Alcohol addiction

Written by Quek Ten Cheer

Edited by Sasinthiran


Alcohol addiction is a serious societal issue that can lead to many domestic and social problems. One way to prevent this issue from becoming worse is to understand more about how alcohol, as a drug, causes these problems. In this article, we aim to inform readers on the biological effects of alcohol, especially on the brain, and how addiction is currently being treated medically.

Alcohol and crime

Alcohol has been implicated in between 57% and 85% of violent crimes1. In addition, many suicides are committed under the influence of alcohol2. The most likely mode of action for alcohol in stimulating aggression is its general disinhibiting effects on behaviour. Alcohol silences higher cortical areas responsible for impulse control, often leading to behaviour that is normally actively suppressed, including aggression.

What is alcohol?

Alcohol is a psychotropic drug, which means that it is a drug that affects our mental state. This places alcohol (commonly referred to as ethanol in scientific literature) in the same category as:

  • Cannabinoids (the active material in cannabis, or marijuana);
  • Nicotine (one of the active psychotropic agents in cigarettes and cigars);
  • Psychostimulants, much stronger drugs which include cocaine, MDMA (commonly known as ecstasy), and methamphetamine (you might know it as the blue ‘meth’ from Breaking Bad);
  • Opiates, morphine-like drugs such as heroin (diacetyl morphine).3,4

In addition, alcohol is a biphasic drug5; small amounts act as a stimulant by reducing inhibition and producing mild euphoria. Higher doses depress the central nervous system (CNS) that will initially promote relaxation but lead to the person experiencing effects such as ataxia (uncoordinated movement), sedation and general ‘drunkenness’.

Fun fact: Asian Flush

Some of us get the ‘Asian flush’, i.e. our faces become reddish from drinking (because the body is unable to quickly metabolize acetaldehyde, a by-product of alcohol metabolism). (Acetaldehyde is the main culprit behind headaches, nausea, and hangovers).

In fact, the reaction that breaks down acetaldehyde, by means of the enzyme aldehyde dehydrogenase, is faster in alcoholics than in non-alcoholics.6


Alcohol addiction

What makes a person addicted to alcohol? The 5th edition of the Diagnostic and Diagnostic and Statistical Manual of Mental Disorders (DSM-V), recognises excessive use of alcohol as a disorder in which patients are diagnosed with the substance use disorder when they display at least 2 of the following 11 symptoms within a 12 month period:

  • Consuming more substance than originally intended
  • Worrying about stopping or consistently failed efforts to control one’s use
  • Spending a large amount of time using the substance, or doing whatever is needed to obtain them
  • Use of the substance results in failure to “fulfil major role obligations”
  • “Craving” the substance
  • Continuing the use of a substance despite health problems caused or worsened by it
  • Continuing the use of a substance despite its having negative effects in relationships with others
  • Repeated use of a substance in a dangerous situation (e.g. when driving a car)
  • Giving up or reducing activities in a person’s life because of the substance use
  • Building up a tolerance to the alcohol or drug. Tolerance is defined by the DSM-V as “either needing to use noticeably larger amounts over time to get the desired effect or noticing less of an effect over time after repeated use of the same amount.”
  • Experiencing withdrawal symptoms after stopping use. Withdrawal symptoms typically include, according to the DSM-V: “anxiety, irritability, fatigue, nausea/vomiting, hand tremor or seizure in the case of alcohol.”

As can be seen from the DSM-V definition of alcohol use disorder, the interpretation of an individual’s use of alcohol as being excessive and leading to dysfunction is subjective and must be considered together with environmental and contextual factors.

However, alcohol addiction is also largely a problem that needs to be treated by addressing the environmental factors in addition to its targeted pharmacological treatment; prescribed medicines alone cannot fully treat the condition.

There is a plethora of literature on many illicit drugs of abuse, in particular cocaine. They demonstrate the pharmacological basis by which people become addicted to these drugs, in hopes of deriving better pharmacological treatment which targets, mainly, the addiction pathways in the brain.

Let’s talk about the brain

Firstly, if we want to know anything about alcohol addiction, we need to start with the very-important mesolimbic pathway, commonly called the ‘reward pathway’ for its role in addiction and associated disorders. You can recall this term and its position in the brain by the fact that ‘meso’ means ‘middle’ in Greek, and it is located in the middle of the brain. Thus ‘mesolimbic’ also means the midbrain, or ‘middle brain’.


