Abstract

Based on empirical evidence that suggests that failing to recognize a stimulus as emotionally relevant results in hypoactivity of the orexinergic cells in the hypothalamus, this article proposes a physiological model of boredom that makes depression a consequence of a chronic reduction of monoamines in the brain combined with increased levels of norepinephrine and cortisol. The studies proposed here look to find supportive evidence for two assumptions of this model: 1. That the negative affect associated with boredom results from a conscious assessment of the situation; 2. That activity of the orexinergic neurons can increase both positive and negative affect, depending on the assessed valence of a stimulus.

A Physiological Model of Boredom and its Relationship with Depression

A recent longitudinal study that followed a group of Spaniards through eight-and-a-half years (Sánchez-Villegas, Ruíz-Canela, Gea, Lahortiga, & Martínez-González, 2016) proposes that adherence to a Mediterranean lifestylereduces the likelihood of depression, as far as fifty percent for the most committed individuals. Per this study, the most prominent benefits from following a Mediterranean lifestyle, defined as high in adherence to a Mediterranean diet, as well as to high in physical and social activities, come mostly from increased physical and social activity (Sánchez-Villegas et al., 2016). I speculate that the particular circumstances of Spanish societies, with high urban density, which promotes pedestrian traffic, rich in culture, and high in social activities, leaves little time for the typical Spaniard to get bored and therefore, depressed.

Empirical research suggests that boredom has indeed a positive, strong association with depression (German & Latkin, 2012; Goldberg, Danckert, 2013; Isacescu, Struk, Danckert, 2016; Mercer-Lynn, Hunter, & Eastwood, 2013; Spaeth, Weichold, & Silbereisen, 2015; Tilburg & Igou, 2017). Boredom also correlates with a number of negative emotions such as sadness, anger, frustration, hostility, (Isacescu et al., 2016; Tilburg & Igou, 2017), anxiety (Fahlman, Mercer, Gaskovski, Eastwood, & Eastwood, 2009), and aversive states such as motor impulsiveness (Mercer-Lynn, Flora, Fahlman, & Eastwood, 2011), life dissatisfaction, and lack of life meaning (Fahlman et al., 2009; Mercer-Lynn et al., 2011).

Here, I present a physiological model of boredom that explains its link with depression and propose two studies which could provide supporting evidence for the model.

 

Boredom

Eastwood, Frischen, Fenske, and Smilek’s (2012) define boredom as “the aversive experience of wanting, but being unable, to engage in satisfying activity” (p. 482) and make it a consequence of an individual’s realization of her failure to focus her attention on a present activity.

Coming from a functional perspective that makes emotions indicators of progress toward a goal, Bench and Lench (2013) propose that boredom is a discrete emotion that results from “a diminishing emotional response to the [current] situation” (p. 461). Thus, for Bench and Lench (2013) boredom becomes a cause for, rather than a consequence of, reduced attention. Bench and Lench (2013) argue that boredom’s function is to serve as a signal that it is time to pursue a different goal. Accordingly, attention to one’s present situation will depend on one’s subjective measure of its relevance to one’s particular goals, as well as one’s mood, disposition, and cognitive skills. Congruent with this, Spaeth et al. (2015) speculate that the neural changes throughout puberty make children less able to cope with inadequate stimulation and thus more prone to experience boredom and with the negative affect associated with boredom. Goldberg and Danckert (2013) ran a study that offers support to this hypothesis. They found a positive relation between boredom proneness and depression which was stronger in those patients with moderate-to-severe traumatic brain injuries. Their findings suggest that failure to recognize the stimuli in the external environment as relevant and, therefore, worthy of one’s attention, is what causes boredom. Hence, what a child finds boring an adult may not and vice-versa. Then again, if boredom arises as other emotions fade, as Bench and Lench (2013) propose, boredom cannot be an emotion, but the lack of emotion. Likewise, rather than a signal for a need to change one’s present activity, boredom should be the absenceof a signal to continue being engaged—the signal being the recognition of a stimulus as either an impending threat or a potential reward, both of which circumstances would demand increased attention.

