The taste of yellow: Synesthesia and a crossing of the senses

Synesthesia is loosely defined as a merging of the senses, the notion that one sensation can trigger a separate perception. This is most commonly manifested as individuals who perceive color with letters or numbers (known as grapheme-color synesthesia), however other variants include experiencing taste with words, texture with taste, or color with music. It is important to note that the secondary, or concurrent, sensation does not replace the primary, or inducer, perception, but is instead experienced in addition to it. There are currently 61 known variants of synesthesia, spanning the perceptual spectrum of color, taste, sound, touch, and even higher level cognitive conceptions, such as language. At first glance, these phenomena seem quite unique and binary (after all, you either taste rectangle or you don’t), and the prevalence of synesthesia was originally thought to be roughly 1 in 1000. However, new research on sensory integration has revealed that varieties of synesthesia may be much more common than originally thought, and that there may be a sliding scale in the amount of sensory cross-talk among individuals.

Synesthesia is thought to derive from the periphery activation of neurons in unrelated sensory regions from the primary stimulus. For example, regions involved in processing linguistic or textual information may “bleed over” and begin to activate neurons in the area of the visual cortex pertaining to color. Functional imaging analyses confirm these suspicions, with both primary (inducer) and secondary (concurrent) neural regions experiencing activation upon an encounter with a trigger stimulus, such as the activation of both the auditory and visual cortices while listening to music. This phenomenon is also associated with a crucial increase in connectivity between the relevant regions, with an increase in white matter tracts (myelinated axons that carry signals throughout the brain) demonstrated using diffusion tensor imaging analysis. However, how these connections are created or maintained is not as well established.

One hypothesis is that as children our brains are much more malleable, containing many more synapses between neurons and allowing the potential for any number of neural connections to be made. However, as we age these connections are pruned out, leaving only those that are most highly utilized. This process is extremely important and beneficial to our cognitive development, allowing us to become much more efficient at common processes and behaviors. However, this does mean that we lose some of the more unusual connections that are not typically used, perhaps including some of these inter-sensory interactions. If you indulge in the type of thought processes that would activate these connections as a child though, such as pondering about the precise burnt shade of the number 5 (does it have more of an orange or red tint?), then perhaps these connections may remain.

Adults who report experiencing strong sensations of synesthesia are acutely aware of these extra perceptions, the blues from Beethoven’s 9th Symphony being quite pronounced and demanding attention. However other individuals may have much more subtle experiences, feeling merely a suggestive halo of violet in accompaniment. Furthermore, interactions between the senses are not limited to just those few who experience synesthesia. A recent article by Courtney Humphries from the Boston Globe highlighted how some restaurant, manufacturing and marketing companies are trying to tap into the common cross-sensory phenomena that we all have to make the consummatory experience more enjoyable. For example, research out of UCLA and Oxford University on the perceptual effects of the interactions between senses have shown that the crisp, both in regards to texture and sound, of a potato chip can alter the way we taste it, and that the color of a strawberry mouse influences our perception of its sweetness.

Finally, on a less scientifically established note, is the idea of reading people’s “auras”. These claims are often disregarded as quack extrasensory phenomena, but is it possible that some individuals may experience the cross-talk between color and identity that others have with numbers or days of the week? The fusiform face area (FFA) is a highly established region of the visual cortex that is crucial in processing facial information. Could the perception of auras arise from an interaction between color modalities and the FFA? In her article in the British Journal of Psychology, psychologist Julia Simner touches on this greater conceptual notion of synesthesia, citing individuals who experience an anthropomorphism of letters or numbers, associating them with personality traits. Although not a merging of the senses per se, this ordinal linguistic personification does share similar tendencies to the more traditional sensory grapheme-color associations, as well as the potential merging of color and person-hood.

Regardless of its form, synesthesia provides us with yet another reason to explore the fascinating world of neuroscience in a less conventional way, and helps us to remember just how intricate and magical our brains can be.

(Thanks to Sam Greenbury, Josh Keeler, and Lindsey Heck for the inspirational discussions for this post. For those who are interested in more information on synesthesia, I highly recommend the book “Wednesday is Indigo Blue: Discovering the Brain of Synesthesia” by Dr. Richard Cytowic and Dr. David Eagleman.)

