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. http://doi.org/10.1001/archneurol.2011.548

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 http://researchfeatures.com/2017/06/30/plants-provide-hope-epilepsy-initiative/  

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: https://www.epilepsy.com/learn/types-epilepsy-syndromes/lafora-progressive-myoclonus-epilepsy  

Chelsea Gerber’s LD research fund: https://chelseashope.org/  


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: https://www.ncbi.nlm.nih.gov/books/NBK1389/ 

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