If boredom originates from an individual’s realization of her inability to sustain her attention on the task at hand as Eastwood et al. (2012) propose, boredom cannot be a discrete emotion either, but a mixture of cognitive considerations and feelings born from an individual’s assessment of her present situation as unrewarding. Since mind-wandering follows a loss in attention and does not necessarily entails negative affect (Eastwood et al., 2012), a state of mind-wandering cannot be part of a state of boredom, either, because boredom necessarily entails negative affect. I propose, then, that boredom, as an aversive state, will only occur when to an emotionally “neutral” state, follows the conscious desire to engage in a more rewarding activity combined with one’s perceived inability to abandon the present task—the “wanting, but being unable” from Eastwood et al.’s (2012) definition. Accordingly, the negative affect associated with boredom will be a consequence of an individual’s assessment of her present situation as meaningless. Consequently, under circumstances in which attention can be readily shifted from irrelevant (or no longer relevant) stimuli to stimuli that will provoke an emotional response—as when, for instance, one browses through a series of photographs and as the interest for one fades another one captures our attention—boredom will likely not occur. Similarly, should an individual’s goal be to reduce her emotional response to the environment, as when she tries to rest or willingly engages in mind wandering, a state of boredom should not occur either.

For this to be true, an experience of boredom should be preceded by reduced physiological responses: low arousal, decreased neural activity in the prefrontal cortex, mind wandering, and an initial reduction on the production of the monoamines associated with arousal, followed by high arousal, as the individual assesses one’s present circumstances as “boring” and thus as a stressor, increasing the release of norepinephrine and the activity of the hypothalamus-pituitary-adrenal axis. Recent empirical evidence suggests that this is the case.

 

The Physiology of Boredom

Merrifield and Danckert (2013) ran an experiment attempting to describe the psychophysiological signature of boredom as a state of low or high arousal by measuring changes in heart rate, skin conductance, and cortisol levels, and comparing these changes to changes reported during induced states of increased interest or sadness. Merrifield and Danckert (2013) found that experiencing boredom led to lower skin conductance than when experiencing increased interest or sadness, which they associated with a decrease in attention, and thus low arousal. Boredom also led to higher heart rate and cortisol levels than when experiencing sadness, however. Merrifield and Danckert (2013) interpreted this as a higher response from the autonomic system to stress and thus high arousal. Furthermore, Merrifield and Danckert (2013) found that individuals with a higher proneness to boredom showed higher changes in heart rate, suggesting that these individuals were more distressed by a boring experience.

Likewise, studies that use measures of brain activity through EEG and fMRI as proxies for attention found that inducing a state of boredom leads to decreased neural activity. Tabatabaie et al. (2014) ran an experiment that exposed the participants to various pieces of music and compared the participants’ self-reports of boredom assessment with EGG readings of their left dorsolateral prefrontal cortex activity. They found that the measured Beta 2 power activity (16-20 Hz) was significantly lower for those participants that assessed the music pieces as boring, a finding that implies lower cognitive processing.

The association between arousal and attention suggests that the hypothalamus, which indirectly regulates sleep, must be involved in recognizing stimuli as emotionally relevant.

Because of its extensive connections throughout the brain, specifically with the amygdalae, the cerebral cortex, the preoptic area, as well as the ventral tegmental area, and the areas that produce monoamines in the brain stem and forebrain (Mileykovskiy, Kiyashchenko, & Siegel, 2005), the hypothalamus plays an essential role in regulating motivational processes by producing orexin, a peptide that works as a neurotransmitter increasing appetite, arousal, and wakefulness (Calipari & España, 2012; Mahler, Moorman, Smith, James, Aston-Jones, 2014; Numan & Woodside, 2010), as well as in regulating responses to stress by producing corticotropin releasing hormone, which indirectly promotes the production of corticoids (Numan & Woodside, 2010).

Using antidromic and orthodromic electrical stimulation of the axonal connections of the hypothalamus with the ventral tegmental area and the locus coeruleus, Mileykovskiy et al. (2005) identified the location of several hundred orexinergic neurons in the perifornical and lateral areas of the hypothalami in rats. Then, using micro-wire insertions on nine of these orexinergic cells, they measured their electrical activity and found a negative correlation between the firing of these neurons and EEG spectral power in the Delta (under 3 Hz), Theta (4-8 Hz), Alpha (8-12 Hz), and Beta (13-30 Hz) frequency waves as measured in the prefrontal cortices of the rats, as well as a positive correlation between the firing of the orexinergic neurons with EEG measures produced by arousal (i.e., exploratory behavior) that increased desynchronization and the power of the Gamma (30-75 Hz) frequency waves. That is, they found that the activity of the orexinergic neurons correlated with increased cortical activity. Mileykovskiy et al. (2005) hypothesized that the firing of orexinergic neurons in the hypothalamus occurs in response to emotionally arousing conditions and to promote attention.

