Gustotopic mapping in humans: a high resolution fmri study to assess detailed topography and modulations

How and why do individuals perceive tastes differently? Our sense of taste evolved to encourage the consumption of nutrients, and to avoid ingestion of dangerous substances. However, today, the positive experience of sweet and salty taste can lead to the overconsumption and its associated detrimental effects on health. Conversely, bitterness and acidity can also prevent some individuals from consuming healthier foods such as bitter tasting green vegetables. Research progressing our fundamental understanding of taste perception will inform nutritional policy makers and the food industry to develop healthy diets and food products, hence improving the health and well-being of society in general.
There are five categories of taste: sweet, bitter, umami, salty and acidic, and the receptors for these tastes have been identified on taste receptor cells housed in papillae on the tongue. This proposal focuses on mapping how the brain processes these taste signals from the mouth. Modern neuroimaging methods have made it possible to study many neuroscience questions directly in the human. By using functional magnetic resonance imaging (fMRI), for example, we can track changes in the local blood flow that accompanies increased neural activity. We can measure which parts of the brain are more active while subjects consume different tastants. One of the problems with studying the neural mechanisms underlying our sense of taste is that in the human brain, these responses are relatively small. Using cutting-edge technology we can measure neural responses in the human cortex at very high spatial resolution in the living human brain. By using ultra-high-field magnetic resonance imaging techniques, we can measure robust neural responses non-invasively at a much higher spatial resolution than has previously been possible, whilst concurrently assessing perceived taste sensations, linking perception and the brain's responses.
In this proposal, we will investigate whether specific areas of the brain in the primary taste cortex can be identified that process sweet, bitter, umami (a savoury sensation), salty and sour tastes using improved state-of-the-art brain scanning technology. There is debate as to whether certain other 'tastes' exist, in particular 'fat' (fatty acid) and metallic 'taste'. We plan to determine if, and where, these stimuli are processed in the primary taste cortex, providing evidence as to whether these sensations should be termed tastes.
In addition we will study a recent phenomenon known as thermally induced taste whereby some individuals report a taste sensation, although there is no physical taste stimulus present, when the tongue is rapidly heated or cooled. As sensitivity to taste varies across individuals, we will determine how brain processing is affected by these known differences in taste perception. We are also interested to see if, and how, the phantom taste induced by temperature changes the brain's response in the primary taste cortex. The brains of thermal tasters (previously reporting sweet or bitter taste upon thermal stimulation) will be scanned whilst their tongue is rapidly cooled or warmed. This will enable us to determine if the phantom taste sensation modulates the same area of the primary taste cortex as is related to real taste stimuli.
Using different concentrations of taste stimuli we will also explore how concentration modulates brain response. Combinations of tastes are known to modify perception, for example sweetness reduces bitterness, and umami enhances saltiness. In a final experiment, we will ask the question of why mixing tastants can lead to enhancement or suppression of taste perception by assessing the brain's response to paired mixtures of tastants, and investigating the cortical representation of these suppression and enhancement effects.
Overall, this research will considerably advance our understanding of human taste perception.

There are five basic tastes: sweet, salt, bitter, acid, umami. Animal studies using extracellular recordings suggest a chemotopic organization of the primary gustatory cortex (PGC), and a recent optical imaging study supports the preferential response to tastants in defined spatial areas of the PGC. A number of functional MRI (fMRI) studies have assessed the brain's response to tastants, however no human studies to date have achieved the high spatial resolution required to assess responses at the level of a chemosensory gustotopic map.
Our research will use experimental designs and analyses of ultra-high field (UHF) MRI data to map the representation of tastants in the PGC at very high spatial resolution. We have pilot data to show that bitter and sweet tastants are separated in the PGC. This proposal builds on this, forming a gustotopic map of primary tastants and examining other putative 'metallic' and 'fat' tastes.
Taste perception varies depending on PROP phenotype/gustin genotype, and a new thermal phenotype called 'thermal taster status', for whom thermal stimulation to the tongue elicits a phantom taste. We will investigate variation in gustotopic maps across these phenotypes. We will also directly examine the phenomenon of thermal taster status, studying how phantom taste modulates responses in the PGC. We will determine how cortical response is modulated by increasing tastant concentration to establish whether this is a linear response or saturates. We will then address the question of intra-modal responses, assessing combinations of tastants that lead to enhancement (umami/salt) or suppression (bitter/sweet), and how they modulate activity in the PGC.
Taste stimuli for fMRI studies will be well characterised using a sensory panel, and assessed by all subjects to link the brain and perceptual responses. These neuroscience questions fit squarely in the BBSRC remit of understanding normal human function and have a strong interdisciplinary component.

We believe the research outlined in this proposal would benefit several potential stakeholders outside the immediate academic research arena, the current focus of industry focussed initiatives to understand taste perception include the need to combine behavioural sensory measures and neuroscience.
In the short term, basic and clinical neuroscience researchers would benefit from a neuroimaging tool to address this important research question. There have been 152 fMRI studies on taste perception (reported on Web of Knowledge) in the previous 5 years. The development of the acquisition and image analysis techniques for ultra-high field fMRI will improve the spatial resolution and sensitivity to assess taste processing. The impact in academic research is necessary to provide in the longer term wider industrial, clinical and economic benefits, and will also improve the clinical relevance of UHF fMRI.
The investment by Unilever in this project highlights the economic value of the work to the food industry. [ANNA - please add to this]. The collaborative nature of this project, with state of the art MR facilities, only available in two sites in the UK, will enhance the research capacity of business (here, specifically Unilever). The success of this project would attract R&D investment from further global business in both the food industry and clinical setting.
This project addresses several of the areas highlighted in the mission statement relevant to the Health and Wellbeing including the need to understand food choice. Changes in life style have led to increased consumption of pre-prepared, industrially-processed foods, which are generally high in sugar and salt. Obesity and associated metabolic disorders (diabetes, fatty liver and cardiovascular disease) now constitute the number one public health problem. As there is currently no evidence for a change in these social trends, this problem must be addressed by concerted efforts from many parties including the UK food industry to improve our understanding of how taste is perceived.
New windows into brain function will also fuel the public's interest in neuroscience and taste perception, creating educational impact across all age and societal groups, highlighting the importance of health and well-being and food choices. The project will improve the understanding of taste perception in individual subjects (here by phenotype), however it could be further developed as a clinical tool to assess cortical changes in patient groups such as schizophrenia and dementia.
Dr's Hort and Francis have over 10 years of experience working closely with industrial partners in the global food industry, with a previous BBSRC grant to assess cortical response to fat, which has led to a number of high impact papers, and media interest, and we believe that this work will equally attract such interest and outcomes. There are currently few sites researching taste perception, here we use state of the art technology coupled with renowned sensory expertise, placing the UK at the forefront of multidisciplinary taste research.