The mesolimbic pathway, highlighted in the opaque blue in the above figure7, connects the ventral tegmental area (VTA) to the nucleus accumbens (NAC). It is also referred to as a dopaminergic pathway (abbreviated DAergic pathway) because it transmits the neurotransmitter dopamine throughout the two areas.8 Don’t underestimate its small size! It is the most significant neural pathway in the brain within which changes occur in all known forms of addiction. It is widely studied in the reward circuitry underlying drug abuse, depression, addiction, as well as conditioning and studies on human behaviour.

The brain is addicted to pleasure and positive effects; more specifically, it craves any activity which leads to the activation of dopaminergic pathways that trigger the brain’s reward response with the release of the neurotransmitter dopamine 9. Research shows that addictive substances such as alcohol are in fact addictive primarily because they activate such pathways leading to a reward response, leaving the brain craving for more 10. In other words, the more a particular behaviour, such as taking alcohol, triggers the reward centers of the brain, the more the brain seeks out such behaviour through learned operant conditioning by positive reinforcement. This then increases the occurrence of that behaviour in the future (thus, addiction).


A 2003 study done by Boileau et al.  have found that the consumption of alcohol stimulates the release of dopamine in the nucleus accumbens12. Dopamine (commonly abbreviated as DA in literature) was synthesised over 100 years ago (in 1910), but was recognised to be a neurotransmitter many decades later, in the 1950s. In the brain, dopamine is produced in hypothalamic neurons as well as neurons of the VTA and substantia nigra.13


After secretion of DA into the synapse, the intact molecule is reabsorbed into the neurons by a specific transporter, the dopamine transporter (DAT). They are then metabolised within cells by monoamine oxidase (MAO) or catecholamine O-methyl transferase (COMT); both enzymes convert dopamine into inactive products.

Compounds that inhibit DAT, such as cocaine (meaning the effect of dopamine is prolonged in the synapse as its concentration remains elevated), cause mood elevation and addiction.

Compounds that inhibit MAO (meaning DA does not get broken down after being re-uptaken) are effective antidepressants, which includes selective serotonin reuptake inhibitors (SSRIs), such as Prozac (you might know it as ‘fluoxetine’ or ‘fluoxetine HCl’ if you’ve ever had hypochondriac tendencies).

Neurotransmitters/neuropeptides that influence alcohol consumption

In alcohol addiction, there are several neurotransmitters and neuropeptides in the brain that influence alcohol consumption. These include Glutamate, GABA (gamma-aminobutyric acid), nACHR/glycine, DA/5-HT, Cannabinoids, Opioids, and CRF/NPY.11


Potassium channels and GABAA receptors in the VTA

Among the potential means by which alcohol might influence the firing rate of dopaminergic neurons in the brain, the best studied are the actions of ethanol on potassium channels and GABAA receptors in the VTA.

Alcohol functions as an agonist of GABAA receptors and its binding to these receptors leads to the inhibition of the post-synaptic neurons. Alcohol, by binding to GABAA receptors on VTA GABAergic interneurons, may disinhibit (activate) VTA dopaminergic neurons that project to the NAc (nucleus accumbens) which is involved in producing a feeling of pleasure and mood elevation (Nestler, 2005)14.

Interestingly, autopsies of alcoholics’ brains have revealed that they were in a hypodopaminergic state, which explains why alcoholics would continue to seek out more alcohol to achieve the sensation of pleasure and mood elevation they have learnt to associate with alcohol consumption.


Pharmacology of alcohol on the brain

Alcohol is generally viewed as being an unspecific pharmacological agent, but based on recent studies it has been shown to act by disrupting distinct receptor or effector proteins via direct or indirect interactions. There is a widespread plethora of literature on the abuse of psychostimulants, especially cocaine. (There is, however, scarce publications on abuse of alcohol.)