Forget the stair master, brown fat is where the burn is at

There has been a flurry of articles recently about brown fat, the holy grail of body tissues. Brown fat is “good” fat that helps keep the body warm by burning a large number of calories, thereby helping to rid the body of “bad” fat. Until three years ago, brown fat was thought to exist only in rodents, where it was most commonly seen in the young and in thinner animals. However, we now know that brown fat is also present in human infants and is important for keeping newborns warm because they cannot shiver to create their own body heat. Brown fat was thought to gradually disappear as individuals age, but scientists now believe that adults can retain small levels of their brown fat from childhood, with thinner individuals maintaining a greater amount. What’s more, exercise can aid in this retention.

How brown fat promoted weight loss was not understood until recently. Researchers from Canada shed light on this process using PET-CT scans to identify the metabolic processes involved in brown fat. Published this month in the Journal of Clinical Investigation, the researchers subjected participants to acute cold exposure by placing them in a special liquid thermo-controlled suit at a temperature of 18 degrees Celsius (64 degrees Fahrenheit) for 90 minutes. During the course of this exposure, brown fat in the upper back experienced a significant increase in cell metabolism while working to keep the body warm, a process dubbed “cold-induced nonshivering thermogenesis.” The scientists hypothesized that this increase in brown fat metabolism was initially fueled by elevations in extracellular glucose and fatty acid uptake, and when these levels were depleted, the tissue began drawing on stores of intracellular triglycerides, meaning that brown fat was burning off lipid reserves during cold exposure.

As such, total energy expenditure of participants increased during the study by a whopping 80%, resulting in an average burn of an additional 250 calories. Curiously, there was no significant interaction between the amount of brown fat an individual had and their caloric expenditure, despite a wide variability in brown fat levels. However, this lack of effect could be due to the small study sample size, with only six participants. There was an interaction between brown fat and thermogenesis, though, with the added increase in metabolism helping to keep an individual warmer longer, and the more brown fat a participant had, the longer and colder conditions he or she could stand before starting to shiver.

A second study on brown fat looked at a more elusive type whose production is promoted through exercise. Published this month in the journal Nature, researchers at the Dana-Farber Cancer Institute discovered a new hormone–christened irisin–that transforms white fat into brown fat. This conversion is dependent upon the transcriptional co-activator PGC1-α, a protein found in muscle tissue that is generated during exercise and involved in metabolism, cell genesis, and protection against muscle atrophy.

Knowing its vast beneficial effects, scientists bred mice to have elevated levels of PGC1-α to determine its influence on brown fat and energy expenditure. Although increasing the levels of the protein had no effect on either brown or white adipose tissue, there were effects in a special type of subcutaneous white fat that is more susceptible to “browning.” This process involves increases in levels of the protein UCP1, which is highly active in brown fat cells and is involved in thermogenesis. These same effects also occurred following a regular exercise program in the mice, facilitated by changes in mRNA expression that was induced by increases in PGC1-α and subsequent protein production.

Through several elaborate experiments, researchers were able to narrow down the proteins to those affected by the gene expression of FNDC5, including the newly discovered irisin. Irisin is significantly elevated in both mice and humans after exercise, and it appears to be the key ingredient in the expression of UCP1 in the transition from white to brown fat. Direct injections of the protein resulted in increased levels of UCP1 in subcutaneous white fat, as well as subsequent increases in metabolism and small decreases in body weight in obese mice 10 days after exposure.

While both of these studies are still in their infancy, their potential implications for future research are very exciting. In the mean time, if you want to lose weight try going for a run, the benefits may be twofold. Alternatively, if you’re too lazy to work out you could try sitting outside in the cold for a while.*

*Please note, I do not actually recommend this as a safe or valid weight loss plan.