The findings from another experiment that measured the activity of the hypothalami through fMRI reached similar conclusions. Karlsson et al. (2010) exposed participants to funny and sad images and found that the regions corresponding to orexinergic neurons in the hypothalami activated in response to the valence of the funny or sad stimuli but not in response to the neutral stimuli. Karlsson et al. (2010) also found that this activation corresponded to ipsilateral activation of the amygdalae.

If orexin indirectly regulates sleep by inhibiting the activity of sleep producing neurons in the ventrolateral preoptic area, which in turn inhibit the activity of the arousal system (Carlson, 2013), could the negative affect associated with boredom be a consequence of the impossibility to fall asleep? After all, boredom leads to lethargy. Mahler et al. (2014) propose that the role of orexin in regulating behavior extends beyond promoting wakefulness and so, they link the secretion of orexin to reward-seeking and adaptive activities in addition to circadian rhythms. Mahler et al.’s (2014) model proposes that orexinergic neurons, because of the heterogeneity of their efferent and afferent axonal projections, serve an integrative role in regulating behavior by increasing their rate of firing whenever a stimulus is recognized as a sign for action, correspondingly affecting the activity of the hypothalamic-pituitary-adrenal axis, the amygdala, the medial prefrontal cortex, the ventral tegmental area, as well as the brain stem and the forebrain to provoke a series of behavioral and physiological responses appropriate to the situation. Here may lie the relationship between boredom and depression. Upon recognition of a stimulus as emotionally irrelevant, orexinergic hypoactivity will reduce the secretion of monoamines, including those whose shortage in the extracellular fluid has been associated with lack of motivation and depression: serotonin, norepinephrine, and dopamine (Calipari & España, 2012; Walling, Nutt, Lalies, & Harley, 2004; Wingen, Kuypers, Ven, Formisano, & Ramaekers, 2008), as well as acetylcholine (Villano et al., 2017) resulting in a loss of attention and potentially inducing a state of mind-wandering. Upon becoming aware of this loss of attention and unable to engage in a more rewarding activity, the individual may assess the previously irrelevant stimulus as a stressor. As a result, the orexinergic neurons will stimulate the secretion of norepinephrine by the locus coeruleus as well as the secretion of corticotropin-releasing-hormone by the paraventricular nucleus of the hypothalamus into the pituitary gland, which in turn will secrete adrenocorticotropic hormone, ultimately elevating the levels in the blood of cortisol as well as of epinephrine, through indirect activation of the adrenal medulla. High levels of cortisol as well as low levels of monoamines, but especially serotonin, have been associated with depression (Herbert, 2013; Wingen et al., 2008).

There is extensive empirical evidence of the effect that orexin has on the production of acetylcholine and monoamines as well as the effect of these on attention. Liu, Van den Pol, and Aghajanian, (2002) electrically stimulated orexinergic neurons in rat brain slices causing postsynaptic responses in the serotonergic neurons in the raphe nuclei. In a review on the effect of orexin-producing neurons on the basal forebrain cholinergic system, Villano et al. (2017) mention that orexin secretion reaches a maximum at wake but also in response to stimuli that increases positive affect, while socializing, and during episodes of anger, fomenting the release of acetylcholine by the basal forebrain in the cortex. Similarly, in a series of experiments that measured the development of substance dependence in mice and rats, Calipari and España (2012) found that injecting orexin directly into the rats’ ventral tegmental area, made the release of dopamine caused by the consumption of cocaine rise dramatically in comparison to the levels of dopamine observed in rats treated with an orexin inhibitor, SB-334867. Calipari and España (2012) also found that increased levels of orexin increased a rat’s willingness to work for drugs, while orexin knock-out mice developed less dependence to addictive substances, further supporting the integrative role of orexin in regulating reward-seeking behavior. Walling et al. (2004) found that infusing orexin into the locus coeruleus promoted the secretion of norepinephrine in the hippocampus, causing long-lasting potentiation in the dentate gyrus. Recently Unsworth and Robison (2017) found that variabilities in the production of norepinephrine in the locus coeruleus correlated with variabilities in working memory and that low working memory individuals had more attentional failures and episodes of mind-wandering during activities that required a high attentional effort.