At concentrations in the 5-20mM range, which is the legal intoxication range for driving in many countries, alcohol directly interferes with the functions of several ion channels and receptors.11

Recent molecular pharmacology studies demonstrate that alcohol has a few primary targets, which include NMDA, GABAA, 5-HT3, nAChR, as well as L-type Ca2+ channels and GIRK, where concentrations as low as 1mM produce alterations in the functions of these receptors and ion channels. Some of these are outlined below:

NMDA receptors

NMDA receptors are commonly associated with excitatory glutamatergic activity and in the formation of Long Term Potentiation (LTP) which is essential for memory formation. Disruption of this receptor function by alcohol explains why many would find it difficult to remember the events of a night out when heavily intoxicated15– also known as ‘blackout’.

More inhibitory GABAA receptor activity

Moreover, alcohol has been found to stimulate inhibitory GABAA receptor activity by serving as an agonist in the hippocampus, an area of the brain associated with memory formation, contributing to this brief amnesic episode16.

Alcoholic activation of inhibitory GABAA activity of neurons projecting to higher areas of the cortex brings about reduced inhibitions and anxieties and facilitates better social interactions while reducing impulse control.

In fact, recovering alcohol addicts often experience life-threatening seizure episodes as a withdrawal symptom due to a rebound effect whereby inhibitory GABAA receptors become hypoactive in the absence of alcohol.


Alcohol also functions as an endorphin, mimicking the effects of opiate drugs and producing an endorphin ‘high’ associated with the use of such drugs.

More inhibitory neuromodulator activity

Alcohol has also been found to increase the activity of inhibitory neuromodulators such as adenosine which leads to sedative effects and a reduced state of awareness.

Treatment of alcohol addiction

It is estimated that 7.9% of people 12 years or older in the U.S. require help for alcoholism, more than twice the percentage of the population estimated to require treatment for the abuse of all illicit drugs collectively.

Alcohol use has been linked to diseases and ailments such as malnutrition (due to the ‘empty calories’ of alcohol) and in particular fetal alcohol syndrome (which causes developmental and physical abnormalities in the offspring of mothers who consume alcohol during pregnancy).

Alcohol abuse has been linked to domestic abuse, sexual assault, and can destroy families.

Treatment of alcohol addiction is largely based on psychological and psychiatric help, as compared to pharmacologically-based treatment.

Alcohol addiction requires a multi-pronged approach to treatment. Drugs alone show little effect insofar as treatment is concerned; environmental factors need to be addressed when treating alcohol addiction. Treatment involves the facilitation of abstinence and the prevention of relapse.

Pharmacologic treatment is often used to reduce withdrawal symptoms, but thus far has not been effective in preventing relapse. It is a theoretical possibility, however, that medications which block the reinforcing effects of drugs or drug-induced plasticity might reduce drug craving and the likelihood of relapse. Such medications can be effective if they can act without interfering with the body’s responsiveness to natural rewards (e.g. anhedonia, when the abuser suddenly finds a drastic disinterest in normal daily activities). Currently, no reward-reducing drug treatment has yet been established for clinical use.


  1. Cacioppo J., Freberg L., 2013. Discovering Psychology: The Science of Mind, Briefer Version. Wadsworth, Cengage Learning, Chapter 11, pp. 600.
  2. Sher L. (2006). Alcohol Consumption and Suicide. QJM, 99(1):57-61.
  3. Nestler, E. J.; Hyman S. E.; Malenka R. C. Molecular Neuropharmacology: A foundation for clinical neuroscience (2nd) McGraw-Hill. pp. 364-388
  4. Pierce, C.R., Kumaresan V., 2006. The mesolimbic dopamine system: The final common pathway for the reinforcing effect of drugs of abuse? Neuroscience and behavioural reviews, 30, Issue 2, pp. 215-238.
  5. Glossary: Drugs and Alcohol. (n.d.). Retrieved July 16, 2016, from
  6. Campbell, M. K., Farrell, S. O. (2009,2012). Biochemistry. Brooks/Cole Cengage Learning. pp. 689.
  7. Mesolimbic pathway. (2015) [Image from]
  8. “Mesocorticolimbic Dopaminergic Neurons.” Neuropsychopharmacology: The Fifth Generation of Progress. Retrieved from
  9. Insel, T. R., 2003. Is Social Attachment an Addictive Disorder?. Physiology and Behavior, 79(3), pp. 351-357.
  10. Koob, G. F. & Moal, M. L., 1997. Drug Abuse: Hedonic Homeostatic Dysregulation. Science, Volume 278, pp. 52-58
  11. Vengeliene V.; Bilbao A.; Molander A.; Spanagel R. Neuropharmacology of alcohol addiction. British Journal of Pharmacology (2008) 154, 299-315.
  12. Boileau I. et. al, Alcohol promotes dopamine release in the human nucleus accumbens. Synapse 49:226-231 (2003). Retrieved from
  13. W. Pfaff (ed.), Neuroscience in the 21st Century, DOI 10.1007/978-1-4614-1997-6_51, # Springer Science+Business Media, LLC 2013
  14. Nestler, E. J. Is there a common molecular pathway for addiction? Nature Neuroscience 8, 1445 – 1449, 2005
  15. Lovinger, D. M.; White, G.; Weight, F. F. NMDA receptor-mediated synaptic excitation selectively inhibited by ethanol in hippocampal slice from adult rat. Journal of Neuroscience 10:1372. 1379, 1990.
  16. Weiner, J. L.; Zhang, L.; Carlen, P. L. Potentiation of GABAA-mediated synaptic current by ethanol in hippocampal CA1 neurons: Possible role of protein kinase C. Journal of Pharmacology and Experimental Therapeutics 268:1388. 1395, 1994

