Feeding the Brain: Neuroscience Research Techniques and Nutrition

The intricate relationship between food and the body has been extensively researched in previous decades. Food is everywhere. Diet regimes are everywhere. We are forever being told which foods we should and should not eat, leading to the consequential pang of guilt when you reach for the third digestive biscuit to dunk in your tea. Instagram now has the capability to provide you with a 365 day meal plan, in addition to a constant stream of aesthetically pleasing ‘health’ food and celebrities trying to fob you off with a supplement pill that will make you lose ten billion stone in a day.

At this time, it is therefore of great importance that emphasis is placed on the quality of research involving nutrition. Following the advice from research that has not been executed in a valid, replicable way can be quite dangerous. I personally have encountered numerous studies that claim to have found the wonder food that will cure cancer, yet upon reading further than the abstract I discover that the sample size is dramatically small. This. Is. Not. Good. Research.

How is neuroscience relevant to this you may ask? As a novel, ever advancing field of scientific research, neuroscience brings to the table highly advanced, reliable experimental techniques that can be adopted in nutrition research. I give you ‘Nutritional Cognitive Neuroscience’. This is a field of neuroscience that I have developed a personal passion for, and thus would like to share some of the most interesting studies that I have read about so far.

The Northern Manhattan Study

The development of magnetic resonance imaging (MRI) scans has revolutionised the world of brain research. It is now possible to create a detailed picture of the brain using magnetic field and radio waves that are of higher quality than other scanning techniques. A comprehensive study took place in 2012 that utilized MRI techniques to investigate the association between a Mediterranean-style diet (MeDi) and brain white matter hypersensitivities (WMH) in Northern Manhattan individuals (Gardener et al., 2012). WHM are markers of small vessel damage, and can be indicative of vascular risks such as stroke and the development of dementia. The MeDi diet, representing the dietary habits of the populations bordering the Mediterranean Sea, consists of a relatively high intake of fruit, vegetables, monounsaturated fat, fish, wholegrains, legumes and nuts, moderate alcohol consumption, and a low intake of red meat, saturated fat, and refined grains. The MeDi diet has long been referred to as a diet that ‘feeds the brain’.

The study adopted a large sample size of 1091 participants. The inclusions criteria for the study highlighted that the subjects had to have never received a stroke diagnosis and were required to be over 40 years of age. Individuals meeting these criteria were identified, and were provided a questionnaire that, upon completion, produced a MeDi score depending on the number of MeDi foods included in the diet. A total of 996 individuals completed both the questionnaire and had an MRI scan in a subsequent period ranging from 2 to 14 years later. The results of the study suggested that there was a lower burden of WMH, thus suggesting a lower risk of developing stroke and dementia, in individuals that consumed a largely Mediterranean diet (and therefore had a high MeDi score).

As with most research, there are limitations to the study. The sample can be considered to lack representation of the wider population (65% of the participants were Hispanic, 16% were white, and 17% were black) and in the time period between conducting the questionnaire, the participants could have adjusted their diets. Nonetheless, the study evidences the potential uses of modern neuroscience technology to investigate the relationship between food and the brain. In addition, the comprehensive study structure permits replication on a much larger, potentially world wide scale.

Lighting the Way – Understanding Nutritional Brain Circuits

Several of our articles have featured optogenetics, an exciting, novel technique to look at the relationship between genes and aspects of how the brain performs. Briefly, optogenetics involves using light to activate or turn off specific genes – literally at the flick of a switch. Several studies have utilised animal models to investigate how certain genes are involved in our relationship with food. Agouti-related protein (AGRP) is a neuropeptide that is produced by AGRP neurons in the hypothalamus. Using optogenetics, researchers have shown that activation of these neurons in mice is sufficient for the mice to rapidly increase their food intake. The extent of the eating is dependent on how many of these neurons are in their excitable state (Aponte et al., 2011). If these neurons are permanently activated, there is reduced energy expenditure and consequential weight gain in addition to increased fat storage. How does this translate to humans I hear you ask? Whilst mice are obviously animals and there are limitations to their use, they share many common genes with the human species. Therefore, it could be suggested from this research that obese individuals potentially have chronic activation of the AGPR neurons, and this may contribute to rapid weight gain that is extremely difficult to lose. It provides a possible genetic explanation for obese tendencies in certain populations. The power of such knowledge is phenomenal. Looking at the role of genetics in appetite and our body size opens many avenues for research that would not be possible without the utilisation of mice models.

What Next?

Nutritional neuroscience is an emerging field that will no doubt reshape the health research landscape. Utilising cutting-edge techniques, nutritional cognitive neuroscience offers the potential to further our understanding of how food can nurture the brain, the potential implications of a poor diet on the health of our brains, and even how the genetic make-up of our brain can influence our relationship with food.

Author: Molly Campbell


Gardener, H., Scarmeas, N., Gu, Y., Boden-Albala, B., Elkind, M. S. V., Sacco, R. L., … Wright, C. B. (2012). A Mediterranean-Style Diet and White Matter Hyperintensity Volume: the Northern Manhattan Study. Archives of Neurology69(2), pp. 251–256.

Aponte,Y., Atasoy, D., and Sternson, SM. (2011). AGRP neurons are sufficient to orchestrate feeding behaviour rapidly and without training. Nature Neuroscience. 14(3), pp. 351-355.





Lafora Disease: A fatal form of Epilepsy

Lafora disease (LD) is a rare, fatal genetic disorder, which remains unknown to many people. Gonzalo Rodrίguez Lafora first described it as a progressive myoclonic epilepsy, but it is also considered a neurodegenerative and a glycogen metabolism disorder. The extent of LD is devastating, with affected people losing their ability to carry out daily activities and eventually requiring comprehensive care. Unfortunately, there is no prevention or cure, and therefore it’s important to educate others about this condition to create awareness and to encourage fundraising to enhance the scientific research in this area . 


LD begins to manifest in late childhood or early adolescence, and the prognosis is poor. The first noticeable features are seizures, often myoclonic seizures which cause involuntary jerking movements. These gradually worsen after onset of the disease, becoming more frequent and less responsive to anticonvulsant medication, making them difficult to treat. Hallucinations also start to appear, and the individual may experience partial loss of vision (scotomata). Eventually, cognitive decline and dementia follows. Towards the end of the disease the individual enters a vegetative state, and death occurs around 10 years post-onset. Death is often due to status epilepticus, where the individual experiences a continuous epileptic fit over several minutes, without recovery of consciousness (Turnbull et al., 2012).  


A pathological hallmark of LD is the presence of Lafora bodies, which are aggregations of intracellular polyglucosans. These lack glycogen’s normal branching structure, rendering them insoluble (Kecmanovic et al., 2016). They are commonly found within several tissues such as the brain, muscle and liver; all of which have a high glucose metabolism. However, clinical manifestations of LD are solely within the central nervous system (CNS) (Ganesh et al., 2005). The formation of Lafora bodies within neurones are thought to be the cause of epilepsy and neurodegeneration, although the mechanism behind this is still not fully understood.  


LD is an autosomal recessive disorder, and therefore 2 mutated alleles must be inherited for the disease to be expressed in the phenotype. So far, research has determined that 90% of cases are caused by mutations in either the EPM2B or the EPM2A gene, and it is thought that another unidentified gene may also play a role (Couarch et al., 2011). Evidence shows that LD is more prevalent in areas that have a high rate of consanguinity, such as India and Pakistan. However, exact prevalence figures are not available due to rarity of the condition (Jansen and Andermann, 2015).  

