brainstem

On the nature of pain

Posted on by Iasmina Hornoiu

Last week, a manatee was found in Florida waters, with the word ‘Trump’ scraped on its back. Although this kind of ruthless mutilation is horrific in itself, I started wondering if the animal felt any kind of pain.

I must admit, up until I came across the news about what happened to the manatee in Florida, I knew very little about manatees, in general. And my first thought was whether, during the scraping proccess, this manatee suffered at all. To my dismay, there were not many scientific papers dealing with the somatosensory system in manatees. However, I did find something that eased my soul a little bit: one of the articles reporting on the dreadful event states that the scratch was done in the algae growing on the animal’s back. Still, in the same article it is said that manatees have sensory hairs and nerves in their skin, which means that, if the cuts had touched the skin, they could have caused pain; not to mention the infection that the skin was at risk of, due to the open wounds.

The video below shows the above-mentioned manatee swimming, with the human-made scars on its back.

After reading all these news articles, I was left with some questions that kept occupying my mind: What are manatees?; To what extent can they feel pain?; And can we talk about ‘pain’ at all in manatees, or just nociception? Lastly, how did pain evolve throughout the animal kingdom?

What are mantees?

Also known as ‘sea cows’, manatees (Trichechus manatus latirostris) are herbivorous acquatic mammals of the Order Sirenia. As the name of their order suggests, manatees are believed to be the animals behind the myths of mermaids. For those interested in how manatees inspired mermaid legends, please check out the video below.

Manatees are the largest vegetarian animal to inhabit the sea, and they communicate with each other through high-pitched sounds. They are also very gentle and lack defense mechanisms, given that they do not have any natural enemies. However, they have become and endangered species, due to human activity, which is the manatee’s greatest threat. According to the Florida Fish and Wildlife Conservation Commission, the year 2020 was a hard one for manetees as well: 637 of them died, 90 of which were victims of boat collisions, and another 15 were killed by other interactions with humans.

Although manatees do not possess a highly acute visual system, they compensate for that by the presence of tactile hairs, or vibrissae, spread all over their body, especially on the face. This distribution of vibrissae is something unique among mammals, and to manatees it is highly useful in allowing them to navigate in the water.

Since mantees rely tremendously on tactile inputs, it comes as no surprise that their brains are organised to support somatosensation. The primary somatosensory cortex of manatees occupies 25% of their neocortex. Moreover, the sixth layer of their cortex contains clusters of neurons, known as Rindenkerne, which are believed to process information related to the manatee’s facial and bodily vibrissae. Although the Rindenkerne cells of manatees are somewhat similar to other cortical representations of vibrissae, termed ‘barrels’, in rodents, shrews, opposums and hedgehogs, Rindenkerne are unique to sirenia. These neuronal aggregates become active when manatees engage in tactile exploration and object recognition.

At the subcortical level, manatees possess three types of somatosenroy nuclei in their brainstems, namely the Birchoff’s nucleus, which receives information from flukes, the cuneate-gracile nucleus, which processes inputs from flippers and body trunk, and the trigeminal nucleus, which receives sensory inputs from facial vibrissae. Figure 1. below shows the somatosentory representations of the manatee’s body parts, in a coronal section of the brainstem. The thalamus also has specialised somatosensory nuclei, which differ in size, depending on their functional relevance to somatic sensation.

Figure 1. Left diagram based on image by Isuru Pryiaranga. Right image from Sarko et al. (2007), showing functional divisions withing the brainstem, corresponding to the manetee’s body parts. 

Given that somatosensation is so developed in manatees, one burning question is whether they feel pain.

What is pain?

Pain is different from nociception. However, pain from injury cannot occur without nociception. The latter reffers to the process of detecting injury by the activation of a special class of receptors found in the skin, as well as deep tissues and organs, known as nociceptors. The detection of potentially or actually damaging stimuli is followed by a reflex withdrawal reaction, or nociceptive behaviour, mediated by nerves in the spinal cord. The nerve fibres that detect noxious stimuli are Aδ fibres and C fibres, which have their cell bodies in the dorsal root ganglion (DRG) of the spinal cord, as shown in Figure 2.