Workshop on Neuroimaging

Written by Yingchen

Edited by Xin Chen, Sasinthiran and Keshiniy

Figure 1: Members of NUS Neuroscience Student Interest Group at Clinical Imaging Research Centre

On the 22nd of February 2016, members of NUS Neuroscience Student Interest group attended a workshop on Neuroimaging hosted by A*STAR-NUS Clinical Imaging Research Centre (CIRC).

The Workshop started with an introductory lecture by Dr John Totman, Head of Imaging Operations at CIRC. He recounted the history behind various imaging techniques such as Ultrasound, X-Ray, CT, PET and MRI, and gave a brief overview on the science behind these techniques, their limitations and common uses, for example, in the field of nuclear medicine.

One of the most common imaging techniques, ultrasound makes use of the Doppler Effect.  Ultrasound waves are emitted from the probe, which then detects the reflection of those waves off anatomical structures to construct an image of the structure; similar to echolocation used by dolphins and bats. Ultrasound is not commonly used in neuroimaging because sound waves cannot penetrate the skull.

Another commonly used technique, X-ray works on the principle that structures in the body attenuate x-rays that are projected on one side of the body such that the rays emerging from the other side expose a sheet of film to produce an image reflecting the body structures. However, the images produced are two-dimensional and thus may miss out certain structural details. As a result, multiple images at different sections of the body are required for a more accurate representation of the body structures.

A variant of X-ray imaging is Computerized Tomography (CT). It uses a rotating x-ray emitter and detector to provide a 3D reconstruction of anatomical structures. It is commonly used in neuroimaging to provide the structural information that aids in medical practices, such as detecting tumours and aneurysms. The grey and white matter of the brain can be distinguished clearly on CT images.

Another technique, Positron Emission Tomography (PET) requires an ingestible tracer consisting of glucose in conjugation with radioactive fluorine, which is prepared in the expensive cyclotron reactor by accelerating and colliding sub-atomic particles. Other positron-emitting radionuclides such as oxygen might also be used depending on how long the effect is required to last. When the radioactive substance decays, positrons are released which collide with the electrons released by the PET scanner, producing two gamma rays which scatter in exactly opposite directions. The PET scanner detects these two gamma rays and computes the average distance at which the rays originated to indicate the location of the anatomical structure. PET can be used for functional as well as anatomical imaging. The principle behind anatomical imaging is that cancer cells take up glucose rapidly, but fludeoxyglucose (FDG) cannot be easily metabolised and thus accumulate in these cells and can be detected.

SPECT, which stands for Single-photon Emission Computerized Tomography, is a combination of PET and CT. PET provides metabolic information while CT provides structural anatomical landmarks such as bones to give relevance to the metabolic activity reported by PET scans.

After Dr Totman’s lecture, Ms Caroline Wong, a Research Officer at CIRC, introduced us to Functional Magnetic Resonance Imaging (fMRI), which is the most commonly employed imaging tool for functional studies in neuroscience research. fMRI provides both structural and functional information of the brain. The basic unit of fMRI images is the voxel, which is a 3D pixel with modifiable size and length. Smaller the voxel, greater is the time required to acquire it, but more detailed the image would be, which is analogous to having thinner slices: many voxels make up a slice, and many slices make up the volume.