Mutations and mechanisms  

EPM2A encodes laforin, and EPM2B encodes malin. Both of these are proteins that form a complex which is thought to prevent a dangerous build-up of glycogen within tissues that do not normally store it, such as the CNS. Loss-of-function mutations in either EPM2A or EMP2B prevent the formation of malin or laforin, respectively. Therefore, these proteins cannot form a complex and evidence has suggested that this leads to glycogen accumulation, hence the formation of Lafora bodies (Ganesh et al., 2002).


Figure 1: The mechanisms involved in the formation of nsoluble Lafora bodies, leading to Lafora disease. Taken from  

Management of LD 

Currently, there remains no cure for LD and we are still unable to slow its progression. Medications are prescribed to manage seizures, although anticonvulsant drugs, such as phenytoin, can actually worsen myoclonus. Recent research has identified that perampanel can improve seizure frequency and decrease spontaneous myoclonus (Dirani et al., 2014), and clinical trials in 2016 have shown that it has some efficacy in treating LD myoclonus specifically (Goldsmith and Minassian, 2016). Although this offers a promising step forward for sufferer’s, there remains no treatment for loss of cognition, which also plays a huge role in this disabling condition.  

LD in canines  

LD is naturally occurring within canine breeds such as Bassett Hounds, Beagles and miniature Wirehaired Dachshunds (MWHDs). In 2005, it was first reported that 5% of MWHDs suffered from LD due to autosomal recessive inheritance caused by a single loss-of-function mutation in the canine EPM2B gene. More recent research has also demonstrated that the disease process of LD in canines is similar to its development in humans. This is of great importance to researchers as these animals can be used as models in the search for a better understanding of LD, and for possible therapeutic treatments (Swain et al., 2017).     

Lafora Epilepsy Cure Initiative (LECI) 

The LECI was created in an effort to search for a cure for LD, and improve its diagnosis and treatment. Researchers from the U.S., Canada and Europe are all working together within a team directed by Professor Matthew Gentry at the University of Kentucky College of Medicine. Currently, each lab is focusing on different aspects of the disease, and they have already made progress by discovering that reducing glycogen synthesis can cure LD in mouse models.  


For more information on Lafora disease: 

Epilepsy foundation:  

Chelsea Gerber’s LD research fund:  


Author: Abbie Houghton

Edited by: Molly Campbell


Couarch, P., Vernia, S., Gourfinkel-An, I., Lesca, G., Gataullina, S., Fedirko, E., Trouillard, O., Depienne, C., Dulac, O., Steschenko, D., Leguern, E., Sanz, P. and Baulac, S. 2011. Lafora progressive myoclonus epilepsy: NHLRC1 mutations affect glycogen metabolism. Journal of Molecular Medicine. 89(9), pp.915-925. 

Dirani, M., Nasreddine, W., Abdulla, F. and Baydoun, A. 2014. Seizure control and improvement of neurological dysfunction in Lafora disease with perampanel. Epilepsy and Behaviour Case Reports. 2(1), pp.164-166. 

Ganesh, S., Delgado-Escueta, A., Sakamoto, T., Avila, M., Machado-Sala, J., Hoshii, Y., Akagi, T., Gomi, H., Suzuki, T., Amano, K., Agarwala, K., Hasegawa, Y., Bai, D., Ishihara, T., Hashikawa, T., Itohara, S., Cornford, E., Niki, H. and Yamakawa, K. 2002. Targeted disruption of the Epm2a gene causes formation of Lafora inclusion bodies, neurodegeneration, ataxia, myclonus epilepsy and impaired behavioural response in mice. Oxford University Press. 11(11), pp.1251-1262. 

Ganesh, S., Puri, R., Singh, S., Mittal, S. and Dubey, D. 2005. Recent advances in the molecular basis of Lafora’s progressive myoclonus epilepsy. Journal of Human Genetics. 51(1), pp.1-8. 

Goldsmith, D. and Minassian, B. 2016. Efficacy and tolerability of perampanel in ten patients with Lafora disease. Epilepsy & Behaviour. 62(1), pp.132-135. 

Jansen, A. and Andermann, E. 2015. Progressive Myoclonus Epilepsy, Lafora Type. Gene Reviews. [Online]. [Accessed 21 October 2017]. Available from: 

Kecmanovic, M., Keckarevic-Markovic, M., Keckarevic, D., Stevanovic, G., Jovic, N. and Romac, S. 2016. Genetics of Lafora progressive myoclonic epilepsy: current perspectives. The Application of Clinical Genetics. 9(1), pp.49-53. 

Swain, L., Key, G., Tauro, A., Ahonen, S., Wang, P., Ackerley, C., Minassian, B. and Rusbridge, C. 2017. Lafora disease in miniature Wirehaired Dachshunds. PLOS. 12(8), pp.1-13. 

Turnbull, J., Girard, J., Lohi, H., Chan, E., Wang, P., Tiberia, E., Omer, S., Ahmed, M., Bennett, C., Chakrabarty, A., Tyagi, A., Liu, Y., Pencea, N., Zhao, X., Scherer, S., Ackerley, C. and Minassian, B. 2012. Early-onset Lafora body disease. Brain. 135(9), pp. 2684-2698

World Mental Health Day

Today, October 10th, is world mental health day, a day that promotes awareness of mental health conditions and provides support to those who suffer. Truth is we all have a brain, therefore we ALL have mental health. However, the most recent statistics suggest that one in four individuals in the world will be affected by mental health disorders at some point in their lives, and that currently, 450 million people are suffering. The likelihood is, therefore, that you know someone who is dealing with a mental health issue, whether they make that public knowledge. The brilliant thing about studying neuroscience as a degree is that you learn so much more information about these conditions than what your typical google search reveals, and with that, you learn about the constant endeavors of scientists desperately seeking how to treat them. It is sad, but very true that mental health discrimination is still most definitely prevalent in today’s society, and often those that suffer can face shame or stereotyping – the classical ‘it’s all in your head’ springs to mind. Today, we decided to cover the science of some of the most common mental health conditions, and discuss with you why they are very much real. We hope that by understanding some of the known, proven science of why these disorders occur in people, we will raise awareness and also compassion for those that experience them.

Anxiety and OCD – Rosie Porter

Obsessive Compulsive Disorder (OCD) is classified as an anxiety disorder where suffers often experience intrusive thoughts. These thoughts bring about compulsive and repetitive behaviours in an attempt to alleviate their anxiety (Figure 1). It is ranked as one of the world’s top 10 disabling conditions by the World Health Organisation and can affect up to 12 in every 1000 people. While the individual understands the thoughts are irrational, sufferers are unable to control their anxiety and behaviours. Actions such as compulsive cleaning, hoarding and trichotillomania (where a person feels compelled to pull their hair out) are common.


Figure 1 The OCD cycle

The underlying pathology behind OCD is still being discovered. However, with recent advances in technology some developments have been made. In a study conducted using resting-state functional-connectivity MRI, the connections in the brains of OCD patients and their family members were compared. The imaging found that siblings of patients had increased connections within and between areas of the brain responsible for cognitive control (fronto-parietal and cingulo-opercular regions). These pathways that are diminished are hypothesised to give an impaired ability to control their own cognition, and therefore their anxiety and behaviour. Patients were also found to have increased connectivity within the fronto-limbic pathway; an area responsible for our emotions (Froukje et al., 2017).

Other studies have found that the orbitofrontal-basal ganglia pathways are altered in OCD (a pathway related to cognitive control of movement), as well as abnormal volume and function in the amygdala (an area responsible for emotion; Nutt and Malizia, 2006). Alterations in the amygdala are seen in most anxiety related disorders, but OCD is unique in that sufferers help relieve their anxiety by performing impulsive behaviours (Figure 1).