In summary, and to reconcile Eastwood et al.’s (2012) definition of boredom with its argued functionality, as proposed by Bench and Lench (2013), and with Mileykovskiy et al. (2005) and Mahler et al. (2014) hypotheses of orexin function, I propose that:

1. The inability to recognize one’s present activity as emotionally relevant (i.e., as a threat or a reward) lowers the activity of the orexinergic cells in the lateral hypothalamus, which causes a reduction in the amount of the monoamines secreted in the brain, resulting in a loss of attention and reduced motivation.
2. This loss of attention leads the brain to a temporary state of mind wandering.
3. As the individual becomes aware of this attentional failure but also of her inability to re-engage, she will now recognize the present situation as toxic, leading to a rise in the levels of stress hormones.

Boredom could be defined then, as either the cause and the consequence of the loss of attention, and thus as a mental process that involves reduction of affect, mind wandering, then an increase in negative affect, or as the consequence of a loss of attention, and thus, as a mental state purely associated with negative affect. Either way, in the long run, chronic boredom, as it may result from a life poor in rewarding stimuli, may cause depression-like symptoms.

Orexinergic cells hypoactivity would explain as well why a bored individual will show not only demotivation but also increased hostility and impulsivity since these behaviors have been associated with a reduction in serotonin and its interaction with dopamine (Seo, Patrick, Kennealy, 2008). This supports the idea that boredom can lead to risky behavior such as drug and alcohol addiction, gambling (Eastwood et al., 2012), delinquency, and promiscuity. For instance, in an experiment with mink, Meagher and Mason (2012) found that mink kept in impoverished environments made faster contact with aversive, rewarding or ambiguous stimuli (e.g., a predator silhouette, a moving toothbrush, or a candle) than mink kept in rich environments, and that mink kept in an impoverished cage also spent more time exploring ambiguous stimuli. Although experiments like this support the hypothesis that boredom leads to impulsivity as well as preference for novel stimuli, including those involving potential risk, recent empirical evidence suggests that the association of boredom with increased risk is mild at best (German & Latkin, 2012; Mercer & Eastwood, 2010; Mercer-Lynn et al., 2013; Spaeth et al., 2015), and that this association is modulated by gender, age, temperament (Spaeth et al., 2015), and sensibility to reward (Mercer & Eastwood, 2010), or, in the case of sexually risky behavior, by the concurrence with depression (German & Latkin, 2012) or lack of social connectedness (Chaney & Chang, 2005). Furthermore, a recent study by Tilburg and Igou (2016) found that individuals in an induced state of high boredom were more willing to engage in prosocial activities than individuals in a state of low boredom. Tilburg and Igou (2016) findings suggest that while bored individuals may become more impulsive, they actively discriminate among alternative activities rather than simply wishing to engage in any new activity as Bench and Lench (2013) had suggested.

 

The Studies Proposed

A physiological model of boredom based on the activity of the orexinergic neurons makes two assumptions: 1. That the negative affect associated with a state of boredom results from a subjective measure of the experience, and thus that boredom is a conscious mental state; 2. That the activity of the orexinergic neurons causes a change in the valence of affect reliant on an individual’s assessment of a stimulus—as either a threat or a reward—and, therefore that there must be two (or more) corresponding pathways for affect.

 

Study 1: Boredom as a Conscious State

As proposed above, boredom cannot be a discrete emotion but a conscious state which results from assessing the present situation as toxic. Thus,

Hypothesis 1.1: Individuals exposed to an emotionally irrelevant stimulus will show lower activation of the prefrontal cortex as indicated by a predominance of lower frequency bands in EEG readings

Hypothesis 1.2: Individuals exposed to an emotionally irrelevant stimulus yet allowed to engage into mind wandering freely will present lower levels of stress hormones (i.e., salivary cortisol) than those individuals who are also exposed to an emotionally irrelevant stimulus but dissuaded from engaging into mind-wandering.

 

Methods, participants, and design.

The participants will be chosen among individuals with similar demographics and no hearing impairments, then divided into a treatment and a control group at random.