The science behind MRI is that protons have different spins in random directions, which align when placed in a magnetic field. When the MRI scanner emits radio frequency pulses, the protons are tilted out of alignment from each other. When the radio frequency pulses stop, the protons lose energy and return to their baseline aligned state, thereby releasing electromagnetic waves that are detected by the scanner.

In fMRI practice, active areas of the brain receive more oxygenated blood flow due to the dilation of local cerebral blood vessels. The protons in oxygenated haemoglobin and deoxygenated haemoglobin have different rates at which they return to their baseline aligned state. Moreover, oxygenated blood is diamagnetic, does not distort the surrounding magnetic field and thus there is no signal loss. In contrast, deoxygenated blood is paramagnetic, distorts the surrounding magnetic field and thus there is signal loss. These differences are used to highlight brain areas that are active during a task, since active areas are marked by a higher level of oxygenated blood flow. A more detailed relation is displayed by Figure 2, the hemodynamic response function profile.

Figure 2: Hemodynamic Response Function Profile (

In Figure 2, the initial dip is due to blood oxygen taken in by active brain areas from surrounding blood vessels. The rapid rise is due to overcompensation of blood flow due to dilation of blood vessels, which usually lasts for around 4-8 secs, but the exact time period depends on the brain area. The post-stimulus undershoot is due to elastic recoil of expanded blood vessels. Meanwhile, voxel colour changes with the time course of the curve.

Typical fMRI task designs include the block design, which consists of periods of rest between periods of activity; the slow event-related (ER) design, which has been phased out as it is inefficient; the rapid counterbalanced ER design, which is the fastest; and the mixed design, which consists of both block and ER. One difficulty with fMRI is that it requires minimal movement of non-task related areas of the body since movements may create “noises” that confound the results. Another difficulty is that brain functions are not localised to particular areas; meanwhile, the same area may be involved in many different functions. Notably, synchronisation between multiple brain areas that process the same cognitive properties have been seen to be out of synchrony in patients with neuropsychological disorders such as schizophrenia and bipolar disorder. Thus, careful interpretation of neuroimaging results is necessary.

After the presentations, we were invited to visit the fMRI laboratory, and witnessed several interesting phenomena such as the strong force of attraction between metal objects and the fMRI scanner, and the fact that conductors would fall due to gravity when suspended, albeit at a slower than expected rate in the fMRI scanner chamber due to electromagnetic induction. Towards the end of the workshop, Ms Caroline Wong also indicated that Dr Qiu Anqi from NUS Computational Functional Anatomy Lab was looking for research assistants. Details can be found in this link:

Within the two-hour session, the workshop provided us with an essential foundation for appreciating the various neuroimaging techniques used in neuroscience research and clinical practice. We would like to thank the Clinical Imaging Research Centre (CIRC) for accommodating our group and conducting this workshop.


“MDPI Open Access Publishing”, MDPI AG, 1996-2016. Accessed 7th March 2016. (

The Neuroscience of Love

Writen by Sasinthiran

Edited by Xin Chen, Yingchen and Keshiniy


“How on earth are you ever going to explain in terms of chemistry and physics so important a biological phenomenon as first love?”

–Albert Einstein

While science has taught us much about the complexities of human behaviour, nothing seems to be as enigmatic as the concept of love. Love is such a powerful force that it has driven some to start great wars while inspiring others to produce marvelous works of art, poems, songs and novels. It is both rewarding and punishing, is often unpredictable and drives one to act in irrational, sometimes ridiculous ways. Einstein might be right in that this complex concept of love cannot be simply reduced to basic principles in science. However, in light of Valentine’s Day, let us review some of the insights neuroscience research has given us on how the brain handles matters of the heart.

Love, sex and other drugs

When falling in love, most people experience a rise in the levels of the stress hormone cortisol (a corticosteroid) which helps in overcoming the initial neophobia characteristic of the initial phases of starting a relationship with someone special (de Boer, et al., 2012). Many would also relate to experiencing changes in sleep patterns, a general loss of appetite and occasional mood swings when falling in love. These changes are an effect of depleting Serotonin (a neurotransmitter in the brain) levels which are inversely correlated with the levels of corticosteroids.