Research conducted into the genetic basis behind OCD has flagged up the hSERT gene; hSERT encodes a serotonin transporter in synpases. Serotonin is a neurotransmitter that is thought to be imbalanced in different anxiety disorders and depression. A mutation that has been detected in the hSERT gene (I425V) leads to significantly less serotonin in the synapses of OCD sufferers. This mutation underlies the theory that people can have a genetic predisposition to OCD, that environmental factors can exacerbate.

These discoveries linking dysfunctional neural connections and proteins with behaviour provide evidence for the underlying pathology of the disorder. With further research, the hope is to better understand the disorder and find more effective ways to manage and treat it.

Schizophrenia – by Rachel Coneys

From being one of the most misunderstood and negatively portrayed mental disorders, there has been a new wave in the attempt to decode Schizophrenia’s complex causes and pathologies, to break the misconceptions and develop more effective treatments. Schizophrenia, meaning to ‘spilt mind’ is a severe and progressive psychiatric illness, emerging in young adults at the prime of their lives, spanning all socio-economic and cultural groups. Symptoms vary for each individual and are grouped as positive or negative depending on the type of impairment. Positive symptoms describe experiences such as hallucinations or delusions. Negative symptoms include lack of motivation and social withdrawal.

For over a decade, neuroscientists have been trying to uncover the pathology behind Schizophrenia. A universal belief is that there is a strong genetic predisposition, which when coupled with certain environmental factors, triggers Schizophrenia.

Neurochemical Pathology
Until recently the dominant theory was that of an up-regulation of the neurotransmitter Dopamine within the brain. This was centered on the action of anti-psychotic drugs, which work by blocking dopamine receptors. However it became clear these drugs were ineffective at treating negative symptoms, indicating that another neurochemical system must be involved, otherwise these drugs would work.

The latest theory attributes the major excitatory neurotransmitter Glutamate and the receptor that it binds to, ‘NMDAr’, as key players. The suggestion of an NMDAr ‘hypo-function’ in Schizophrenia came from studying drugs that block this receptor (e.g. Ketamine) and therefore induce psychotic symptoms. Scientists believe that in schizophrenic patients, reduced NMDAr functioning occurs during post-natal development, resulting in structural and behavioural changes. During this period, NMDAr are needed for neuronal signaling and survival, and since NMDAr are widespread throughout our brain, loss of function can have devastating effects. NMDAr dysfunction in the prefrontal cortex (Figure 1) is thought to have a downstream effect on Dopamine and GABA (inhibitory neurotransmitter) networks, resulting in psychosis later on in life. This theory is effective at explaining both the positive and negative symptoms.


Figure 1: The Prefrontal cortex is located in the frontal lobe and is implicated in complex executive functions and personality development. NMDAr dysfunction in this area implicates Dopamine and GABA networks, consequently impairing the prefrontal cortex’s functioning.

Genetic Predisposition

Additionally, there is a strong genetic element to Schizophrenia, with a 50% concordance rate in identical twins. Until recently the genetic risk factors were elusive, but thanks to a remarkable study they are being identified. This Genome Wide Association Study found the expression of a certain variant of a gene called ‘C4’ was elevated in patients with Schizophrenia. C4 is implicated in synaptic pruning (removing the connections between neurons that communicate with one another in the brain) during development. They hypothesized the elevated C4 variant leads to excessive synaptic pruning, causing a thinner cerebral cortex (a physiological hallmark in Schizophrenic patients), and consequent psychotic symptoms.

The Future
The identification of clear genetic associations and development of more eloquent neurochemical models is a huge step forward. Increased understanding of causes and pathologies can help pave the way for more effective treatments for patients with the hope of allowing them to live a less debilitating lifestyle.

Major depressive disorder – Molly Campbell

Depression is a disorder that is heterogenous in nature, meaning that there are different types of depression that vary in severity, from mild to extreme, in which a sufferer may present with psychotic symptoms. Major depressive disorder (MDD) is one of the most common psychiatric diseases and is an example of one of the types of depression. The diagnostic and statistical manual of mental disorders bases a diagnosis of MDD on the presence of low mood or inability to experience pleasure, or perhaps both, for more than two weeks; in addition to profound cognitive dysfunction and sleep disturbances. However, it should be considered that difficulty arises in the diagnosis and treatment of MDD due to the fact that these diagnostic criteria are somewhat arbitrary.

A universally effective treatment for MDD remains to be found, and this is due to the fact that the associated neurobiology remains ambiguous. The credibility of the infamous monoamine hypothesis, in which alterations in levels of the monoamine neurotransmitters serotonin and nor-adrenaline were deemed responsible, is now heavily questioned. This is due to the fact that unfortunately, various monoaminergic antidepressant drugs that rely on this theory are not clinically effective across all patients. For some individuals they appear to work, however in the majority they do not, and so alternative neurobiological theories have arisen (Aan het Rot et al., 2009)

One proposed theory – genetics

Multiple scientific studies have aimed to identify a genetic cause for MDD, as there is strong evidence of heritability due its presence through families. An interesting study by Hyde et al (2016) looked at data from 75,607 European individuals that had received a clinical diagnosis. They identified five independent variants from four regions of the genome associated with self-report of clinical diagnosis of MDD. Further analysis found a total of 17 single-nucleotide polymorphisms associated with a diagnosis of MDD. Put simply; it was found that a significant number of individuals who had received a diagnosis of MDD had differences in their DNA compared to individuals that did not have MDD. The genetic variant that was most strongly associated with MDD was MEF2C (unfortunately, genes are often given pretty complicated names!), a gene involved in the regulation of synapses. Synapses are essentially the communication points between neurones, and this gene has also been shown to be involved in epilepsy and intellectual disability.

Whilst this is only one example of research that investigates the neurobiology of MDD, I think it is particularly interesting as it highlights the emerging role of pharmacogenomics in the treatment of mental health conditions – essentially tailoring the treatment for individuals who are suffering based on the make-up of their DNA.

Bipolar Disorder – Kate Pearman

Bipolar disorder (BD) is a psychiatric disorder that progresses through an individual’s lifetime.  More than 3 % of people are affected worldwide. Individuals with BD experience recurring episodes of depression and mania which significantly affect an individual’s quality of life and is positively associated with an increase in risk of suicide. Around a third to a half of BD patients attempt suicide on one occasion in their lifetime and an estimated 15-20% of these attempts are successful (Schaffer et al 2015). BD is also primarily diagnosed in young adulthood and thus affects the economically active population and therefore causes high costs to society (Gardner et al 2006). Therefore, highlighting the severity of this disorder and the need for a greater understanding into the pathology of BD for possibility of more efficacious treatment methods.

Knowledge of the pathogenesis and pathophysiology of BD has significantly increased over the last few decades. BD is one of the most heritable psychiatric disorders however, a multifactorial model in which both gene and environment interact, is thought to describe the disorder most appropriately. Mood disorders were thought to be caused by an imbalance in monoaminergic neurotransmitter systems, in regards to BD the dopaminergic. Although evidence has shown these circuits are likely to have a role in BD, no singular dysfunction of these systems have been identified. However, modulation of synaptic and neural plasticity is thought to be important in the circuitry regulating cognitive functions (Martinowich et al 2009). Neurotrophic molecules like the brain-derived neurotrophic factor, have a strong role in signalling pathways such as dendritic sprouting and neural plasticity. Dendritic spine loss has been observed in post-mortem brain tissue of patients with BD (Konopaske et al 2014). Alternative pathways that can affect neuronal interconnectivity are also being investigated such as mitochondrial dysfunction and endoplasmic reticulum stress, neuroinflammation, oxidation, apoptosis and epigenetic changes, particularly histone and DNA methylation (Berk et al 2011). Also due to the main phenotype of BD being a biphasic energy shift the monitoring of phasic dysregulation in mood, sleep and behaviour is also being investigated. The understanding of underlying pathogenesis of BD is crucial in discovering novel drug targets and the development of biomarkers for the prognosis, risk and therapeutic response.