Figure 2. Illustration taken from a student presentation at Heidelberg University, Germany.

Aδ fibres are mechano-nociceptors, meaning that they are activated by high mechanical pressures. C fibres are polymodal, which means that they respond to a variety of noxious stimulations, such as noxious chemicals (e.g., acids), extreme temperatures and high mechanical pressures. They not only encode the stimulus modality (type), but also their intensity and duration, which are relayed to reflex centres in the central nervous sytem, mediating withdrawal reactions.

The nociceptive information travels from the DRG to different parts of the brain via spinothalamic tracts (from the spinal cord to the thalamus) and sensory fibres of the trigeminal tract (from the face to the thalamus). And it is within the brain that pain happens.

Pain is a complex feeling. Many brain areas are involved in not just generating pain, but also in ameliorating it. Structures from the limbic system, such as the amygdala, receive and integrate nociceptive and affect-related information. The amygdala can lead to increased nocifensive and affective pain behavior, while, under certain circumstances, it can also contribute to endogenous pain inhibition. Pain is also processed in the hypothalamus, the basal ganglia, the insula and the somatosensory cortices. Because these areas play a role in metabolism, as well as fear, pleasure and homeostasis, the nociceptive information is integrated and modulated according to the current state of the individual. In some situations, pain becomes pathological, as it is the case in neuropathic pain, where either previously innocuous stimuli become painful (aka, allodynia), or previously painful stimuli become even more painful (aka, hyperalgesia).

There are two brainstem structures, which are highly involved in controlling pain and generating analgesia. One of them is the periaqueductal grey (PAG) and the other is the rostral ventromedial medulla. These regions exert control over pain to prioritise competing stimuli, and to maintain homeostasis and survival. You might have noticed that, in highly stressful situations you do not feel pain. This is known as stress-induced analgesia, a phenomenon whereby the brain responds to stress by the production of endogenous opioids that act as natural analgesics in the nervous system. The opioid receptors found in the brain are the same ones which analgesic drugs, such as synthetic opioids and morphine, act on to relieve pain.

The evolution of pain

Many animal taxa have nociceptors. A schematic of the evolutionary development of nociceptors and the types of noxious stimuli they respond to is presented in Figure 3. In order to process nociceptive inputs, animals need a central nervous system (spinal cord and brain). It might come as a surprise that such a system, though at different levels of complexity, is found in all kinds of animals, including insects (like Drosophila melanogaster, the fruit fly), C. elegans (a type of worm highly studied in neurosciences), fish, amphibians, reptiles, birds and, of course, mammals.

Figure 3. The different types of nociceptors across animal taxa, from an evolutionary perspective.
Taken from Sneddon (2017)

Life-history shapes pain perception. A very interesting example is the African naked mole rat, which lives in underground burrows that are poorly ventilated, hence contain high carbon dioxide levels. As a result, the C fibres of the naked mole rat are unresponsive to acid, which means that, while other mammals find acidic environments nociceptive, the African naked mole rat does not.

When it comes to acquatic animals, such as manatees, they are expected to have differences in their sensory system compared to terrestrial ones, due to distinct ecological and evolutionary pressures. In water, any chemicals become dilluted, shifts in temperatures are less common, and there is no mechanical damage due to falling. Thus, acquatic animals are possibly at a lower risk of damage than terrestrial animals, which has implications on their nociceptive system.

As far as manatees go, it is still unclear to what extent they feel pain. The fact that they are an endangered species makes is difficult to study them. But given that they posses a very well-developed somatosensory system, which is even more advanced than in other mammals, it is expected that manatees are familiar with pain. Moreover, we still do not know enough about their stress, fear, memory and pleasure systems, which all play a role in pain processing.

It would be great if we managed to achieve a better understanding of these amazing marine animals. But, until then, let us enjoy their existance peacefully, without interfering violently with their lifestyles and without exposing them to any potential pains.