The brain has evolved several mechanisms to keep the passion burning after the initial period of falling in love. Most people will find it difficult to accept the idea that love is in fact an addiction. The brain is addicted to pleasure and positive affect, more specifically, it craves any activity that leads to the activation of dopaminergic pathways which trigger the brain’s reward response with the release of neurotransmitter dopamine (Insel, 2003). This pathway, known as the mesocorticolimbic pathway (see image below), originates in the ventral tegmental area (VTA) which project to the nucleus accumbens which in turn projects to the ventral pallidum and thalamus (midbrain structures as labelled below). Neurons from the thalamus then project to the prefrontal and cingulate cortex (PFC) (Everitt & Wolfe, 2002).

Image: The Mesocorticolimbic Pathway (

Research shows that addictive drugs such as cocaine are in fact addictive primarily because the activate such pathways leading to a reward response, leaving the brain craving for more (Koob & Moal, 1997). In other words, the more a particular behaviour such as taking cocaine triggers the reward centres of the brain, the more the brain seeks out such behaviour through learned operant conditioning by positive reinforcement. This then increases the occurrence of that behaviour in the future (addiction). Interestingly, in an fMRI study whereby participants were shown pictures of people they ‘liked’ versus people they ‘loved’, it was shown that the latter group elicited a greater activation of the brain’s reward pathways (Bartels & Zeki, 2000). Hence, being in love , just like drugs, triggers the same reward pathways of the brain and this leaves the brain craving for more due to positive reinforcement.

The effects of Oxytocin (OT) and arginine Vasopressin (AVP) have been extensively studied in bonding studies involving voles, comparing those that by their own nature, have monogamous relationships (prairie voles) with those that are polygamous (montane voles) (Young & Wang, 2004; Lim & Young, 2006). From such studies, it was found that blocking the release of these two hormones caused the prairie voles to be promiscuous while injection of the hormones into these voles caused them to be faithful to their partners, even when they were prevented from having sex. It would then be reasonable to expect that injecting the hormones into promiscous individuals could reduce this behaviour (many have actually suggested this as a ‘cure’ for human promiscuity!). However,  injection of the hormones into montane voles which are promiscuous by nature, did not render them monogamous and it was found that the reason for this was that montane voles did not have a sufficient number of receptors for these hormones in the reward centres of their brains (Edwards & Self, 2006). Hence, they were not responsive to the reinforcing effects of oxytocin and vasopressin. This possibly suggests that certain individuals lacking the receptors for these hormones (and hence not responsive to them) are actually predisposed to exhibit promiscuity!

Oxytocin and Vasopressin are both synthesized in the brain’s hypothalamic paraventricular and supraoptic nuclei and secreted by the posterior pituitary into circulation. Both neuropeptide hormones are known to released during breastfeeding, child birth and sexual stimulation and have a neuromodulatory effect on different regions of the brain (Insel, 2010). Some of these brain regions are involved in regulating social behaviour which is then modulated as a result. Oxytocin in particular, reduces fear and anxiety related to social situations by reducing amygdala activity (Neumann, et al., 2000; Kirsch, et al., 2005), enhances social memory (Insel, 2010) and activates reward circuits in the brain involving dopamine release (Lim & Young, 2006). In fact, Oxytocin receptors have been identified in the nucleus accumbens (Insel & Shapiro, 1992) and the V1a Vasopressin receptor has been identified in the ventral pallidum (Insel, et al., 1994), both of which are part of the mecocorticolimbic pathway described earlier. Ultimately these hormones help modulate social behaviours favouring the long term maintenance of monogamous relationships through operant conditioning by rewarding such pro-social behaviours via brain’s reward system (Insel, 2010).

Quite predictably, couples with higher blood plasma oxytocin levels were found to have more positive communication behaviours (Gouin, et al., 2010), greater perceived spousal support and a higher frequency of hugs and massages (Grewen, et al., 2005). Research has also found that an individual becomes a stronger learned stimuli for oxytocin release in their partners with each successive sexual encounter with that person (Witt, 1997), proving that sex itself can be addictive. This then helps to facilitate a deeper bond between the sexual partners and increase the likelihood that they will stay together, which from an evolutionary perspective, will be essential for raising a child since the act of copulation eventually leads to begetting an offspring.