Figure 1- Life chart showing the progression of bipolar disorder, with severity, manic and hypomanic symptoms registered above the phase of euthymia (normal mood state) whereas depressive symptoms depicted below.


Thanks for reading…

We hope you found this article an interesting and insightful snapshot of the research into mental health conditions. Please note this article is for informative purposes and should not be used as a tool for self-diagnosis based on the symptoms we have discussed. If you, or anyone you know are suffering from a mental health condition, this is a great source of information for the various charities that can help:


Mental health is equally as important as physical health, and we at All That Is Neuro wish to help to fight the stigma and encourage awareness.




Snyder, M. A., & Gao, W.-J. (2013). NMDA hypofunction as a convergence point for progression and symptoms of schizophrenia. Frontiers in Cellular Neuroscience7, 31.


Nakazawa, K., Jeevakumar, V., and Nakao, K. (2017). Spatial and temporal boundaries of NMDA receptor hypofunction leading to schizophrenia. Npj Schizophrenia, 3(1), 1. Doi:10.1038/s41537-016-0003-3


Sekar, A., Bialas, A. R., de Rivera, H., Davis, A., Hammond, T. R., Kamitaki, N., McCarroll, S. A. (2016). Schizophrenia risk from complex variation of complement component 4. Nature530(7589), 177–183.


Rompala, G. R., Zsiros, V., Zhang, S., Kolata, S. M., & Nakazawa, K. (2013). Contribution of NMDA Receptor Hypofunction in Prefrontal and Cortical Excitatory Neurons to Schizophrenia-Like Phenotypes. PLoS ONE8(4), e61278.


Schizophrenia (2017). Mind. [Online] Accessed from:





Froukje E. de Vries, Stell J. de Wit, Odile A. van den Heuvel, Dick J. Veltman, Danielle C. Cath, Anton J. L. M. van Balkom and Ysbrand D. van der Werf (2017). Cognitive control networks in OCD: A resting-state connectivity study in unmediated patients with obsessive-compulsive disorder and their unaffected relatives. The World Journal of Biological Psychiatry.

Nutt D, and Malizia A (2006). Anxiety and OCD – the chicken or the egg? Journal of Psychopharmacology, 20(6). 729-731.

Imaged sourced from:



Aan het Rot, M., Mathew, S. J., & Charney, D. S. (2009). Neurobiological mechanisms in major depressive disorder. CMAJ : Canadian Medical Association Journal, 180(3), pp. 305–313.


Hyde, C., Nagle, M.W., Tian, C. et al. (2016). Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nature genetics. 48(2016), pp. 1031-1036.


Bipolar disorder


HH Gardner, NL Kleinman, RA Brook, K Rajagopalan, TJ Brizee, JE Smeeding

The economic impact of bipolar disorder in an employed population from an employer perspective. J Clin Psychiatry, 67 (2006), pp. 1209-1218

A Schaffer, ET Isometsä, L Tondo, et al. International Society for Bipolar Disorders Task Force on Suicide: meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder. Bipolar Disord, 17 (2015), pp. 1-16.


K Martinowich, RJ Schloesser, HK Manji. Bipolar disorder: from genes to behavior pathways

J Clin Invest, 119 (2009), pp. 726-736.

M Berk, F Kapczinski, AC Andreazza, et al. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev, 35 (2011), pp. 804-817.


GT Konopaske, N Lange, JT Coyle, FM Benes. Prefrontal cortical dendritic spine pathology in schizophrenia and bipolar disorder. JAMA Psychiatry, 71 (2014), pp. 1323-1331




Can you trick yourself into being confident? The big debate.

After watching a TED Talk by Amy Cuddy about how our body language affects our confidence (which I highly recommend for anyone interested), I wanted to look at the chemical changes that occur within the brains neurotransmitter levels (the chemicals that transmit information in our brain and body) in relation to the content of her talk.


Firstly, what was the summary of her research? She found that by standing tall with your arms outstretched – in a “high-power” pose – neurotransmitter levels are altered in the body. The hormone testosterone (responsible for giving us confidence) increases and the neurotransmitter cortisol (the stress hormone) decreases. When a “low-power” pose was adopted (when subjects hunched over and hugged themselves) the opposite effect occurred –  testosterone levels decreased and cortisol levels rose.

What I found really fascinating was her claim that this change was perceivable to other people. In her experiment, a group of subjects underwent a fake job interview presentation. They were split into two groups; one group performed “high-power” poses prior to the interview, and the other performed “low-power” poses. The interviewers were not aware which candidates had adopted which pose. Despite not knowing which candidate did what, they preferably chose to hire those who had adopted the “high-power” pose before the interview, despite that fact that the prior body position had no effect on body language during the presentation.


Top Line “High-power” poses. Bottom Line “Low-power” poses. (Amy Cuddy, Harvard University).

Is this really true? Can you really trick your body into being confident when you don’t feel it? As a neuroscientist, I was interested in the chemical changes that were claimed to occur – could this simple act of standing tall really change the chemicals released by the body?

Upon further investigation, I found a furious debate between researchers on whether “high-power” posing actually works, or whether it was just a placebo effect with no change in neurotransmitter levels. A lot of research has been conducted attempting to replicate the results found by Amy Cuddy’s team – with very little success. The overwhelming evidence has shown that while these power poses make people feel more powerful, the biological and behavioural translation is minimal. In fact, one of the original co-authors to Cuddy’s work, Dana Carney, has since spoken out about the conflicting scientific evidence, stating it shows that the effects of “high-power” posing cannot be replicated and therefore cannot have a biological cause.

In studies that replicate the methodology of the original study (but with larger sample sizes), the results were disappointing. Several studies showed that interviewees performed no differently, and “high-power” posers were not hired at a greater rate than “low-power” posers. Studies that examined the changes in hormone levels were consistent with the evidence that “high-power” posing has no effect on confidence, or neurotransmitter levels.

Despite this, the TED talk is really convincing and does pose a dilemma for me. I wanted to believe this was true – that I could change the way I act and feel just by posing by myself for 2 minutes. There have also been millions of viewers to this TED talk that have self-reported the miraculous effect that “high-power” posing has had for them. For me, I have had to accept that while I may wish it to be true, there is little evidence to prove that “high-power” posing effects your neurochemistry. But despite this, I think if you’re going for that job interview, or a big meeting, or you’re just not feeling great that day, take two minutes to adopt some power poses – tell yourself you can do it, and trick your body into being confident. It may not have a chemical basis behind it, but who doesn’t love a good old placebo effect?

Author: Rosie Porter

Edited by Molly Campbell


Cuddy, Amy J.C., Caroline A. Wilmuth, and Dana R. Carney. “The Benefit of Power Posing Before a High-Stakes Social Evaluation.” Harvard Business School Working Paper, No. 13-027, September 2012.

The link to Amy Cuddy’s TED talk:

Michigan State University “‘Power Poses’ Don’t Work, Studies Suggest.” NeuroscienceNews. 11 September 2017. []

To read more about Dana Carney’s viewpoint you can read this statement released by her:

Modulation of microglia as a potential therapy for Alzheimer’s disease

In an ever-growing, ageing population, neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease are becoming more and more prevalent. Years of research have uncovered many key players in the origin and progression of these diseases, though an effective therapy is still much sought after.