For a more in-depth view on pain, as well as more information about manatees, I highly encourage you to read the papers and articles listed in References.

Special thanks to Isuru Priyaranga for creating the cover image. He is a fellow blogger and YouTuber, and I highly recommend visiting his blog and YouTube Channel.

References

Oxytocin and Social Bonding

Posted on by Iasmina Hornoiu

While most of us would be able to describe what being affectively close to someone feels like, we might find it harder to explain why and how such a connection forms.

Why do we love and what makes us love certain people? Why is love so different depending on the subject of our affection? Is it possible to measure love? What does the complete absence of love in an individual reveal about their health state? With so many questions having been formulated throughout centuries, no wonder love has become a universal conundrum. Traversing various disciplines, it not only represents the realm of the literary, but it has increasingly become one of the central focuses in philosophy, biology, social sciences and neuroscience.

As far as the neuroscientific approaches to love go, this concept is represented by affiliative bonds. Therefore, from now on we shall refer to love as such. For the sake of the reader’s personal interest, we shall further discuss affiliative interactions as they appear and manifest in humans. Affiliation describes the ability of an individual to form close interpersonal bonds with other individuals of the same species. Three prototypes of affiliation have been identified: parental (between children and their parents), pair (between romantic partners) and filial (between friends).

This article is intended to introduce the reader to the evolutionary significance and neurochemical mechanisms underlying social bonding/affiliation. As such, the above-mentioned types of affiliative behaviours will be only in part separately discussed. Instead, we shall focus on what these categories share in common, particularly, the hormone-neurotransmitter oxytocin and the concept of synchrony.

Synchrony refers to the process by which the members of a social group collaborate with each other, in order to achieve a social goal. This kind of collaboration involves concordance in time between members, at the level of behaviour and physiological processes (e.g. hormonal release, neural firing). Through these synchronous processes underlying social reciprocity, each member is introduced to the social milieu, becomes adapted to his/her environment and learns how to survive.

Intimate reciprocal relationships between two individuals in a social group help shape the individual’s moral, empathic and pro-social orientation, as well as social adaptation and self-regulation. The interaction between mother and infant is critical to the social maturation and well-being of the young. Human mothers, just like other mammals, exhibit specific postpartum behaviours, such as affectionate touch, high-pitched vocalisations, expressing positive affect, which lead to the notoriously strong mother-infant bond.

This type of specific attachment relationship coordinates the physiology of the infant with the behaviours of the mother. Moreover, this mother-infant synchrony enables the temporal alignment of the infant’s inner state with the responses of the social environment (via the mother). The absence of a proper interaction between mother and child, especially within the critical period (between 3 and 9 months after birth), has been shown to contribute to the development of autism spectrum disorders (for more information on autism, check out this previous article – Decoding autism).

Romantic attachment is another type of social bonding in humans, with significant implications to the normal psychological functioning of the individual. According to recent studies, both parental and romantic relationships share similar behavioural characteristics (gaze, touch, affects, vocalisations and coordination of these behaviours between the members of the pair) and rely on similar neuroendocrine mechanisms. These mechanisms mainly involve a nine amino-acid neuropeptide known as oxytocin.

Oxytocin acts as both a hormone and a neurotransmitter. It is associated with a variety of functions including the initiation of uterine contractions during parturition, homeostatic, appetitive and reward processes, and last but certainly not least, the formation of affiliative bonds. For the latter, oxytocin plays a very important role in social recognition, maternal behaviour and development of partner preferences.

Oxytocin is produced in the hypothalamus, by the magnocellular neurones clustered in two types of nuclei: the supraoptic and paraventricular. These neurones send projections to the posterior pituitary gland, thus engaging the oxytocin system with the hypothalamic-pituitary-adrenal axis, mediating the stress response, as well as parturition, lactation and milk ejection. Other projections from the paraventricular nucleus go to various forebrain limbic structures (e.g. amygdala, hippocampus), brainstem (e.g. ventral tegmental area) and spinal cord. There are also other areas, apart from the brain and spinal cord, which receive oxytocin signalling, such as the heart, gastrointestinal tract, uterus, placenta, testes etc. With such extensive projections, it comes as no surprise that oxytocin is involved in a wide variety of processes.