Interestingly, it seems that love can even be affected at the genetic level. High levels of a polymorphic variant of the V1a Vasopressin receptor gene, with a variation in the RS3 344 section, has been found to correlate with lower partner bonding, higher incidences of marital crises within a year and an increased likelihood of cohabitating as compared to  being married to a partner in a self-report study that studied men in long-term relationships (Walum, et al., 2008).

The Social Brain

The Belongingness Hypothesis states that people have a pervasive need to form and maintain significant interpersonal relationships with others (Baumeister & Leary, 1995). In fact, research shows that the need for social interaction may be more profoundly felt than other basic needs such as hunger (Baumeister & Leary, 1995; Cacioppo, et al., 2000). Socialising with others was an essential skill for survival and reproduction in the hunter-gatherer days of human history (Baumeister & Leary, 1995). The brain has evolved over the years to become a highly social organ with specific neural networks that have been perfected over thousands of years of evolution to support this function.

One of the ways the brain has evolved to support social bond formation is by differentiating the cognitive processing of information pertaining to significant others as compared to general acquaintances. Memories and information relating to those with whom we share a significant personal relationship is processed in a unique person-by-person basis while cognitive processes for other acquaintances are stored, organised and processed on the basis of general attributional categories such as preferences, traits and duties instead of person categories (Pryor & Ostrom, 1981; Ostrom, et al., 1993). One might hypothesize that the purpose for such a distinction in cognitive processing might be to improve the speed and efficacy of the recall of information pertaining to significant people in our lives. In fact, it was reported that recall for information about both groups of people did not actually differ significantly. However, another possibility is that the specific neural networks catered to processing information about significant people may also project to emotion processing areas of the brain and thus allow for the addition of an extra layer (emotion) to the retrieval of stored information about them since relationships and attachment are closely tied to affect. This could also explain why recalling information about significant people often triggers positive emotions.

Love is blind and unconditional

The frontal cortex is the central executive centre of the brain that processes higher cognitive functions such as logical thinking, judgements, decision making and morality. In an fMRI study it was found that brain areas associated with negative emotional processing (the parietal cortex and temporal lobe) as well as other areas involved in assessing the emotions and intentions of other and other aspects of social judgements (the frontal cortex) were less active when viewing pictures of people they ‘loved’ versus pictures of their friends (Bartels & Zeki, 2000).

It then comes as no surprise that people in a relationship tend to demonstrate a self-serving bias when interpreting their partner’s outcomes in an experiment by giving them credit if they succeeded and not attributing blame to them when they fail (Fincham, et al., 1987). They also demonstrate this bias in giving their partners a  more favourable interpretation of their role in causing events (causal attribution) (Craig, 1991). This probably relates to why we tend to overlook the flaws of those we are smitten over as this is probably an adaptation of the brain to aid in maintaining an existing relationship.

Researchers have also found that activity in the amygdala which is associated with fearful situations, is reduced when viewing pictures of their partners (Zeki, 2007). The suppression of judgment and increase in trust as a result of diminished fear (amygdala activity suppression) leads to increased bonding between partners and may also account for the irrational behaviour of people in love.

Rejections are painful – literally

Some of us might have had the unfortunate experience of a break-up and we know that it can be an unpleasant experience. What is interesting though, is that the brain perceives the pain of social rejection the same way it would physical pain. This has been demonstrated in fMRI studies which have shown that the same brain areas, such as the anterior cingulate cortex (ACC), anterior insula (AI) and the right ventral prefrontal cortex (RVPFC), that are activated when processing the ‘affective’ or unpleasant component of physical pain, are also activated in response to social rejection (Eisenberger, et al., 2003). In fact, in one fMRI study it was found that presenting participants a picture of their ex-partners who rejected them not only activated the ACC but also triggered activity in the regions of the somatosensory cortex such as S2 which respond directly to physical sensations of pain (Kross, et al., 2011).

Image: Pain processing pathways in the brain (Bushnell et al., 2013)

It has been suggested that social system of the brain may have evolved to rely on the neural pathways for processing physical pain to indicate when social relationships are threatened, given that social connections are important for human survival (Panksepp, 1998). This further lends support to the role of operant conditioning in helping to maintain relationships. An individual learns the appropriate behaviours that will keep a relationship healthy through positive reinforcement in terms of triggering reward pathways of the brain that encourages future occurrence of such behaviour, as well as through positive punishment in terms of the pain associated with social rejection in response to behaviours that threaten relationships (Eisenberger, 2011).