Neurodegenerative diseases have many pathologies and causes that are specific to each type. Alzheimer’s disease is characterized by the accumulation of toxic proteins called Amyloid beta and a reduction in the connections between neurons (called synapses) in the brain. One common aspect present in all neurodegenerative diseases is neuroinflammation, an immune response mediated largely by cells in the brain called microglia. Microglia make up 5-20% of brain cells and play a significant role in disease and injury. They help to ‘clean up’ in the brain removing dead cells and debris to keep the brain functioning healthily. When the brain is under stress or experiences injury, the microglia are activated and release pro inflammatory mediators called cytokines, such as IL-6 and TNF-a, as a protective mechanism. In a healthy brain, the release of these molecules produces local inflammation that signals back to the microglia that they are needed to clear and repair the injury. In chronic neuroinflammation, the constant activation of microglia leads to sustained release of toxic cytokines and an excessive, pathogenic inflammation ensues. Such chronic inflammation of the nervous tissue triggered by persistent injury or toxic protein build up in the brain is detrimental and eventually results in the microglia damaging the neurons.

In Alzheimer’s disease, it was believed that microglia were initially activated as a defensive response, to fight against and remove the toxic build up of Amyloid beta. It is now hypothesized that as the microglia become chronically activated, they not only act on toxic proteins but start to indiscriminately destroy synapses in the brain. It is at this point that microglia activation may become a damaging pathogenic response, leading to the exacerbation and development of Alzheimer’s disease. Excessive microglia activity on synapses is likely to play a crucial role in the loss of cognition and memory.

An alternate theory proposes a ‘yin and yang’ role of microglia in Alzheimer’s disease. This suggests early on in disease states, microglia are helpful and are positively recruited to sites of toxic Amyloid Beta build up. However as the disease progresses the microglia become overwhelmed, and signal this through excessive release of toxic pro-inflammatory cytokines. One study using brain scanners describes a ‘twin peak’ of microglia activation in patients suffering from Alzheimer’s Disease – an early protective peak and a later pro-inflammatory peak (Wood, H. 2017).

Aligned with the ‘yin and yang’ theory, microglia can exist in one of two phenotypes; a pro-inflammatory form, associated with neurotoxicity (M1) and an anti-inflammatory form associated with neuroprotection (M2) (Song, G.J. and Suk, K. 2017). M1 phenotypes produce toxic pro-inflammatory mediators such as TNF-a and IL-6, which activate the cells to deal with infection or injury. After an initial first response of the M1 microglia, M2 phenotypes produce anti-inflammatory cytokines such as IL-10, which lead to brain repair. Chronic exposure to the pro-inflammatory toxic amyloid beta plaques maintains the activation of M1 microglia, which eventually contributes to neuron and synapse damage, leading to neuronal degeneration. Identifying the mechanisms that modulate the M1/M2 phenotypes could help uncover how local CNS inflammation can lead to the devastating effects of neuronal degeneration. Additionally, finding ways to control and reduce this chronic microglia activation and inflammation in Alzheimer’s’ disease could have huge therapeutic benefit. Several pharmacological interventions to modulate the microglial phenotypes have been investigated, however all have had limited efficacy when tested in clinical trials. A better understanding of the mechanisms involved in microglia activation and polarization is needed to go forward.

Possible therapeutic interventions

One avenue currently being explored involves a class of drug called Histone Deacetylase inhibitors (HDACi). Histone deacetylase’s are enzymes that remove acetyl groups from lysine amino acids in proteins and are involved in regulating gene expression within our cells. Research has shown HDAC’s are implicated in inflammatory responses (Kannan, V. 2013), interacting with the microglia in our brains. It is clear that inhibitors of HDAC suppress this microglia-activated immune response and push microglia towards the protective M2 phenotype (Waang, G. 2015), but exactly how they do so is not known.

It was assumed HDAC inhibitors achieve this by increasing gene expression within microglia. However recently published research by neuroscientists at the University of Leeds (Wood, I. 2017) has shown that HDAC inhibitors can still inhibit microglia activation even when the synthesis of new proteins is stopped, suggesting that their ability to increase gene expression is not important for their effect in microglia. Studying where in the cell that the HDACs exert their effects is the first step in identifying the important target protein, and will ultimately lead to uncovering the mechanisms by which they work to push microglia towards the M2 phenotype, hence reducing the inflammatory response.

One problem with using HDAC inhibitors as a therapeutic intervention is that they act in a very broad non-specific fashion, affecting many cell processes. Uncovering how HDAC inhibitors work to reduce M1 microglia activation would allow an opportunity to develop more targeted and specific therapeutic interventions for Alzheimer’s disease with reduced potential for deleterious side effects. Chronic neuroinflammation is a common pathology shared with other neurodegenerative disorders, and thus finding ways to control and reduce microglia activation using HDAC inhibitors will not only be crucial in Alzheimer’s disease, but will be beneficial more widely.

Author: Rachel Coneys

Edited by: Molly Campbell


Wood, H., 2017. Alzheimer disease: Twin peaks of microglial activation observed in Alzheimer disease. Nat Rev Neurol. 13(3):p129

Wood, I., Grigg, R., and Durham, B., 2017. Inhibition of histone deacetylase 1 or 2 reduces microglia activation through a gene expression independent mechanism. Found online at:

Song, G.J., and Suk, K., 2017. Pharmacological Modulation of Functional Phenotypes of Microglia in Neurodegenerative Diseases. Front Aging Neurosci. 15;9:p139

Kannan, V., Brouwer, N., Hanisch, U.K., Regen, T., Eggen, B.J., and Boddeke, H.W., 2013. Histone deacetylase inhibitors suppress immune activation in primary mouse microglia. J Neurosci Res. 91(9):p1133-42

Wang, G., Shi, Y., Jiang, X., Leak, R. K., Hu, X., Wu, Y., and Chen, J., 2015. HDAC inhibition prevents white matter injury by modulating microglia/macrophage polarization through the GSK3β/PTEN/Akt axis. Proceedings of the National Academy of Sciences, 112(9), 2853-2853.


Through Your Mind

Through Your Mind

This week we bring the audience of All That is Neuro something that is a little out of the ordinary for our blog. You may be aware that the 8th-14th of May marked Mental Health Awareness week – where people from all over the world took it upon themselves to help spread awareness of mental health and help fight the stigma. Continuing the pledge to ‘spread the word’, here we feature a post about the work of Chloe Thomas, a final year graphic design student at Nottingham Trent University who utilised her artistic talents to portray the anxious mind in its many different states.

What is the topic of your project, how did you approach it and why? 

Anxiety is something that is really close to my heart. I struggle to express how it is making me feel sometimes and don’t believe that people fully understand it. With the “Through Your Mind” project, I aim to raise awareness of what it feels like to be anxious by creating visual representations of the anxious mind. 

I asked friends and family who suffer from anxiety to draw diagrams of what their brain ‘looks like’ when they are feeling anxious. Using this research, I then recreated their ‘brain drawings’ as 3D sculptures.

Discovering mould-making and casting recently has really inspired my work, so I really loved being able to use what I’ve learned in the studio in my final year of university to make something tactile and visually interesting.”

What are the key features of your designs and how do they relate to anxiety? 