Both groups will listen for twenty minutes to a piece of text as it is read by a computer. This could be done by using the text-to-speech capabilities of a smartphone and headphones. The text will be previously chosen as boredom inducing, for instance, by choosing an academic article beyond the participants’ competence. Their levels of salivary cortisol will be measured before and after the experiment takes place, and their cortical brain activity recorded through an EEG cap. Their heart rate will be measured as well, throughout the reading. Since wearing an EEG cap could make the participants nervous, the experiment should not begin until their heart rate is normal.

Participants in the control group will be told that the study intends to measure the efficacy of artificial speech on transmitting a message and thus that they should pay careful attention to the text. While they listen, these participants will sit on a chair that does not allow them to be too comfortable and allowed to take control the flow of the text as it is read, in case they miss something important. The researcher will remain in the room with the participants to monitor their experience but will not make verbal contact with them or allow them to talk among themselves.

Participants in the treatment group will be told that the study intends to see whether artificial speech can “fool” their brains into thinking that the text is being read by a real person and that the researchers will be able to interpret this from the EEG readings, so that the participants should not feel pressured to pay attention. The participants will be invited to lie down on a couch and be left alone while the experiment lasts so that they do not feel intimidated by the presence of the researcher.

After finishing the experiment, the participants will be debriefed and dismissed.

 

Results and discussion

The EEG readings of the participants of both groups will be compared. I expect to find frequent periods of low activation of the prefrontal cortex indicated by a predominance of Alpha (8-12 Hz), and Beta 1 power (12.5-16 Hz) frequency waves over higher frequency waves in both the treatment and control groups. However, I expect the periods of low-frequency waves to be much more frequent in the treatment group, those who would be allowed to engage in mind-wandering.

The measures of salivary cortisol will also be compared. I expect to find that the levels of salivary cortisol will be significantly lower in the treatment group.

Should the results be as predicted, the findings of this study will offer support to the idea that the aversive experience of boredom is a mental state reliant on a conscious assessment of the situation.

 

Study 2: Distinct Pathways of Affect.

In a study that attempted to map the neural pathways of affect, Mathiak, Klasen, Zvyagintsev, Weber, & Mathiak (2013) subjected the participants to alternate episodes of flow and boredom while playing a video game and analyzed the participant’s brain activity through fMRI. Mathiak et al. (2013) found two distinct networks which they associated with positive and negative affect. Increased positive affect correlated negatively with activation of the amygdala and the insula, while negative affect correlated positively with increased activity of the ventromedial prefrontal cortex and negatively with increased activity of the hippocampus. Unfortunately, their study did not explore activation of the lateral hypothalamus. What role do orexinergic neurons play in defining the valence of affect?

To date, researchers have discovered two types of Orexin: A and B, as well two types of receptors, OX₁and OX₂. Orexin-A has an almost equal binding affinity with both receptors (Gotter, Webber, Coleman, Renger, & Winrow, 2012), while Orexin-B has a high affinity with OX₂receptors but between 10 to 100 times less affinity with the OX₁receptors (Ammoun et al., 2003). That is, OX₁receptors will bind mostly with Orexin-A but not with Orexin-B, while OX₂receptors will bind with either type of orexin. The tuberomammillary nucleus, which produces histamine, has mostly OX₂receptors, and thus responds to either type of orexin. The laterodorsal and pedunculopontine tegmental nuclei in the brainstem, which produce acetylcholine, have both kinds of receptors, and so does the ventral tegmental area, which produces dopamine, as well as the raphe nuclei, which produces serotonin; hence, all these areas respond to either type of Orexin as well. The locus coeruleus, which produces norepinephrine, has mostly OX₁receptors (Gotter et al., 2012), and so does the cortex. What this suggests is that secretion of Orexin-A will excite cholinergic, noradrenergic, serotonergic, and histaminic neurons, but the secretion of Orexin-B will mostly fail to excite noradrenergic neurons in the locus coeruleus, which chiefly expresses OX₁receptors, and will produce lower excitation of the ventral tegmental area and the raphe nuclei as well. Some researchers propose that, rather than positive and negative affect pathways, the axonal projections of the orexinergic neurons may involve arousal, via the OX₂ receptors, and reward-seeking, via the OX₁receptors, pathways (Baimel et al., 2014; Gotter et al., 2012).