The rules of attraction

An experiment involving the use of PET (positron emission tomography) to measure regional cerebral blood flow (rCBF) as a means of identifying brain areas that are more active (with more cerebral blood flow), identified that increased activity in the left insula correlated with reporting of the attractiveness of unfamiliar faces (Nakamura, et al., 1999). In what seems to be eerily similar to mind control, researchers have demonstrated that judgements of physical attractiveness can be manipulated by evoking different emotions in participants through music (May & Hamilton, 1980). It was found that evoking positive affect such that the brain’s reward pathways are activated through rock music increased perceptual judgements of attractiveness.

Anthropological research has shown that since the stone ages, people will select mates who stand out from the rest of the crowd when presented with a choice of mates of equal value (Frost, 2006). Researchers have found that the mere exposure effect, a principle in which regular exposure to a neutral of positive stimuli generally increases the liking for that stimuli (Zajonc, 1968) can be applicable to humans as well (Swap, 1977). This probably explains why some men finally win over the woman they court after some time. Either that or the women are just playing hard to get! Studies have shown that sharing a meal has a profound effect on human bonding as higher levels of oxytocin release has been measured in such settings (Wittig, et al., 2014). Hence, a nice romantic dinner on the first date might not be a bad idea after all.

In romantic situations, males use more uncommon, fancy words than they do in other situations (Rosenberg & Tunney, 2008). This could serve as a litmus test for knowledgeable women to identify if someone is trying to impress them! In one study, higher levels of fertility in women was found to be associated with lower levels of linguistic matching in their male partners in experimental setting (Coyle & Kaschak, 2012). Linguistic alignment is usually used to signal affiliation (Giles, et al., 1991) and leads to increased liking between participants in social interactions (Chartrand & Bargh, 1999; Cheng & Chartrand, 2003). However, it was noted that men paired with women in the fertile stages of their menstrual cycle, chose to use different syntactic structures in their speech and not mimic that of their partners (non-conforming behaviour) as one would expect. The men seemed to have picked up subtle subconscious cues about the female partner’s fertility and coud be presenting their non-conforming speech behaviour as a display of their fitness as a mate.

Having a sense of humour is a common feature that both men and women look for in their ideal mates, albeit with a significant difference. Men prefer women who appreciate their jokes, and not necessarily women who are funny themselves, while women prefer men who made them laugh (Bressler & Balshine, 2006). It was also observed from the study that women signal their level of attraction to their partners by the frequency of their laughter while men’s laughter was not correlated to their degree of attraction to a potential mate.

Studies have shown that men and women in a romantic relationship share fundamental differences in areas of the brain that are more active. Men, have been found to have increased activity in areas of the brain involved in integrating visual stimuli (Narumoto, et al., 2001) while women have greater activation in areas associated with memory, attention and emotion (Gray, et al., 2002; Maddock, et al., 2003; Velanova, et al., 2003). This is supported by the evolutionary view of gender priorities in looking for a mate as males look for healthy mothers to carry their child while females look for possible security and resources offered by a male mate in raising her child (Fisher, 2004).

Through better or worse

In one particular fMRI study, women who held their husband’s hands were found to have reduced activity in parts of their brain involved with processing the emotional and arousing aspects of pain when they were told to anticipate an electric shock, as compared to women who were alone (Coan, et al., 2006). Interestingly, it was found that the reduction in pain-associated activity correlated with the quality of their marriages such that happily married women had a greater degree of reduction in activity. Another observation from the study was that women who held the hands of men they did not know also showed a reduction of activity in pain processing, albeit a smaller reduction than the women who held their husband’s hands. This shows that love, or any relationship for that matter, may have a protective effect on the brain in terms of reducing the processing of unpleasant or noxious stimuli.


As reviewed in this article, neuroscience research may provide some insight, and at best, a fragmented view on neurological basis for some behaviours demonstrated by people in love. However, love is a complex emergent behaviour which we can never fully appreciate and artificially re-create even with the advances in knowledge.


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