“For this project, I built three brains:

  • One in concrete (to represent the heaviness that an anxious brain can feel).

brain 1.jpeg

  • A pink plaster brain covered in silly string (to communicate the confusion and muddled thoughts that can be felt).

brain 2

  • A black and white layered brain (cast in resin to show the lack of enthusiasm and motivation that anxiety can leave you with).”brain 3.jpeg

What do you hope your project will bring to the general public? 

“I’d love to continue with Through Your Mind by creating a larger collection of brain sculptures to represent more individuals. This would show that anyone can suffer from anxiety in their own individual way – which I think is a really important message to communicate.”

I’d like people to feel able to open up about their anxieties by seeing others who have done so. I’d also like to be rid of the stigma attached to anxiety by helping people to gain some understanding of what it feels like and see the sheer number of people who suffer from anxiety. It’s completely normal and nobody should feel that they can’t speak out about it!” 


If you are feeling inspired and want to have a gander at more of Chloe’s work, please take a look at her portfolio:


By Molly Campbell








Can your gut give you depression?

Do you get butterflies in your stomach when you get nervous or anxious? Ever wondered why this happens? Turns out your gut could play a larger role in your mood than you thought. In recent years’ scientists have been linking disturbances in gut bacteria to several various conditions; including Parkinson’s disease, allergic reactions and depression (Evernsel and Ceylan, 2015).

Mice that are raised in a completely sterile or “germ-free” environment develop an overactive Hypothalamus-Pituitary-Adrenal (HPA) axis (Sudo et al. 2004). This axis is involved in controlling the release of certain neurotransmitters and hormones, including the stress hormone cortisol. Exposing the gut of these mice to certain bacteria leads to recovery of normal function of the HPA system. It is therefore suggested that the bacteria in the gut – or microbiota – can alter the development of their brains. These mice were also found to have altered neurotransmitters such as noradrenaline and serotonin, known to influence mood.


Figure 1 Visual demonstration of how the gut bacteria can influence brain activity. Taken from:

In patients that suffer from major depressive disorder, an altered HPA axis has been observed (Dinan and Cryan, 2013). For example, patients often have higher levels of the stress hormone cortisol. Current antidepressants work by changing the levels of noradrenaline and serotonin in the brain. If you link this with the evidence that the bacteria in the mice gut could alter these neurotransmitters, you can hypothesise that altered gut microbiota in humans could cause depression (Figure 1). Alternatively, altering the gut bacteria could potentially treat depression.

The next step for neuroscientists is to actually prove that altered gut microbiota can cause depression or vice versa (Figure 1). Park et al, 2013 used a mouse model of depression to examine HPA alterations and gut microbiota. The mice that presented with chronic depression-like and anxiety-like behaviours also had an elevated HPA axis (and therefore an elevated stress response), and altered gut flora as well as gut motility. These same effects could be brought about by direct administration of corticotropin-releasing hormone.

A proposed theory is that chronic stress causes increased levels of stress hormones from the HPA axis. This can act on the gut to alter bacterial levels and distribution, altering motility and causing diseases such as Irritable Bowel Syndrome (IBS). This further disturbs gut bacteria that can then feedback to the brain, potentiating the stress-response, leading to a cycling that could result in depression. These gut disturbances could explain why patients with IBS also often suffer from depression (Park et al, 2013). The feedback from the gut to the brain is proposed to be brought about by the immune system through activation of inflammatory chemicals that can travel in the blood to act on the brain (Dinan and Cryan, 2013; Figure 1).

Whilst it is easy to get excited about a new possible, effective treatment for depression (something we are sorely lacking), we must bear in mind that these links between gut microbiota and depression have only been shown in preclinical animal models, and the findings are yet to be replicated in humans. It is also still being examined whether the changes in gut bacteria are a primary cause, or a secondary effect from depression. However, full research may lead to the potential of probiotics being used to treat depression (Dinan and Cryan, 2013).

Author: Rosie Porter

Editor: Molly Campbell


Evrensel, A. and Cevlan, M.E. (2015) The Gut-Brain Axis: The Missing Link in Depression. Clinical Psychopharmacology and Neuroscience. 13(3): 239-244

Dinan, T.G. and Cryan, J.F. (2013) Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterol. Motil. 25: 713-719

Park, A.J. Collins, J. Blennerhassett, P.A. Ghia, J.E. Verdu, E.F. Bercik, P. and Collins, S.M. (2013) Altered colonic function and microbiota profile in a mouse model of chronic depression. Neurogastroenterol. Motil. 25(9): 733-741

Sudo, N. Chida, Y. Aiba, Y. Sonoda, J. Oyama, N. Yu, X.N. Kubo, C. Koga, Y. (2004) Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol. 558(1): 263-275


Creativity: Nature or Nurture?

Creativity exists as an amalgamation of innate talent and acquirable skills, making it the subject of an enduring and complex debate; is creativity a result of nature or nurture? And why are some people more creative than others? Over the years, lesion studies have provided considerable insight regarding the relationship between brain structures and artistic abilities. Additionally, the ever-growing documentation (and scrutiny) of savant/autistic individuals has created a quest to understand and explain the neurological basis of these findings.

What is creativity?

Caselli (2009) conspicuously defined creativity as ‘an attempt to bridge the gap between what is and what should be’ using original or imaginative ideas. The complexity of this debate arises due to the fact that individuals can express creativity across a multitude of disciplines and at different points along a continuum. Innovative behaviour is not restricted to humans, however what separates us from the rest of the animal kingdom, is our utilisation of art as a communicative system. With respect to this, artistic creativity can therefore be defined as a conscious and cognitive process involving several key phases: preparation, incubation, illumination (eureka moment) and production (Heilman, 2016).

So what do we know about the brain already…?

The brain’s outer membrane, and the image people most typically envisage when they imagine the brain, is the cerebral cortex (or cerebrum), which is separated into four lobes: parietal, occipital, temporal and frontal. A structure termed the corpus callosum facilitates communication between the left and right hemispheres – structures that we now understand to differ in their specialities. Information concerning the integration and understanding of stimuli, analysis, language and serial movements (e.g. throwing) are functions belonging to the left hemisphere. The right side of the brain deals with anything concerning visual stimuli e.g. processing, memory, imagery, colour discrimination, as well as the integration of information from all brain regions (Lusebrink, 2004). Just beneath the cerebrum lies the limbic system – a collection of structures responsible for a number of functions including motivation, behaviour, long-term memory, olfaction and (of particular concern in this article) emotion. Despite it being an extensive complex, for the purpose of this article it can broken down into the following critical components: (1) the thalamus – a relay station for all sensory processes occurring in the brain, (2) the hippocampus – crucial in the formation (but not storage) of long-term memories, (3) amygdala – emotional integration of both the conscious (left side) and non-conscious (right side) variety, (4) basal ganglia – the planning and execution of movement.


Figure 1: the visual pathway from the eye to the brain. Taken from

The visual cortex, found in the occipital lobe, (as shown in figure 1) serves as the final destination for visual information (colour, texture, direction and movement) entering the brain before processing begins. Separation of the visual pathway into two distinct streams, originating in the occipital lobe, forms the basis of the ‘two-stream hypothesis’ and is shown in figure 2. It proposes that form, shape and colour information is received and conveyed to the temporal lobe via the ventral stream, leaving the dorsal stream as the pathway responsible for spatial information travelling to the parietal lobe (Lusebrink, 2004). As the complexity of art increases, recruitment of neurons in the frontal cortex (responsible for higher processing) also increases. Neurons that fire together, wire together’ is a phrase denoting the fact that brain stimulation facilitates brain growth e.g. musicians have been found to have a larger auditory cortex than non-musicians (Heilman, 2016). Nonetheless, this certainty is a source of controversy as it further blurs the boundaries between nature and nurture as explanations for creativity.