It has been proposed, as well, that recognition of a stimulus as aversive or not depends on the integration of the hypothalamus with the amygdala. Kim and Han (2016) found that subjecting mice to a condition of high stress by restraining them for 2 hours every day for 14 days reduced their levels of sociability and increased their immobility in tail suspensions and forced swim tests compared to controls, suggesting that the restrained mice developed depressive symptoms. Upon analysis of the mice brain’s, Kim and Han (2016) found that the basolateral amygdalae of the stressed mice had increased the number of OX₁receptors. Kim and Han (2016) also found that injecting either orexin or melanin-concentrating hormone (also produced in the lateral hypothalamus) in the amygdalae replicated the symptoms induced by stress. In similar experiments, Arendt et al. (2014) found that inducing chronic defeat in mice increased the number of OX₁receptors and decreased the number of OX₂receptors in the basolateral amygdalae of susceptible animals. Arendt et al. (2014) concluded that OX₂receptors in the basolateral amygdala could help in alleviating anxiety and panic symptoms while OX₁receptors have the opposite effect. Since OX₂receptors bind with either type of orexin while OX₁receptors bind mostly with Orexin-A, these findings suggest that emotional valence may depend on the proportion in which the orexinergic neurons secrete Orexin-A and -B peptides. Thus,

Hypothesis 2.1: Administering an Orexin-B agonist to individuals before exposing them to stimuli that increases the reactivity of their hypothalamus will significantly improve their mood compared to controls.

 

Methods, participants, and design.

My knowledge of psychopharmacology is quite limited. Thus, this proposed study works under the assumption that administering an Orexin-B agonist such as 7,8-Dihydroxyflavone (DHF) to humans is safe. I propose the use of this agonist based on the findings of Feng, Akladious, Hu, Raslan, Feng, and Smith (2015), which showed that administering DHF to mice resulted in an increase of Orexin-B and a decrease of Orexin-A in their hypothalamic tissue.

Participants will be chosen among individuals with similar demographics and divided at random into two groups. Before treatment, the mood of the participants in both groups will be assessed via a mood assessment test such as the Mood Self-Assessment Quiz from the NHS which can be found online at https://www.nhs.uk/conditions/stress-anxiety-depression/mood-self-assessment/. Their levels of salivary cortisol will be measured as well.

Individuals in the treatment group will receive safe doses of DHF one hour before the experiment begins. Individuals in the control group will be administered a placebo. Then, individuals from both groups will watch a movie chosen by its capacity to arouse both positive and negative affect, for instance, Life is Beautiful(Benigni, 1997). After ending the movie, the participants’ moods will be measured again as well as their salivary cortisol levels. They will be then debriefed and dismissed.

 

Results and discussion.

The mood scores and the levels of salivary cortisol of both groups will be compared. I expect to find a more significant improvement in the mood of the participants in the treatment group as well as lower levels of salivary cortisol. This would suggest that increased binding of Orexin-B with OX₂receptors combined with stimulating activities can help decrease depression-like symptoms.

 

Conclusions

While no one factor can explain the occurrence of mood disorders, empirical evidence suggests that depression has a positive association with boredom. Modern western societies put a higher value on privacy than communality, opting for urban designs that foment isolation and thus, more frequent episodes of boredom. Similarly, education practices are frequently monotonous, demotivating students. The model presented here suggests that boredom acts as a stressor on the central nervous system, and, consequently, that the lack of stimulating events can increase an individual’s likelihood of suffering depression. For certain individuals, increasing the number of social activities or choosing a media diet that by its rich emotional content will cause hyperactivity of the orexinergic system may reduce the need to resort to anxiolytic drugs for the treatment of depression.

 

References

Ammoun, S., Holmqvist, T., Shariatmadari, R., Oonk, H. B., Detheux, M., Permentier, M., . . . Kukkonen, J. P. (2003). Distinct recognition of OX₁and OX₂receptors by orexin peptides. Journal of Pharmacology and Experimental Therapeutics,305(2), 507-514. doi:10.1124/jpet.102.048025

Arendt, D. H., Hassell, J., Li, H., Achua, J. K., Guarnieri, D. J., Dileone, R. J., . . . Summers, C. H. (2014). Anxiolytic function of the orexin 2/hypocretin A receptor in the basolateral amygdala. Psychoneuroendocrinology,40, 17-26. doi:10.1016/j.psyneuen.2013.10.010

Baimel, C., Bartlett, S. E., Chiou, L., Lawrence, A. J., Muschamp, J. W., Patkar, O., . . . Borgland, S. L. (2014). Orexin/hypocretin role in reward: Implications for opioid and other addictions. British Journal of Pharmacology, 172(2), 334-348. doi:10.1111/bph.12639

Bench, S., & Lench, H. (2013). On the function of boredom. Behavioral Sciences, 3(3), 459-472. doi:10.3390/bs3030459

Chaney, M. P., & Chang, C. Y. (2005). A trio of turmoil for internet sexually addicted men who have sex with men: boredom proneness, social connectedness, and dissociation. Sexual Addiction & Compulsivity, 12(1), 3-18. doi:10.1080/10720160590933671

Carlson, N. R. (2013) Sleep and biological rhythms. InPhysiology of Behavior. 288-322.