In romantic and parental attachment, oxytocin induces the motivation to initiate sexual behaviour, the formation of sexual preferences and the increased stimulant value of the infant for its mother, via its connectivity with the mesolimbic dopaminergic neurones. The neurotransmitter dopamine plays a major role in the reward-motivated behaviour. Therefore, the oxytocin-dopamine interaction is key to the motivation to bond between members of romantic or child-parent relationships.

If you were wondering why the parental attachment has so far been presented only from the perspective of the mother-child relationship, that is because in males a different hormone mediates parental behaviour. Vasopressin can be seen as the male equivalent of oxytocin, as it modulates affiliation, aggression, juvenile recognition, partner preference and parental behaviour in males. Having said that, there are studies which show that oxytocin also supports paternal behaviour and is linked to the father-typical affiliative behaviour.

Oxytocin is also very important in establishing close connection with our best friends (what is known as filial attachment). According to research in this area, children start showing selective attachment to a ‘best friend’ around the age of 3. This kind of interpersonal interaction represents the first attachment to non-kin members of society, therefore, a crucial step in the normal development of any human being.

Depending on the level of synchronous parenting children experienced during infancy, their interactions with best friends can vary in the degree of reciprocity, emotional involvement and concern for the friend’s needs. These behaviours are modulated by oxytocin. During the first 3 years of life, oxytocin secretion in humans depends on the parent’s postpartum behaviour (which is predicted by the parents’ own levels of oxytocin) and, in turn, determines the degree of empathy between close friends. Therefore, a reasonable assumption, which has been recently proven, is that children benefiting from high parental reciprocity during infancy develop better social adaptation, are more friendly and cooperative, and show greater empathy.

All in all, the social bonds we form with members of our social group, be they our family, romantic partners or friends, are dependent on certain hormones and behaviours occurring at critical stages of development. Close attachment bonds with our parents, during early infancy, are later translated into affiliations to non-kin members of the social groups, who we come across during childhood, evolving into intimate friendships during adolescence, which eventually shape the ability of the adult human to form and maintain romantic connections and provide nurture for the next generation.

What we have just discussed is of importance for different aspects. Focusing on oxytocin and synchrony provides better understanding of neurodevelopmental disorders such as autism. At the same time, this focus offers some answers to questions regarding the reasons and mechanisms underlying the many types of love us humans experience throughout our lives.

References

Feldman, R. (2012). Oxytocin and social affiliation in humans. Hormones and Behavior, 61(3),  380-391. 

Hammock, E. A. ., & Young, L. J. (2006) Oxytocin, vasopressin and pair bonding: implications for autism. Philosophical Transactions of the Royal Society B: Biological Sciences, 361(1476), 2187–2198. 

Why “sleep”?

Posted on by Iasmina Hornoiu

In a previous article, we talked a bit about narcolepsy as one of the very intriguing sleep disorders. It was perhaps easy to understand why people suffering from narcolepsy could have a pretty hard time performing several normal tasks; however, most of us would probably relate less to narcolepsy. But something which almost everyone can agree to have experienced regularly, in one way or another, is sleep. In comparison with disorders associated with it or derived from its impairments, sleep itself might not seem so interesting. We all do it and we can’t deny how much we enjoy it and long for it after it stops. Yet, there is much more to sleep than we think.

Sleep is very important for the normal functioning of any being. For animals as well as for humans, sleep helps in energy conservation, body restoration, predator avoidance and learning aid. Different animals have different sleep-wake cycles, from nocturnal animals (like rodents), which sleep during the day and are active at night, and animals which sleep with only half of the brain (like dolphins), all the way to diurnal animals, like humans. Although humans are advised to sleep approximately 8 hours per night, some people sleep very little (around 2-3 hours/night) and still function perfectly fine. An example of such a situation is presented in the textbook of Rosenzweig et al. (pg. 389).