Nature or nurture?

The theory of natural selection by Charles Darwin proposes sexual selection as a biological underpinning of art; animals use embellishment and behavioural displays to lure potential sexual partners e.g. peacock’s displaying their tail or the colourful plumage of birds. Such behaviours persisted and evolved with the rise of the Homo sapiens e.g. the use of decorative face paint in African tribes (which is akin to the application of make-up by women in contemporary society). This behaviour highlights many desirable characteristics such as intelligence, creativity and physical aptness that reflect the condition of the brain and body in the flaunting individual (Zaidel, 2010).


Figure 2: the ventral and dorsal visual pathways originating from the occipital lobe. Taken from

Additionally, conclusions drawn from experiments by Reader and Laland (2003) revealed that many birds and non human primates exhibit creativity in the form of cunning and deceptive behaviours, e.g. pigeons teaching each other how to reach food in a difficult place/situation or monkeys rinsing the sand off their sweet potatoes before eating them and passing this on to their relatives. There are many more documented examples of animals using creative methods for survival, leading to an explanation of creativity in humans ‘as an extension of the fundamental biological survival functions’ (Zaidel, 2014) – though this can be extended as an explanation for both sexual and survival functions.

Studying the effects of brain damage, disease or abnormalities can shed some insight into the importance played by specific brain structures or regions. Research concerning savants for example, has been used to try and enhance our understanding of anatomical differences underlying their creative abilities. The term ‘savant’ refers to individuals that possess a constrained yet exceptional level of intellect, in an otherwise defective brain. Savant syndrome can be split into a 50:50 ratio between those who suffer autism and those who have acquired the condition as a result of some form of CNS damage (also known as acquired savant syndrome) (Zaidel, 2014). For example, an interesting MRI study by Treffert (2009) reported the absence of the corpus callosum in the brains of savants that were able to simultaneously scan and interpret two different pages of text. This echoes a fascinating finding by researchers at Cornell University, which found a smaller corpus callosum in writers, musicians and artists (Cox, 2013). Since a component of creativity is considered to be a consequence of the brains’ communicative ability (established previously as the primary role of the corpus callosum), these findings do prove somewhat counterintuitive. Whilst a correlation does not always imply cause and effect, it may be worth looking into this further; perhaps the augmentation of creativity in this way requires that the brain and its hemispheres specialise in a different way by sacrificing efficiency or function in other regions. Of course there is a possibility that multiple factors are at play and that genetic codes have a lot more to answer for. Additionally, lesion studies examining pre and post-damage productivity by artists uncovered the resilience of their skills, regardless of the extent or lateralisation of damage. Artists suffering with dementia and other neurodegenerative diseases display a similar level of resilience even into the later stages of their disease, where a diminished motor activity is what finally stops their art production (Zaidel, 2010). Therefore the extent of the evidence discussed, points towards creativity being an intricate process with no single brain region or pathway playing a dominant role.

Art and emotion: what can art therapy tell us?

Emotion affects almost every aspect of cognition: memory, attention, information processing, etc. (Zaidel, 2010), therefore it is conceivable to propose that art, with the ability to evoke the most powerful of emotions, should have the same effect. A compelling argument states that artistic abilities have evolved as a compensational mechanism allowing the retention of communication in the face of adversity (Zaidel, 2014). This is supported with the emergence of art therapy as a method of treatment for many patients suffering with brain trauma or disease. This technique focuses on how visual and somatosensory information reflect emotions, which in turn affect our experiences, behaviour and thoughts. In this way, art therapy can used to improve emotional and cognitive maturity and has been used to repair damaged cortical pathways. Since all forms of art involve motor movement, victims of stroke, Alzheimer’s disease and schizophrenia were exposed to art therapy in an attempt to activate the basal ganglia – a bridge between motor association and the somatosensory cortices – resulting in a reduction of impairment in these pathways.

The science underlying this therapeutic phenomenon is neuroplasticity – pertaining to the brains’ capacity to reorganise itself in response to injury, disease, new situations or changes in the environment. The success of art therapy is a consequence of its dynamic nature; interaction with art media calls on the activation of sensory, motor and cognitive (interpretation, decision-making, forming internal images) systems (Lusebrink, 2004). Whilst promising, this method remains slightly ambiguous and relatively new. Only time can reveal its efficacy, yet for the sake of this debate it does say a lot about the role of nurture.

So…what can we conclude?

Art is a uniquely human construct that allows us to reflect upon reality as we see it; stylised by our own sense of individuality. Creativity, on the other hand, is subject to influence by both nature and nurture. As already outlined, basic neural underpinnings for creativity can be explained as an evolutionary adaptation for reproduction and survival that grew in complexity as brain anatomy developed. Everyone is innately creative and we use it in our everyday life for a multitude of reasons: negotiations in the workplace, daydreaming, cooking, choosing your clothing and decorating your home. To the contrary, artistic creativity relies very heavily on nurture; an individual’s environment can ease or impede ones artistic faculties.

As Picasso once said:

All children are artists. The problem is trying to stay an artist once one grows up’.

Author: Tiffany Quinn

Edited by: Molly Campbell


Cox, B. (2013). Are some people born creative?. The Guardian. [online] Available at: [Accessed 5 Feb. 2017].


Heilman, K. (2016). Possible Brain Mechanisms of Creativity. Archives of Clinical Neuropsychology, [online] 31(4), pp.285-296. Available at: [Accessed 3 Feb. 2017].


Lusebrink, V. (2004). Art Therapy and the Brain: An Attempt to Understand the Underlying Processes of Art Expression in Therapy. Art Therapy, [online] 21(3), pp.125-135. Available at: [Accessed 1 Feb. 2017].


Roeser, S. (2010). Emotions and risky technologies. 1st ed. Dordrecht: Springer, pp.62-63.


Treffert, D. (2009). The savant syndrome: an extraordinary condition. A synopsis: past, present, future. Philosophical Transactions of the Royal Society B: Biological Sciences, [online] 364(1522), pp.1351-1357. Available at: [Accessed 1 Feb. 2017].


Zaidel, D. (2010). Art and brain: insights from neuropsychology, biology and evolution. Journal of Anatomy, [online] 216(2), pp.177-183. Available at: [Accessed 3 Feb. 2017].


Zaidel, D. (2014). Creativity, brain, and art: biological and neurological considerations. Frontiers in Human Neuroscience, [online] 8. Available at: [Accessed 2 Feb. 2017].



In this blog article I will underline the key pathophysiology surrounding attention deficit hyperactivity disorder: ADHD

Brain pathophysiology

Many of the brain pathophysiological defects of ADHD are linked with that of the prefrontal lobe, an area which plays a large role in cognition. Therefore, it is uncoincidental that the symptoms linked with the disorder include poor concentration, impulsivity and hyperactivity (R.A. Barkley 2003).  With the use of functional neuroimaging techniques such as FMRI and PET scans, we are able to understand differences in the brain function and structure of ADHD patients, the most prominent of which is seen when using structural MRI. Scans have revealed specific areas in subjects with ADHD are smaller than an individual that does not had ADHD. These areas include the prefrontal lobe, caudate, cerebellum and cerebellar vermis (Zang Yu-Feng 2006).  Using a regional homogeneity method to characterise the local synchronisation of spontaneous brain activity in individuals with methylphenidate and those with placebo. It was seen that in those with the placebo the regional homogeneity of activity was decreased in the bilateral dorsolateral prefrontal cortices. Contrastingly regional homogeneity increased in the bilateral sensorimotor and parieto-visual cortices. Furthermore in those with who taken the methylphenidate, the major effect was down regulation in the right parietal cortex. This down regulation was correlated with decreased symptom scores after 8 weeks of acute methylphenidate doses (Li An et al 2012).