Calipari, E. S., & España, R. A. (2012). Hypocretin/orexin regulation of dopamine signaling: Implications for reward and reinforcement mechanisms. Frontiers in Behavioral Neuroscience, 6(54)1-13. doi:10.3389/fnbeh.2012.00054

Eastwood, J. D., Frischen, A., Fenske, M. J., & Smilek, D. (2012). The unengaged mind. Perspectives on Psychological Science, 7(5), 482-495. doi:10.1177/1745691612456044

Fahlman, S. A., Mercer, K. B., Gaskovski, P., Eastwood, A. E., & Eastwood, J. D. (2009). Does a Lack of Life Meaning Cause Boredom? Results from Psychometric, Longitudinal, and Experimental Analyses. Journal of Social and Clinical Psychology, 28(3), 307-340. doi:10.1521/jscp.2009.28.3.307

Feng, P., Akladious, A. A., Hu, Y., Raslan, Y., Feng, J., & Smith, P. J. (2015). 7,8-Dihydroxyflavone reduces sleep during dark phase and suppresses orexin A but not orexin B in mice. Journal of Psychiatric Research, 69, 110-119. doi:10.1016/j.jpsychires.2015.08.002

German, D., & Latkin, C. A. (2012). Boredom, depressive symptoms, and hiv risk behaviors among urban injection drug users. AIDS and Behavior, 16(8), 2244-2250. doi:10.1007/s10461-012-0247-5

Goldberg, Y., & Danckert, J. (2013). Traumatic brain injury, boredom and depression. Behavioral Sciences, 3(3), 434-444. doi:10.3390/bs3030434

Gotter, A. L., Webber, A. L., Coleman, P. J., Renger, J. J., & Winrow, C. J. (2012). International union of basic and clinical pharmacology. LXXXVI. Orexin receptor function, nomenclature and pharmacology. Pharmacological Reviews, 64(3), 389-420. doi:10.1124/pr.111.005546

Herbert, J. (2013). Cortisol and depression: Three questions for psychiatry. Psychological Medicine, 43(3), 449-69. doi:10.1017/S0033291712000955

Isacescu, J., Struk, A. A., & Danckert, J. (2016). Cognitive and affective predictors of boredom proneness. Cognition and Emotion, 31(8), 1741748. doi:10.1080/02699931.2016.1259995

Karlsson, K., Windischberger, C., Gerstl, F., Mayr, W., Siegel, J., & Moser, E. (2010). Modulation of hypothalamus and amygdalar activation levels with stimulus valence. NeuroImage, 51(1), 324-328. doi:10.1016/j.neuroimage.2010.02.02

Kim, T., & Han, P. (2016). Functional connectivity of basolateral amygdala neurons carrying orexin receptors and melanin-concentrating hormone receptors in regulating sociability and mood-related behaviors. Experimental Neurobiology,25(6), 307. doi:10.5607/en.2016.25.6.307

Liu, R., Van den Pol, A. N., & Aghajanian, G. K. (2002). Hypocretins (orexins) regulate serotonin neurons in the dorsal raphe nucleus by excitatory direct and inhibitory indirect actions. The Journal of Neuroscience, 22(21), 9453-9464.