But what triggers sleep and how is it regulated?

Most of us are certainly able to recall a dream the next morning and the memory of that dream is usually accompanied by feelings and emotions we sometimes do not even experience in real life. We are often under the impression that our dream has lasted the whole night. In fact, there are two stages of sleep, one of which is associated with the formation of dreams. These stages, known as non-REM sleep and REM sleep, succeed each other in cycles lasting approximately 90 minutes. Just to define the terms, REM means rapid eye movement and represents the part of sleep with the most increased brain activity. Interestingly, during REM the brain seems to consume more oxygen than during arousal!

Normally, when we fall asleep we slip into the non-REM stage or the slow-wave sleep (SWL). This, in turn, is divided into four other stages: from light sleep to very deep sleep. During this phase, the brain is said to be truly resting and the body appears to repair its tissues. No dreams can be seen! The movement of the body is reduced, but not because the muscles are incapable of moving; it’s the brain which does not send signals to the body to move! One interesting feature of non-REM sleep is sleep-walking. This peculiar behaviour some people show while asleep usually takes place during the fourth (last) part of the non-REM sleep, when the person is the deepest sleep. This is the reason why it is very difficult to wake a sleepwalker up.

In turn, REM sleep (which starts after a 30-minute non-REM period) is the “active” part of our sleep. This time, the brain sends commands to the body, but the body seems to be in an almost complete state of atonia (immobility). The heart rate and breathing become irregular and the brain is not resting. In fact, our dreams happen during this time and more importantly, our long-lasting memories are thought to be integrated and consolidated.

FullSizeRender-2

When it comes to sleep regulation, many neuroendocrine systems and brain functions play a role. The circadian (or sleep-wake cycle), which is controlled primarily by the suprachiasmatic nuclei, in the hypothalamus, need special attention. For the purpose of this article, I won’t focus on the circadian clock now, but I will come back to this in a future article. The autonomic nervous system and parts of the brain such as the brainstem, the limbic system, especially the amygdala, and the forebrain modulate different aspects and stages of sleep. Amygdala, which I mentioned in a previous article about emotions and decision-making, is a brain region involved in the emotions such as fear. It also appears to be very active during REM-sleep and may account for the awful nightmares we often experience.

Many cognitive functions, such as intelligence, performance and emotions are associated with disrupted non-REM as well as REM sleep. To be more specific, REM-sleep loss appears to be associated with increased anxiety and stress and loss of emotional neutrality – this means that a person deprived of REM-sleep is more likely to react negatively to neutral emotional stimuli than in normal conditions. The explanations vary, but most of the studies agree that impaired REM sleep triggers increased release of noradrenaline, hyperactivity of amygdala and decreased function of prefrontal cortex (which tells “stop!” to the amygdala when it goes crazy). At the same time, people deprived of non-REM sleep could experience depression, due to deficiency in another neurotransmitter, this time an inhibitory one, called GABA (gamma-aminobutyric acid). Other problems linked to sleep deprivation are attention deficits, working memory impairments and usually affected divergent thinking (creative, innovative thinking).

Aging people seem to sleep less and this deprivation is also associated with conditions like Alzheimer’s. Moreover, sleep deprivation can kill you! Sustained sleep loss can cause low immune system and drop in body’s temperature, which can make bacterial infections fatal. Another consequence of sleep loss is increased metabolic rate, which leads to weight loss and eventually death. Don’t think this could be a good idea for a diet! More like for “die”!!! Having said that, most people should try their best to get enough hours of sleep.

