electroencephalography (EEG) found that, when controlling for the amount of positive affect individuals typically report experiencing, greater left prefrontal cortex (PFC) activation is associated with high eudaimonic well-being (e.g., having a sense of purpose in life), but is not associated with high hedonic well-being (e.g., pleasure, “feeling good”) (Urry et al., 2004). Yet another study induced happiness in participants and then observed that their subsequent vagal tone (which, broadly, is an index of socioemotional well-being) was correlated with activation in the medial PFC, the midbrain, part of the ventral striatum, and the left midinsula (Lane et al., 2009). Taken together, these findings suggest that positive emotions are uniquely situated within the brain.

Although knowing where in the brain positive emotions exist is great in and of itself, I believe it’s even more intriguing to see where these emotions are regulated; in other words, what neural substrates contribute to making us feel less negatively (or more positively)? One study has shown that while up-regulating emotions (feeling more of either positive or negative emotions) and down-regulating emotions (feeling less of either positive or negative emotions) calls upon some related neural networks, up-regulating positive emotions seems to uniquely activate the bilateral ventral striatum, which has been implicated in the processing of rewards (Kim & Hamann, 2007). Relatedly, an fMRI study showed that there are both general and valence (positive or negative)-specific neural substrates that underlie emotion regulation, and that increased activation in both the dorsolateral prefrontal cortex (DLPFC) and the insula is uniquely associated with the regulation of positive emotion (Mak et al., 2009). Thus, there seems to not only be differences in where individuals experience positive and negative emotion in the brain, but also in where they regulate them.

Where Do We Go From Here?

By now you’ve hopefully come to a basic understanding of how positive and negative emotions manifest in the brain. Now that you are aware of these differences we can spend next time covering how wanting to feel good can sometimes be bad (and, relatedly, how wanting to feel bad can sometimes be good!). In subsequent weeks we’ll get into how positive emotions can be implicated in various psychopathologies, like depression and bipolar disorder, as well as into just how much cultural variation exists in terms of positive emotion valuation and expression (spoiler alert: there’s a ton).

References

Jefferson, T. (1776). Declaration of Indpendence. Retrieved from National Archives
website: http://www.archives.gov/exhibits/charters/declaration_transcript.html

Kim, S., & Hamann, S. (2007). Neural correlates of positive and negative emotion
regulation. Journal of Cognitive Neuroscience, 19(5), 776-798.

Lane, R. D., McRae, K., Reiman, E. M., Chen, K., Ahern, G. L., & Thayer, J. F. (2009).
Neural correlates of heart rate variability during emotion. Neuroimage, 44(1), 213-222.

Mak, A. K., Hu, Z. G., Zhang, J. X., Xiao, Z. W., & Lee, T. (2009). Neural correlates of
regulation of positive and negative emotions: An fMRI study. Neuroscience
Letters, 457(2), 101-106.

Urry, H. L., Nitschke, J. B., Dolski, I., Jackson, D. C., Dalton, K. M., Mueller, C. J., … &
Davidson, R. J. (2004). Making a life worth living neural correlates of well-being.
Psychological Science, 15(6), 367-372.

Vytal, K., & Hamann, S. (2010). Neuroimaging support for discrete neural correlates of
basic emotions: A voxel-based meta-analysis. Journal of Cognitive Neuroscience, 22(12),
2864-2885.

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