Mahler, S. V., Moorman, D. E., Smith, R. J., James, M. H., & Aston-Jones, G. (2014). Motivational activation: A unifying hypothesis of orexin/hypocretin function. Nature Neuroscience, 17(10), 1298-1303. doi:10.1038/nn.3810

Meagher, R. K., & Mason, G. J. (2012) Environmental enrichment reduces signs of boredom in caged mink. PLoS ONE 7(11): e49180. doi:10.1371/journal.pone.0049180

Mercer, K. B., & Eastwood, J. D. (2010). Is boredom associated with problem gambling behaviour? It depends on what you mean by ‘boredom’. International Gambling Studies, 10(1), 91-104. doi:10.1080/14459791003754414

Mathiak, K. A., Klasen, M., Zvyagintsev, M., Weber, R., & Mathiak, K. (2013). Neural networks underlying affective states in a multimodal virtual environment: Contributions to boredom. Frontiers in Human Neuroscience, 7. doi:10.3389/fnhum.2013.00820

Mercer-Lynn, K. B., Flora, D. B., Fahlman, S. A., & Eastwood, J. D. (2011). The measurement of boredom: Differences between existing report scales.Assessment, 20(5), 585-596. doi:10.1177/1073191111408229

Mercer-Lynn, K. B., Hunter, J. A., & Eastwood, J. D. (2013). Is trait boredom redundant?Journal of Social and Clinical Psychology, 32(8), 897-916. doi:10.1521/jscp.2013.32.8.897

Merrifield, C., & Danckert, J. (2013). Characterizing the psychophysiological signature of boredom. Experimental Brain Research, 232(2), 481-491. doi:10.1007/s00221-013-3755-2

Mileykovskiy, B. Y., Kiyashchenko, L. I., and Siegel, J. M. (2005). Behavioral correlates of activity in identified hypocretin/orexin neurons. Neuron 46, 787–798. doi: 10.1016/j.neuron.2005.04.035

Numan, M., & Woodside, B. (2010). Maternity: Neural mechanisms, motivational processes, and physiological adaptations. Behavioral Neuroscience, 124(6), 715-741. doi:10.1037/a0021548

Sánchez-Villegas, A., Ruíz-Canela, M., Gea, A., Lahortiga, F., & Martínez-González, M. A. (2016). The association between the mediterranean lifestyle and depression. Clinical Psychological Science, 4(6), 1085-1093. doi:10.1177/2167702616638651

Seo, D., Patrick, C. J., & Kennealy, P. J. (2008). Role of serotonin and dopamine system interactions in the neurobiology of impulsive aggression and its comorbidity with other clinical disorders. Aggression and Violent Behavior, 13(5), 383-395. doi:10.1016/j.avb.2008.06.003

Spaeth, M., Weichold, K., & Silbereisen, R. K. (2015). The development of leisure boredom in early adolescence: Predictors and longitudinal associations with delinquency and depression. Developmental Psychology, 51(10), 1380-1394. doi:10.1037/a0039480

Tabatabaie, A. F., Azadehfar, M. R., Mirian, N., Noroozian, M., Yoonessi, A., Saebipour, M. R., & Yoonessi, A. (2014). Neural correlates of boredom in music perception. Basic and Clinical Neuroscience, 5(4), 259-266

Tilburg, W. A., & Igou, E. R. (2016). Can boredom help? Increased prosocial intentions in response to boredom. Self and Identity, 16(1), 82-96. doi:10.1080/15298868.2016.1218925

Tilburg, W. A., & Igou, E. R. (2017). Boredom begs to differ: Differentiation from other negative emotions. Emotion, 17(2), 309-322. doi:10.1037/emo0000233

Unsworth, N., & Robison, M. K. (2017). A locus coeruleus-norepinephrine account of individual differences in working memory capacity and attention control. Psychonomic Bulletin & Review, 24(4), 1282-1311. doi:10.3758/s13423-016-1220-5

Villano, I., Messina, A., Valenzano, A., Moscatelli, F., Esposito, T., Monda, V., . . . Messina, G. (2017). Basal forebrain cholinergic system and orexin neurons: Effects on attention. Frontiers in Behavioral Neuroscience, 11(10), 1-11. doi:10.3389/fnbeh.2017.00010

Walling, S. G., Nutt, D. J., Lalies, M. D., & Harley, C. W. (2004). Orexin-A infusion in the locus ceruleus triggers norepinephrine (NE) release and NE-induced long-term potentiation in the dentate Gyrus. The Journal of Neuroscience, 24(34), 7421-7426. doi:10.1523/jneurosci.1587-04.2004

Wingen, M., Kuypers, K. P., Ven, V. V., Formisano, E., & Ramaekers, J. G. (2008). Sustained attention and serotonin: A pharmaco-fMRI study. Human Psychopharmacology: Clinical and Experimental, 23(3), 221-230. doi:10.1002/hup.923