I hope this article convinced you of the importance of sleep and as usual, any questions or comments are welcome 🙂

Further information:

Article 1 – about REM-sleep and emotional discrimination 

Article 2 – about non-REM sleep and GABA 

Article 3 – about how sleep loss affects behaviour and emotions

Article 4 – a review on many articles about the link between sleep deprivation and emotional reactivity and perception

Bear et al., 2006. Neuroscience – Exploring the Brain. s.l.:Lippincott Williams & Wilknins 

Rosenzweig et al., 2010. Biological Psychology – An Introduction to Behavioural, Cognitive and Clinical Neuroscience. 6th edition. Sinauer Associates Inc.,U.S., pg. 380-401

Both images by Gabriel Velichkova

Emotions and the brain

Posted on by Iasmina Hornoiu

Once upon a time, I promised I was going to write an article about how emotions affect our decision-making and why it is actually important not to ignore the feelings we have in certain situations…For several, unexplainable reasons I kept postponing this idea, and for that I am very sorry. Having said that, there is no better way of making up for this than to finally keep my promise. So, here we go!

I think I should start off with a small mention: emotions and feelings are distinct things, according to neuroscientist Joseph LeDoux. As he well puts it: “…feelings are what happen when we become consciously aware that our brain is reacting to some significant stimulus,” while it is possible that some brain structures, such as the amygdala “respond to emotional stimuli without the organism being aware of the stimulus.”

In order to achieve a better understanding of what the process of forming emotions involves, scientists talk about emotional experience and emotional expression. The latter refers to body manifestations and behaviours in response to certain stimuli, for example changes in facial expression, heart rate, sweating, skin conductance etc. It has been a subject of debate for several decades whether emotional experience or emotional response is the one responsible for formation of the other, or that they act independently. It is now believed that different emotions depend on specific parts of the brain and are determined by different neural circuits.

But why should we care about emotions in the first place? Some of you might find it strange, but emotions are intensely interconnected with reasoning and decision-making. And no, I don’t mean that they impair the process of making the right decision, it’s actually quite the opposite: most of the times we need emotions in order to be able to do what is best for us in a certain situation.

An interesting case: Phineas Gage 

A man who has gone down in history for surviving a terrible accident at the work place, but maybe mostly because of his importance in understanding the role of emotions in decision-making, is a late 19th century foreman, Phineas Gage. He had been hired as a foreman on a railroad construction site in Vermont and one of his tasks was to sprinkle explosive powder into blasting holes. This sounds like a dangerous thing to do, but Gage was regarded as one of the best people in this field: he was said to be very efficient, energetic, balance-minded, tenacious, a smart and successful business man etc.

One moment of carelessness dramatically changed his life forever, and at the same time had a huge impact on the way scientists began to think of emotions. The powder exploded and a tamping iron entered Gage’s head under his left eye, passing through his left frontal lobe, and exited the skull, leaving a hole which measured more than 9 cm in diameter.

Gage survived, but he “was no longer Gage”, as his friends and acquaintances used to say. Apart from losing vision in his left eye, the man had no motor or sensory deficits, he could hear, touch, sense, walk and talk. It was his personality that was completely changed. He became capricious, irreverent, impatient, and behaved as if he did could not predict, nor care about any professional or personal failure. He was soon fired and found different jobs over time, most of which were related to the accident and the iron rod, which had turned him into some sort of freak.

Some explanations and brain functions

The limbic system is probably the first to come to mind if you refer to brain areas involved in emotions. It consists of structures around the thalamus or in the temporal lobe, such as the amygdala, the hypothalamus, the limbic cortex, the cingulate gyrus, the fornix, the corpus callosum etc. Each one of these structures is involved in specific types of emotion and in triggering certain behaviours or responses through the autonomic nervous system. For example, the amygdala is linked to fear and aggression. Different regions (nuclei) in the amygdala are associated certain functions, so that both emotional expression and experience require the amygdala in order to be formed. Projections from amygdala are sent to the hypothalamus, which determines the autonomic response, the brain stem for behavioural reaction and the cerebral cortex, which is involved in emotional experience. The amygdala is also thought to play a role in enhanced emotional memory.

Regulation of specific emotional behaviours depending on the limbic system is facilitated by one of the major neurotransmitters, serotonine. Neurones containing serotonin originate in the brain stem (in the Raphe nuclei) and send projections to the hypothalamus. Serotonine is associated with a decrease in aggressive behaviour, but at the same time is involved in dominance, as proven by studies in rhesus monkeys.