A predisposition for drug addiction? Shared traits between stimulant dependents and their siblings

An exciting new study published in Science this week attempts to answer the chicken-or-egg question pervasive in drug addiction research of, “Which comes first, drug use or brain abnormalities?” Dr. Karen Ersche from the University of Cambridge* approaches this question with a new perspective, investigating the biological siblings of dependent drug users. And as is the case with most seemingly dichotomous questions in science, the answer is: both.

Dr. Ersche’s group studied 50 stimulant-dependent individuals, 50 of their healthy, non-dependent biological siblings, and 50 unrelated control volunteers on a barrage of cognitive tests, personality measures, and brain imaging techniques. Throughout the assessments, there was a striking pattern of similar responding between the drug users and their siblings, significantly differing in their results from the control participants. Specifically, drug users and their siblings were both significantly more impaired on the Stop Signal Reaction Time Task (SSRT), a test of inhibitory control that measures how well an individual can stop an ongoing response when triggered. Impulse control and inhibition are traits known to be impaired in drug-dependent individuals, and poor performance on the SSRT has previously been associated with an increased risk for drug abuse. However, these dysfunctions have long been debated as to whether they can be attributed to accumulated years of drug use and its effects on the brain, or are instead a predisposing factor that places an individual at an increased risk for drug dependence. In the current study, sibling participants performed as poorly on the SSRT as drug-dependent individuals, requiring more time to inhibit their actions. This would suggest that poor impulse control is a shared trait that is present in drug-dependent individuals before the onset of abuse. However, impaired inhibition is clearly not a determining variable, as dysfunction in the siblings did not lead to subsequent drug abuse or dependency.

The brains of stimulant users and their siblings were also structured similarly as compared to control volunteers, with an increase in gray matter in limbic and striatal regions such as the amygdala and putamen, areas important in emotion regulation and habit formation. Drug addiction is often seen as a disorder involving dysfunctional habits, and the putamen is implicated in the acquisition of these compulsive behaviors, targeted by an influx of dopamine and commonly a site of subsequent adaptations in the brains of heavy drug users. Additionally, the postcentral gyrus was significantly smaller in both groups as compared to healthy volunteers, indicating further pre-morbid differences.

Finally, white matter tract integrity, the neuron fibers that travel throughout the brain relaying messages from one region to another, were less intact in both the drug users and their siblings, signifying a decrease in brain connectivity in these groups as compared to the control participants. This was particularly evident in the inferior frontal gyrus, a region implicated in impulse control, supporting the findings of impaired self-regulation characteristic of compulsive drug users. Changes in connectivity in this area were also associated with an increase in impulse control dysfunction on the SSRT, with decreases in this region accounting for 6% of the variability in SSRT scores. Additional damage to white matter tracts and gray matter regions were also seen in the stimulant-dependent group, correlating with years of stimulant abuse and suggesting further damage and dysfunction due to chronic drug use itself.

Taken together, the abnormalities in the limbic and striatal regions, which have projections to the frontal cortex, as well as the decrease in frontal cortical volume and impaired connectivity between these key areas, confirms prior research indicating the importance of the cortico-limbic-striatal circuitry in drug dependence. These differences in the brains and behaviors of drug users and their siblings could potentially serve as endophenotypes for the development of drug dependence, characterized as stable inherited traits that are seen in clinical disorders and that can serve as indicators or predictors of pathology, both in patients and in their biological relatives. As such, these abnormalities in key regions for drug addiction could act as biomarkers for an increased risk of dependence.

However, the key question arises as to what protective factors could exist in the siblings to prevent them from trying or developing dependence on drugs. Sharing 50% of their genetic make-up, as well as familial environments growing up, drug-sibling pairs have highly similar brains and behaviors. However, clearly the differences that do exist between these groups are incredibly important. Early drug experimentation may exacerbate the structural abnormalities seen in these individuals, increasing the risk for later dependency, or even creating an epigenetic effect as has been seen in previous studies investigating early cigarette smoking and its link to later drug dependence. Alternatively, protective factors in the siblings could include greater education, outside interests or hobbies growing up, or even an increase in exercise and physical activity.

The question of the path to drug dependency is still very much open, however this study may take us one step closer to finding the answer.

*Disclaimer: I am a member of the Ersche lab at Cambridge, but was not involved in this study.