Structural connectivity

Diffusion tensor imaging allows for the imaging of axonal connections between brain areas.  The technique relies on the free movement of water molecules where there are no means of restriction. DTI allows for analysis of the white matter tracts of the brain, where it can map the orientation of the axon and the location. From this, we can image and see the specific connection between brain areas (Konrad and Eickhoff 2010).  Decreased fractional anisotropy (FA) in the right supplementary motor area, right anterior limb of internal capsule, right cerebral peduncle, left middle-cerebellar peduncle, and left cerebellum can be seen in children with ADHD. These results were consistent with those seen with MRI.  Fractional anisotropy is most simply the degree of which the water molecule is directionally dependent as a result of cell membranes and myelin sheath, to that which is free moving with Brownian motion. Finding of lower FA in children with ADHD specifically in these areas is intriguing, as the supplementary motor area has a role in planning, initiation, and execution of motor acts. Additionally, the  right frontostriatal circuitry is thought to be important in the development of organisation and planning (Ashtari et al 2004), which could be linked to poor organisational skills displayed. Consequently, they were able to piece to together links between brain regions and behaviour.

In a study exploring the relationship of frontostriatal structure in ADHD children and behaviour, Casey et al (1997) adopted MRI and behavioural tests. A correlation was found between impulse control and volumetric measure of globus pallidus and basal ganglia. Maps of cortical thickness showed ADHD patients to have a thinner cortex in bilateral frontal regions and the right cingulate cortex, in contrast to those without the disorder. There is now substantial evidence amounting to the role of the cerebellar region in ADHD, as the fractional anisotropy of the area is significant in inattention subscale scores (Durston et al 2003).


Genetics accounts for 75% of ADHD cases, as shown by data gathered across four genome-wide association scans investigating the disorder’s heritability. Furthermore, this research placed emphasis on the rarer variants of genes associated with ADHD, such as those coding for DRD4 and DRD5 dopamine receptors (Neale et al 2010).   Further genome-wide association scans show limited overlap  apart with the CDH13. Typically, many of the genes involved are involved in dopaminergic signalling. These include DAT, DRD4, DRD5, TAAR1, MAOA, COMT, and DBH. A mutation in the DRD4–7 receptor results in a wide range of behavioural phenotypes, including ADHD symptoms such as split attention (Kebir et al 2009). Furthermore, polymorphisms of this gene show significance in attention sustained performance tasks (Kieling et al 2006) Given the evidence obtained as a result of the study and meta-analysis, is it clear that DRD4 mutations are influential in displaying ”ADHD-like” phenotypes.  Other genes associated with ADHD include SERT, HTR1B, SNAP25, GRIN2A, ADRA2A, TPH2, and BDNF.


In conclusion, ADHD presents as difficulties in maintaining attention and concentration, but also can affect social aspects. Studies to find clear brain pathologies through imaging techniques have highlighted defects the prefrontal lobe and cerebellum and thus these regional defects are said to contribute to the symptomatic phenotype of the disorder.  There is a clear involvement of biogenic amines, specifically dopamine, with current models showing emphasis on the  mesocorticolimbic dopamine pathway and the locus coeruleus-noradrenergic systems. Furthermore, abnormalities may exist in other pathways such as glutamatergic, serotonergic or cholinergic neurotransmission.   Genetic studies have shown the significance of specific gene variants in contributing to the disorder, specifically those linked to the G-protein coupled receptors DRD4 and DRD5.  Genetic   and phenotypic heterogeneity amongst individuals could explain differences between genetic studies.  However, these differences may exist in different pathways but present the same phenotypic behavioural traits. Meta-analyses have produced a more reliable result than gene-wide association scanning alone, however, the association found only accounts for a small proportion of the genetics of ADHD. Approaches in neuroimaging genetics and epigenetic studies are being investigated to aid a clearer picture of the genetic component of this disorder.

Author: Liam Read

Editor: Molly Campbell

AN, L., CAO, X.-H., CAO, Q.-J., SUN, L., YANG, L., ZOU, Q.-H., KATYA, R., ZANG, Y.-F. & WANG, Y.-F. 2013. Methylphenidate Normalizes Resting-State Brain Dysfunction in Boys With Attention Deficit Hyperactivity Disorder. Neuropsychopharmacology, 38, 1287-1295.

ASHTARI, M., KUMRA, S., BHASKAR, S. L., CLARKE, T., THADEN, E., CERVELLIONE, K. L., RHINEWINE, J., KANE, J. M., ADESMAN, A., MILANAIK, R., MAYTAL, J., DIAMOND, A., SZESZKO, P. & ARDEKANI, B. A. 2005. Attention-deficit/hyperactivity disorder: A preliminary diffusion tensor imaging study. Biological Psychiatry, 57, 448-455.

BARKLEY, R. A. 2003. Issues in the diagnosis of attention-deficit/hyperactivity disorder in children. Brain and Development, 25, 77-83.

CASEY, B. J., CASTELLANOS, F. X., GIEDD, J. N., MARSH, W. L., HAMBURGER, S. D., SCHUBERT, A. B., VAUSS, Y. C., VAITUZIS, A. C., DICKSTEIN, D. P., SARFATTI, S. E. & RAPOPORT, J. L. 1997. Implication of Right Frontostriatal Circuitry in Response Inhibition and Attention-Deficit/Hyperactivity Disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 36, 374-383.

KEBIR, O., TABBANE, K., SENGUPTA, S. & JOOBER, R. 2009. Candidate genes and neuropsychological phenotypes in children with ADHD: review of association studies. J Psychiatry Neurosci, 34, 88-101.

KONRAD, K. & EICKHOFF, S. B. 2010. Is the ADHD brain wired differently? A review on structural and functional connectivity in attention deficit hyperactivity disorder. Human Brain Mapping, 31, 904-916.

NEALE, B. M., MEDLAND, S. E., RIPKE, S., ASHERSON, P., FRANKE, B., LESCH, K.-P., FARAONE, S. V., NGUYEN, T. T., SCHÄFER, H., HOLMANS, P., DALY, M., STEINHAUSEN, H.-C., FREITAG, C., REIF, A., RENNER, T. J., ROMANOS, M., ROMANOS, J., WALITZA, S., WARNKE, A., MEYER, J., PALMASON, H., BUITELAAR, J., VASQUEZ, A. A., LAMBREGTS-ROMMELSE, N., GILL, M., ANNEY, R. J. L., LANGELY, K., O’DONOVAN, M., WILLIAMS, N., OWEN, M., THAPAR, A., KENT, L., SERGEANT, J., ROEYERS, H., MICK, E., BIEDERMAN, J., DOYLE, A., SMALLEY, S., LOO, S., HAKONARSON, H., ELIA, J., TODOROV, A., MIRANDA, A., MULAS, F., EBSTEIN, R. P., ROTHENBERGER, A., BANASCHEWSKI, T., OADES, R. D., SONUGA-BARKE, E., MCGOUGH, J., NISENBAUM, L., MIDDLETON, F., HU, X. & NELSON, S. 2010. Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 49, 884-897.

YU-FENG, Z., YONG, H., CHAO-ZHE, Z., QING-JIU, C., MAN-QIU, S., MENG, L., LI-XIA, T., TIAN-ZI, J. & YU-FENG, W. 2007. Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. Brain and Development, 29, 83-91.