The Papez Circuit (named after the neurologist James Papez who came up with the idea of an “emotional system”) is composed of interconnected anatomical structures (many of which are part of the limbic system) that link emotional expression and emotional experience together. Papez proposed that the cingulate cortex determines emotional experience, while the major structure involved in emotional expression is the hypothalamus. 

Below I have inserted a diagram showing the Papez Circuit, based on information from Bear et al. Note that the hippocampus is now thought to have less importance in the process of emotion formation.

The Papez Circuit

The discussion above does not fully explain what happened in the case of Phineas Gage. There is much more to emotion than that! Given the fact that the iron rod severely affected Gage’s frontal lobe, we should definitely focus our attention on this structure, too. The frontal lobe and the prefrontal cortices are involved in planning, reasoning, social behaviour, motivation, defining our personalities etc. Damage to these regions, especially to the ventromedial prefrontal cortices, results in decision-making impairment. While the intelligence and the other body functions remain intact, the patient who has suffered the damage is no longer able to exhibit normal social behaviour. The patient becomes emotionless and this lack of emotions and self motivation makes them incapable of making the right decisions.

If instead of the ventromedial prefrontal cortices, another region of the prefrontal cortices is affected, there is a very strong possibility that the patient’s intellectual abilities are compromised, along with their ability to form emotions. This region is called the dorsolateral prefrontal cortices. The person with a damage in this brain area would encounter severe difficulties when it comes to operations on numbers, words, space etc.

Another brain structure involved in the process of emotion forming is located in the right hemisphere. If the somatosensory cortices of this area are injured, the result would be similar to what can be seen in the case of a damaged ventral prefrontal cortex, but there is something more…the processes of basic body singling are also disrupted. This can be observed in patients suffering from anosognosia, a disease in which the patient is unaware and denies their disability.

I have tried to comprise a lot of information and simplify things as much as possible. If you managed to get here with both eyes open, I couldn’t be happier. Hopefully, you can see now why we should also “think with our hearts” when we need to decide about a certain situation…because the “heart” is somewhere in the brain and it knows better than us what we need to do.

For further information:

Antonio Damasio,1995. Decartes’ Error. Vintage Books

Bear et al., 2006. Neuroscience – Exploring the Brain. s.l.:Lippincott Williams & Wilknins pp. 564-581

Article about Phineas Gage

Image by Isuru Priyaranga 

Mechanisms of schizophrenia

Posted on by Iasmina Hornoiu

It took me a while to figure out whether to divide this article into two parts or to sum up everything in one long, possibly tedious reading. Honestly, I still don’t know, so I’ll just start writing and we shall see what it turns out to be.

I’m sure you’ve all heard of schizophrenia – the disease of thought disorder, or know people who suffer from it. But only a few actually understand what it is about.

No wonder scientists have been struggling to develop efficient treatments for schizophrenia; not only is it largely uncommon (1% of the world’s population is affected), but also its causes are usually unknown. Scientists generally refer to schizophrenia as a psychiatric disease involving a progressive decline in functioning, which begins in early adolescence and persist throughout the patient’s life. Due to its heterogenous symptoms and multiple possible causes, there are many hypotheses that intend to explain what triggers schizophrenia and how it develops.

In spite of the fact that is it a genetic disorder, the environment and external factors (such as viral infections during the intrauterine and infant period) may be crucial to the development of schizophrenia. The symptoms have been divided into two categories. The positive symptoms include thought disorder, hallucinations, delusions, disorganised speech etc., whereas the negative symptoms are characterised by poverty of speech, reduced expression or emotion, memory impairment, anergia, abulia etc. In addition, the brains of schizophrenics show structural macroscopic abnormalities (for instance, the enlarged ventricles and the shrinkage of the surrounding brain tissue), as well as microscopic changes, such as the dysregulation of dysbindin gene in the formation of abnormal dendritic filopodia. There are three types of schizophrenia, according to its symptoms: paranoid schizophrenia – auditory hallucinations, delusions, strong belief of being chased by powerful people; disorganized schizophrenia – reduced emotions and lack of emotional expressions, incoherent speech (mostly negative symptoms); catatonic schizophrenia – impairment of movement, usually immobility and catatonia, bizarre grimacing (this is similar some of the symptoms of hysteria, which has been described as a sexually related and later on, as a psychiatric disorder up until the beginning of the 20th century).

But enough with the boring general details! Let’s get to the fun part: The monoamine hypothesis of schizophrenia! Here we are going to talk about two very important neurotransmitters in the central nervous system: dopamine and glutamate. The second one is the main excitatory neurotransmitter in the brain. There are four main types of glutamate receptors: AMPA, NMDA, kainate and mGluRs. It has been demonstrated that reduced activity of the NMDA receptors can result in some of the negative symptoms of schizophrenia (lack of social behaviour, catatonia).

Dopamine is the metabolic precursor of another neurotransmitter, noradrenaline (norepinephrine). But there is a lot more to dopamine and its roles in the brain than this. There are four main dopaminergic pathways: the mesolimbic pathway – related to the “reward” system and significance; it has its roots in the ventral tegmental area and projects to the nucleus accumbens (in the ventral striatum) and the limbic system; the mesocortical pathway – involved in cognition and motivation; the tuberoinfundibular pathway – roles in lactation; these dopamine neurones originate in the hypothalamus; the nigrostrial pathway – involved in movement planning and connects the substantia nigra (midbrain) to the striatum.

Schizophrenia and another mental illness, a neurodegenerative one, Parkinson’s disease, are also linked to dopamine. When it comes to schizophrenia, it seems that the mesocorticolimbic pathways have more influence on its onset: the ‘positive’ symptoms appear to be triggered by dopaminergic hyperactivity in the mesocorticolimbic system. At the same time, hypoactivity of dopamine is this region is the cause of ‘negative’ symptoms. Nevertheless, it has been discovered that overexpression of the dopamine receptor D2 (DRD2) gene in the striatum also reduces motivational behaviour in mice, therefore mimicking psychotic ‘negative’ symptoms. Similar findings show that increased density of dopamine D2 receptor in the striatum, along with lower thalamic density of this receptor appear to induce divergent thinking, which is associated with schizophrenia.  

All these changes may account for the abnormalities that we see in “mad” people. It seems that we are so fragile, given that often small chemical and physical disruptions can trigger something as big and terrifying as schizophrenia. Imagine hearing, seeing, feeling, smelling things everyone says are not real (schizophrenics often have multiple hallucinations: auditory, visual, gustatory, tactile, olfactory). But to you they are so real and disturbing! Many schizophrenics even hear their own thoughts as if they are coming from the outside and therefore believe that everyone knows what’s in their heads. Imagine having the constant feeling that someone is after you (paranoia) or being certain that you are dead (the Cotard’s Syndrome) or that your husband has an affair (the Othello Syndrome).

I think this topic can never be fully covered and we would spend days talking about schizophrenia, so this article should better come to an end. As I am sure you have lots of questions and comments, don’t be shy and post anything you think it’s relevant to what has been discussed above. Hope you enjoyed this reading.

For further information: 

Bear et al., 2006. Neuroscience – Exploring the Brain. s.l.:Lippincott Williams & Wilknins, pp. 679-684

de Manzano et al., 2010. Thinking Outside a Less Intact Box; Thalamic Dopamine D2 Receptor Densities Are Negatively Related to Psychometric Creativity in Healthy Insividuals. Public Library of Science

Jia et al.,  2014. The Schizophrenia Susceptibility Gene Dysbindin Regulates Dendritic Spine Dynamics. The Journal of Neuroscience, Oct.pp. 34-41

Kandel et al., 2011. Modeling Motivational Deficits in Mouse Models of Schizophrenia: Behavior Analysis as a Guide for Neuroscience. Behavior Processes, pp. 149-156

Kolb et al., 1996. Fundamentals of Human Neuropsychology. 4th Edition ed. s.l.:W.H. Freeman and Company

Image by Damaris Pop